For human subjects, how do we identify those studies that are ethical?  At UW–Madison, and nationally, this is accomplished by requiring that any proposed study be evaluated and approved by a review board before it can be started.  In other words, the decision is made on a case-by-case basis.

For animal subjects, we and other institutions do the same thing.  As a guiding tool, we employ the ethical philosophy of utilitarianism, in which actions are justified only after benefits are balanced against harm: any ethical analysis must consider both.  Nationally, the elements of this analysis are described by the “U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training”.

Consider Principle Ⅱ in this document: “Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society”. Here is an explicit requirement to evaluate whether a given study has the potential to produce benefits.  Compare this with a question on the UW–Madison application for animal use:  “Outline the specific scientific goal(s) and significance of this research. Be convincing as to why this work is important for advancement of knowledge, improving human or animal health, or for the good of society.”  Other principles outlined in the document identify the need for pain relief, veterinary care, and appropriate animal housing and husbandry, explicitly addressing potential for harm.  Each is matched with a corresponding request for information on our animal use application.

Thus, ethical considerations are built in to every single review of proposed animal use.  In this way, UW–Madison Animal Care and Use Committees answer the question of whether experimenting on primates, or any animal, is ethical.  Just as for experiments involving humans, only if the answer is yes will an animal study be allowed to proceed.

Ethical consideration of animal use is not limited to application review.  Review committees on this campus have discussed ethics explicitly.  Graduate students and other research trainees take a class on research ethics that includes a unit devoted to animals, and this provides them with the framework to develop their own ethical stand on the issue.  Campus-sponsored seminars have included animal ethicists, and faculty and staff participate in public programs and debates about animal use and ethics.  Nationally, scientific societies, funding agencies, and the federal government review, refine, and set standards for animal use based on both ethical and scientific considerations.  Policy-guiding ethical decisions are made at the national level, balancing the public’s interests in animals and its desire to find treatments for disease.

The people who work with animals are themselves members of the “general public”, and have ethical standards of their own.  They have pets, have families, contribute to social causes, and donate time and money to charities.  Most feel passionately about both the importance of their work and the wellbeing of their animal subjects.  These are not contradictory feelings; rather, they exemplify essential elements of the balancing test that informs both personal and institutional use of any animal in research, education, and outreach.

“Research in animal models is essential to deepening our understanding of the human brain, how it works, and how alterations in brain function result in mental illnesses such as anxiety disorders, depressive disorders, PTSD, schizophrenia, and autism. Dr. Kalin and his colleagues have made significant contributions to our understanding of the brain mechanisms that lead to anxiety and depressive disorders. His work is particularly relevant to children suffering from these disabling illnesses. Dr. Kalin’s earlier work with young rhesus monkeys has revealed the brain alterations and molecular underpinnings that create childhood risks that can develop into anxiety and depression. This work not only demonstrates the specific parts of the brain that have altered function but also shows that this altered brain functionality is inherited. Findings from his primate studies have also identified new molecular targets that have the potential to create novel treatment strategies aimed at early intervention or even prevention.

“Mental illnesses are common in the United States as over 43 million Americans suffer from some mental illness. We need more effective treatments and we do not have a cure. Studies in rhesus monkeys are critical because they provide an animal model that is most relevant to human psychiatric illness.

“The monkeys involved in Dr. Kalin’s research are treated humanely and their use and care is overseen by numerous entities including the United States Department of Agriculture and the National Institutes of Health (NIH). In addition, the University of Wisocnsin’s Institutional Animal Care and Use Committee has approved and supports Dr. Kalin’s research.

“Dr. Kalin has a superb record of extramural NIH funding and his publications have been cited in numerous journals including the Journal of Neuroscience, Proceedings of the National Academy of Sciences and Nature Neuroscience. As measures of his respect in the field, he was president of the Society of Biological Psychiatry, as well as a member of the American Psychiatric Council on Research. He will receive the 2015 Anna Monika Award, and international honor given to an individual who has made important and outstanding achievements to the field of psychiatry. In addition to his research and leading major department of psychiatry, he also treats patients suffering from treatment-resistant anxiety and depression.

