Tag Archives: NIH

Animal welfare inspectors clear UW-Madison cat research of PETA allegations, important hearing research continues

A second federal agency charged with oversight of animal research has completed a thorough investigation of an animal rights group’s complaints about sound localization research with cats at the University of Wisconsin. Summary of the result:  “there was no direct noncompliance with the PHS Policy or serious deviation from the provisions of the Guide for the Care and Use of Laboratory Animals.”

We have written previously (here, here, here) about reviews conducted by the United States Department of Agriculture (USDA). This time the report is from the National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW).  Once again, the complaint by PETA is based on hundreds of pages of records that the animal rights group received from the UW via open records requests.  In response to these complaints both federal agencies have sent teams that include veterinarians to look at the animals, records, and research at UW-Madison.

new graphic - AR cycle 10.07.13 ajbIn addition to the USDA and OLAW reviews, during this period the NIH institute funding the sound localization project, the National Institute on Deafness and Communication Disorders (NIDCD), also took action. NIDCD suspended one part of the research— but not the entire project— from April-September 2013 when the final report was issued. Whether the suspension was the result of PETA’s allegations is not clear. What is clear is that the NIH and scientific community have long supported and valued this specific research and– more broadly–  the contribution of animal models to success in this field and advances in scientific understanding and human health. The PI of this work, Professor Tom Yin, has been funded by NIH for many years. As is the case of all NIH-funded research, a competitive expert scientific panel provides rigorous critical analysis of the proposed science. Only a small fraction of proposals are identified as valuable, worthwhile, and likely to succeed. In this case, the PI’s research was deemed justifiable and worthy following scientific review, NIH review, and IACUC review. Furthermore, the scientific contributions Yin’s work is evident in many ways. For example, it is widely cited in the field (e.g., over 5000 citations of his scientific papers). Yin discusses the targeted research in these videos:

In brief, Professor Yin’s laboratory conducts fundamental basic research that has resulted in better understanding of complex brain function and how hearing works. By using a combination of electrophysiological recordings, anatomical studies and behavioral studies, the lab is studying the mechanisms used by the brain to put together inputs from the two ears to improve hearing. The scientific discoveries have public benefit because they provide foundational understanding with broad applicability. Knowing how the brain integrates sound received by both ears and how that allows for localization of sounds is an important part of work towards improving the quality of life and functioning of millions of people with hearing impairment.

Many types of research in this area require recording and studying a real functioning brain, there are no non-animal alternatives. Cats are among the best animal models for this work for a number of reasons. Among them: most of the information we have about the auditory system comes from studies in cats, they are nocturnal hunters with excellent sound localization abilities, and what we know about the cat’s nervous system shows that it is very similar to that of humans. The importance of cats and other animal models to research in this field is widely acknowledged, including by this year’s Lasker-DeBakey Clinical Medical Research Award, and particularly the work of Graeme Clarke, which laid the foundations for the development of multichannel cochlear implants through studies in cats and rats.

As we have discussed previously, consideration of the use of animals in research includes not only weighing its potential benefits, but also evaluation of the animals’ welfare. The welfare of all of research animals is a priority and one that is ensured through the careful efforts of research, veterinary, and animal care personnel. Furthermore, oversight of animals’ care and treatment occurs at individual, institutional, and federal levels. A small number of cats (less than a dozen) participate in UW-Madison’s sound localization research. The cats are healthy and well-adjusted to their work, play, and living environments as was documented in the OLAW report. In that report, external reviewers who had thoroughly reviewed the lab and records, examined the animals, and interviewed the animal care and veterinary personnel, research staff, and scientists were satisfied with the animals’ condition and treatment.  Potential for pain or suffering is minimized through careful efforts: Surgery is performed under deep anesthesia, just like surgery for humans. Infections are a risk, but they affect the animals only a fraction of the time they are in study. Furthermore, infections are caught early through extensive and careful monitoring, treated immediately and resolved quickly in all but a very small number of cases. In no cases are they allowed to be untreated or to cause suffering or unrelieved pain.

OLAW’s summary conclusion, released September 30, confirmed that the research and animal treatment were appropriate: “there was no direct noncompliance with the PHS Policy or serious deviation from the provisions of the Guide for the Care and Use of Laboratory Animals.” Furthermore, the report concluded that PETA’s specific allegations were unsupported. The report also acknowledged UW’s efforts to continue refinement in the animals’ care and treatment:  “OLAW found that while the specific allegations did not accurately reflect the entire clinical and research condition of the cats, changes were made to enhance the care of the animals and potentially improve research outcomes.” Furthermore, the report includes many extremely positive descriptions of the animals’ condition and care.

