Veterinary Care for Laboratory Animals

Publication Details

Standards of Veterinary Care for Laboratory Animals

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In June 2007, in association with the Federation of European Laboratory Animal Science Associations and the International Council on Laboratory Animal Science (FELASA/ICLAS) meeting in Como, Italy, ILAR and the International Association of Colleges of Laboratory Animal Medicine (IACLAM) invited representatives of laboratory animal medicine organizations from around the world to meet and initiate a dialogue about appropriate veterinary care standards for laboratory animals. Participants included individuals knowledgeable in regulations and guidelines pertaining to veterinary care of laboratory animals from organizations such as the American College of Laboratory Animal Medicine (ACLAM), Canadian Association of Laboratory Animal Medicine (CALAM/ACMAL), India’s Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), European College of Laboratory Animal Medicine (ECLAM), European Society of Laboratory Animal Veterinarians (ESLAV), FELASA, Singapore’s National Advisory Committee on Laboratory Animal Research (NACLAR), and the United States Department of Agriculture (USDA).

The sources of the various international standards were reviewed and summarized. These sources include standards established by government agencies, in the form of legislation, regulations, or policy, but also guidance derived from professional organizations primarily composed of laboratory animal veterinarians.

Based on presentations summarizing those guidelines and regulations, three main themes of interest could be distilled from the discussions: (1) the qualifications of the veterinarian, (2) the authority of the veterinarian within the program, and (3) the role of the veterinarian. Both convergence and diversity of approach to these three points were described by the participating representatives, suggesting that harmonization is occurring in some areas of veterinary care while in others there remain differences, some of which could be quite significant.

Qualifications of the Veterinarian

Table 1 depicts the wide variety of degrees that denote training in veterinary medicine. Some are bachelor’s degrees in veterinary medicine or veterinary science, others are doctorate degrees. Some reflect two years of undergraduate education, others four or more years of undergraduate and graduate education. Some degrees include coursework in laboratory animals, or even a “track” in research, others do not. This range of training may be augmented by postgraduate education or it may not—depending on the country’s available educational opportunities. Some veterinarians working in laboratory animal medicine obtain on-the-job training at institutions outside their country, thereby further enhancing their knowledge and expertise in the field.

TABLE 1. Veterinary Degrees Granted Around the World.

TABLE 1

Veterinary Degrees Granted Around the World.

To illustrate this point, the following descriptors of necessary veterinary qualifications are drawn from a sampling of different countries that may serve as a model for developing nations in terms of stipulating the precise qualifications of the veterinarian. The content of the veterinary care program under the direction of these individuals is remarkably consistent:

  1. The proposed revision to the European Directive 86/609/EEC (CEC 2008a) states: “To ensure the ongoing monitoring of animal welfare needs, appropriate veterinary care should be available at all times and a staff member should be made responsible for the care and welfare of animals in each establishment.” An approved amendment to Article 20 of the proposed revision further notes that “Member States shall ensure that, for the purposes of the authorization, the persons referred to in paragraph 1 have the appropriate veterinary or scientific education and training and have evidence of the requisite competence” (CEC 2008b).
  2. The proposed revision to the Council Directive builds on the current Directive (EEC 1986), which states: “persons who take care of animals used for experiments, including the duties of a supervisory nature, shall have appropriate education and training…. Adequate arrangements shall be made for the provision of veterinary advice and treatment…. A veterinarian or other competent person should be charged with advisory duties in relation to the well-being of animals.” Although this language is not very specific, it is clear that “appropriate” training and education will allow the veterinarian to provide sound guidance and treatment for the care and use of animals.
  3. The United Kingdom’s Animals (Scientific Procedures) Act (Home Office 1985) stipulates that “the well-being and state of health of such [laboratory] animals are monitored by a suitably qualified person in order to prevent pain or avoidable suffering, distress or lasting harm.” The A(SP)A further requires that “no place shall be specified in a project license or as a breeding site unless it is so designated by a certificate, which in turn requires a veterinary surgeon or other suitably qualified person to provide advice on animal health and welfare.”
  4. The section of the USDA regulations (USDA 1991) that addresses membership of the institutional animal care and use committee (IACUC) requires that a Doctor of Veterinary Medicine with training or experience in laboratory animal science and medicine serve as a member of the committee. Under the section on veterinary care, the regulations require that the personnel involved in animal care and use be qualified to perform their duties. Similarly, the proposed revision to the European Directive includes a requirement for the designated veterinarian to serve on the ethical review committee as well as membership of “the person responsible for the welfare and care of the animals in the establishment.”
  5. Singapore has established excellent standards for the credentials of the veterinarian associated with a laboratory animal program. The NACLAR (2004) Guidelines state that “every licensee shall employ an Attending Veterinarian (full or part time) with relevant training or experience in laboratory animal science and medicine. The veterinarian must also be licensed by the Agri-Food and Veterinary Authority (AVA).”
  6. The Guide for the Care and Use of Laboratory Animals (NRC 1996) was the most specific of the guidelines discussed during the roundtable. The Guide makes it quite clear that “A veterinary care program is the responsibility of the Attending Veterinarian who is certified or has training or experience in laboratory animal science and medicine or in the care of the species being used.” The reference to certification in the Guide may be met by specialty board examination, for example by ACLAM, ECLAM, the Japanese College of Laboratory Animal Medicine (JCLAM), or the Korean College of Laboratory Animal Medicine. It may also be met by the FELASA Category D (Specialists) certificate of competence. The individual certified at this level must be able to do the following (USDA 1991):
    1. Manage all animal, human, and physical resources in a laboratory animal facility;
    2. Make provisions for the health and welfare of animals;
    3. Provide advice, instruction, and assistance to investigators on laboratory animal–related matters and provide practical support of research programs;
    4. Ensure compliance with all the laws, regulations, and guidelines relevant to the production, maintenance, and use of laboratory animals and related to management of the animal facility;
    5. Be responsible for the development and presentation of internal and external education programs in the humane care and use of laboratory animals, which continue to develop the concept of the Three Rs (Russell and Burch 1959);
    6. Contribute to the in-depth development of innovative concepts in the humane care and use of laboratory animals, including carrying out research in laboratory animal science.

Thus, Category D includes veterinarians and other professionals of similar qualification. A third example is the certificate in laboratory animal medicine conferred on Canadian veterinarians.

Authority of the Veterinarian

Although this is one of the most important aspects of the veterinary care program, most countries do not describe in detail (or sometimes even mention) the authority the veterinarian must have to ensure good animal health and welfare in the laboratory animal care and use program. However, when the topic is addressed, there is a great deal of general convergence among the various guidelines. In summary, the consensus is that the veterinarian must have appropriate authority to execute the duties inherent in ensuring the adequacy of veterinary care and in overseeing other aspects of the program of animal care and use.

Role of the Veterinarian

Multiple roles are attributed to the veterinarian, and the scope of these varies among countries. Many guidelines and regulations do not describe expectations for the veterinarian in any detail. What follows is a compilation of the numerous roles defined for the laboratory animal veterinarian.

Often, the veterinarian is referred to as an advisor. The veterinarian may be expected to give guidance regarding surgical techniques, selection of pharmacologic agents, selection of animal models, periprocedural care, euthanasia, and/or training of other individuals in the program (to name a few key areas). Occasionally, this advisory role is augmented to an oversight role, particularly in the United States, where the veterinarian would have an oversight role through his or her function on the institutional animal care and use committee.

As might be expected, the role of the veterinarian in ensuring the health and well-being of the animals used for research, testing, or teaching is a point of convergence among the various regulatory and guidance documents. The source of the animals and transportation of those animals from that source to the institution, quarantine and stabilization, health monitoring, preventive medicine, disease surveillance, diagnosis, treatment, control of disease, surgery, pain and distress, medical records, euthanasia, and/or other clinical duties are listed as key responsibilities of the veterinarian.

Adjunctive roles of the veterinarian include participating in the training of staff; providing expert guidance to the occupational health and safety program (e.g., about zoonotic diseases, animal allergens, and other conditions); advising on biological and chemical hazard policies of the institution; monitoring and advising on hygiene standards; providing guidance on animal facility design; and providing input into the development of the disaster plan.

The Como meeting highlighted two common systems used internationally for the oversight of animal health and welfare: one relies on a veterinarian and supporting animal care staff, and an equally vibrant system in several parts of the world relies on someone other than a veterinarian who has the requisite expertise (e.g., in the species of animals used, the type of research, laboratory animal science), such as a scientist. In the latter system, the veterinarian often has a secondary role in terms of authority and responsibility. Not unexpectedly, these different systems may be correlated with significant differences in the education and qualifications of the veterinarian, as well as his/her authority and role in the program. Individuals who work in countries where the veterinarian has more primary responsibility for animal health and welfare are likely to receive a more extensive education (through the veterinary curriculum and/or postgraduate training and certification) and are more often considered partners in the research enterprise. In countries where the veterinarian serves in a more technical role, the lead scientist often has primary responsibility for animal care and use oversight.

Elucidation of international similarities and differences in the qualifications, authority, and role of the veterinarian in animal research programs will facilitate efforts to harmonize standards of animal care and welfare. It is important to understand the cultural and regulatory framework in which veterinarians work around the world, as well as the educational opportunities available to them. We should be familiar with the type of education and postgraduate experience achieved by the veterinarian to better gauge our expectations for the responsibilities and expertise of that individual. Any consideration of harmonizing veterinary care should include an assessment of the veterinary school curriculum, opportunities for postgraduate training (either in-country or outside the country), the country’s regulatory requirements, and training material resources (especially online resources in a variety of languages).

References

State of Laboratory Animal Medicine Around the World

Europe

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The most credible training for veterinarians in the area of laboratory animal medicine is through the European College of Laboratory Animal Medicine (ECLAM). Diplomate status in ECLAM goes beyond FELASA Category D, and I personally refer to it as FELASA Category E. It would be desirable to have European governments accept that requiring laboratory animal veterinarians to become diplomates is the best way to control and govern animal experimentation. In Europe, we have a long-standing history of laboratory animal science associations, whose membership is about 50% veterinarians and the other 50% those trained in biomedicine or biology or other sciences. The laboratory animal science perspective, therefore, is encompassed by FELASA.

To address the laboratory animal medicine side of things, in the UK there is the Royal College of Veterinary Surgeons as well as the British Laboratory Animals Veterinary Association. Both are long-standing and laboratory animal medicine has always been an important issue with them. The primary body in Europe is the European Society of Laboratory Animal Veterinarians (ESLAV), which initiated the European College of Laboratory Animal Medicine (ECLAM). However, this is a relatively new approach.

Of the 27 member states in the European Union, 26 have veterinary schools. Europe in total has 31 countries and 80 veterinary schools, but this number does not reflect the size of the population or the culture of the countries. For example, there are 16 veterinary schools in Italy and 16 in Spain, but only one in the Netherlands. Programs in laboratory animal medicine are relatively rare.

Veterinary training in accordance with FELASA Category D occurs in Italy, Germany, the Netherlands, Spain, and Sweden. The program in laboratory animal science in Milan, Italy, includes two years of training. In Germany, specialists in laboratory animal science have to train for four years. In the Netherlands, laboratory animal specialists undergo government-recognized training in Utrecht and several other places for 18 months. In Spain there is a master’s degree program in laboratory animal science and welfare in Barcelona and Madrid that lasts two years. Sweden also has a two-year master’s degree at Uppsala. Thus there is quite a variety in the training of laboratory animal science specialists.

In Europe, veterinarians have a special legal responsibility and professional obligation, especially in treating animals with medications, using anesthesia, or administering analgesics, all of which are not permitted to any other profession. However, from a regulatory perspective, there are differences among countries as to how much veterinary involvement is permitted in animal experimentation aside from the requirements for medications or prescriptions and anesthesia. These differences are apparent going from west to east in Europe, with some of the new countries in the EU being rather undeveloped in the field of laboratory animal medicine.

Programs for FELASA Category D based on veterinary training or in veterinary medicine are in Italy, Belgium, Germany, the Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. Again, there is inconsistency in the requirements of the various programs. In Italy, a diploma in laboratory animal science takes three years, while in Belgium it takes only two years. In Germany, the program is provided through the veterinary boards and training in approved institutions and takes three to four years; the four-year program is for laboratory animal science or laboratory animal medicine, while the three-year program is for animal welfare, which is also accepted under Category D. In the Netherlands the program is one and a half years, in Norway three years, Spain two years, Sweden two years, Switzerland four years. The United Kingdom has a two-tiered approach, with a certificate in two years and the diploma provided by the Royal College of Veterinary Surgeons in five years.

ECLAM was established in 2000 and in 2008 received permanent recognition by the European Board of Veterinary Specialization, which is our governing and controlling group, to which we must report directly. The founding of the College was an initiative of ESLAV and covers everything important in laboratory animal medicine.

The leadership of ECLAM identified the issues important to the organization and proposed initiating discussion on including ethics in addition to improving animal welfare in order to make these issues permanently a part of the organization’s goals.

ECLAM has established guidelines for examination and qualification of veterinarians for diplomate status. Although the examination is difficult, those who pass are highly qualified to direct a program in laboratory animal medicine.

ECLAM encourages research and promotes the communication and dissemination of knowledge in the field of laboratory animal medicine. The European Board of Veterinary Specialization has required training programs to be four years long, at least two and a half years of which should be under the supervision of a diplomate. There are 23 different veterinary specialty colleges and all are expected to have minimum standards.

The alternate training program takes two more years, but again two and a half years under the supervision of a diplomate. There are currently eight programs in various European countries. Once again, there is diversity among the programs. However, regardless of the training program, all who pass the exam are able to [attain] diplomate status. Reevaluation occurs every five years based on a 100-point credit system.

ECLAM and ESLAV have been involved with FELASA on defining appropriate veterinary care of laboratory animals. A paper describing the guidelines for veterinary care of laboratory animals was published by the FELASA/ECLAM/ ESLAV working group in 2008. The working group agreed that care of laboratory animals may be pursued by various professionals with different backgrounds, but the veterinarian is unquestionably the most appropriate person to provide veterinary care. The concepts presented in the paper have not been accepted as yet throughout the European Community.

The guidelines indicate that the professional judgment of a veterinarian trained in laboratory animal science is essential in the application of the recommendations on animal care and use to the specific institution. Veterinarians have specific legal responsibilities and professional obligations with respect to regulatory bodies.

A key part of the guideline paper is that education provides the basic knowledge and enables a person to work as a veterinarian, although legal and professional obligations vary among the countries. Undergraduate education emphasizes mostly the treatment and care of companion and farm animal species without much [attention] to laboratory animals. Because of this, it is critical that the laboratory animal veterinarian obtain specific education, training, and competence in dealing with these species.

Education in laboratory animal medicine needs to be improved throughout Europe and especially in the Eastern European countries. Generally, it is not the veterinary schools that train specialists in laboratory animal medicine; such training is done at medical schools where the actual research on the animals is conducted.

The European legislation currently does not specify further educational requirements for a veterinarian with legal responsibilities for longitudinal care, even in the most recent draft. The multilateral consultation of parties to the convention has adopted the resolution on education and training of persons working with laboratory animals. This resolution is based on the FELASA recommendations for the education and training of persons involved in animal experiments. These recommendations were suggested to be included in EU Directive 86/609, which currently reads “a veterinarian or other competent person.” It should be changed to read “a veterinarian trained and experienced in laboratory animal medicine or, exceptionally, another competent person” should be charged with advisory duties in relation to the well-being of the animals, but that person should also have the appropriate authority. Based on the FELASA recommendations, these would be persons trained under Category D and in rare exceptions Category C.

It is now possible to say that consistent veterinary postgraduate specialty training and certification has been fully established in Europe through the efforts of the veterinary profession, arising from the advice of the Commission’s Advisory Committee on Veterinary Training and overseen by the European Board of Veterinary Specialization. There is a recognized European veterinary specialization in laboratory animal medicine, as well as training, certification, and continuing education organized by ECLAM and ESLAV in addition to other organizations such as Royal College of Veterinary Surgeons and other veterinary boards. The Royal College of Veterinary Surgeons announced that, once ECLAM had achieved permanent recognition, they would drop their own diploma in favor of the ECLAM diploma.

Finally, I want to comment on the information received by FELASA and other organizations about the revision of the EU directive. It seems that the various commission directorates, in particular the directorate of research, have not been able to agree on the draft text of the EU directive. The Commission has therefore decided that it will submit the text as it stands to the “oral procedure.” This means that the College of Commissioners will decide whether to release the text as it stands into the codecision process or with only minor amendments, or they may decide it requires more extensive amendment and postpone its adoption.

Another possibility is that the College of Commissioners might decide that the directive requires more extensive amendment and may postpone the adoption of the draft. Apparently also in the Members of Cabinet meeting many objections were raised, especially in relation to the current draft, and thus no consensus could be reached.

The discussion that seemed to be most important concerned the excessive limitations on the use of nonhuman primates in Europe and there was potential bureaucracy originating from unclear definitions in the draft.

This may all change with the upcoming elections to the European Parliament in the spring. Also, quite a number of new commissioners will be appointed next year, so there will be different groups of people in Brussels as well as in Strasbourg.

Latin America

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Latin America is the region south of the border of the United States to Chile near the Antarctic. It includes 21 countries, 21 million square kilometers, and purchasing power of $5 trillion. Although most Latin American people are Western oriented, it really is not considered for some cultures part of the West but rather a unique and different region.

Latin American countries share many things, such as language, Spanish-Portuguese background, culture (to a greater or lesser extent) with Indian roots. Some of those countries also have scientific traditions, such as Mexico, where José de la Luz Gómez, using the Pasteur method, produced rabies vaccine in 1888 and became the first laboratory animal veterinarian in Mexico. Carlos Juan Finlay y Barres from Cuba identified the mosquito as the yellow fever agent and was the first scientist to identify an insect as a biotransmitting agent. Oswaldo Cruz, from Brazil, was probably the most well known veterinarian, and Bernardo A. Houssay from Argentina was the first Latin American to win the Nobel Prize in medicine, in 1947.

However, in spite of this glorious past, the present panorama for research and development is not equal and sustained for all Latin American countries. Latin American countries are divided into blocs of nations with respect to the potential economic impact of the region. Countries like Brazil, Argentina, Chile, Colombia, Mexico, and Costa Rica have enough resources and capacity to support the training of researchers [whereas] other countries do not.

The importance of the number of PhDs earned in a country has already been discussed. There is a very large gap between North America and Latin American countries as well as among the Latin American countries. Brazil has the highest number of students enrolled in tertiary institutions. This is also evident in the investment of the various countries in scientific research; on average

Latin American countries allocate less than half a point of their GNP, [only] Brazil allocates more than 1%. Latin American countries are trying to encourage their populations to pursue university educations. Mexico, Cuba, Colombia, Brazil, and Argentina have a large number of universities, but even so they are still distantly behind the United States and Western Europe. Similarly, Latin American countries lag the four top countries—the US, England, Germany, and Japan—in the number of highly cited researchers.