“We are proud that Dr. Kalin is a member of the American Psychiatric Association and the fact that his research is critical for developing new and better treatments for our patients. We wholeheartedly support his work. Thank you for your consideration.”

— Saul Levin, CEO and medical director, American Psychiatric Association

Read the letter here. (PDF)

“The purpose of this letter is to convey the position of ACNP that research using nonhuman primate animal models is essential to deepening the understanding of human health, including psychiatric disorders, and must be protected as such. Psychiatric disorders are among the most common and disabling illnesses; twenty-five percent of the population, including children, suffer from psychiatric disorders and suicide is among the leading causes of death in adults and adolescents. It is ACNP’s mission to advance the understanding of the causes, prevention and treatment of diseases of the nervous system including psychiatric, neurological, behavioral and addictive disorders. The research work of our esteemed members includes clinical and basic science research and makes use of a wide array of models that include humans, rodents, and nonhuman primates. Studies using nonhuman primates are just a small portion of all animal studies undertaken and are only conducted when all other models, animal and otherwise, have proven to be insufficient. The use of nonhuman primates is subject to comprehensive and exacting examination by federal review panels and institutional review boards.

“Research conducted in Dr. Kalin’s laboratory is critical to furthering our understanding of the risk factors underlying the development of anxiety and depression. His work combines molecular, animal and human models, and imaging studies to identify mechanisms underlying anxiety and affective disorders. Findings from his developmental primate studies point to novel molecular targets as the basis for interventions aimed at altering the expression of specific amygdala neuroplasticity genes. Dr. Kalin has a superb record of extramural NIH funding where scrutiny of ethical treatment of animals is required for approval. Also, his publications are highly cited in journals that include Nature, Science, PNAS, Nature Neuroscience and Journal of Neuroscience, where again reviewers are required to comment on the proper and ethical treatment of animals used in the research. In addition to both NIH and publication review of animal use in Dr. Kalin’s research, the University of Wisconsin IACUC has approved and agrees that Dr. Kalin’s research meets the highest standards of animal care and use in experimental protocols. As measures of his respect in the field, he is a fellow with the American Association for the Advancement of Science (AAAS), he has served as President of the International Society of Psychoneuro- endocrinology (ISPNE) and is the current President of the Society of Biological Psychiatry (SOBP). He will receive the 2015 Anna Monika award, from the European College of Neuropsychopharmacology (ECNP), for his outstanding achievements.

“The campaigns waged against the University of Wisconsin by ALDF, PETA and the others are designed to undermine the university’s mission to pursue excellence in research. We urge the administration of the University of Wisconsin to stand firm against these attacks against a distinguished investigator carrying out research with nonhuman primates according to NIH and IACUC approved standards of care and experimentation.”

— Raquel Gur, president, American College of Neuropsychopharmacology

Read the letter here. (PDF)

But we don’t appreciate the way petition’s author, Dr. Ruth Decker, misrepresents the research. By piling up mistakes, myths and exaggerations, and omitting important information, she asks well-meaning people to speak out with little understanding of the real science and the long, deliberative process through which it was approved.

This isn’t fair to the people who signed the petition, or to UW–Madison psychiatry professor Ned Kalin and the scientists involved in the work, or to the millions of people who suffer from mental illness for whom available treatment methods offer little relief.

The truth is of little concern to activists who wish to end animal research, no matter the benefit to humans and animals. We don’t share that sentiment. We prefer people make their judgments on animal research with a fuller understanding of the research — of both its costs and potential benefits.

So, if you have read the change.org petition, please also consider these corrections and additional information:

• This is not a repeat of experiments UW–Madison psychology professor Harry Harlow conducted as many as five decades ago, some of which subjected animals to extreme stress and isolation. The methods for the modern work were selected specifically because they can reliably create mild to moderate symptoms of anxiety in the monkeys. They were chosen to minimize discomfort for the animals, and to minimize the number of animals required to provide researchers with answers to their questions.