UW responded:

“The OLAW investigation is the third review of the lab and its animal subjects by the federal government, all instigated by PETA within the past year. To date, none of the many allegations of mistreatment made by the organization to the U.S. Department of Agriculture or OLAW have been substantiated. ‘Contrary to the misleading claims made by PETA, the conclusions cited in the OLAW report reflect our view that the animals in the study are in excellent health, are well treated and cared for, and used to further important research in an appropriate and humane manner,’ says Dan Uhlrich, UW-Madison associate vice chancellor for research policy.  ‘Significant university and federal resources have been repeatedly redirected to respond to these unfounded allegations. This is a questionable use of scarce and valuable public resources, which we feel damages the best interests of the public, science, affected researchers, and the dedicated animal care and veterinary staffs responsible for the health and wellbeing of our animals.”

The OLAW summary report, including 36 appendix exhibits, can be found on their website. The UW has also shared detailed information about the research, the reviews, and the animal program with the broad public via its website, release of hundreds of records, and videos in which the scientist and others speak about the value of the work and how it is conducted.  In other words, as we’ve noted before, there are many venues for the public to learn more about the work, its conduct, and the detailed process of regulatory oversight.

What was PETA’s response?

Hint:  It did not include acknowledgement that OLAW, USDA, and the University of Wisconsin gave serious consideration to PETA’s complaint, performed a thorough investigation, and provided a detailed, specific public response on each of the allegations that the animal rights group raised. Nor did PETA’s response include an acknowledgement that perhaps they were wrong.  And nothing in their public responses indicated – front and center – that PETA’s mission and objective is to end all animal research. PETA’s position is fundamentally absolutist. Regardless of animals’ welfare and regardless of the consequences for the public that benefits from responsible, ethical and humanely-conducted animal studies, PETA is opposed to all use of nonhuman animals. Thus, there are presumably no conditions under which PETA would find laboratory animal research acceptable. (We welcome correction from PETA if this is a misrepresentation of their position.)

It is not surprising then that, as reported in the Wisconsin State Journal, PETA’s spokesman did not accept the OLAW conclusion, but rather vowed:  “This campaign is going to continue until that lab is empty and there are no cats in it,’” Goodman said without specifying the group’s next steps.”

PETA’s next steps in its quest to close the laboratory will probably include some of the characteristic stunts for which they are famous. At the UW this has included small protests on campus, the PETA mobile billboard truck driving around Madison, and an actor and PETA staffer gaining media coverage for disruption and arrest at a UW System Board of Regents meeting. Review of their campaign strategy thus far provides a few other clues for what to expect at the UW and elsewhere. For example, last week PETA set up at the campus job fair to recruit for an “undercover investigator.”  PETA’s Jeremy Beckham netted a local television interview with the tactic. Not a new tactic for animal rights groups, as seen in this campaign directed at Oregon Health Sciences University several years ago.

As we’ve written before however, focusing on these stunts and underestimating the broader gains that PETA has made and that negatively affect science and public interests can be a mistake.  In the case of this campaign and all of the associated events, two things in particular are worth notice by the broader community.  First, the way in which PETA used the openness of records and the public responsiveness of the regulatory process to feed their campaign; and second, the use of emotive tactics that encourage harassment of scientists and others in research institutions. The graphic above captures the general strategy used by many activist groups, highlights the costs, and raises a number of questions. In particular, one question that merits serious discussion is how to better assess the full range of actual costs and critical evaluation of realized benefits to animal welfare, science, and public interests.

Despite the conclusion of multiple federal reviews that failed to support their allegations, PETA is continuing to smear the research and to promote petition and email campaigns to the NIH, UW-Madison, and others. As one of the exhibits in the OLAW report shows, the NIDCD received 562 phone calls and approximately 190,000 emails about cat research. While that represents a tiny fraction of the American public and likely includes many form messages, its inclusion in the OLAW report suggests it may have been relevant to the NIH’s response.  No doubt that number increased after PETA linked a form email to its mixed martial arts assault on scientists videogame in order to encourage players to complain to NIH about the UW research.  Of course the game also encourages players to entertain the idea of harming scientists. As we’ve seen before, these highly emotional tactics can have the general effect of eliciting threatening and disturbing messages from those who follow PETA. For example, this recent tweet:

Beth Carter 10.5.13 tweet

The PETA campaign and response following the USDA and OLAW reports makes their objective clear once again:  to end research and close labs. Nothing new there. The question to ask now however, is how research institutions, scientists, federal agencies, and the public should respond to campaigns like this. In particular, this set of events provides additional strong evidence that there is little broad value in engagement with groups that have a singular agenda and little interest in serious dialogue, accuracy, or acknowledgement of the complex issues and choices in animal research conducted for public benefit.  For scientists and research institutions interested in dialogue and better understanding of animal research, using that time and energy to communicate directly with the public about their research, why they are doing it and what it involves makes more sense.