The scientific productivity of Latin America represents only 4% of that of the world. However, Mexico, Cuba, Brazil, Argentina, Uruguay, and Chile are striving to do high-quality science, in part by producing and using transgenic animals.

Most of the countries have institutional standards, ethics committees, or institutional animal care and use committees, but only Costa Rica (1994), Mexico (2002), and Brazil (2008) have national laws for the care and use of laboratory animals.

In Latin America there are several associations for laboratory animal science; these exist in Argentina, Brazil, Colombia, Cuba, Mexico, Peru, Uruguay, and Venezuela. There are also associations that bridge more than one country, like the Central American, Caribbean, and Mexican Association for Laboratory Animal Science (ACCMAL), and federations, like the South American Federation for Laboratory Animal Science (FeSSACAL), which includes countries in the southern part of Latin America. It is important to note that these associations include not only veterinarians but also technicians and scientists working in the field; there is no specific association or college for veterinary practitioners.

Appropriate courses in a formal educational program for laboratory animal medicine are found only in Cuba, which awards a master’s degree in laboratory animal science. Brazil, Argentina, Chile, and Mexico don’t have specific programs for laboratory animal science, but it is possible to get master’s or PhD degrees in the field by selecting credits on related subjects at veterinary, pharmacy, or medical schools. This is possible in at least two universities in Mexico, several in Brazil, and at the Universities of La Plata and Buenos Aires in Argentina.

In undergraduate veterinary medicine education in Mexico, it is possible to get a four-hour introduction to laboratory animal science, and students who are interested in pursuing laboratory animal science may take a 48-hour laboratory animal course. Similar programs exist in Argentina at La Plata University and Buenos Aires University. In other Latin American countries it is the pharmacy schools that teach care and pharmacologic use of animals, but not breeding, health, genetics, or environmental control.

The majority of animal facilities in Latin America do not have a full- or part-time appointed veterinarian except in Argentina, Mexico, Cuba, Venezuela, and some parts of Brazil.

Distance education is viewed as a very important endeavor in the future. The veterinary school in Mexico is working to sign an agreement with the University of Guelph in Canada to be able to use a Spanish version of their animal medical certification program to provide education not only in Mexico but in all countries interested in the field. Other programs are available in both Spanish and English—e.g., a bilingual institutional training program for scientists offered by the University of Miami.

A certification program run by ConeVet (National Council for Veterinary Medical Education, the academic branch of the Mexican Veterinary Medical Association) for laboratory animal veterinarians aims at improving the quality of education. There are actually two programs, one for accreditation of veterinary schools and one for certification of practitioners. The certification program is board-specific for each species, and each candidate must pass one of two boards: one based on credentials for those who have a lot of training or experience, and the other on an exam for those newly coming into the field. The credential certification process occurred only in 2006, for the initial certification period. The assessment was based on professional experience (500 possible points), continuing education (500), professional education (400), teaching or academic activities (200), publications (400), and related association/college membership (150). The minimal certification score for this evaluation was 1100 points.

For the laboratory animal medical certification process by exam, there is an agreement between CENEVAL (National Center for Higher Education Evaluation) and ConeVet. CENEVAL is an independent organization for testing, very similar to the Educational Testing System in the United States, and runs the license and certification examinations. The certification is actually given by ConeVet.

The exam is long—two days for four hours each day—and is divided into different sections covering diverse areas of knowledge and professional abilities. It is given twice a year, in April and December during the AMCAL (Mexican Association for Laboratory Animal Science) meeting.

The future holds some interesting opportunities. While Latin America covers a large area, there is a real advantage because the countries share the same language (with the exception of Brazil, but Portuguese may actually be closer to Spanish than British English is to American English). Therefore, if we work together to establish high-quality courses for this kind of education, we may be able to consolidate the examination process, particularly if we share experience with similar certification bodies, not only from Latin America but also from Europe or Asia.

We can also benefit by working together to establish an umbrella organization, a Latin American Association for Laboratory Animal Science. This may also serve to help establish a Latin American College for Laboratory Animal Medicine or a Laboratory Veterinary Association. In these ways, we will have an opportunity to encourage and improve the quality of veterinary education in laboratory animal science in these areas.

North America

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I would like to address a very serious issue in terms of the state of comparative medicine and laboratory animal medicine worldwide, particularly the state of the veterinary medicine profession in North America.

I urge all who have not seen the Foresight Report (J Vet Med Ed 34:1-41; 2007), commissioned by the American Association of Veterinary Medical Colleges (AAVMC), to read and digest it since I believe it is critical for the progress and the future of veterinary medicine in general, and certainly for comparative medicine. The summary of the report states that veterinary medicine is the only profession in the health and medical field whose members are trained in comparative medicine. Veterinarians are critical components of public health and essential health care providers to society locally, nationally, and internationally in light of their concern for animals, their health and well-being, and their interface with people. However, the summary also states that veterinarians must first demonstrate relevance to new societal needs and trends in order to be recognized and remunerated for their knowledge, compassion, integrity, and judgment.

Since 1989, the veterinary profession in the United States has been fairly static in terms of the number of veterinarians graduated, which is a little over 2,000 per year. Based on public demand, veterinary schools are primarily training veterinarians to fulfill roles in small animal practice. So about 44,000 veterinarians practice small animal medicine, while a much smaller number are involved in large animal and equine medicine, with the remainder in public and corporate veterinary medicine.

Thus with respect to the veterinary curriculum, the disciplines of laboratory animal medicine and biomedical research are competing against tremendous odds for young veterinary professionals. Several publications of the National Research Council—National Needs and Priorities for Veterinarians in Biomedical Research (2004), Critical Needs for Research in Veterinary Science (2005), and an earlier document, New Horizons in Veterinary Medicine (1972)—stress the need for the veterinarian to become involved in corporate veterinary medicine, academia, and industry to fulfill societal needs.

In recognition of these reports and the Foresight Report, the National Research Council has appointed a committee to assess the current and future work-force needs in veterinary medicine. The report, which is still in preparation, will be an important report exploring both historical changes in veterinary medicine and the adequacy of the current supply of veterinarians in different occupational categories and employment sectors. The report will also explore factors that will likely affect the future demographics of veterinarians.

It has been well documented that there is a tremendous need for adequately trained laboratory animal medicine veterinarians and veterinarians involved in biomedical research. From 1999 to 2002, the average numbers of job postings per year for these positions were 68.5 in academic institutions, 28.3 in industry, and 7.5 in government. Those numbers are not likely to be different now.

What are we doing as a profession in the United States to fulfill the needs in these three sectors? In looking at the number of diplomates of the American College of Laboratory Animal Medicine (ACLAM), from 1996 to 2002 there was a 3% annual increase in membership; from 2002 to 2008, the total number has increased to 718 diplomates, but over those six years there was only a 7% overall increase, a little over 1s a year.

The numbers clearly indicate that the profession has not met the needs of the academic, industrial, and government sectors. Compounding the problem is the significant number of retirements that will occur over the next 20 years. Although we practice the 3Rs and are looking for in vitro models and other alternative methods with which to conduct biomedical research, there is no doubt that animal use is going to remain a considerable part of the biomedical research engine.

In reviewing the NIH grants portfolio over the last 20 years, the data show that an average of 50% of grants involve the use of laboratory animals. It is very likely that the use of laboratory animals in research institutions continues to grow but at a more modest rate in the last several years because of the constraints of the NIH budget. Given the continued need for animal research, we must meet the challenge of eliciting interest and enthusiasm for comparative medicine in our young veterinary colleagues. While veterinary medicine is thought of as a clinical-based profession we need to provide persuasive arguments and opportunities in public health, regulatory agencies, academic, industry, and biomedical research. In addition, we need to promote and transmit this breadth of opportunity to our young colleagues and to the public in general.

The veterinary profession must exert coordinated efforts to communicate to students beginning in middle and high school, provide research opportunities to undergraduates, and, importantly, provide opportunities to veterinary students to work in research laboratories.

Another approach to meeting the needs is to diversify the career interests of the veterinary student body. This means that we must include in the applicant pool individuals who are interested in diverse careers, including biomedical research and comparative medicine. The admission process for veterinary schools must reflect this need.

One of the recommendations that came out of the 2004 NRC report was that all veterinary schools should offer at least an elective course in laboratory animal medicine and more veterinary schools should require course work in this specialty. Also, the National Examination Board should include questions germane to the subject matter on the national veterinary boards. Comparative medicine specialists should actively seek out and mentor students with an aptitude for and interest in comparative medicine.

ACLAM did a survey in 2006; this project, led by Lesley Colby, is in review and will soon be published. The committee asked the question that we posed in our Academy report: Is a laboratory animal medicine course offered as part of the current curriculum to your students? In a somewhat reassuring response, 65% said yes, but 35% said no. Asked whether the students received lectures in laboratory animal medicine as part of other courses, a higher percentage (87%) said yes because having a few lectures scattered through the course is easier in terms of curriculum development. However, when asked if laboratory animal medicine–related problems were used in case studies, only 29% responded yes.

So it is clear that we are not doing a very good job of exposing veterinarian students to career potential in comparative medicine or biomedical research. Dr. Steve Barthold illustrates this outcome very effectively by comparing career choices with pipes: the largest-volume pipe is the one for clinical practice; the pipes for science and laboratory animal medicine are much smaller.

One obstacle in attracting veterinary students into biomedical research is financial debt. A survey of veterinary students revealed that they averaged over $100,000 of debt at graduation. They must weigh this loan repayment obligation with salary expectations over their career. In addition, choosing a career in biomedical research presents the daunting task of having to successfully secure funding over the duration of their career from NIH and other external sources.

These impediments must be considered when trying to help the students understand that the profession of laboratory animal medicine is a viable alternative to clinical practice in terms of remuneration and biomedical research. This requires mentoring and an environment in the laboratory to set the proper tone for a research experience.

I would like to share a quote with you from one of the students at the conference last year: “A brilliant mentor with a great sense of humor will undoubtedly be more inspiring than a brilliant mentor who won’t crack a smile or works 18 hours a day.” This quote makes me think of my friend Steve Barthold. One must balance the successes and the satisfaction gained from a career in laboratory animal medicine and must transmit that enthusiasm to younger colleagues and high school students to let them know that research and involvement in corporate practice is a satisfying career.

There has been a very aggressive effort by ACLAM as well as the American Society of Laboratory Animal Practitioners and others to establish, critique, and approve training programs in the United States. There are currently 41 of these training programs that cover a wide spectrum of opportunities for students, including positions in medical schools, veterinary schools, research institutions, pharmaceutical companies, primate centers, and the military.

An important component to consider is funding. The NIH National Center for Research Resources (NCRR) has historically been the catalyst and the major provider of training in laboratory animal medicine and biomedical research, and it continues to do so. Although its efforts and the successes of these programs over the years are truly appreciated, the amount of dollars put into these programs for biomedical training programs has been flat over the last 20 years, with the exception of the relatively new T-35 program, which continues to grow and provides a summer research fellowships for veterinary students. The number of trainees has grown to 146 per year. These are the students who can be cultivated into postgraduate careers in laboratory animal medicine. We must continue to help our colleagues at the NIH convince the legislators of the importance of this occupation as part of the biomedical research enterprise.

NCRR recently announced its intention to build the research workforce as part of its strategic plan. One of its central recommendations is to increase the number of qualified research veterinarians and ensure that veterinarians are recognized partners on translational research teams. This presents a real opportunity for all of us to embrace this plan and to champion the concept of one medicine, one health. We must capitalize on the opportunity and move forward.

In conclusion, there clearly are challenges that lie ahead for us. We have to convince the deans and professors in the veterinary schools that there is a vital place for a veterinarian in a research setting. Clinician scientists may also be involved, but the goal is to create a higher profile for veterinarians in their professional training so they may reach out beyond the clinical track. We want to encourage new career paths and role models. We must try to effect substantive curriculum change in the veterinary profession and encourage students to apply for these T-35 training programs. In addition, we need to expand our opportunities in the comparative medicine programs, not only in veterinary schools but also in other research institutions, including medical schools.

I leave you with the epilogue of the Foresight Report: “This is…a pivotal point in time for the veterinary profession and for veterinary medical education. A decision to broaden the scope and potential of veterinary medical education is fundamental for the profession to navigate this transition.”

And finally, as Paulo Coelho said, “The truth is that all problems seem very simple once they have been resolved. The great victory, which appears so simple today, was the result of a series of small victories that went unnoticed” (from Warrior of the Light, 2003).

A Path Forward

Role of the OIE

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This presentation is an overview of the nascent role of the OIE in animal welfare, and will emphasize where that role might relate to the theme of this session and perhaps the overall theme of the conference.

One must bear in mind that the OIE’s involvement in animal welfare goes back only six or seven years, so we are looking at relatively recent international involvement. My presentation is made wearing two hats, both as Director of Animal Welfare for the New Zealand Ministry of Agriculture and Forestry and as Chair of the OIE Animal Welfare Working Group.

The OIE consists of 172 countries, making it bigger in terms of membership than the WTO, which has approximately 149 countries. Therefore, by any standards, an intergovernmental organization representing 172 countries has a significant role to play in influencing public policy in governments around the world, and also plays a key role in implementing agreed policy.

The raison d’être of the OIE relates to ensuring transparency related to global animal disease and zoonoses, and also to coordinating the collection, analysis, and dissemination of scientific animal health information. The OIE is very conscious of the need to work closely with scientists in a whole range of disciplines. The organization strives to improve the legal framework and resources of national veterinary services and to provide expertise and encourage international solidarity in the control of animal diseases.

In the WTO mandate, the international standards of the OIE safeguard world trade by publishing health standards for international trade in animals and animal products, to provide a better guarantee of animal production food safety and to promote animal welfare through a science-based approach.

Since its inception the OIE has operated from a relatively small central bureau in Paris, with about 40 staff members. It has a network of reference laboratories and collaborating centers around the world, totaling almost 200. Reference laboratories exist for specific disease entities, such as blue tongue, rabies, or foot and mouth, and the collaborating centers are centers of excellence from which the OIE can draw expertise to assist [in the] achievement of its mission. Currently, there are 171 reference laboratories and 24 collaborating centers.

Animal welfare is a new area for the OIE. There is potential for collaborating centers to be established in each of the OIE’s regions to support its work in animal welfare. A group in Italy that has recognition for veterinary training, epidemiology, and food safety is also playing a role in animal welfare. We in New Zealand sought recognition for the animal welfare science and bioethics center at Massey University headed by Professor David Mellor. There is opportunity for other centers to achieve that recognition and assist the OIE over the next few years and decades.

Two or three years ago, the 172 member countries expressed a desire that the OIE play some role in the laboratory animal welfare area. The initial decision was to establish a dialogue with existing international organizations, particularly ICLAS and IACLAM, and to identify common interests. A formal memorandum of understanding (MOU) has now been signed with ICLAS, which is similar to the OIE’s MOUs with other international organizations to allow for information sharing and mutual participation in identifying areas for synergy, with the goal of emphasizing the role of the veterinary profession generally and of veterinary services in particular.

The OIE has a four-year strategic planning cycle and in the period from 2001 to 2005 some building blocks for animal welfare were established, and guiding principles in animal welfare were identified at the first OIE global conference in Paris. The profile of animal welfare was further enhanced in the strategic plan for the period 2006–2010. The OIE has published and promulgated a set of nine guiding principles, with emphasis on the linkage between health and welfare, something that often is not fully appreciated and recognized by the public at large or by politicians.

The OIE has a mandate on animal welfare in the use of animals in scientific studies and education. OIE supports appropriate animal use in the fields that are relevant to animal health and welfare and animal production food safety, including research and development of veterinary medicines, diagnostic tests and vaccines, and education of veterinarians and other professionals. Another program established under OIE auspices is the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH). In addition, the OIE can help in the international facilitation of adoption of nonanimal tests where scientifically validated. This will complement work done in Europe by the European Center for the Validation of Alternative Methods (ECVAM) and work done in the US by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

The mission of the OIE Animal Welfare Working Group, which I have chaired since 2002, is to provide international leadership in animal welfare through the development of science-based standards and guidelines, provision of expert advice, and the promotion of relevant education and research. The working group represents the five OIE regions; Professor David Fraser from the University of British Columbia represents the Americas. We consider the available science, but also highlight the importance of ethics to ensure that we take a holistic approach to our mission. The detailed work on producing standards and guidelines is carried out by expert ad hoc groups established by the OIE Director-General; we have had six ad hoc groups established over the six-year period, and the process works very effectively.

The working group follows the established guiding principles and takes an outcomes rather than an inputs approach. The principles emphasize the importance of the linkage between health and welfare, the Five Freedoms,1 the Three Rs, and the need for a scientific basis for standards, and recognize that better animal welfare can improve productivity and deliver economic benefits.

In 2005 the OIE developed four sets of standards for the transport and slaughter of livestock. At the time, there was concern about diseases like BSE (bovine spongiform encephalopathy) and avian influenza, slaughter practices, and the ethical acceptability and economic justification for transporting animals large distances for slaughter. The OIE is working to implement these standards by using its regional infrastructure to facilitate the process.

We are now following the same process for laboratory animals by looking at principles and guidelines for animals used in regulatory testing and teaching. We are also liaising with the VICH and making sure that we engage with all the international stakeholders, be they industry groups or welfare NGOs. An ad hoc group was established to develop the guidelines, which is the OIE’s modus operandi for such tasks. Several participants in this conference are members of the ad hoc group that met for the first time in December of 2007 and will meet for a second time in December 2008. They will address these topics: animal care and use program and committee; assurance of training and competent provision of veterinary care; physical facility and environmental conditions; husbandry; source of animals; occupational health and safety; and importance of postapproval monitoring and validation. The group also identified veterinary training in laboratory animal medicine, transportation of animals, and regulatory testing as topics to be examined in the future.

A second global conference, to be held in Cairo in October 2008, will be a further manifestation of the relevance of global standards particularly to the developing world.2

Information on OIE activities is available on its considerably enhanced website or in the OIE Bulletin or Scientific and Technical Review Series publications.

It is certain that the OIE’s involvement will not be transient. In addition, the OIE is heavily wedded to the One Medicine, One Health concept. Over the next one to two years there will be a major conference sponsored by the OIE and attended by veterinary deans from around the world to ensure that veterinary education meets the needs of society. There will also be a major review of future needs in veterinary education published in the OIE scientific and technical review series in 2009.

Introduction to AAVMC

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I will give a very brief introduction of the Association of American Veterinary Medical Colleges (AAVMC) and some of the key activities in this area, and then introduce Dr. Chaddock, our Deputy Director, who will make the main presentation.

The Association of American Veterinary Medical Colleges represents and has as members all 28 colleges of veterinary medicine in the United States as well as all five colleges of veterinary medicine in Canada and nine departments of veterinary science in the US. AAVMC membership is open to departments of veterinary sciences and comparative medicine. Members also include institutions that provide significant training in veterinary medicine, three colleges of veterinary medicine from the UK, one from Ireland, three from Australia, and one from New Zealand. AAVMC coordinates the affairs of all these institutions.