• There is no “solitary confinement.” The animals live in cages with other monkeys of their own age, a method of care called peer rearing. This method is often used when mothers reject their infant monkeys, which happens regularly in situations from nature to zoos to clinical nurseries with first-time mothers or following caesarean-section births. In a group setting, even veterinarians would have difficulty distinguishing the peer-reared animals from those that that were maternally reared.

The purpose of peer rearing is not to demonstrate that removing a monkey from its mother causes anxiety, a common misconception we have heard from people who have signed the petition.

Again: peer rearing was chosen because it is known to produce mild to moderate anxiety symptoms. With a group of animals predisposed to anxiety raised in a controlled setting, researchers can use state-of-the-art techniques to observe and measure even very subtle differences in brain chemistry and structure. Those chemical and anatomical differences may suggest new treatments — via nutrition, exercise, meditation, drugs or another approach — for people suffering from mental illness.

• The animals in the study are not “terrorized,” and do not experience “relentless torture.” Most of their time is spent as a house pet would spend its days — grooming, sleeping, eating and playing with toys, puzzles and other animals.

On occasion, to assess the monkeys’ level of anxious temperament, they are observed under two anxiety-provoking conditions. The first involves the presence of an unknown person who briefly enters the room, but does not make eye contact with the monkey. The second involves the monkey being able to see a snake, which is enclosed in a covered Plexiglas container in the same room, but outside the monkey’s cage.

After each event, the animal’s brain activity is monitored by a non-invasive functional magnetic resonance scan, and blood samples are taken. The stress the monkeys experience is comparable to what an anxious human might feel when encountering a stranger or a snake or a nurse with a needle.

• No one was “left out” of the review by UW–Madison oversight committees. Several university committees spent a great deal of time assessing Dr. Kalin’s anxiety research, and each committee found it to be acceptable and ethical. These were groups of researchers, veterinarians and public representatives tasked with considering animal research on ethical grounds, and with ensuring potentially beneficial research will subject the fewest animals to the least invasive measures.

As the petition notes, an animal rights group took allegations about the committee process to the U.S. Department of Agriculture. What the petition does not mention is that USDA conducted an investigation in August in response to that complaint. Inspectors found the complaint lacking merit, and the process to be entirely within compliance with federal regulations.

And, as with all animal research on campus, specially trained veterinarians will care for the monkeys involved and ensure that all the work is done in accordance with federal regulations enforced by the National Institutes of Health and the USDA.

• Most importantly, the petition repeatedly maligns the research as “needless” and “unnecessary.” We and many others think otherwise. Dr. Kalin, who treats human patients with anxiety and depression disorders, has worked for more than 30 years to understand both inherited and environmental causes of mental illness. His research was also reviewed and supported by panels of scientists at the National Institutes of Mental Health.

The decision to study animal models to understand human psychiatric disorders is not made lightly. Roughly a quarter of the people in the United States, including children, suffer from mental illness. Their conditions subject them to immeasurable disability and dysfunction. And the worst outcome, suicide, is increasing and already among the leading causes of death in adolescents. To develop effective treatments that may alleviate the suffering of millions, it is necessary to understand the root cause of psychiatric illnesses.

In this case, the human suffering is so great that Kalin, the National Institutes of Health and UW–Madison’s review committees believe the potential benefit of the knowledge gained from this research justifies the use of an animal model.

More information on the anxiety and depression research is available at animalresearch.wisc.edu.

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— Tom Insel, M.D., director of the National Institute of Mental Health (NIMH)

Read the letter here. (PDF)

While we respect the viewpoint of those who oppose research on animals, we feel that the potential benefits to human welfare, animal welfare and basic knowledge about life are too important to not do the research. An argument can be made that refraining from this research would actually be unethical.

The review and approval for an animal care and use protocol follows these steps:

• Protocol application is prepared by the investigator and submitted to the Research Animal Resource Center (RARC), which assigns the protocol to the appropriate Animal Care and Use Committee for review.
• The ACUC can approve the protocol as is, approve it pending answers to certain questions, or require substantial revision.
• RARC staff communicates the ACUC’s approval or request for further information/revision to the Investigator.
• Research can begin after the protocol is approved.

Prior to making any significant change to the protocol, investigators must get approval of the relevant ACUC.