More here:




The Double Life of Dr. Lawrence A. Hansen

Dr. Lawrence A. Hansen has a double life he is proud to publicize in his writings and interviews.

On one hand, he is a neuroscientist at one of the finest institutions in the country — the University of California at San Diego.  On the other hand, he is a member and a mouthpiece for People for the Ethical Treatment of Animals.

PeTA, of course, is an animal rights organization that holds the view that all living beings have the same basic right to life and freedom. A corollary of this position is that  animals cannot be used by humans in any way, including their use in scientific research designed to advance human health and medical knowledge.

Dr. Lawrence Hansen regularly attends the Society for Neuroscience Annual Meeting, where he joins his PeTA colleagues in order to protest the organization’s stated goal of broadening support for animal research.”

He has  written numerous opinion pieces (for example, here, here and here) asserting with confidence that animal research will not lead to any advancements in human health, that the experiments are unnecessary because they can be conducted in human volunteers, and that the treatment of the animals in our nation’s laboratories amount to torture.


Dr. Lawrence Hansen (left) demonstrating at the Society for Neuroscience meeting. He is accompanied by PeTA’s Justin Goodman (right).

Dr. Hansen is wrong on all counts.

Animal research has contributed widely to human healthMultiple layers ensure the welfare of animals during experimentation. Methods do not exist today that would allow scientists to study the cellular and molecular mechanisms underlying disease in human volunteers non-invasively. This is what is really required to understand the evolution of a disease in a living organism and how we can interfere with its development. Indeed, a recent poll by the journal Nature revealed that nearly 92% of scientists agree with the statement “animal research is essential to the advancement of biomedical science.”  The  fact is that there are no current alternatives — otherwise, they would be used.  This is the reason the scientific consensus on the topic is nothing short of overwhelming.

Being wrong is just one problem with Dr. Hansen.  The other is the level of hypocrisy required for a scholar like him to criticize animal research while simultaneously being involved in the work.  Specifically, Dr. Hansen is a co-author in animal studies that use transgenic mice to model Alzheimer’s disease in humans: here, here, here and here.

Justification for all these studies relies on the notion that one can model the disease in mice in ways that might be relevant to human patients — an idea that Dr. Hansen rejects vociferously.  Was authorship on these studies forced upon him?

Perhaps Dr. Hansen will argue that he played a minor role in these studies, merely providing resources and reagents for the studies?  This seems unlikely, as at least in one instance Dr. Hansen’s role is listed as having “conceived and designed the experiments.”

All these articles list the Neuropathology Core grant (NIH P50 AG005131), of which Dr. Hansen is the responsible Principal Investigator, as partly funding them.  In other words, Dr. Hansen’s own federal grant has funded the animal research he presumably opposes.  (Incidentally, as far as we can tell, the Aims of the grant do not include any animal research.)

Perhaps Dr. Hansen approves only of work with mice but not in other species? If so, it seems he fails to understand the concept of “animal rights.”  The notion that all living beings have a right to live free from all human intervention would render his own work ethically wrong as well.  Or does PeTA make an exception for his mice work?  Maybe membership has its privileges?

Perhaps Dr. Hansen thinks that for some magic reason his work with mice is guaranteed to translate to humans, while findings in other species will not?  One wonders if there something magical about the biology of mice?  If mice can be used to model human disease, why couldn’t other animals? However, it doesn’t seem that Dr. Hansen holds mice work in high regard.  Last year, in an interview, he stated:

“the amoral scientific problem with using rodents as models for neurodegenerative diseases is that rodents do not naturally develop Alzheimer disease or Parkinson`s disease. The only way to get what looks even a little like AD or PD pathology in rats and mice is to make them transgenic — that is, to insert human disease causing genes into the rodents. This does create a Frankenstein-like mutant model with some expression of AD or PD pathology which can be manipulated to make it go away. But reversing artificially induced AD or PD changes in animals that never naturally develop them is a far cry from curing the human diseases. The “cures” that work in the rodents have never worked when applied to humans. 