The mission of AAVMC is to improve the quality of life for people and animals by advancing veterinary medical education, improving animal health and welfare, strengthening biomedical research, promoting feed safety and food security, and enhancing environmental quality. Animal care and welfare are of major importance to us in all of these avenues in achieving our mission. One of our major programs is advocating with the US Congress to increase resources for colleges of veterinary medicine in order to increase class sizes. We need more veterinarians, as there has been no increase in the number of veterinary graduates (2,500) in 30 years. If the number of veterinarians going into laboratory animal medicine tripled, there would be shortages in food animal medicine, public health, or companion animal medicine. We need to recruit more veterinarians into all of these critical areas.

A second major AAVMC program is the development of a strategic plan, which has not been done before. The board of directors, whose president is Dr. James Fox, has undertaken this effort; he has provided leadership in the avenue of animal care and welfare that is so important to education and research.

In considering the roles of the veterinary colleges, a couple of important questions have come up:

  1. How should the use of animals in education and research in colleges of veterinary medicine be addressed?
  2. What should our veterinarians in colleges of veterinary medicine or veterinary students be taught in this area?

To address these issues, our board of directors has partnered with the American Veterinary Medical Association, the US Department of Agriculture, and the National Institutes of Health NCRR to hold a scientific meeting on animal care and welfare ethics in November 2009 (the agenda and papers are available at www.avma.org/awsymposium).

Dr. Chaddock is our lead in working with partners to plan and conduct this meeting. He is a veterinarian who joined AAVMC with a whole career’s experience in different perspectives, working in various areas of our profession and in leadership.

AAVMC Strategic Plan

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I will discuss a very exciting program that the AAVMC in collaboration and partnership with AVMA will have here soon. It is important to emphasize Dr. Fox’s leadership not only with AAVMC and ILAR but with the AVMA. In the last year, he chaired the animal care welfare committees of both the AVMA and the AAVMC, so it is his vision and his leadership that brought this together for the event that is going to occur. I also want to mention the Morris Animal Foundation, which will help to support this venture.

The title of the conference is Animal Welfare as an Evolving Discipline, and Educating Veterinarians to be Effective Decision Makers and Advocates.1 It is an international educational symposium that will be held November 8–11, 2009, at one of our premier member institutions, Michigan State University in East Lansing. The program is being designed with requested input from all of our member institutions. It is important to emphasize that our intended audience will include scholars involved in animal welfare, the laboratory animal community, and veterinary medical students in the international realm. The intention is to satellite broadcast the program.

On the first day, the program will address the role of science in society and will include the definition of animal welfare, key policy statements in this area, and how different stakeholders frame and discuss animal welfare issues. The point is to address animal welfare from a scientific point of view, determine how it is measured, how it is perceived by different people, and ethical approaches to assessments of animal welfare. The role of ethics will include cultural norms, differences in religious expectations, morality, and cost/benefit from the perspective of the role of science in society.

The next topic area will be entities and agreements and will consider the different groups involved in animal welfare decisions about which veterinary medical students must know; these groups include veterinarians, scientists, researchers, industry leaders, retailers, advocates, animal welfare groups, the public, lobbyists, and attorneys who are involved in the animal welfare area. The groups will be brought together to speak and participate in roundtable discussions with the aim of informing students about important issues to consider such as agreements, standards, available voluntary schemes, regulations, legal considerations, and international differences. The speakers will address research, the history of animal welfare and animal care research, and the current state of that research today worldwide. It is important to have international presentations so that the students get a well-rounded view of the issues. After the presentations will be roundtable discussions that will include the students so that we can learn what they are being taught in their schools.

The second day will focus on the topic of meeting societal needs through veterinary education and research and will examine models for veterinary animal welfare education. In advance of the meeting, we intend to survey deans, department heads, faculties, and students about how animal welfare is and isn’t considered in DVM degree programs. The survey will query the students about what they learned and whether their expectations were fulfilled during the four-year program.

In addition, we will look at preveterinary education and students’ background before attending veterinary school. We need to examine the selection criteria for veterinary students in animal care and welfare from [the point of view of] both US and international expectations. This session will also include a roundtable discussion with student participation.

We also want to center some of these discussions on post-DVM education. Since education is a lifelong process, continuing education is essential. The session will include graduate program specialization and the Foresight Report to delve into how we are meeting societal needs in educating not only our students but also our practicing veterinarians.

The last part of day two will present a model for animal welfare research. We will look at program design, the applied priorities of our research programs, access to results, and the application of the research to teaching veterinary students and how to apply it to meet societal needs. We will also address funding for animal welfare research, both private and public. We would like to develop a clearinghouse of funding information resources so new graduates and veterinarians will know how to access funding.

We will conclude on day three with a session on moving forward, focusing on communications with respect to animal welfare. This session will also look at veterinary culture in relation to animal welfare, particularly some special challenges faced by veterinarians employed by industry or a producer or somebody who owns animals in carrying out animal welfare. For example, how can the veterinarian bridge the gap between what an employer or animal owner wants and societal needs and expectations?

Finally, the conference will address the issue of advocacy—how can we get veterinarians involved in becoming activists, community leaders, possibly running for Congress, to be the senator that Dr. Pappaioanou says we need to contact? Veterinarians need to step up to the plate rather than letting somebody else do it. So the sessions tackle how to become involved, what to advocate, and how to educate the public.

We believe this will be an excellent symposium and encourage all of you to attend. Drs. Golab and Granstrom at AVMA are the lead people for this program.

Online Training and Distance Learning

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My presentation will continue with the theme of providing adequate veterinary care for animals used in research, teaching, and testing. One potential solution for providing veterinary training in this area is through online training and distance learning.

I will focus on some of the challenges in providing adequate veterinary care for animals used in research, teaching, and testing, particularly the aspect of veterinary training. I will also discuss trends in educational delivery that are occurring at universities and colleges across North America and may be occurring in Europe as well. Finally, I will talk about online learning programs for veterinarians and provide an example,1 with some potential future applications.

Current challenges in laboratory animal medicine (LAM) occur because there is now an increasingly complex globalized research environment, with companies and institutions having multiple sites around the world, and there is difficulty ensuring adequate veterinary care and harmonization of training across all these sites.

Even in countries where there are well-established training programs, there are shortages of well-trained personnel. Increased public expectations for the accountability of scientists and institutions, and for providing adequate veterinary care and ensuring research animal welfare, have led to an increased need for veterinarians. This has resulted in increased employment opportunities for veterinarians; however, there are not enough adequately trained veterinarians to fill these roles.

In addition, there is difficulty in recruiting enough veterinarians to return for graduate work and specialization in residencies in some of these programs, primarily due to debt load. In North America, veterinary students graduate with huge debt load and they cannot afford to come back for additional education or training, although they might like to. The stipends may or may not be attractive to these new graduates, and we don’t have enough stipend positions to bring these veterinarians back. Furthermore, the traditional methods for training specialists in laboratory animal medicine are expensive and not necessarily efficient. I say this as a program leader for our research-intensive ACLAM-recognized doctoral training program at the University of Guelph. I still believe this is the gold standard for LAM training, but it isn’t geared for a high volume of trainees because it is based on one-on-one intensive mentoring—the program can produce only one graduate every three years, which is not sufficient. Together, all the institutions that are producing these very intensively trained specialists cannot meet the employment opportunities and needs out there.

Other training options to bring enough veterinarians into the field and ensure that they are adequately trained must be explored. The immediate problem is that there is an urgent need for entry-level training for licensed veterinarians in laboratory animal medicine to fill some of these roles. This population includes licensed clinical veterinarians who may be looking for a career change, some who own clinics, who are working or consulting at a biotechnology company or community college, or who are working full-time in a field but are unable to return for graduate studies or a residency because of location, financial constraints, or because they have no desire to go back to school for another three to five years. A new approach is needed to attract these adult learners and provide them with the basic education they need to fulfill their responsibilities as attending veterinarians in these institutions.

Distance education has been increasing in popularity in recent years. One of its main advantages is that the participants are not required to travel to commit to an institution. They may do it from a distance, hence its name. Also, participants can study when it is convenient, allowing them to work full-time and attend to family needs at home, then study during evenings or weekends, when they have free time. I would argue that a distance education program is very well suited for providing both basic and, perhaps in the future, advanced information to veterinarians in laboratory animal medicine.

Current trends in educational development are toward an increasing number of courses taught in the online classroom. Many full-time students attain degrees with these blended programs, with traditional didactic courses on-site and up to 50% of the program provided in online courses. Students seem to like a combination of both. Even with traditional courses, the online classroom is becoming increasingly used, so students may be given an assignment in class, and then a portion of their grade will be assigned to an online discussion group that is monitored by teaching assistants (TAs) or the professors.

However, the program needs to be very well structured with very clear objectives to be effective in educating students. There is no daily face-to-face meeting with the TA or the professor, so the course goals and progression need to be very well structured, learner-centered, geared to developing problem-solving skills, and still provide the interaction that is normally achieved in the classroom, tutorial, or seminar.

Online course participants need to be motivated since they are working on their own. This format is not suitable for everyone, since it is not easy to work an eight-hour day and come home and have to study at night. However, with motivation it can be done successfully.

It should be noted, however, that it is not necessarily less work for the instructor to conduct online courses. There is a lot of development work in terms of setting up the program, and then in providing feedback and facilitating instruction during the course period. In addition, this format is very different from traditional teaching forums and involves a different educational philosophy. It does not involve just taking PowerPoint presentations, taping an audio, and putting it on a website. This format focuses on short bursts of intensive learning followed by some type of application to evaluate consolidation of learning.

MIT has an absolutely astounding open courseware project with over 1,800 courses available online. Tufts University also has some excellent open courseware available. The MIT Open Courseware website has PowerPoint presentations from all the courses offered at MIT. However, while the information is freely available, the certificate, diploma, and degree programs are not free. Also, it should not be assumed that, because the information is provided for free to the public at large, people are consolidating and learning it. The skill is in the instructors’ abilities to provide the information in an online setting to educate people.

It should also be noted that there are costs involved in online courseware: software costs for those writing online platforms, costs for staff who are doing the administration, and in some cases an honorarium for the course instructor.

I would now like to provide an example of how we have tried to deal with the challenge of providing adequate veterinary care for animals used in research, particularly veterinarians working in laboratory animal medicine.

Canada is a large country with a relatively small population. There are about 220 veterinarians in laboratory animal medicine, working across the country in a variety of sectors, often in very remote locations. We sometimes have a language barrier since there are two official national languages.

Since for many years there was only one formal training program in Canada, at the University of Guelph, with a low graduate output, most of the veterinarians working in laboratory animal medicine have entered the field through experience rather than by formal training in LAM. These veterinarians are very well qualified with solid skills in clinical medicine and surgery typical of small animal practice. Several years ago, it became evident that there were facility compliance issues at some smaller institutions because of a lack of adequate veterinary training. Veterinarians did not always understand their full responsibilities as the attending veterinarian in these facilities. In conjunction with the Canadian Association for Laboratory Animal Medicine (CALAM/ACMAL) and the Canadian Council on Animal Care (CCAC), we determined that it was necessary to provide theoretical and applied training to bring veterinarians up to speed quickly. It was also deemed necessary to have mentoring contacts, because these people were physically isolated in many cases.

This situation led to the development of the LAM certificate program, a university-approved academic program of study consisting of a minimum of 160 hours of effort. That time is what the university has approved, but it may actually take a little longer for participants to work through all the material.

There are four courses in the program. The first is the web-based program that is a self-study course. It provides broad-based theoretical information on major themes in LAM. This is followed by three skills-based courses that are held at regional training sites across the country; I will talk about each of these in a little more detail. The LAM certificate program is partnered with the Office of Open Learning at the University of Guelph to provide the distance education platform and the technical support for running these programs.

The curriculum was developed in part from the Federation of European Laboratory Animal Science Associations (FELASA) guidelines for Category D specialists as well as from recommendations developed by the American College of Laboratory Animal Medicine (ACLAM) for formal training of laboratory animal veterinarians. An advisory committee comprising laboratory animal veterinarians from across Canada edited and produced the course content and assisted with question bank development; other veterinarians were conscripted as needed in the program to develop skills lists or to review materials. A skills list has been developed for the applied courses.

Participants who enroll in this program theoretically could complete it in as short as a month but we provide them with up to two years. Some participants are clinical vets who may own a practice and cannot take off four weeks in one year to complete the program. This program is envisioned as an entry-level tool and is not in competition with postgraduate training programs in this area. It is intended for a completely different population of veterinarians who have no intention of returning to school for further specialization.

The course covers bioethics, regulations, animal care committee function, anesthesia, analgesia, euthanasia, occupational health and safety, biosafety, and animal models. It is set up as a combination of online notes and heavy HTML mining, primarily to enable veterinarians to learn how to find sources of information through relevant websites and electronic resources. The program is multimedia to accommodate different types of learning, so participants receive a hard copy reader containing key papers, references, regulatory guides, short video clips, CDs, and DVDs. Some of these items can be used in their training programs in their own facility. Evaluations are both formative and summative. There are several short written assignments submitted electronically for evaluation by the coordinator, as well as multiple choice quizzes for each online topic. Participants must achieve at least 80% on these to pass, and they only get two chances to take any quiz, so the program of study is rigorous and must be taken quite seriously by the participants. Because we have a large question bank for each quiz, participants won’t get the same quiz twice.

There are currently three entry points for enrollment in the program throughout the year: October, February, and May. Once the participants are enrolled and the online course starts, they have nine weeks to complete the material, because we want to give them some structure for completing the course in a timely period.

The applied courses consist of 40-hour one-week applied placements at regional facilities across Canada. The sites were selected based on the experience of the veterinarians, the number of vets per site, the quality and diversity of the programs, the species, and locations, with efforts to have wide geographical distribution and inclusion of French language sites. All training sites are CCAC-assessed. Participants take a skills list with them to use as a training passport and placements are facilitated by a course coordinator. The areas in which they receive training are somewhat tailored to their area of employment; for example, if they work with aquatic species they will focus on aquatic training, without much training in nonhuman primates.

The program is approved and has been recognized by the CCAC, which is important in terms of regulatory recognition, as is the professional recognition given by CALAM/ACMAL. Upon successful completion, participants receive a certificate in LAM and can receive a transcript of their marks.

The accompanying slides represent some screenshots from the program. The Home Page has a number of hot links across the top and gives general information and announcements. The Course Outline page provides an introduction, information about the course development, expectations for learning, and other resources. The Time Line for the course shows various activities occurring each week, and assignments and quizzes that are to be done at each time point. The expectation is that participants will move sequentially through each topic before advancing to the next. In terms of actual topic content, there are brief instructors’ comments and other readings students must do to consolidate the knowledge.

The Course Resources page includes a broad range of references from many organizations including the Canadian Association for Laboratory Animal Science, ACLAM, and ILAR. Most importantly, the website contains contact information for the course instructor and there is 24/7 online support for participants provided by the Office of Open Learning.

Ongoing related projects include working together with a number of ACLAM diplomates in the US to develop a similar entry-level US certificate program, which will become available soon. In addition, we have been in discussions with veterinary colleagues in Southeast Asia and Latin America to develop similar online programs to meet some of the veterinary training needs in those regions. The online format affords many opportunities to provide more advanced training in other LAM areas such as imaging, cardiology, and pathology, among others.

An example of an advanced program is that being developed by Dr. Bob Cardiff, a comparative pathologist at University of California at Davis. He is developing online courses in genomic pathology geared to different levels of instruction for technicians, graduate students, pathology trainees, and scientists. This program will provide information on informatics, basic pathology, and recognition of lesions in tissues as well as histologic phenotyping. These will be tuition-based courses and will offer credits for graduate students anywhere in the world.

The advent of slide scanning and related software now provides the option of developing online comparative pathology programs for advanced training. Glass slides can be scanned in at very high magnification with excellent resolution for students viewing from their desktops. The particular software (ImageScope, Aperio) is free, and students can download it as long as they can access a server that has the slides saved onto it. Students can annotate the slides by, for example, circling lesions or putting arrows on different parts, save the changes, and send them back to the instructor as part of their online training. This is an excellent opportunity for coaching and facilitation of learning in comparative pathology.

So in summary, we are at a very early stage in the veterinary medical field and in particular in laboratory animal medicine and science for implementing some of this technology. However, there are a lot of exciting opportunities in the future to use online training as one potential tool to provide for harmonization of veterinary training and ensure at least a minimum level of training of veterinarians for the provision of adequate care of laboratory animals.

International Approaches and Principles for Distress, Pain, and Euthanasia

Distress

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Mental distress is arguably the biggest single enduring adverse effect on laboratory animals during their lives, and with the greatest impact on the science. It is not pain but fear and poor housing and poor husbandry systems that inflict most animal suffering during their lifetimes.

Although pain and distress are addressed in guidance and legislation, distress is still overlooked as a source of poor animal welfare and also poor science. In my view, pain has been overemphasized, mainly because it is of greater public concern and a more obvious target for nongovernmental organizations. However, this is now changing with current public concern about the welfare of animals in zoos, breeding of companion animals, and particularly farm animal husbandry and rearing systems.

The debate has moved away from pain to one about the quality of an animal’s life and how we can measure that. Even though there may be events that cause temporary pain, it is the suffering over a lifetime that probably matters most. Captive animals, including those kept for research, are held in impoverished conditions compared with the ecological niches into which they have evolved. In other words, we do not really meet their physiological and mental needs in terms of their evolutionary background. But of course we meet their vital needs; we have to.

Many laboratory animals have well-developed senses like smell, sound, sight, touch, and taste to survive in the world, and husbandry systems do not normally fulfill many of these evolutionary needs. Neither has domestication removed them, as, when domesticated animals are released into the wild, they soon adopt the ways of their progenitors. So there is still a need to meet these needs.

Imagine what you would miss if you were kept in a cell in solitary confinement. The same diet day in day out, without any sun, wind, rain and other forms of precipitation, with little sensory changes in sound, textures other than metal bars, bedding, or plastic, concrete, metal floors and walls, no choice of mates, without space to run, being unable to go where you want to go, and so on. This is why I say that keeping animals in captivity is impoverished for them. So keeping animals in such life-sustaining but otherwise inadequate housing conditions for the whole of their lives may cause considerable long-term suffering. That is one reason for my statement that fear, poor housing, and poor husbandry systems inflict most animal suffering during their lifetimes. Even best practice still compromises animal welfare considerably.

Of course there is no easy answer to this conundrum, as we have to confine animals to carry out research on them. But I believe we can do more to improve the quality of their shortened lives.

Furthermore, the evidence for what is acceptable or at least unacceptable for the animals is often not there. Only when animals die prematurely is there concern. In the meantime, how does one decide what to do, what to provide? Who gets the benefit of the doubt when the science can provide no answers—is it the human or the animal?

In science, the traditional surgical and physiological procedures that were once carried out are gradually being replaced by investigations using transgenic and genetically modified animals and this makes the issues of meeting their mental needs even more of an imperative. For instance, in the UK in 2007, genetically modified and mutant animals and their breeding accounted for nearly 50% of all animal experiments. Only 39% underwent “traditional” procedures of such severity that they required an anesthetic, and the number used for human clinical research was less than 1%. However, there will be more animals undergoing surgical interventions for purposes other than clinical research and all animals in laboratories will suffer the chronic distress of poor living conditions.

While pain is a well-defined and relatively well-understood area of animal physiology and pathology, it is treatable, and so it is often not necessary to keep animals in pain or to cause pain to animals unless there is an overriding scientific reason—for example, research on pain. This is yet another reason why poor mental health (i.e., distress) is so important: it is often unavoidable. I’m not saying that pain is unimportant—it is (Matt Leach will address pain in his talk); but distress is a neglected source of animal suffering.

The annual reports on animal suffering show some interesting differences between countries and the way they handle distress. Most do not separate distress but combine it with pain. Others do not separate intensity and duration of either pain or distress in any meaningful way. Most countries record only predicted adverse effects, while others estimate the adverse effects that actually occurred (i.e., a retrospective recording). The important point is that all countries recognize the term distress as well as pain. So how do we go about measuring pain and distress?

To understand animal suffering it is important to appreciate that animals cannot just be reduced to their component parts, which is the traditional scientific reductionist approach. Pain and distress are more than the sum of their component parts.

Mental distress (which I see as part of mental health) is reflected in several emotional states and is a more complex experience than pain. It embraces feelings like fear, boredom, frustration, malaise, inappetence, thirst. Animals are conscious beings; they respond to adverse external and internal stimuli as a whole, that is, they show an integrated multimodal response to a negative stimulus. Thus animals in pain have raised corticosteroid levels together with a range of physiological and behavioral changes from normal. They are likely also to experience distress states such as fear when they associate their condition with environmental factors such as a particular room or a particular person and an unpleasant experimental intervention, such as an injection. Memory is an important component in mammalian (and probably in all the other classes of the phylum Chordata) pain and distress.

Several of these adverse mental states can occur in the same animal at the same time. An animal is unlikely to experience just one state at a time, especially pain. However, a reductionist approach in science induces us to concentrate on just one aspect at a time. It is very important that a more holistic approach be taken. For example, an animal with a painful broken leg will be in some form of mental distress as well as pain. When the veterinarian who examined the leg reappears the animal may be fearful that she will cause it to feel pain again.

Mental distress causes a mixture of feelings or emotions that can influence bodily responses that increase the possibility for confounding scientific observations. Several years ago, a disturbance index was used to assess how animals behaved after they had had an injection. That was a rather interesting approach, but it has never been followed up. Animals became hyperactive or hypoactive after they had been subjected to a procedure such as an injection of cold saline, or an injection with a large needle size, or large volume. Differences in their responses were observed, and it might be possible to interpret these differences but the work was never completed.

However, there are other indirect and nonspecific physiological measures of distress including blood hormones such as cortisol, organ responses to hormonal changes, neurochemical binding patterns in the brain and spinal cord, and responses to known pharmacological agents. We are aware of many of these responses that potentially will confound the data being collected such as the impact of catecholamines on heart rate and blood pressure, [or] the effects of cortisol on the immune system. We may also be able to use such known actions to make a diagnosis of an animal’s emotional state. For example, if animals change their behavior after they have been given an analgesic, then that is some evidence that they were in pain. Increased heart rate, body temperature, and blood pressure as a result of catecholamine release could be a measure of fear and anxiety. However, measuring hormonal levels is impractical; observing animals for changes in their behavior is more feasible.

Stress physiologists look at hormone levels and use the term “distress” for animals that are not coping with their environment and in which the whole endocrine system can eventually become unresponsive. I call this syndrome dysstress, spelled with a y after the Greek dus, having a connotation of “badness,” as in dyspepsia (bad digestion). It may persist to a point where an animal cannot cope. In Europe, distress is interpreted more broadly than a physiological state of not coping and incorporates mental states rather than physiological states. That is when animals experience adverse feelings such as fear, anxiety, boredom, malaise, frustration, and the like.

There is a continuing debate about whether physiological levels (e.g., of hormones) are “harder” and more reliable scientific measures than measures of behavior. Some people think that signs are objective only if you can measure them and can assign a number on some sort of continuum. However, other signs (parametric) based on clinical signs or an animal’s behavior cannot easily be measured on a continuum (e.g., lameness, difficulty in breathing, stereotypic behavior) but are just as valid and just as objective, in the sense that we can observe them accurately and reproducibly. It is quite important that both sorts of signs be used depending on the circumstances and the adverse effects we are measuring.

Whether metric or parametric measures are used it is still necessary to interpret them in terms of understanding an animal’s mental state. It is this interpretation of an increased heart rate or increased blood pressure or a behavior that is the subjective step. The observation of the behavior and the measurement of a hormone level are both objective, but both have to be interpreted into [a gauge of the] intensity of mental distress.

In my opinion, in the measurement of animal well-being, behavior normally trumps physiology [in the] final integrated outcome of how an animal is feeling, it “votes with its feet.” We could invoke an analogy with people’s experience in hospitals today when they are in pain and do not get the treatment they feel they need. A scenario might occur where the nurse/doctor takes a blood sample and says, “No, you cannot be in pain, your blood hormones aren’t high enough.” What would you say? You know you are in pain and your behavior will most likely show that you are in pain (you may not want to move, feel nauseous, don’t feel like getting out of bed, look grey). All these physiological and behavioral signs are the outward integrated response but how you feel is mostly evidenced by your behavior and that is why I think behavior trumps physiological measurements for those that cannot speak and communicate.

In the ILAR working group on distress there were physiologists from the US who took the view that distress was the result of exposure to long-term stressors (I have referred to this as “dystress” above), and those from Europe who considered that (mental) distress could also result from a short-term exposure to stressors and cause mental states such as fear. Of course, it is very important from an evolutionary standpoint to be able to adapt to external stressors for survival, sometimes referred to as “eu-stress” (Greek eu having a connotation of “good”). I recommend you read the ILAR report on distress; it is an extremely comprehensive document and it describes these tensions.1

I tried to find out for this conference something about the use of the word distress and what was happening in guidance and legislation in various countries. I emailed several colleagues in various countries with the following questions:

How does your country define distress and what emotional states would it cover? Would it for example cover the mental health of animals held for experiment as well as being in an experiment? (Animals are kept in their housing for possibly 100% of their time, but they are not on experiment for all that time.) Some countries provided a definition of distress whereas others preferred a descriptive approach to distress. That was very similar to what we decided in the ILAR group.

How does your country help users recognize distress? Some countries provided a list of signs and a guide to their assessment based on changes from normality —the more the observation deviated from normality, the greater the impact on the animal and the greater the distress.

How does your country help users treat distress? The emphasis here was on withdrawal—withdrawal of the animal from the stressful situation or avoiding it in the first place. Nobody really answered the question, although I was interested to see the Australian guidelines have started to follow the European Food Safety Authority (EFSA) model of welfare risk assessment. That is quite complicated, and I can give you some references to it. It is a rather tedious approach that looks at the intensity of an adverse state, its duration, the numbers of animals likely to be affected, and the likelihood that they will be affected if exposed to a stressor (or hazard in RA terms), but it does present some very interesting observations and challenging data sets to create. The [NRC report] had a section on treatment of distress, but I really don’t think it is going to be practical, because scientists are not going to want to give drugs that are neurologically active in their experiment.

Does your country have any formal guidelines for users? Canada and Australia had some formal guidelines, although I’m not quite sure how practically useful they are. When I looked through the [1996] US Guide for the Care and Use of Laboratory Animals, distress was mentioned only in conjunction with pain (i.e., “pain and distress”); there was no separate guidance on distress. But hopefully the ILAR report on distress will change that.

I received only three or four replies to my e-mail. There was resounding silence from the competent authorities in most countries. However, I received a good response from Australia and New Zealand with some really interesting observations. I would argue that is because they are the ones that have been at the forefront in developing broad-based local animal care and use ethics committees and distress would have been an issue for many lay members. The US was very much ahead in setting up ethics committees in the first place, but the formal composition and skill base of these committees was very narrow and different from those in other countries; for example, they excluded animal protection members and did not mandate those with training in ethics.

I had a detailed response for farm animals from Italy, but unfortunately it was all in Italian. Many of the other countries either gave very general guidelines or simply did not address distress as a separate issue, although they often dealt with pain separately.

In the US, the major emphasis has been on pain but ignores its duration and intensity, and that is common to many other countries. However, that is historical, and maybe the revision of the Guide will include more information about intensity and duration of both pain and distress, in the same way that EFSA’s risk assessment does.

One of the major differences is that the US, in general, is far less willing to give animals the benefit of the doubt in the absence of scientific evidence. This raises interesting and productive tensions, with a more rigorous requirement for validation of welfare measures in the US than in the EU or elsewhere. Validation of welfare measures is becoming a key issue in other areas of animal use—for example, welfare assurance schemes for farmed animals such as the Welfare Quality project in the EU. This is a massive project—17 million euros have been invested in this activity, which includes 44 institutions and 13 member states, plus four in South America. They are trying to develop key welfare indicators that can reflect the quality of life of farmed animals before they are killed—did they have a good quality of life, did they have a life worth living, if you like? The Farm Animal Welfare Council in the UK is also looking into this.

The issues are the same for research animals. How do we assess their quality of life, which will include validation of the measures and how we determine whether a particular measure reflects pain or distress? We need more research on validation of the measures, their robustness, reliability, and how feasible they are to measure, and can they be scored with good observer reproducibility?

The advantage of measuring deviation from normality—measuring the impact of an experiment or system of husbandry on an animal—is that you don’t have to label it with a particular mental emotional state. The only reason one might want to label something as pain or distress is for implementing therapy: if an animal is in pain, it should receive an analgesic. However, distress is far more varied and complex and the cause is very important. Fear (e.g., of humans, rooms), anxiety (a raised awareness in general), frustration and boredom (e.g., because of housing and husbandry), malaise (e.g., because of infection) all have different causes and these have to be identified. Treatment will then be based more on causation as opposed to pain, which is generally easier to predict and diagnose and treat. It is also quite important not to label things too restrictively as various mental states often run together.

Most international guidelines emphasize that one should take steps to avoid any adverse effects for scientific reasons. This can be done through better training of personnel, better techniques carried out competently, closer observations of animals, and early detection of adverse states and their causes.

In conclusion, mental ill health—i.e., distress—is the most common cause of suffering in laboratory animals. It is multifactorial and difficult to treat. There is little guidance in most countries on its recognition, assessment, avoidance, and alleviation. It can be recognized and assessed by measuring the impact of the procedures in animals, but research is needed to identify key validated and robust measures.

Pain: International Differences Across Guidelines and Approaches

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Introduction

Most of the work reported here is the work of the members of the pain systems group at Newcastle University, UK; in particular, the work of Claire Richardson, Claire Coulter, and Paul Flecknell will be referred to.

Before looking at guidelines and approaches a definition of animal pain is required. The most widely accepted definition of pain and the most appropriate in this case is that of the International Association for the Study of Pain (IASP 1994): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”

Guidelines and Codes of Practice

The vast majority of countries that carry out animal-based research have guidelines, almost all of which state that “Pain should be ‘minimized and/or alleviated…’” or have statements to a similar effect (e.g., ILAR, NIH, Australia’s National Health and Medical Research Council [NHMRC], the UK Home Office, the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes [ETS 123], JCS, and CCAC). Pain can be minimized and/or alleviated using the principles of the 3Rs. The use of analgesia is critical. As a consequence of the guidelines that exist we should expect analgesia to be commonplace and extensive guidance on when and how to use analgesics to be in existence. So how widespread is analgesic use?

Analgesic Use in Rodents

A 2005 literature-based survey (Richardson and Flecknell 2005) looked at analgesic use in laboratory rodents undergoing painful procedures. It included papers published in bioscience journals in 1990–1992 (100 papers) and 2000–2002 (100 papers). The proportion of papers reporting no analgesic use, analgesia via anesthesia, and analgesic use is shown in Figure 1.1

Two pie charts show reported analgesic use in rats and mice in bioscience journals in 1990-1992 (100 papers) and 2000-2002 (100 papers). The 1990-1992 chart shows that 83% of the papers reported no analgesia, 14% anesthetic analgesia, and 3% reported the use of analgesia. The 2000-2002 chart shows that 67% of the papers reported no analgesia, 19% anesthetic analgesia, and 14% reported the use of analgesia. Source: Richardson and Flecknell (2005).

FIGURE 1

Reported analgesic use in rats and mice in bioscience journals in 1990–1992 (100 papers) and 2000–2002 (100 papers). Source: Richardson and Flecknell (2005).

The high percentage of rodents that were reported not to receive analgesia is not surprising when we consider analgesic use in veterinary clinical practice in general. The work of Lascelles and colleagues (1999) in cats and Capner and colleagues (1999) in dogs demonstrates this (see Figure 2). The problem of low analgesic use is not a new problem as a similar situation was seen in human medical practice around 20 years ago. The lack of analgesic use in medical and veterinary clinical practice could be due to failure either to appreciate the significance of pain or to recognize signs of pain.

A bar graph shows the percentage of dogs, cats, and small mammals receiving analgesia after different types of surgery in the United Kingdom. For orthopedic procedures, approximately 97% of dogs and 93% of cats receive analgesia. For laparotomies, the percentages are approximately 70% and 58%, respectively. For ovariohysterectomy procedures, approximately 58% of dogs and 25% of cats receive analgesia. For castration procedures, approximately 32% of dogs and 15% of cats receive analgesia. Small animals (e.g., rats, mice, guinea pigs) receive analgesia approximately 15% of the time for any type of procedure. Source: Richardson and Flecknell (2005).

FIGURE 2

Percentage of dogs, cats, and small mammals receiving analgesia after different types of surgery in the United Kingdom. Source: Richardson and Flecknell (2005).

However, is this true for laboratory animals? The literature survey by Richardson and Flecknell (2005) carried a follow-up in which they emailed authors who reported no analgesic use in their papers (67% of papers) and asked whether they had simply not reported analgesia use (underreporting) or had not administered analgesics (underuse). The change in the proportions of papers reporting no analgesic use, analgesic use, and analgesia via anesthesia is shown in Figure 3.

Two pie charts show reported analgesic use in rats and mice in 2000–2002 after email follow-up of authors who reported no analgesic use. The chart for the original reporting shows that 67% of the studies reported no analgesia, 19% anesthetic analgesia, and 14% reported the use of analgesia. After email follow-up, the percentage of authors reporting no analgesia was 58%, anesthetic analgesia 19%, and analgesia 23%. Source: Richardson and Flecknell (2005).

FIGURE 3

Changes in reported analgesic use in rats and mice in 2000–2002 after email follow-up of authors who reported no analgesic use. Source: Richardson and Flecknell (2005).

Analgesic Use in Other Species and across Continents

Two literature surveys in 2007 looked at analgesic use after surgery in rodents (Stokes et al. 2009) and in larger species (rabbits, pigs, sheep, dogs, and primates; Coulter et al. 2009). The survey s covered studies that were carried out in a number of countries around the world and published between 2005 and 2006; for rodents these involved 86 papers in 10 journals and for larger species 75 papers in 61 journals. The results of these surveys are shown in Figure 4.

Two pie charts show reported analgesic use in 2005–2006 after surgery in rodents (Stokes et al. 2009) and larger species (rabbits, pigs, sheep, dogs, and primates) (Coulter et al. 2009). The chart for rodents shows that 55% of the studies reported the use of no analgesia, 25% the use of anesthetic analgesia, and 20% the use of analgesia. The chart for larger species shows that 12% of the studies reported the use of no analgesia, 26% the use of anesthetic analgesia, and 62% the use of analgesia.

FIGURE 4

Reported analgesic use in 2005–2006 after surgery in rodents (Stokes et al. 2009) and larger species (rabbits, pigs, sheep, dogs, and primates) (Coulter et al. 2009).

These data can also be tentatively used to assess analgesic use by the continent on which the work was completed (see Figure 5). These are the only data of their kind as far as we know, and although they are indicative they should be interpreted with extreme care. The surveys were not designed to differentiate between countries, there was an unequal distribution of papers across countries, cultural differences were not taken into account, and the proportion of animal-based research carried out in each country was not taken into account, [any of which] could bias results.

Four pie charts show reported analgesic use by continent in 2005–2006 after surgery in rodents and larger species. The chart for Continent A (58 papers) shows that 60% of the studies reported the use of analgesia, 26% the use of anesthetic analgesia, and 14% the use of no analgesia. The chart for Continent B (46 papers) shows that 74% of the studies reported the use of analgesia, 20% the use of anesthetic analgesia, and 7% the use of no analgesia. The chart for Continent C (30 papers) shows that 70% of the studies reported the use of analgesia, 7% the use of anesthetic analgesia, and 23% the use of no analgesia. The chart for Continent D (8 papers) shows that 50% of the studies reported the use of analgesia, 13% the use of anesthetic analgesia, and 38% the use of no analgesia. Sources: Coulter et al. (2009); Stokes et al. (2009).

FIGURE 5

Reported analgesic use by continent in 2005–2006 after surgery in rodents and larger species. Sources: Coulter et al. (2009); Stokes et al. (2009).

Why Is There Such a Low and Varied Use of Analgesia in Animals?

There are a number of possible reasons for such low and varied use of analgesia in animals despite the prevalence of guidelines:

  • Some consider that animals don’t feel pain and this is dependent on attitudes to pain in animals, which vary among countries and professions.
  • There is no perceived need to give analgesics; however, this is often due to a failure to recognize indicators of pain in animals.
  • Concern over interactions between the analgesics we can administer and the experimental protocol being carried out on animals.
  • Concern over the extent of potential side effects associated with the analgesics we administer.
  • Tradition or historical data showing that a potentially painful procedure has been carried out without analgesics before, used as evidence that it can be again.

In many cases unalleviated pain can cause as much if not more variation in the data as either interactions between the analgesics and experimental protocols or potential side effects associated with analgesics. If there is concern about the effect of analgesic administration on experimental validity then this can be considered with other sources of potential variation in a study (e.g., environmental, surgical) through well-designed and appropriate statistical analysis. In addition, the other effects of unalleviated pain on animal-based research should be appreciated, such as causing the death of animals, which can require the use of additional animals to maintain the study design. Increasing the number of animals used does not fulfill the spirit of the 3Rs.

In Summary

It seems that in many cases the apparent rationales for withholding analgesia do not withstand close scrutiny, which can easily be seen in the peer-reviewed literature, as for a given procedure analgesia will be administered in one case but withheld in another when carried out on different species, or even the same species, both between and within countries. Therefore, despite the prevalence of guidelines there remains considerable variation in the administration of analgesia in animal-based studies.