[...] The species differences that have evolved over millions of years make animal models largely useless, except for the purposes of enhancing scientific careers and attracting lots of grant money.”

If this represents his scientific opinion, why in the world would he participate and fund the very same “unnecessary” experiments that create “Frankenstein-like” animals? Perhaps Dr. Hansen thinks his transgenic animals are under good care and condition, while the other ones down the hall that belong a colleague are being tortured instead?

Perhaps Dr. Hansen believes his studies are restricted to some basic biological process of Alzheimer’s that has no consequence for the human condition?  But then, how would he justify the use of animals?  And why would he write that his work “supports the possibility that modulators of the autophagy pathway might provide potential therapeutic effects.”  Therapeutic effect for mice but not humans?   Again this seems unlikely, as stated that mice do not develop AD or PD pathology naturally, and thus are not in need of any therapeutics.

The fact is that the justification behind his work can be found in the Introduction and Discussion sections within the very same articles he co-wrote.  Dr. Hansen and his co-authors explain, for example, that:

It is important to note that neurogenesis persists in the aged brain; however, its rate declines with increasing age, as revealed by previous studies in rodents (Kuhn et al., 1996Kempermann et al., 1998), nonhuman primates (Gould et al., 1999), and humans (Cameron and McKay, 1999). Despite this natural decline with age, previous studies have shown that the adult brain remains responsive to therapeutic interventions that enhance neurogenesis (Jin et al., 2003Wise, 2003). Understanding the molecular mechanisms involved in AD-related alterations in neurogenesis might help guide the development of new therapies in this direction. 

This is one of several passages illustrating the synergy between human, mouse and in vitro techniques in biomedical research, and highlights the similarities between development of the human disease and its recapitulation in animals models of AD.  These are the very same scientific facts he denies and renounces in his interviews, OpEds, and PeTA demonstrations.

It would be worth for Dr. Hansen to dedicate some effort in justifying his own work with animals, studying a little bit more about the contributions of animal research to human health, and dedicating less of his time demonizing his colleagues for the wrong reasons.

Speaking of Research

Update: There is more discussion going on at DrugMonkey’s blog as well.

Solving the Brain: Animal research at the frontiers of Neuroscience

Regular readers of this blog will be familiar with the important role played by animal research in neuroscience, a post we published to mark Brain Awareness Week earlier this year covered but a tiny fraction of the work being done around the world. Meanwhile some neuroscientists have been thinking big…very big…with the launch of the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative in the USA and the Human Brian Project in the EU, projects that aim to transform neuroscience and accelerate the discovery of novel therapies for neurological disorders. Within the neuroscience world there has been a lot of discussion and debate over whether now really is the right time to launch this initiative,  and whether the budgets allocated are anywhere near large enough to fulfil the ambitious aims, but as the dust settles a little and it becomes clear that these projects will – at least initially – focus on developing research techniques and infrastructure, it is useful to take a look at what is being planned.

Optogenetics is one technology helping scientists to unlock the brain's secrets.

Optogenetics is one technology helping scientists to unlock the brain’s secrets.

In Nature this week Alison Abbott has spoken to several of the main players in these programs in the USA and Europe, and the very first paragraph highlights their ambitious nature.

When neurobiologist Bill Newsome got a phone call from Francis Collins in March, his first reaction was one of dismay. The director of the US National Institutes of Health had contacted him out of the blue to ask if he would co-chair a rapid planning effort for a ten-year assault on how the brain works. To Newsome, that sounded like the sort of thankless, amorphous and onerous task that would ruin a good summer. But after turning it over in his mind for 24 hours, his dismay gave way to enthusiasm. “The timing is right,” says Newsome, who is based at Stanford University School of Medicine in California. He accepted the task. “The brain is the intellectual excitement for the twenty-first century.”

We strongly encourage you to head over to Nature and read the whole article, which provides a great introduction to the different challenges – both scientific and technical – that neuroscientists face, and how they are planning to overcome them.