The final point of this presentation was to ask those who attended this meeting why they think there is such considerable variation in the administration of analgesia in animal-based studies.

References
  • Capner CA, Lascelles BDX, Waterman-Pearson AE. Current British veterinary attitudes to perioperative analgesia for dogs. Vet Rec. 1999;145:95–99. [PubMed: 10461733]

  • Coulter CA, Flecknell PA, Richardson CA. Reported analgesic administration to rabbits, pigs, sheep, dogs and non-human primates undergoing experimental surgical procedures. Lab Anim. 2009;43:232–238. [PubMed: 19116294]

  • IASP [International Association for the Study of Pain] Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2nd ed. 1994. Available online ( www​.iasp-pain.org/AM/Template​.cfm?Section​=Pain_Definitions&Template=​/CM/HTMLDisplay​.cfm&ContentID​=1728#Pain) [PubMed: 3461421]

  • Lascelles BDX, Capner CA, Waterman-Pearson AE. Current British veterinary attitudes to perioperative analgesia for cats and small mammals. Vet Rec. 1999;145:601–604.

  • Richardson CA, Flecknell PA. Anaesthesia and post-operative analgesia following experimental surgery in laboratory rodents: Are we making progress? ATLA. 2005;33:119–127. [PubMed: 16180987]

  • Stokes EL, Flecknell PA, Richardson CA. Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures. Lab Anim. 2009;43:149–154. [PubMed: 19116297]

Euthanasia

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Introduction

Various organizations around the world have developed guidance on euthanasia. Some have developed guidelines that are specific for animals used for scientific purposes, others have a broader mandate. Some of the organizations are also involved in overseeing animal use in science and therefore have tailored their documents to fit their particular national systems. A comparison of recommendations made in recent guidelines drawn from a variety of jurisdictions is provided. Differences in recommendations can be the result of difference in interpretation of scientific evidence, but may also reflect difference in expert opinion, national systems, and societal values.

Guideline Documents

As national authorities overseeing animals used for scientific purposes have evolved, they have either developed or adopted guidelines as a means of holding animal users accountable to prevailing societal values. Guidelines for the ethical use and care of experimental animals provide the basis for acceptable practices relating to animal-based research, testing, and teaching. Guidelines may address particular procedures, conditions of housing and care, and the behavior of individuals carrying out procedures or caring for animals.

The guidelines themselves are usually implemented at the local institutional level, with local and/or national assurance, depending on the country. In some places, the national authority may be the organization that both develops the guidelines and provides assurance that they are implemented at the institutional level (for example, the Canadian Council on Animal Care, CCAC). In other places, guidelines may be developed by one organization (for example, the American Veterinary Medical Association, AVMA) and implemented by another (for example, the Office for Laboratory Animal Welfare, OLAW). To illustrate this point, OLAW interprets and oversees compliance with the US Public Health Service (PHS) Policy on Humane Care and Treatment of Animals, which states that a method of euthanasia used in the United States must be endorsed by the AVMA (OLAW 2002). The organization or authority responsible for overseeing the implementation of the guidelines may itself be operating according to particular legislation or a policy framework that has an impact on the manner in which the guidelines are viewed and implemented as well as on the manner in which they were drafted in the first place.

Development of Guidelines

The development of guidelines involves the translation of scientific evidence into recommendations that can be implemented in practice. Although best attempts are made to ground guidelines in current scientific evidence, there are at least two factors that make straight translation of science into guidelines or policy almost impossible to achieve. First, guideline development happens at a discrete point in time, whereas science is continually evolving. Guidelines therefore need to be sufficiently flexible to accommodate shifts in thinking that may improve the welfare of animals, particularly as guideline documents take a considerable amount of time to produce.

Second, however much one might strive to base guidelines on hard science, in reality that science is subject to expert opinion, the regulatory frame-work within which the animal-based research is carried out, and current societal values, as most oversight systems are either an arm of government or established to act on behalf of the broader public. These additional factors do not dilute the scientific basis for guidelines; rather, they translate hard science into guidance, and in doing so add value to the guidelines. This ensures that the guidelines can be readily implemented and can be defended both to the scientific community and the public at large.

Graph showing how science can be turned into guidelines by factoring in expert opinion, regulatory framework and social concerns.

FIGURE 1International harmonization

International harmonization of guidelines is becoming increasingly important due to the evolving globalization of science. For this reason, the International Council for Laboratory Animal Science (ICLAS), an international scientific organization dedicated to advancing human and animal health by promoting the ethical care and use of laboratory animals in research worldwide, has been working on harmonization of guideline documents. At the ILAR symposium on science-based guidelines held in 2003, it was recognized that, due to differences in national systems of oversight, guidelines can only ever be harmonized and that standardization of guidelines is neither possible nor desirable (Demers 2004a).

Harmonization exercises conducted by ICLAS involve setting up international working groups in various subject areas to establish relevant guiding principles and to formally recognize guidelines that are suitable as international references. This has been achieved for exercises in each of the following areas: euthanasia, humane endpoints, ethical review, and animal user training programs (Demers 2004b; Demers et al. 2006; www.iclas.org/harmonization.htm). The principles are extremely useful as they do not impede a nation’s ability to formulate its own guidance appropriate to the oversight system in place. Rather, they provide keystones upon which guidelines can be built. For example, the 10 principles generated by the ICLAS working group on harmonization of euthanasia guidelines (listed below) formed the starting point for the development of the CCAC guidelines on euthanasia of animals used in science (in preparation; since published, 2010). The principles were interpreted to address the particular Canadian situation and formed the basis for guidelines that adopt guidance that is already well established as well as providing additional information and details where new scientific evidence has become available. This approach would be useful for any guideline development exercise.

ICLAS Principles on Euthanasia

The following ten principles on euthanasia prepared by ICLAS provide a means of evaluating euthanasia techniques (Demers et al. 2006):

  1. Whenever an animal’s life is to be taken, it should be treated with the highest respect.
  2. Euthanasia should place emphasis on making the animal’s death painless and distress-free. The method likely to cause the least pain and distress to the animals should be used whenever possible.
  3. Euthanasia techniques should result in rapid loss of consciousness, followed by cardiac or respiratory arrest and ultimate loss of brain function.
  4. Techniques should require minimum restraint of the animal and minimize distress and anxiety experienced by the animal before loss of consciousness.
  5. Techniques should be appropriate for the species, age, and health of the animal.
  6. Death must be verified before disposal of the animal.
  7. Personnel responsible for carrying out the euthanasia techniques should be trained: (i) to carry out euthanasia in the most effective and humane manner; (ii) to recognize signs of pain, fear, and distress in relevant species; and (iii) to recognize and confirm death in the species.
  8. Human psychological responses to euthanasia should be taken into account when selecting the method of euthanasia, but should not take precedence over animal welfare considerations.
  9. Ethics committees should be responsible for approval of the method of euthanasia (in line with any relevant legislation). This should include euthanasia as part of the experimental protocol as well as euthanasia for animals experiencing unanticipated pain and distress.
  10. A veterinarian experienced with the species in question should be consulted when selecting the method of euthanasia, particularly when little species-specific euthanasia research has been done.

Euthanasia Guidelines

The guideline documents analyzed for this paper (listed below) have been developed by nationally recognized organizations. They were determined to be the most frequently used guidelines in this area, although other guidelines on euthanasia are also available.

  • AVMA Guidelines on Euthanasia (2007, updating the 2000 Report of the AVMA Panel on Euthanasia). This document was prepared at the request of the AVMA Council on Research by the Panel on Euthanasia that convened in 1999 to review and make necessary revisions to the fifth Panel Report, published in 1993. In the 2000 Report, the panel updated information on euthanasia of animals in research and animal care and control facilities; expanded information on ectothermic, aquatic, and fur-bearing animals; added information on horses and wildlife; and deleted methods or agents considered unacceptable. In 2006, the AVMA Executive Board approved a recommendation that AVMA convene a panel of scientists at least once every 10 years to review all the literature that scientifically evaluates methods and potential methods of euthanasia for the purpose of producing AVMA guidelines on euthanasia. During the interim years, requests for inclusion of new or altered euthanasia procedures or agents in the AVMA Guidelines on Euthanasia will be directed to the AVMA Animal Welfare Committee. Revisions are based on a thorough evaluation of the available science and require Executive Board approval. The first interim revision, approved in 2006, added guidance on the use of maceration for chicks, poults, and pipped eggs (AVMA 2007).
  • Recommendations for Euthanasia of Experimental Animals (Close et al. 1996, 1997). These two documents (Parts 1 and 2) were prepared for the EU Directorate-General of the Environment, Nuclear Safety, and Protection (DGXI) to be used with Directive 86/609/EEC of 24 November 1986, on the approximation of laws, regulations, and administrative provisions of the member states regarding the protection of animals used for experimental and other scientific purposes (N° L 358, ISSN 0378-6978). They refer especially to Article 2(1), published by the European Commission in October 1995, which defines “humane method of killing” as “the killing of an animal with a minimum of physical and mental suffering, depending on the species.” These documents are intended to be used in conjunction with the opinion of the Scientific Panel on Animal Health and Welfare (AHAW) of the European Food Safety Authority (EFSA 2005a).
  • Aspects of the Biology and Welfare of Animals Used for Experimental and Other Scientific Purposes (EFSA 2005b). This report summarizes the position of the animal welfare panel of the European Food Safety Authority (EFSA), which was asked to consider the scientific evidence for the sentience and capacity of all invertebrate species used for experimental purposes and of fetal and embryonic forms to “experience pain, suffering, distress, or lasting harm.” The panel also considered and made recommendations concerning humane methods of killing animals. This report updates recommendations made by Close and colleagues (1996, 1997).
  • Review of Schedule 1 of the Animals (Scientific Procedures) Act 1986: Appropriate Methods of Humane Killing (APC 2006). The UK Animal Procedures Committee (APC) was asked in June 2001 to review Schedule 1. Recommendations in the report include advice on humane killing of neonatal rodents; use of argon, nitrogen, or other inert gases; use of CO2; and weight thresholds for cervical dislocation of rodents. The Parliamentary Under Secretary of State for the Home Office responded to the APC’s review in August 2007 (Hillier 2007), requesting further consultation on several of the committee’s recommendations, while accepting the recommendation to provide advice on humane killing of neonatal rodents. These recommendations have not been implemented to date.
  • Public Statement: Report of the ACLAM Task Force on Rodent Euthanasia (Artwohl et al. 2006). This report of the American College of Laboratory Animal Medicine is a response to growing concerns and controversy regarding techniques that were commonly used for rodent euthanasia. Three issues were targeted in the report: euthanasia of fetal and neonatal rodents, the use of CO2 for rodent euthanasia, and the impact of euthanasia techniques on data.
  • Euthanasia of Animals Used for Scientific Purposes (ANZCCART 2001; under revision). The aim of the publication is to provide investigators and members of Australian and New Zealand animal ethics committees with detailed information on methods of euthanasia relevant for animals used for scientific purposes, including species not generally used elsewhere (e.g., dingos and marsupials).
  • Canadian Council on Animal Care Guidelines on Euthanasia of Animals Used in Science (CCAC 2010, updating Chapter XII on euthanasia in CCAC 1993) is based on recommendations made by the International Council for Laboratory Animal Science (ICLAS) Working Group on Harmonization and the two international reference documents on euthanasia recommended by ICLAS: the AVMA Guidelines on Euthanasia (AVMA 2007) and the Recommendations for Euthanasia of Experimental Animals, Parts 1 and 2 (Close et al. 1996, 1997). This information has been adapted to suit the Canadian research environment.

Differences in Approach

The foregoing descriptions of each guideline document underline the fact that there are differences in the intent for each. The AVMA (2007) Guidelines on Euthanasia are primarily to assist veterinarians in exercising professional judgment in the application of euthanasia. The document covers not only animals used for scientific purposes but also those used as companions and for food, animals in the wild, and exotic species. Close and colleagues (1996, 1997) provide guidelines that are specific to animals used for experimental purposes. Euthanasia of these animals would not necessarily be carried out by a veterinarian. The EFSA recommendations are to be used in conjunction with those of Close and colleagues (1996, 1997) and will be legally binding once the new European Directive comes into force. Schedule 1 to the UK Animals (Scientific Procedures) Act 1986 provides a list of methods considered exempt from the requirement for a UK Home Office personal or project license. The CCAC guidelines and the ANZCCART guidelines are specific for animals used for scientific purposes and are targeted to investigators and animal care committees to provide them with the relevant information on which to base their decisions regarding methods of euthanasia.

Irrespective of the framework within which these guideline documents are implemented, there is considerable similarity of intent. In the United States, animals used for scientific purposes essentially fall under the PHS Policy, which requires “avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices” and requires investigators to “consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals” (OLAW 2002b). The Australian Code of Practice for the Care and Use of Animals for Scientific Purposes “assume(s) animals experience pain in a similar manner to humans” (NHMRC 2004). The CCAC policy states that animals must not be subjected to unnecessary pain or distress, and that cost and convenience must not take precedence when deciding on procedures and matters relating to the care of the animals (CCAC 1989). Similarly, European Directive 86/609/EEC requires that “all experiments shall be designed to avoid distress and unnecessary pain and suffering to the experimental animal” (EEC 1986). Last, the UK Animals (Scientific Procedures) Act 1986 regulates procedures that may have the effect of causing the animal pain, suffering, distress, or lasting harm (the inference being that procedures not covered under the Act [methods of euthanasia listed in Schedule1] should not cause more than momentary pain or distress to the animal) (Home Office 1986).

Comparison of Provisions in the Guidelines

A comparison of euthanasia methods across documents is challenging because of the different approaches in the documents. The AVMA Guidelines on Euthanasia (2007) provide a table of methods considered by the panel of veterinarians responsible for drafting the guidelines to be acceptable, as well as tables of methods that they considered conditionally acceptable or unacceptable. Close and colleagues (1996, 1997) and the revised table developed by EFSA provide information based on species groups using a 1–5 rating system. The criteria used to assess the acceptability of euthanasia methods are similar between the AVMA and the EFSA documents, as illustrated in Table 1 below.

TABLE 1. Criteria Used to Evaluate Level of Acceptability of Euthanasia Methods.

TABLE 1

Criteria Used to Evaluate Level of Acceptability of Euthanasia Methods.

Table 2 shows a comparison of methods of euthanasia for rodent species, which are of particular interest because of the large numbers of mice and rats used for research and testing. This table has been prepared using a 5-star ranking, where 1 star indicates that the method is unacceptable under most circumstances; 3 stars indicate that the method is acceptable under some conditions; and 5 stars indicate that the method is acceptable. As the Australian and Canadian guidelines are currently both under revision, t hey have not been included.

TABLE 2. Comparison of Rodent Euthanasia Methods.

TABLE 2

Comparison of Rodent Euthanasia Methods.

Carbon Dioxide

The use of carbon dioxide as a euthanizing agent has been increasingly challenged since the AVMA 2000 Panel Report. The principles espoused by all of the various international systems overseeing animal use in science are based on the premise that pain and distress must be minimized. In addition, the ICLAS principles of euthanasia point not only to minimization of pain and distress but also to immediate loss of consciousness as important in euthanasia. A review of the scientific literature provides substantial evidence that animals euthanized with carbon dioxide experience considerable pain and/or distress (depending on the manner in which CO2 is administered) (Conlee et al. 2005; Leach et al. 2002; Liotti et al. 2001; Niel and Weary 2007; Raj et al. 2004). To try to address these concerns, the following recent publications have made recommendations concerning the euthanasia of rodents by carbon dioxide:

  • Report of the ACLAM Task Force on Rodent Euthanasia (Artwohl et al. 2006)
  • CCAC Guidelines on Euthanasia of Animals Used in Science (CCAC 2010)
  • Guidelines to Promote the Well-being of Animals Used for Scientific Purposes: The Assessment and Alleviation of Pain and Distress in Research Animals (NHMRC 2008)
  • Opinion of the Scientific Panel on Animal Health and Welfare (AHAW) on a request from the Commission related to the aspects of the biology and welfare of animals used for experimental and other scientific purposes (EFSA 2005a)
  • Review of Schedule 1 of the Animals (Scientific Procedures) Act 1986 (APC 2006).

In light of this concern, an international consensus meeting was held at the University of Newcastle upon Tyne in February 2006. The organizers recognized that there was no definitive guidance on whether and how CO2 can be administered humanely, and therefore brought together scientists with research experience in CO2 euthanasia, regulators, and members of the animal care community. The goals of the meeting were to try to reach consensus on the use of CO2, identify further research needed, meet the immediate need for practical guidance, and consider whether any preferable alternatives were currently available. The meeting concluded that there was no “ideal” way of killing rodents with CO2. Both methods currently used—prefill (placing the animals in a chamber already charged with carbon dioxide) or gradual fill (placing the animals in a chamber and then gradually filling it with carbon dioxide)—can cause welfare problems. It was decided that it is not yet possible to recommend the use of other gases (such as argon or nitrogen) that cause death by hypoxia, and that more research is needed into the physiological and affective responses to a range of gaseous agents in order to identify good practice and potential alternatives to CO2 (Hawkins et al. 2006).

In the interim, there are recommendations in guidelines that seek to establish good practice, in line with authors’ interpretation of the current scientific evidence. According to AVMA (2007), CO2 is acceptable for euthanasia in appropriate species; ACLAM (2006) states that the current peer-reviewed literature does not establish consistent requirements for CO2 euthanasia and/or even provide a clear definition of what constitutes a humane death; and EFSA (2005a) recommends that CO2 not be used as a sole agent in any euthanasia procedure unless the animal has first been rendered unconscious, and that its use be phased out as soon as possible. Table 3 provides a comparison of recommendations on the use of CO2 as a method of euthanasia in the guidelines studied.

TABLE 3. Comparison of Recommendations Concerning the Use of Carbon Dioxide as a Euthanasia Agent for Rodents.

TABLE 3

Comparison of Recommendations Concerning the Use of Carbon Dioxide as a Euthanasia Agent for Rodents.

Conclusion

Organizations responsible for the development of guidelines all work to ground their recommendations in sound scientific evidence. Nonetheless, translation of science into policy necessarily includes a variety of factors, such as the particular regulatory framework in which the guidelines will be implemented and the current opinion of experts in the area, as well as current societal values. It has been stated that there is insufficient scientific evidence to be able to harmonize guidelines worldwide (Kastello 2004, 201), and even if this were overcome, these other factors would present obstacles. However, the harmonization exercises organized by ICLAS, which have resulted in sets of internationally agreed principles, can form the basis for the preparation of guidelines tailored to fit particular national systems for overseeing animal use.

References
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International Approaches and Principles for Humane Endpoints

Humane Endpoints in Cancer Research

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The vision of the Institute of Cancer Research is that people may live their lives free from the threat of cancer as a life-threatening disease.

Cancer or malignant neoplasm refers to a class of diseases in which a group of cells display uncontrolled growth (in other words division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spreading to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limiting and do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age; and cancers can affect all animals.

Cancer causes about 13% of all deat hs and, according to the American Cancer Society, 7.6 million people died from cancer in the world during 2007. Where effective anticancer treatments do exist they can be very demanding on the patient.

The objective of using live animals in cancer research is to develop rapid diagnosis, better treatments for existing cancers, and an improved prognosis for patients. With this in mind, scientists engaged in experimental cancer research follow four main areas of investigation, some of which use laboratory animals. Cancer research scientists attempt to discern, detect, identify, and develop.

  • To discern the biological mechanisms, scientists investigate different sites of origin in the body, why particular cancers are more prevalent in some tissues and not others, and the rate of growth and metastases of cancers.
  • The detection of potential carcinogens is an important chain in the link to identify agents in the environment such as chemicals, potential carcinogenic materials, exhaust fumes from motor vehicles, and other agents that may be responsible for carcinogenesis.
  • Identification of individuals at particular risk looks at epidemiological studies and historical data to determine who in the general population may be at greater risk of developing certain types of cancer. This particular area of investigation has taken an important step forward in recent years since the advent of genetic testing. Investigations may involve the examination of particular risk factors, including lifestyle (tobacco use, alcohol consumption, obesity, lack of physical activity) or genetic predisposition.
  • Developing ways to cure or control clinical disease is usually achieved by improving the prognosis for patients through the use of drugs, chemotherapeutic agents, radiation therapy, and/or surgical intervention.

Laboratory rodents, usually mice and rats, have assisted scientists in the field of cancer research and it is clear that they will continue to do so. They are used as experimental models in cancer research studies only where there is a justified need and only if absolutely necessary. The Institute of Cancer Research does not use animals for research if nonanimal alternatives are available, and endeavors to set humane endpoints for all research involving laboratory animals.

Because we need to use live animals in some research programs, it is essential that these living creatures be afforded the best care at all times. Staff tasked with caring for animals in the laboratory are continually striving to improve and enhance animal husbandry and welfare. An important part of this process is the use of humane endpoints in our animal experiments.

[According to] the OECD, a humane endpoint can be defined as “the earliest indicator in an animal experiment of severe pain, severe distress, suffering, or impending death.” Investigators make use of different humane endpoints depending on the tumor model being studied in any particular animal, and try wherever possible to determine accurate, predictive, and reproducible humane endpoints.

Humane endpoints should be a consideration for all experiments involving animals, but are essential in situations that may involve suffering or death (e.g., acute toxicology, infection, cancer, or inflammatory disease). They are just one manifestation in the process of refinement of animal experiments. Humane endpoints are best used with prospective planning for their use, not ad hoc to address specific welfare concerns as they might arise.

There are several considerations in arriving at the objective assessment of pain and suffering and translating this into the appropriate endpoint in a given experiment. An important point is the requirement to continually improve our skills at observing the animals and assigning some objective values to the observations we make (usually these are based on animal behavior and physiology). We also need to know, in any given study, which observations are the most significant indicators of animal pain and suffering, and have scientific acceptance of these measurements; otherwise they become invalid and unworkable. It follows, therefore, that validation and monitoring of other study parameters are required to ensure robust predictability of the endpoint and minimal interference with the scientific objectives.

All personnel contribute to the care and welfare of the animals, and it’s important that these individuals be provided with the correct training and knowledge in order to develop their required skills, and for each to progress to a level of competency. It is impossible to recognize signs of pain, suffering, or distress in any animal if you do not, or are unable to, recognize (and have not received training to be able to do so) normal signs of good health in an animal. Training and competency are very important attributes, especially when dealing with humane endpoints. Staff development of skills is an evolving process, and a clear program of training and mentoring enhances animal welfare and staff morale.

Biomedical research encompasses all types of research including research into cancer. All research can be viewed as a giant puzzle. Humane endpoints are an important and essential part of the discovery process. Everyone in the worldwide research community has an individual role to play in creating parts of the puzzle in order to find new treatments, enhanced therapies, and ultimately attempts to cure some of our more difficult and challenging diseases, not just in the field of cancer research but in all areas.

It’s important that if we continue to use animals for experimental purposes we do this in the most humane manner at all times. All who are involved in animal research must have a clear sense of responsibility, but more importantly a strong sense of compassion for the animals in their care. By the correct use and validation of appropriate humane endpoints we will help to add important parts to the puzzle.

Humane Endpoints in Infectious Disease

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The topic of my presentation is humane endpoints in infectious disease. This is a very sensitive and difficult topic, which I deal with almost every day as the IACUC chair at the United States Army Medical Research Institute for Infectious Diseases (USAMRIID). The opinions I am expressing today are my own and not those of my employer, the US Army.

USAMRIID does infectious disease research on some of the most dangerous viruses and bacteria in the world, and we do this under biocontainment conditions, generally ABSL-3 and -4 conditions. USAMRIID is AAALAC accredited and, as IACUC chair I can avow emphatically, does everything under an approved animal protocol.

The study of infectious disease generally involves studies of disease pathogenesis, immune response to infection, and development of therapeutics and vaccines. Because it is ethically and morally wrong to perform clinical efficacy studies with humans, the FDA has developed the animal rule, which allows new drugs and biologic products to be tested in animals as a means to getting approval for human use. Safety testing must still occur in humans, and the animal model is critical to the success of the FDA approval process. It is necessary to understand that the animal study endpoints must be clearly related to the desired benefit in the human; generally these are related to enhancement of survival or prevention of major morbidity.

The animal welfare regulations require that procedures involving animals avoid or minimize discomfort, distress, and pain to the animals. The Public Health Service Policy states that animals undergoing chronic pain or distress should be euthanized as soon as feasible and appropriate, which leads to a discussion of humane endpoints. Death as an endpoint has always been a difficult issue in infectious disease research. Lack of reproducible animal models often leads to the use of death as an endpoint. The argument to support death as an endpoint is that euthanasia and termination of the study before scientific objectives are met compromise study results. On the other hand, the counterpoint is that progression of infectious diseases to death allows unnecessary suffering, which compromises research results.

Simply put, many animal models of infectious diseases are not clearly defined and it is difficult to reliably differentiate animals that will die from those that will recover despite showing severe clinical signs. There have been many instances in which a severely ill animal recovered from its experimentally induced infectious disease. Death of the animal is the final proof that the challenge was lethal and that the vaccine failed to protect. Therefore some investigators are reluctant to euthanize early or to use anything but death as an endpoint. An argument may be made, however, that actual physiological events are missed when death is the only criterion evaluated. The data gathered from monitoring these events can be used to develop early and humane endpoints. Additionally, for a variety of reasons including tissue autolysis, death of the animal diminishes sample collection. Therefore, it is important to consider requirements for the development of early and humane endpoints.

For an early endpoint to be acceptable, it must meet the following criteria: it must be indicative of inevitable progression to death; it must reliably differentiate the animals that will die from those that will recover despite showing severe signs of toxicity; and it must adequately mimic the death endpoint.

The benefits of humane endpoints are many and should be emphasized during the planning meetings with investigators. Specifically, the development of uniform methods to assess endpoint criteria contributes to the validity and the uniformity of the experimental data. Detailed observations of clinical signs may lead to increased discriminatory experimental power. Last but most importantly, use of humane endpoints avoids or terminates unnecessary pain and distress for the research animal.

It is very important to tailor the endpoints to each animal protocol. Different animal species react differently to the same viral or bacterial challenge. For instance, Ebola Zaire is lethal in five to seven days in cynomolgus monkeys, whereas it is lethal in seven to ten days in rhesus macaques. And in Mauritiusorigin cynos, monkeypox is 100% fatal while in Chinese-origin cynos there may be only a 43% fatality. This emphasizes the importance of picking the right species and understanding the course of that disease in that species. Outcomes must also be defined; will morbidity suffice or must you go to the moribund condition?

The route of the challenge is very important. The exposure route must be similar to that anticipated in humans per the FDA. This affects the time course and pathogenesis of the disease. It may be important to challenge at two or more doses, because this can help differentiate physiological changes between survivors and nonsurvivors. The viral and bacterial strain to be used should also be considered when developing endpoints. Ebola Zaire is uniformly lethal and has a shorter time course than Ebola Reston, which is also lethal but with a prolonged time course. Finally, it is important to consider human safety when dealing with infectious diseases.

When planning endpoints, one must consider observation frequency. It is critical to set reasonable observation frequencies to ensure human safety, the least stress to the animal, and investigator compliance. The frequency should be set to minimize stress but allow for euthanasia, sample collection, and avoidance of progression to death. It is necessary to know whether the animal is nocturnal or diurnal and whether disruption of sleep will adversely affect the study. It is also necessary to determine when to increase your observation frequencies so as not to miss critical events.

As mentioned, human safety must always be considered when dealing with infectious diseases. Promoting animal welfare by increased monitoring of animals after exposure can jeopardize human safety. Therefore, investigators and the IACUC should be encouraged to look for other, less intrusive and safer methods of monitoring the animals, such as telemetry and in-room cameras.

Rodent species present their own challenges when developing humane endpoints. Rodents are generally group housed and they are not always individually identified, making their observation difficult. Additionally, clinical signs of illness in rodents can be subtle and nondiscriminatory in nature.

It may be necessary to consider objective versus subjective endpoint criteria. It is important to use a mixture of both, but when using subjective criteria with three different people observing the animals throughout the day, they must be very adequately trained on exactly what these criteria mean—e.g., “What is ruffled fur in a mouse and should it be added to my score sheet?” The IACUC must work with investigators in the development and use of humane endpoints. In many institutions, the IACUCs have developed strong policies stating that death as an endpoint is not acceptable. The IACUC should also require the use of intervention criteria or score sheets that clearly define when the animal is to be euthanized.

As I have already stated, the IACUC should work with the investigator to determine the best schedule of animal monitoring. Personnel that monitor the animals must understand normal species behavior as well as the clinical signs expected during the course of the disease. Observation frequencies should increase as the clinical signs become more severe and these observations need to be documented.

The IACUCs must ensure that there is an available point of contact for euthanasia so that when the time comes the animal will be euthanized promptly. In fact, it may be wise to have an alternate point of contact to ensure that when the score is met and it is time for euthanasia, this happens promptly.

When the clinical course of the infectious disease is not clearly defined for the animal species, the IACUC should consider the use of a pilot study to allow for criteria development. The IACUC should use subject matter experts to assist in developing the criteria and should consider the use of analgesics for each infectious disease, animal study, or protocol.

The IACUC should review the use of observation documentation as part of its postapproval compliance monitoring. Another issue that the IACUC must discuss is whether the humane endpoints should be the moribund or morbid condition. This is a difficult issue and there is no right answer. Each study must be considered separately. Often in assessing the effectiveness of the treatment or vaccine, the moribund state is used, while the morbid state would be used if it is not necessary to know if the animal will die as a result of the treatment or vaccine failure.

In a score sheet that we use at USAMRIID with filovirus research done in macaques, if the score is equal to or greater than 10, the animal is administered pain alleviation. If it is greater than 20 the animal is considered terminally ill and is euthanized. Exceptions require consultations with the attending vet. The use of score sheets has progressed over the years and with each experiment refinements are made to improve them.

In conjunction with the investigator we have been able to add some objective criteria; e.g., if liver enzymes double, a score of 1 is assigned, and if they triple a score of 3 is given. The hope is to avoid the moribund end state and euthanize when we see liver enzymes increase.

So these are the kinds of things going on at USAMRIID in infectious disease research. Everyone has a score sheet, and every investigator is encouraged to define criteria or do a pilot study within that protocol so that future score sheets may be developed based on these criteria.

In summary, it must be the goal of all infectious disease researchers using animals and of the IACUCs that provide oversight for these animals to develop humane early endpoints. Good science and humane animal care require nothing less.

Humane Endpoints and Genetically Modified Animal Models: Opportunities and Challenges

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Technologies that enable the targeted manipulation of the genome have created new opportunities to study the role and interplay of specific genes in both the regulation and function of physiological and behavioral processes and the development of pathological conditions. Through the development of new or novel animal models, these techniques enable new insights into the molecular basis of disease processes and provide opportunities to develop targeted therapeutic approaches.

Despite the potential benefits from the use of these technologies, there are ethical issues in relation to their application, some of which relate to the impact on the welfare of the animals involved. The establishment of humane endpoints is a key strategy in achieving the goal of refinement; when the use of animals is scientifically justified but where there is a risk of those animals experiencing pain or distress, applying the process by which humane endpoints are implemented and reviewed underpins an informed and strategic approach to managing such risks.

Genetically modified (GM) animal models present particular challenges when developing criteria to set humane endpoints. I will provide an overview of the animal welfare issues presented in the application of GM technologies and discuss the opportunities and challenges to applying humane endpoints when GM animal models are developed.

Introduction

The development of technologies that permit the targeted manipulation of genetic material—be that by transgenesis or targeted mutagenesis—has created opportunities to explore the organization, regulation, and function of molecular processes in both normal and pathological states in ways previously not possible. Further, the application of these methods has expanded the availability of animal models that are more accurate analogues of the underlying disease processes and hence can be used to better understand disease processes and to develop new, targeted therapies.

While the potential benefits of the use of these technologies are recognized (Royal Society 2001; NRC 2002; Nuffield Council 2005), there is continuing public disquiet about their use (Einsiedel 2005). A range of issues are being raised, including fundamental ethical questions about the use of genetic modification (GM) technologies and notions of the sanctity of life and the autonomy of the individual as well as concerns about risks to human health and the environment. The welfare of the animals involved also has been a recurring issue and has been addressed in a number of reports and guidelines (for example, Royal Society 2001; Animal Procedures Committee 2001; Dennis 2002; Robinson et al. 2003; Brown and Murray 2006; Wells et al. 2006; NHMRC 2007; CCAC 2008).

The process by which humane endpoints are developed, validated, and reviewed is a key platform in making progress toward the goal of refinement when animals are used for scientific purposes (Morton 2000; Stokes 2000). Humane endpoints are used for two complementary purposes: identifying the onset of a disease process so that early intervention is possible either to initiate treatment or to enable an early, defined endpoint in a study; or, alternatively, to determine the point when an animal’s condition has deteriorated such that its involvement in the study should be terminated.

Setting humane endpoints involves identifying potential risks and validating criteria to, first, identify specific physiological or behavioral changes associated with the animal model and, second, assess the impact on the animal in relation to both the predicted effects of the experimental treatment and general criteria to assess the occurrence of pain and distress. Thus criteria are established upon which decisions can be based and outcomes reviewed. This is an iterative process that underpins informed decision making and validates the ongoing refinement of experimental procedures. Although the same processes apply to establish humane endpoints with GM animal models, as highlighted by Dennis (2000) there are particular difficulties in these circumstances brought about primarily by the unpredictability of the effects of GM technologies on phenotypic expression.

In recent years there has been a rapid escalation in the development of new GM models. In the biomedical sciences mice are by far the species most often used, but a range of species can be involved, including zebrafish, pigs, and nonhuman primates. Further, the pace and scope of the development of new GM animal models are likely to continue for the foreseeable future, which presents logistical challenges for the effective management of these animals, especially when this involves significant numbers of animals and many lines with differing phenotypes (Comber and Griffin 2007).

Welfare issues have been identified in relation to both the methods used to produce GM animals and the resulting phenotype.

Production of GM Animals

GM animal models are produced by a number of different methods that result in reduced or enhanced expression or inactivation of a gene. The most common methods used involve (1) transgenesis, where exogenous genetic material from either the same or another species is inserted in a fertilized blastocyst by microinjection, electroporation, or a nonpathogenic viral vector and then implanted in surrogate mothers; (2) targeted mutagenesis, which results in the presence or absence of a specific gene (“knock-in” or “knockout”), which is achieved by inserting modified genetic material in cultured embryonic stem cells that are injected into a blastocyst and implanted in surrogate mothers; or (3) random or chemical mutagenesis, where animals or their gametes are exposed to mutagens that increase the rate of mutations, resulting in the production of novel single gene mutations. Only a small percentage of animals produced will carry the modified genome and significant numbers of animals may be required to produce and maintain each GM line. Consequently, relative to the number of GM animals created, significantly more are produced and culled.

A July 2003 report by a Joint Working Party on Refinement in the United Kingdom reviewed the relative advantages and disadvantages of the production of GM animals by either pronuclear injection or embryonic stem cell techniques and recommended strategies to promote both reduction in the numbers of animals involved and refinement of procedures to minimize impact (Robinson et al. 2003). The report recommended criteria to benchmark the efficacy of procedures so as to ensure production methods to maximize the potential to produce GM animals and management strategies to reduce surplus production. For each step in the process, the report recommends performance benchmarks (indicators when there is a need to review that process) and outlines possible causative factors that should be considered. Thus this report sets out current standards of good practice and provides a process to benchmark animal welfare outcomes in the context of the needs and justification for current methods.

With both these technologies, donor animals undergo various, and sometimes multiple, procedures with the risk of associated pain or distress. Strategies to manage and minimize the impact on the donors of surgical procedures, superovulation of females, and tissue biopsy for genotyping are discussed in this report. The recognition and uptake of opportunities to modify and refine these procedures will continue to play an important role in the future development and use of these methods.

While reports such as this highlight the need to be aware of the impact of these procedures on the animals involved in the production of GM animals, in the one study to date these procedures were not shown to have a significant effect on the behavioral and physiological development of mouse progeny up to 30 weeks of age (Van der Meer et al. 2001).

GM Animal Models

GM animal models have been applied to the investigation of a range of human diseases such as diabetes, obesity, atherosclerosis, chronic heart failure, hypertension, cancer, autoimmune disease, and musculoskeletal and neurological disorders. However, not all GM animals are bred as disease models. GM animals may exhibit clinical disease but, given that the rationale behind the development of GM technologies is to tease out the role and function of individual genes or gene sequences, in many cases do not do so and that is not the intended outcome.

Wells and colleagues (2006) observed that in only a minority of GM animals are animal welfare problems evident and that, with transgenic animals where most often the purpose is to study the function of a DNA segment, adverse effects are uncommon and that for GM models developed using targeted mutagenesis (knock-in or knockout) where the purpose is to study the function of a single gene, either embryonic death or animals with no evidence of adverse effects are the most common outcomes. However, they noted that both targeted and random mutagenesis can lead to neonatal mortality or animals with compromised health or welfare.

When adverse effects do occur they either are predicted on the basis of the particular genetic modification or, notably, are not of a kind that was predicted to occur or are seen in circumstances where adverse effects were not anticipated. It is the uncertainty and low predictability of such events that present particular challenges when managing GM animal colonies. Such unpredicted adverse effects may arise for a variety of reasons including the overexpression or the absence of the specific gene, interactions with collocated genes, or the influence of the genetic background of donor animals or the background strain that may interact with the targeted modification. Furthermore, adverse effects may not be evident in the first generation and emerge only in subsequent generations (Dennis 2000).