Alison’s article also highlights the crucial role that animal research will play in this effort, in developing the technologies that the BRAIN Initiative describes:

While these technological innovations have contributed substantially to our expanding knowledge of the brain, significant breakthroughs in how we treat neurological and psychiatric disease will require a new generation of tools to enable researchers to record signals from brain cells in much greater numbers and at even faster speeds. This cannot currently be achieved, but great promise for developing such technologies lies at the intersections of nanoscience, imaging, engineering, informatics, and other rapidly emerging fields of science

New techniques such as optogenetics that allow researchers to precisely control the activity of individual neurons,  CLARITY and  Scale that make tissue transparent so previously hidden connections within the brain become visible, and advanced electrode technology that has allowed the development of neuroprobes that can measure the activity of over a hundred individual neurons simultaneously (earlier versions of which are being used to develop treatments for paralysis), will all play an important role in these programmes, alongside powerful brain imaging technologies and the supercomputers and computational techniques needed to process and make sense of the vast amounts of data that they will yield.

The ambition of these projects is laudable, but it will not be achieved without a lot of investment, and there lies the problem. While $100 million was invested in the BRAIN initiative at it’s launch, this sum was dwarfed by the $1.5 billion slashed from The NIH’s budget by sequestration in March, and promising neuroscientists who might have made great contributions to understanding the brain are no doubt going to be among those whose careers are cut short by lack of funding.  This crisis at a time when we should be looking forward with hope and excitement shows why it is so important to make sure that your political representative understands that to secure future health and prosperity we need #curesnotcuts.

Speaking of Research

Statement on Harvard’s Decision to Close the New England Primate Research Center

Speaking of Research is saddened to learn about Harvard’s decision to wind down operations at the New England Primate Research Center (NEPRC) within the next two years.

Over the years the Primate Center has contributed important discoveries in many fields, including AIDS, Parkinson’s disease, primate retroviruses, addiction, cardiology and stem cells.

The University cited difficult financial times and shifting long-term strategic plans as the reason for the closing.  Meanwhile animal right activists groups fought among themselves to take credit for Harvard’s decision.

Perhaps a combination of both, the planned closure is a reflection of decreasing Federal support for medical research and a growing anti-scientific movement in the United States and elsewhere.

In Harvard’s decision one can find many lessons for the scientific community, NIH and the public at large, which are likely to be the subject of debate and discussion in the near future. The wider research community will need work together with faculty and staff at NEPRC to ensure that Harvard Medical school keeps to its commitment to provide full support to them during this transition, so that vital research programs and gifted personnel are not lost to science.

For now Speaking of Research join others in expressing our surprise and disappointment at these developments, and offer our support for the scientists, staff and others affected by these events.

Speaking of Research

A Public Conversation on Animal Ethics: The good, the bad, and the ugly

The UW-Madison recently hosted a conversation on the ethics of animal research between Rick Marolt, an opponent of animal research, and Robert Streiffer, a bioethicist at the university and member of the Institutional Animal Care and Use Committee (IACUC).

Here are some of my thoughts on this interesting exchange.

The good: Above all, it is good to see a display of open academic dialogue on a controversial topic.  We have tried such a conversation at UCLA in the past with mixed results. This meeting was described as a “conversation” rather than a “debate”.  Such dialogue is a good first step that allow participants to express their positions on the ethics of animal research. In this regard, I think such exercises are a net good and a sign of progress.

The curious: It is perplexing that the conversation centered on the use of a “utilitarian framework” to justify the use of animals in medical research. Why? Because both participants made it clear they are not utilitarians. Instead, they both (wrongly) declared that scientists are, or assumed the only possible justification for their work must be a utilitarian one. The result was that Prof. Streiffer, on more than one occasion, uttered a sentence beginning with “It is because they [scientists] think that..,” while not being clear on what his own ethical framework as Chair of the IACUC has been. Of course, if the participants were seeking an utilitarian justification for animal research they could have invited Peter Singer.

My sense is that scientists hold a wide range of more nuanced views that they certainly include the consideration of benefits, but are not defined by the utilitarian position. Rather than letting someone speak for us, scientists should let our voices be heard, both to explain the science and ethics of the work.

Mind the gap: The discussion centered exclusively on the upper limits of animal research.  In other words, what kind of experiments would one find to be unjustifiable? Marolt and Streiffer probed this issue using a maternal deprivation protocol at UW as a test case. I think this is a good question to ask. At the same time, if one truly want to explore the size of the gap that exists between our respective positions, we must also ask what kind of experiments the critics of animal research would find acceptable and why. This point was altogether ignored and Mr. Marolt offered no examples. Given the ethical principles he cited (see below), I’d guess his answer would be “none at all”. Understanding the gap between opposing views is critical to identify areas of common ground, or lead us to conclude that there cannot be any.

The bad: To a scientist, perhaps the most shocking passage of the exchange came when both participants agreed that “knowledge is not a significant benefit.” Such an insult to reason is deeply troubling because it shows how little the participants know about the scientific process. They also seem not to appreciate the value of negative results (disproving a hypothesis) in scientific inquiry.