Abnormalities in GM animals may affect the viability of offspring and their long-term survival and welfare and may be linked to the specific gene modification or reflect a peculiarity of the phenotype of the background strain. A diverse range of abnormalities have been reported, including hydrocephalus, cleft palate, malformed limbs, absence of teeth, poor mothering, absence of milk, poor thermoregulatory ability, increased aggression and cannibalism, clotting disorders, enhanced growth of tumors and development of metastases often at atypical sites, diabetes, osteoporosis, degenerative joint disease, respiratory disorders, inflammatory bowel disease, ulcerative colitis, liver and kidney dysfunction, seizures, and sensory and locomotor abnormalities affecting sight, hearing, smell, balance, and social interactions. The occurrence of one or more of these abnormalities may necessitate the euthanasia of affected individuals but also may indicate the need to review the ongoing production of a particular line. In some of these conditions the impact can be alleviated by the implementation of treatment programs or changes to husbandry practices such as the provision of special diets, the placement of food and water on the bottom of the cage, and increased volume and changing of bedding (Brown and Murray 2006).

A higher than expected incidence of infectious disease has been observed in GM animals (Dennis 2002). As highlighted in the review by Franklin (2006), GM animals respond to infections in a similar way to immunodeficient animals: they develop clinical infections due to common opportunists or to agents that would normally result in asymptomatic infections. GM may affect host specificity of pathogens and infections may result in unusual or new phenotypes not necessarily due to immune defects.

Humane Endpoints

When developing humane endpoints for GM animal models the uncertainty of the incidence, kind, and timing of adverse events presents a significant challenge (Dennis 2000). Furthermore, when animals develop concurrent diseases —for example, 26% of mice developed diabetes in a transgenic model (R6/2) of Huntington’s disease (Luesse et al. 2001)—the determination of an appropriate endpoint may be confounded. Unquestionably, the development and implementation of monitoring strategies to assess the impact of a specific genetic modification is essential to effectively manage the welfare of GM animals and to enable the development of effective humane endpoints.

When a new genetic line is created a detailed description of its phenotype must be undertaken. With the rapid increase in the number of new lines being created, especially in mice, reference databases have been established that document the methods used to create and maintain the GM line and its phenotype; details in relation to the onset of changes, disease progression, and suggested endpoints are included in some instances.

Although some concern has been expressed that the monitoring of GM animals could focus on a description of the phenotype with insufficient attention given to animal welfare indicators (Brown and Murray 2006), these processes can and should be complementary and there are important benefits in establishing effective humane endpoints when this occurs. A detailed phenotypic description, including animal welfare measures, will provide both a more accurate picture of the time course and characteristics of a phenotype and identify relevant indicators of negative effects on the animal’s welfare. Ideally, the quality of these data will enable a more accurate determination of the specific settings for a humane endpoint by aligning phenotypic changes with animal welfare indicators and identification of special needs that can alleviate some effects.

Monitoring

Several protocols to monitor the welfare of GM animals have been developed (e.g., Dennis 2002; Wells et al. 2006) with many common elements.

Dennis (2002) emphasized the importance of at least daily monitoring when new lines are created to ensure that signs of illness, physical defects, injury, or abnormal behavior are detected and assessed, noting the importance of documenting what may seem to be unimportant changes—the frequency and specific elements of a monitoring program should detect both predicted and unforeseen changes. Dennis (2002) also stressed the need to include regular monitoring of the health status of GM mouse lines, including serological testing and postmortem examination. These measures also are an important component of developing a phenotypic description of a GM line.

Similarly, Wells and colleagues (2006) proposed a structural assessment of the welfare of new GM lines focusing on the initial phase in the creation and phenotypic assessment, the aim being to create a “welfare profile” so that, once a line is established, monitoring would focus on several welfare indicators specific for that line. However, as noted by other authors, there can be discrepancies in the phenotypic description of a given GM line between different institutions. Consequently, this kind of welfare assessment also should be undertaken when GM lines are newly introduced to an institution.

Wells and colleagues (2006) propose specific welfare assessments to be carried out in neonates and at weaning. In neonates, criteria such as skin color, surface temperature, activity, reflexes, response to touch, and evidence of a milk spot are proposed. At weaning, mice are assessed by appearance, coat condition, posture, gait, activity, clinical signs, and relative size; in addition, preweaning mortalities, evidence of aggression or stereotypies, and body weight are recorded, and more detailed behavioral assessments are recommended if behavioral problems are identified. If no animal welfare problems are identified in neonates or weanlings, animals are monitored during routine husbandry procedures. If animal welfare concerns either are identified in the assessment of neonates or weanlings or subsequently emerge, animals then undergo more detailed assessments to identify special needs and criteria for humane endpoints.

There is a convergence between protocols for monitoring animal welfare and for developing a phenotypic profile. As a minimum, Brown and Murray (2006) suggest that the following measures be included in phenotype screening: clinical chemistries, complete blood count, urinalysis, gross and histopathology of major organs, abnormal gross tissues and target organs, and an assessment of general health, sensory function, motor abilities, and behavioral tests as proposed by Crawley (1999). Proposals such as that developed by Rogers and colleagues (1997) and Crawley and Paylor (1997) to develop a comprehensive phenotypic profile have been widely adopted with various modifications and include measures relevant to animal welfare assessment. However, an important addition to these protocols is a comprehensive assessment of behavior that uses a range of laboratory-based tests to assess learning, memory, sensory motor activity, feeding behavior, pain, reproduction, and emotionality. These kinds of data may also assist in evaluating or predicting the impact of the GM on animal welfare.

Finally, when assessing phenotypic changes in GM animals, comparison with their wild-type, littermate controls is important.

Refinement

There are a number of ways to reduce the impact of GM on the welfare of a particular line (NHMRC 2007). The rapid development and refinement of GM technologies that limit temporal or spatial gene expression has resulted in refinements to the way in which the expression of phenotypes can be targeted and benefits the welfare of the GM animal by limiting or negating the expression of negative effects. Two common strategies used in the production and maintenance of GM animals are, when there is an unacceptable level of morbidity, mortality, chronic disease, or abnormal behavior in homozygote animals, to maintain the GM line in heterozygous animals and, when the GM line is no longer needed for current research programs using cryopreservation, to store embryos, sperm, and ovaries.

GM Models in the Neurosciences

There has been a significant increase in the number of GM animal models in the neurosciences used in the study of neurodegenerative diseases such as Alzheimer’s, Huntington’s, or Parkinson’s disease, and psychiatric illness such as schizophrenia, depression, and anxiety, obsessive compulsive disorders, and pain and stress. In some circumstances, for example Huntington’s disease, a single gene may be involved, but many of these conditions involve complex gene interactions and the use of transgenic or knockout models provides new opportunities to study the function and interplay of individual genes to elucidate factors that influence the regulation and modulation of neural substrates (see for example the discussion by Mogil and Grisel 1998 in relation to pain studies, and Muller and Keck 2002 in relation to stress). Furthermore, the development of knockout lines has created the possibility of studying the role and function of a single gene in relation to behavior (Nelson and Young 1998; Anagnostopoulos et al. 2001).

An overview of the scope of GM animal models in the neurosciences provides some insight into the opportunities and challenges that GM animals present.

One of the drivers for the development of a battery of behavioral tests to be used in the development of phenotype profiles for new GM lines has been the potential to use these animal models in the neurosciences. Consequently, one of the defining characteristics of these animal models will be changes to one or more behavioral tasks indicative of cognitive, emotional, sensory, or motor function. Changes in an animal’s ability to perform such tasks may relate to the experience of pain, stress, anxiety, fear, or depression. In further study of these models, a suite of specific behavioral tasks will be selected relevant to the hypothesis being tested (Crawley 1999).

In many GM lines animals do not show any evidence of clinical disease or abnormal behaviors but demonstrate a change in one or more tasks. For example, in a study designed to look at dysfunction in the serotonergic system, which is implicated in psychiatric conditions such as anxiety and depression, compared to their wild-type controls 5-HT1A knockout mice showed increased anxiety in the elevated-plus maze test and decreased reactivity in the open-field test, whereas 5-HT1B knockouts showed the reverse, but neither line showed any difference in development, feeding behaviors, reproductive performance, or any other evidence of abnormalities (Zhuang et al. 1999). Changes in behavior such as increased aggression, altered maternal care, seizures, and impaired motor coordination and sensory abilities are seen in knockout mice where such changes are linked to the targeted gene (Nelson and Young 1998; Anagnostopoulos et al. 2001). Furthermore, transgenic and knockout mice with these kinds of modifications may develop changes that affect their ability to interact with their physical and social environment. For example, changes to genetic components of the dopaminergic system in mice are associated with changes to their olfactory ability (McGrath et al. 1999), resulting in increased aggression, changes in their social interaction (Rodriguiz et al. 2004), and increased fear response (El-Ghundi et al. 2001).

In these kinds of models, setting criteria for humane endpoints presents particular challenges. This is not an issue when animals display signs of clinical disease or abnormal behaviors, such as seizures, but when the only evidence of behavioral change is in the performance of a behavioral task during a brief exposure to an artificial environment and there is no evidence of change in any other measures, the decision is not so clear. Evidence of altered emotionality or cognitive ability in a behavior test does not indicate that such experiences are part of an animal’s day-to-day condition. The animal’s negative experiences may be limited to the brief test period and in these circumstances the frequency of testing should be considered in limiting impact. However, the occurrence of these kinds of behavioral changes concurrent with evidence of changes under normal living conditions shifts the weight of evidence and may indicate animal welfare concerns. For example, mice deficient in the extracellular matrix glycoprotein tenascin-R (TN-R) showed increased anxiety when tested in the open-field and elevated-plus maze tests and decreased locomotor activity, but also showed significant changes in circadian activity in their home cage (Freitag et al. 2003).

There are differing views as to the interpretation of stereotypic behavior in relation to animal welfare and, as shown in a review by Mason and Latham (2004), although in most circumstances where this occurs it is likely to be linked to poor welfare, there are exceptions. There are a number of reports where transgenic or knockout mice display stereotypic behavior with a range of genetic modifications (for example, Ambree et al. 2006; Berger et al. 2006; Chartoff et al. 2001; Hines et al. 2008; Mohn et al. 1999; Rodriguiz et al. 2004). A recent report on the recognition and alleviation of distress prepared by an ILAR committee (NRC 2008) concluded that stereotypies are undesirable and their prevention is likely to improve animal welfare. The weight that is given to the presence of stereotypies in setting humane endpoints may be contentious. The context in which these occur may be relevant, but a special case would need to be made to maintain animals exhibiting stereotypies that cannot be alleviated under home cage conditions.

In the context of neurodegenerative models where there is progressive deterioration of an animal’s condition over a prolonged time, there are examples of where the early detection of the onset of the disease identifies early intervention points and provides an opportunity to test therapeutic efficacy. For example, a transgenic model of Huntington’s disease measuring behavioral changes in open-field and elevated-plus maze tests detected the onset of a deterioration in motor activity prior to evidence of changes in anxiety levels (Klivenyi et al. 2006), and the development of a transgenic model of Alzheimer’s disease showed cognitive and neurophysiological defects before the development of overt neuropathology (Gimenez-Llort et al. 2007). Further, a report by Drage and Heinrichs (2005) shows not only how the husbandry of a seizure-prone E1 mouse can be modified to eliminate the onset of seizures when the mice are held by the tail but also evidence of behavioral and cardiovascular changes that can be used as predictors before the onset of seizures.

There are ongoing challenges in the interpretation of behavioral phenotypic changes in relation to the fidelity to specific gene effects, including the confounding influences of husbandry and housing conditions, which are relevant to the setting of humane endpoints. Changes that result from compensation or developmental effects of the mutation, the influence of the genetic background strain, the influence of maternal behavior on adult phenotype, or pleiotropy can all confound interpretation of a phenotype (Gingrich and Hen 2000); differences in the background strain can result in significant phenotypic differences in pain-related measures (Lariviere et al. 2001); and rearing conditions and neonatal handling can affect behavioral responses to pain and stress in adult mice (Sternberg et al. 2003; Parfitt et al. 2004).

A number of studies have demonstrated the influences of laboratory conditions on phenotypic expression (Crabbe et al. 1999; Wahlsten et al. 2003). Würbel (2001) has argued that more attention should be given to the animal’s living conditions and hypothesized that animals that experience an enriched environment (EE) would be less susceptible to minor environmental changes and therefore provide a more “standardized” response to test conditions. Although Wolfer and colleagues (2004) showed that EE did not result in differences in behavioral tests when applied to two inbred mouse strains and their F1 hybrids, studies in transgenic models of Alzheimer’s disease indicate the need to carefully evaluate the influence of EE in specific GM animals (Jankowsky et al. 2003; Richter et al. 2008). Recent studies showing that even subtle changes in EE or cage design are associated with significant changes in tests used for behavioral phenotyping (Tucci et al. 2006; Kallnik et al. 2007; Pietropaolo et al. 2007) highlight the urgent need to further investigate these kind of effects.

Conclusions

The establishment of humane endpoints in GM animal models presents particular challenges due to the unpredictable nature and occurrence of adverse events. However, the scope and depth of monitoring required to accurately describe a phenotype, together with careful monitoring to assess animal welfare, provide a comprehensive framework to establish humane endpoints with a high level of accuracy as well as informing the development of effective strategies to reduce the impact of a specific genetic modification. Studies that can identify and demonstrate ways to modify confounding influences on the phenotypic expression of a specific gene will enable refinement of the setting of humane endpoints that will benefit both scientific and animal welfare outcomes.

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Cross-Cultural Ethical Perceptions and Ways to Resolve Challenges

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The concept of animal welfare is inextricably bound up with ethics, with an ethics component. Animal welfare is in essence what we owe an animal and to what extent. This is not very well understood by animal users, particularly by the agricultural community. I was on the Pew Commission where we frequently heard that animal welfare is simply a matter of sound science. It is not. It is a combination of sound science and ethics.

The relevant ethics that figures in the animal welfare equation comes from the societal ethic for animals, and there is in fact a new societal ethic emerging over the past 40 years that will likely dominate not only the West but, insofar as the West is the source of science in the East and elsewhere, the East as well.

In recent years ethnocentrism has become a dirty word and a variety of factors have converged to create a bias against the bias in favor of our own culture. Postmodernism, feminism, atonement for past imperialistic sins, political correctness have all converged in favor of a putative neorelativistic tolerance for multiculturalism that we would have historically dismissed offhandedly.

In fact, we do not accept many principles from other cultures. We don’t accept tribal butchery, we don’t accept clitoridectomies in young women, we don’t accept the Taliban repression of women. But multiculturalism has certainly exacted some costs. Consider for example the extraordinary proliferation of evidentiary baseless alternative medicine, some of which is purportedly borrowed from the traditions of “other cultures” and on which the US public spent no less than $40 billion in 2005. This is not based in evidence and not based in science.

Hence too our current concern: How do we arrive at a conception of animal welfare that does justice to the bewildering array of views of this concept across different cultures? Part of the reason this issue creates perturbation among scientists is their historical disavowal of ethics being integral to science. The mantra is: “Science is value free in general and ethics free in particular.”

When I was trained in science in the ’60s I got that mantra. My students are still getting it, although it is not quite as widespread as it was, fortunately, because it really is a detriment to the thriving of science in our society, which already is facing formidable obstacles.

Thus it is widely believed that animal welfare can be explicated without reference to values, simply on the basis of objective biological fact. In reality, the variation across cultures in views of animal welfare can be found historically intraculturally. It is simply magnified by considerations of cultural variability.

Consider the following: In 1981 in response to burgeoning societal concerns about animal welfare, the US agricultural community, represented by the Council for Agricultural Science and Technology (CAST), published Scientific Aspects of the Welfare of Food Animals. Reflecting a ubiquitous view among producers, the CAST report spoke of welfare as follows: The principal criteria used thus far as indices of the welfare of animals in production systems have been rate of growth or production, efficiency of feed use, efficiency of reproduction, mortality, and morbidity. In other words, the welfare of an animal is defined and determined by how well it fulfills the human purpose to which it is put, with no reference to how it feels, whether or not it suffers pain, distress, anxiety, boredom, loneliness, frustration, inability to move or be with conspecifics, and so on.

Implicit in this definition are a set of values and a set of moral obligations that are easily extracted: Humans are morally obliged to provide animals only with a set of conditions that allows the animal to fulfill the purpose for which it is kept by humans. In Kant’s terminology, then, animals are in no way ends in themselves, they are strictly means to an end, a human end. Animal welfare is based solely on these human ends. In metaphorical terms, welfare is to animals as sharpness is to a saw, what is needed for both to be functional tools.

At roughly the same historical moment, the early 1980s, other definitions of animal welfare were promulgated. In the writings of Marian Dawkins, Ian Duncan, and myself, one essential feature of welfare was argued to rest in what the animal experienced, its subjective states. The moral position implicit in such views was that animals ought to be at least in some measure in Kantian terms “ends in themselves” because they were conscious, and what they experienced mattered to them. By the way, at that time much of the scientific community was agnostic about the concept of animal consciousness. They overtly denied either the existence or the knowability of animal consciousness; therefore what we did to animals and how we forced them to live didn’t matter.

In my view of welfare, animals have intrinsic value rather than merely in‐strument value—that is, value merely as tools—because they are capable of valuing in their subjective life what happens to them. There were other definitions of welfare—e.g., the Farm Animal Welfare Council (FAWC) notion of the Five Freedoms1 that grew out of the Brambell Commission, and so forth. The point here is that even in British and American culture, one could find numerous very obviously different and incompatible definitions of animal welfare, based in radically differing views of the moral status of animals, separated irreconcilably by disparate ethical values underlying them. Thus, the existence of divergent views of animal welfare, differing across cultures, does not raise any new conceptual problems that were not already present by virtue of the intracultural value-based differences in views of what constitutes animal welfare.

It is in no way surprising that animal welfare should have emerged as a moral issue in the latter part of the 20th century, because of the precipitous changes in the nature of animal use that transpired in the mid-20th century. For the entire history of civilization, the overwhelming use of animals in society was in agriculture—food, fiber, locomotion, and power—and the key to success in agriculture was good husbandry. Husbandry meant putting your animals in the optimal conditions dictated by the animal’s biological natures and needs, and augmenting their native ability to survive and thrive by provision of food during famine, water during drought, help in birthing, medical attention, and protection from predation.

This has been called the ancient contract. It was based on the insight that producers did well if and only if animals did well, and vice versa. Thus, husbandry was, in equal measure, a prudential and a moral imperative, sanctioned by what is after all the ultimate motivation for human beings, self-interest. Thus defining animal welfare and animal ethics was a nonissue.

In fact, the only animal ethic that was needed and can be found as early as the Bible arose from the need to cover the case of the small number of psychopaths and sadists who were unmoved by self-interest. In other words, if you were using animals in an agricultural way, which was the primary use of animals, you needed to put them in decent conditions and provide for their needs during famine and drought and so forth and so on in order to be financially successful.

Defining animal ethics and animal welfare became an issue when the nature of agriculture changed from husbandry to industry. The values changed as well. Primacy was now given to the values of efficiency and productivity. Whereas one can characterize husbandry as putting square pegs in square holes, round pegs in round holes, and creating as little friction as possible doing so, the Industrial Revolution provided us with “technological sanders,” as it were, that allowed us to force square pegs into round holes, round pegs into triangular holes, while still keeping animals productive—things like air-handling systems, antibiotics, vaccines, etc. If one had tried to develop these systems during the era of animal husbandry, the animals would be dead in weeks of disease spreading like wildfire, but with these sanders we can force square pegs into round holes.

What was lost was the isomorphism between the animal well-being and productivity that characterized husbandry, and thus animal welfare and animal ethics became an issue instead of a presupposition of animal use. This was potentiated by the advent at roughly the same time, the 1940s, of large amounts of animal research and testing, again representing significant animal use that violated the symbiosis inherent in husbandry.

The research community typically deflected this issue by being agnostic both about the relevance of ethics to science and about animal consciousness. I was a principal architect of the 1985 federal laboratory animal laws in the United States. In 1982 when I went before Congress to defend them, I was asked to prove that there was a need for such a law. The research community claimed they were already controlling pain in research animals.

So I went out and, with a colleague at the Library of Congress, did a literature search on laboratory animal analgesia. How many papers did I find? I found none on laboratory animal analgesia. When I broadened it to animal analgesia, I found two, one of which said there ought to be papers, and the other said here is what we know: it was a one-pager in the Journal of the American Veterinary Medical Association and it was very honest about not knowing anything and how there was a moral imperative to know.

As public cognizance of the radical changes in animal use grew beginning in the 1960s and 1970s, efforts in favor of restoring fairness to animal use began to pervade Western society, beginning in Britain in the 1960s and resulting in the view that animals were entitled to the famous five basic freedoms. The ensuing years saw the emergence in Western society of “the new social ethic for animals.”

As anyone attending to cultural history can easily determine, the issue of animal treatment assumed major social prominence beginning about 1970. Whereas 30 years ago in the United States one would have found no federal bills pending in Congress pertaining to animal welfare, the last decade has witnessed up to 50 and 60 per year. On a state level in 2004, there were well over 2,100 bills proposed in state legislatures pertaining to animal welfare; there were over 200 in California alone.

Most Western countries have recently adopted new laws protecting laboratory animals and ensuring control of their pain, often despite opposition from the research community, which preferred a laissez-faire approach. Britain is of course a notable exception, given the act of 1876.

Much of Northern Europe and the European Union have introduced major restrictions on confinement agriculture, probably the most dramatic being the Swedish law of 1988 that abolished confinement agriculture as taken for granted in the US, and created what the New York Times very presciently called in 1988 a “bill of rights for farm animals.”

Although the US has been slow in developing its concern for agricultural animals, in the last few years it has tended to accelerate, partially due to referenda, legislative initiatives to abolish the most egregious of practices. The Pew Commission report (PCIFAP.org) also educated a myriad of people who didn’t really know about agriculture before.

Well, we can proffer evidence indefinitely, but I think enough has been said and placed in evidence to buttress my claim regarding social concern. So the question that arises is, if there is that much social concern, how is it expressing itself ethically?

Historically, both the laws protecting animals and the social ethic informing them were extremely minimalist, in essence forbidding—and this is language from the legal system, from the cruelty laws as well as from judicial interpretations of those laws—deliberate, willful, sadistic, deviant, extraordinary, unnecessary cruelty not essential, as one judge put it, to ministering to the necessities of man, or completely outrageous neglect.

Those of you involved in animal welfare may well be aware that early efforts to regulate animal research invoked the cruelty laws and tried to present in evidence certain research that was “cruel,” and the universal judicial assessment was that research is not the sort of thing that can be cruel. It is not deviant, it is not sadistic, it does not betoken psychopathic behavior, etc. That is why it was essential to develop, as one judge put it, a new ethic for animals, by going not to the judiciary but to the legislature.

The ethic of anticruelty is found in the Bible and in the Middle Ages. St. Thomas Aquinas, while affirming that although animals were not direct objects of moral concern, nonetheless forbade cruelty to them on the grounds that those who would be cruel to animals will inexorably graduate to people. This is an insight that has subsequently been buttressed by decades of social scientific research —our last dozen serial killers all had early histories of animal abuse. Those involved with battered women’s shelters know that provisions must be made for the woman’s animal or the husband who is a batterer will go back and hurt the animal to get back at the woman. Psychiatrists acknowledge animal abuse…as sentinel behavior for subsequent psychopathology.

Roughly beginning in 1800, anticruelty laws, reflecting the anticruelty ethic, were codified in the legal systems of most Western societies. The key notion explaining why there was a demand for a new ethic can be found in the fact that the old ethic was so restricted in scope. If I draw a pie chart representing all the suffering that animals experience at human hands, how much would you say was the result of deliberate cruelty, a lot or a little? Every audience says a little. One week I spoke to PETA at San Francisco State and the Billings Rodeo Association of Montana, and they both said 1%. Well, if only 1% is covered by the cruelty ethic, then 99% is not. What that means is, as society has begun to concern itself with the other 99%, it has sought a vocabulary, an ethic, of expressing that concern in a manner that doesn’t invoke cruelty, which is essentially irrelevant.

Most animal suffering results from putatively reasonable and defensible uses—industrial agriculture, which is meant to provide cheap and plentiful food; scientific research, which advances knowledge, cures disease, and provides medicaments.

In the 1970s when I was hired by a veterinary school to develop the field of veterinary ethics, I realized pretty early that the moral status of animals was a fundamental question in veterinary ethics. That led me to think about what sort of ethics society was likely to develop if indeed it was to continue to be concerned about animals. It dawned on me after about two years that ethics does not come ex nihilo—it doesn’t come out of nothing. As Plato said, all ethics builds on preestablished ethics. I surmised that society would look to the ethic we have for people and modify it, change it—mutatis mutandis, as philosophers say— appropriately change it to fit the animal situation.

What aspect of our ethics is in fact being extended? One that is applicable to animal use is the fundamental problem of weighing the interests of the individual human against the general public. Different societies have provided different answers to this problem. Totalitarian societies opt to devote little concern to the individual, favoring instead the state or the Reich or the Volk or whatever their version of the general welfare may be. At the other extreme, anarchical groups such as communes give primacy to the individual and very little concern to the group; hence they tend to enjoy a very transient existence, such as the communes of the 1960s did.

In Western society, however, a balance is struck. Although most of our decisions are made to benefit the general welfare, fences are built around individuals to protect the individual’s basic human interests from being sacrificed for the majority. Thus we protect individuals from being silenced even if the majority disapproves of what they say. We protect individuals from having their property seized without compensation, even if such seizure benefits the general welfare. We protect individuals from torture, even if they planted a bomb in an elementary school and refuse to divulge its location.

What are these interests that we protect? We protect the interests of the individual that we consider essential to being human, to human nature, from being submerged for the sake of the common good.

What are these fences around human individuals called? They are rights. I’m not obviously going to be using the animal rights locution in the same way as the animal rights people do. What they really mean is animal liberation. All the legislative flurry of activity, the 2,400 bills proposed and similar acts, is an attempt to provide societal guarantees of proper animal treatment since husbandry no longer ensures it. It is absurd to suggest that these are the same rights that humans have, because animals do not have the same natures that humans have. I thought about not using the locution of rights, but I knew you would realize that the concept was being invoked. However, it is the concept being invoked by the general public.

If you look at surveys (which I don’t really tend to trust but they are indicators), close to 90% of the public will affirm that animals have rights. I have lectured to 15,000 Western ranchers in every ranching state. What percentage of them would say animals have rights? In my experience, well over 90% would.

An example of that occurred when the governor called a conference on the effects of animal welfare and animal rights on Colorado agriculture about 18 years ago. The opening speaker was the head of the Colorado Cattlemen’s Association. He said, “If I had to raise animals like the chicken people do, I’d get the hell out of the business.” I work very closely with these people. I just brokered a deal between the Humane Society of the United States and Colorado agriculture to avoid the costly referendum that took place in California, Proposition 2, banning veal crates and battery cages and gestation crates. It would have cost Colorado agriculture $12 million to fight it and lose two to one, and they didn’t have $12 million, so we were able to broker a compromise.

People are seeking to build fences around animals. There were two surveys, one done by Gallup, one by Oklahoma State University, both of which had almost identical results, although you would expect a discrepancy because Oklahoma State is a very strong agricultural school and the poll was not particularly agriculturally oriented. They both found that 80% of the general public wants to see proper treatment of farm animals ensured by legislation.

People in society are seeking to build fences around animals to protect the animals and their interests and their natures, which following Aristotle I have called telos. Those of you who studied Aristotle know what he means by telos: the biological and behavioral and psychological needs and interests that are constitutive of a given type of animal—e.g., the pigness of the pig, as one of my book reviewers once wrote, or the cowness of the cow. They are trying to protect that from being totally submerged in the quest for human general welfare, and are trying to accomplish it by going to the legislature.

With good husbandry, respect for telos occurred automatically. In industrial agriculture where it is no longer automatic, and also in animal testing, people wish to see it legislated.

Very simply, the new ethic recognizes that fish must swim, birds must fly. Clearly, then, the notion that animals ought to have legal protection for fundamental aspects of their natures, a notion actualized in the Swedish agricultural law of 1988 and implicit in the Brambell Commission, is a mainstream phenomenon.

One of the most extraordinary things about writing the laboratory animal laws was the fact that the public did not divide on party lines. Support for controlling pain and suffering in animals, for example, was invariant across Democrats and Republicans.

People were not saying do not use animals in research. What they are saying is, if you use animals in research, control the pain, control the distress. Distress is demarcated from pain in the US laws.

Conceptually speaking in terms of legal theory, animals cannot have rights because they are property. The old slave decisions established that anything that is property cannot have rights. This is a solecism, a legal oxymoron. However, this could not be changed without a Constitutional amendment although a lot of legal scholars are trying to do precisely that.

There was an animal law conference at Harvard Law School two years ago where 350 people filled every space and 300 were turned away. Over 100 law schools have courses in animal law, and a big thrust of most of those law professors is enfranchising animals and abolishing invasive animal use. But the same functional goal can be accomplished by restricting how animal property is used, which is exactly what the proliferation of laws attempts to do, including the laboratory animal laws. The day they passed I was sitting with Tom Wolfle from NIH and Dale Schwindaman from USDA, and they both shook my hand saying, “Congratulations, you have established certain minimal rights for animals.” These men were hardly radicals and essentially what they were saying was that an animal now had the right to have its pain controlled if pain is inflicted in the course of research, unless you were studying pain.

The good news is that we have gone from two published papers on analgesia to more than 11,000, with a correlative increase in its use, however deficient that use may still be.

So with this analysis in mind, we can begin to answer the question of cultural relativity of concepts of animal welfare. If our account is correct, there is not great disparity across at least different Western societies: all believe morally that animals should legally have their natures and interests protected and this should be accomplished by the legal/regulatory system. This is perhaps truer in Europe than in America.

Insofar as this notion seems to pervade Western democratic societies, which dominate the world politically and economically, it appears that this notion will dominate as the key notion of animal welfare, even as Western democratic notions of human rights have dominated discourse regarding human ethics.

People in other countries are beginning to realize that this notion will dominate. For example, two years ago I addressed 300 Southeast Asian agriculture animal producers who were greatly interested in what is happening in the West because they knew that they would have to abide by those standards if they were going to trade with the West. Recent announcements by Chinese government officials explicitly state that pressures of globalization are forcing China to consciously consider animal welfare and animal welfare legislation for the first time in its history.

As more and more US research is being shipped to other countries for economic reasons, we can be morally certain that public opinion will demand that it be accompanied by the new ethic. Judy MacArthur Clark has a project to try to bring Western ethical standards to these countries where the research will be exported.

As we argued earlier, the concept of animal welfare is deeply value-laden, both in what we choose to consider ingredient in an animal’s welfare and to what extent we are willing to satisfy those welfare concerns. This in turn first led to producers saying that welfare is what the animal requires to do the job we expect of them. That has been turned around by the new ethic and placed the locus of welfare in the animal, not in our generosity or largesse. That is the source of the notion of rights, that they are entitled rather than simply being a matter of our will.

We have argued that the new ethic is intended to restore the fair contract inherent in husbandry, and it is primarily agricultural. It happened with research first in the US because we are removed from agriculture. My average Columbia PhD friend still thinks farms are Old McDonald’s farms. We have argued that the new ethic is intended to restore the fair contract inherent in husbandry and to ensure that animals lead decent lives. We have further argued that the source of our primary obligation to animals is derived from attending to the animals’ natures, even as the rights of humans are based in respecting the essentials of human nature. How does this notion transfer to animals?

In the US Constitution and in the foundational documents of other demo‐cratic societies, the relevant concept of human nature was derived from people’s reaction to being denied certain things, from oppression. Having been denied freedom of religion or belief, people demanded that such belief be protected from governmental intrusion. Similarly, this is true of the seizure of property. Philosophically, the notion of human nature is of course very problematic, with many theories abounding about what human nature is and with some philosophers, notably existentialists and Marxists, affirming that there is no such thing. Interestingly enough, I would argue that whatever position you take on human nature, the notion of animal nature is far less problematic than the notion of human nature.

Animal life is far less plastic than human nature and is far less influenced by culture, and is thus far easier to define. It is more obvious, for example, that lions are predators than that humans are. Determining what animals are evolved for is simpler than answering the same question about humans. So obvious is it that animals have a nature that Aristotle, the greatest philosopher of common sense in antiquity, made it the cornerstone of his biology, and correlatively made biology based in telos the root metaphor for explaining everything in the universe. Whereas for Cartesian and post-Cartesian modern biology, biology is best expressed in terms of physics and chemistry, for Aristotle physics and chemistry were to be explained using functional biological categories. Physics was for Aristotle the biology of dead matter, to put it paradoxically. Biological categories, functional categories, are the most appropriate categories for explanation when it comes to living things.

So in De Anima, which is his biology, Aristotle lays out a functional template for biology that still serves as the framework for the way biology is taught in high school. Any living thing, says Aristotle, is a constellation of functions constitutive of its nature, and all living things are to be described in terms of how they fulfill these functions—locomotion, reproduction, nutrition, excretion, sensation, and so on. We characterize living things in terms of how they fulfill these functions. These functions, then, I would argue, constitute the telos of any type of animal—the pigness of the pig, the dogness of the dog. Aristotle says, tellingly, this nature is knowable simply by intelligent and repeated observation. Respect for the animal’s nature was essential for traditional agriculture: the greater the respect, the better the husbandry, the more productive was the animal. The fact of agricultural success attested to knowledge of animal telos. Under extensive conditions, productivity did betoken good welfare.

Modern agricultural use circumvents respect for telos and forces square pegs into round holes. Other animal uses ignore telos—for example, zoos and maintenance of animals in research settings, where animals are housed in conditions developed largely out of convenience for us but in violation of the needs flowing from their natures, as when nocturnal burrowing creatures are kept in polycarbonate cages under bright illumination or when social animals are kept in isolation in zoos, or the most egregious example I ever experienced in my youth, a giraffe cage in which the giraffe could not stand up. Such a situation would not occur today, which in a weak way attests evidentially to the claim that society is worried about animal telos.

Both Tom Wolfle and I in the early 1980s and David Morton today have pointed out that the conditions under which we keep animals are probably more invasive and more harmful to the animal than the number of overt invasive protocols. My understanding is that maybe 10–15% of protocols are seriously invasive in research. But 100% of animals are kept under conditions that are inimical to their basic natures.

I would thus argue that in today’s world, animal welfare is being defined in terms of animal telos—that is, meeting the needs and interests that matter to the animal by virtue of its biological and psychological nature. According to my analysis, complete satisfaction of the animal’s telos would constitute what could be legitimately called happiness for the animal. Thus, a happy lion would be a lion kept under extensive conditions with other lions, allowing the full range of lion behavior, including predatory behavior. A miserable lion would be one kept alone in a small cage. The relevant ethical judgment for lions in captivity would be to create a space that functionally approximates the ideal, as the research community has done with primates. Thus, pigs in a straw-based pen system would be happier than a sow in a sow stall, but not as happy as a sow with free access to foraging and shelter from inclement weather. There is a huge body of empirical data from Edinburgh on natural behavior in pigs, particularly sows. In my view, part of the job of what is called animal welfare science is getting as close as possible to happiness for the captive animal.

So there is more to being ethical to the research animals than simply minimizing pain. There are all these other parameters. I find personally talking of animal happiness unproblematic. Indeed, I would argue that animal happiness is far clearer than human happiness, given the curse of human reflective consciousness. A person may have every wish he or she ever wanted fulfilled, yet not be happy for a multitude of reasons. Everyone has friends like this—for example, people possessed of neurotic worry about losing it, neurotic worry about whether they deserve it or not. We have no reason to believe that animals are capable of such nonproductive navel-gazing. There are few human cases of happiness as paradigmatic as the horse let out of the small corral after winter into a large green pasture, after being fenced for months: the kicking up of the heels, the breaking of wind, the exuberance of the gallop, and the whinny express joy more clearly than any human affirmations. Typically, animals don’t lie.

In sum, we have argued that emerging social ethics for animals in democratic societies will largely dictate the form animal welfare takes, and particularly in the research area, since social and economic pressure will help impose it on other societies. This emerging ethic emphasizes the rights animals should have based on their biological and psychological natures or teloi. The extent to which such telos can be accommodated will vary with circumstance, but the ideal remains clearly demarcated. This idea was necessary to counter the 20th century tendency to see animal welfare as strictly determined by the human purposes to which the animal is put.

Footnotes

1

These are freedom from thirst, hunger, and malnutrition; freedom from discomfort; freedom from pain, injury, and disease; freedom to express normal behavior; and freedom from fear and distress; available online (www​.fawc.org.uk/freedoms.htm).

2

The 2nd OIE Global Conference on Animal Welfare: Putting the OIE Standards to Work was held October 20–22, 2008; the program and presentations are available online (www​.oie.int).

1

The resulting meeting summary, Swimming with the Tide: Animal Welfare in Veterinary Medical Education and Research, and related documents are available online at www​.avma.org/awsymposium.

1

The slides that accompanied this presentation are available in the online posting of this report at www​.nap.edu.

1

Recognition and Alleviation of Distress in Laboratory Animals (2008). Washington: National Academies Press.

1

The figures in this article appear in color in the online posting of this report at www​.nap.edu.

1

These are freedom from thirst, hunger, and malnutrition; freedom from discomfort; freedom from pain, injury, and disease; freedom to express normal behavior; and freedom from fear and distress; available online (www​.fawc.org.uk/freedoms.htm).