Presumably, neither Marolt or Streiffer see much value in proving abstract mathematical theorems, engaging in space exploration, trying to manipulate single atoms, proving the existence of the Higgs boson, or placing a telescope in space to peek into the boundaries of the universe. They are apparently oblivious, for example, as to the origins of the medical imaging technologies such as X-rays, PET, ultrasound, and MRI. (Hint: basic knowledge.)

The inconsistent: Prof. Streiffer explained how he arrived at the conclusion that a protocol under discussion was unjustified based on his cost/benefit analysis. However, he previously stated that he didn’t fully understand how is that the scientists would be analyzing the data to determine the molecular pathways involved in anxiety. How was he able to assess the potential benefits of the work without such understanding?  It is not clear.

The double standard: Mr. Marolt tried to explain his opposition to animal research based on his “moral intuitions.”  However, he is unwilling to accept the use of “moral intuitions” argument from others, demanding instead solid ethical reasoning. He should apply the same high standards of ethical reasoning he demands from scientists to himself.

The “moral intuitions”: So what are Marolt’s moral intuitions? He said that in his view “life matters” and that we should not deprive anyone from the opportunity to life.

Does he mean this in absolute terms? Is he anti-abortion? Does he believe the use of violence to end slavery or free concentration camps was unjustified?  Does he see any situation at all in which taking a life may be justified?

He said that “suffering matters,” and that he feels the suffering of the monkeys in labs while lying in bed at night. I know that those working with animals also feel in such a way, but they also feel for the mothers that fight breast cancer, the children with leukemia, the elderly with Alzheimer’s or Parkinson’s. Their suffering matters to them too.

We all protect our children against enormous suffering by vaccinations that were developed through the use of animals in research.  We recognize the moral dilemma of the work. Not having children of his own Marolt did not have such experience, but he found no shortage of words when it came to offer suggestions as to how others must educate their children on moral issues.

Marolt said that species membership is not morally relevant because “he does not feel that.” Once again, if we accept this justification, those who support the work could simply respond that “we feel otherwise.” But it is unlikely that he would accept such explanation. What we would like to know is why he thinks we owe the same exact level of moral consideration to a mouse as to a human. We are asking for a reason, not a feeling.  Here are some reasons why cognitive abilities matter, as they impact the level of suffering of different organisms.

Finally, Marolt asserted that if faced with a situation where he had to choose between two living beings, a human and an animal, he would save the life of a human. But he explained he would not be able to rationalize his choice.

One can only infer that if Marolt had a better understanding of the science he would  approve of animal research.  Indeed, scientists feel we are in a sort of burning house scenario. Most of us feel that human lives will be lost if we stop the work and that, at present, there are no viable alternatives. We accept we have to live with the uncertainty of the benefits that any one experiment could yield. At the same time we are certain of the benefits of the work as a whole, as proven by medical history.  We are convinced that stopping scientific work with animals means that many areas of medical research would come to a full stop, with tremendous harm done to humans and animals alike.

Rick Marolt, and other animal rights activists like him, have to justify their inaction and their demand to have this type of work abolished. Not with feelings and intuitions, but with moral reasoning. They have not yet produced a compelling argument, and their absolutist, moral intuitions are wrong.

A Closer Look at How Animal Research Progresses from Idea to Study

Unfortunately, the “how” and “why” of the research process is of much less interest, and receives far less attention, than the “what did they find?!” part of research. The latter is what you’ll see—if we’re lucky from the science outreach perspective— on television, in the science and popular media, Facebook, Twitter, and conversations world-wide. Meanwhile, the former will be relegated to websites of federal agencies, scientific societies, and animal research advocacy groups and are read less widely.  In fact, it is entirely possible that a great many bets could be won by wagering that the public generally doesn’t care to read up on regulation or processes governing the research behind the cool discoveries that make news.

In the case of animal-based research (and some other controversial fields), the “how” and “why” do sometimes generate some public interest because they are keystones in considering questions about its ethical basis and evaluation.  Public understanding and discussion of the process by which science moves forward is important. It provides appropriate context for fact-based dialogue about the ethical evaluation, decision-making, and regulation that govern a wide range of science conducted within our democratic system. Thus, many scientists and advocates not only welcome public interest in the conduct of science, but also actively promote thoughtful, engaged, and informed collaboration on efforts for improving research practices.

Why? One reason is that the ultimate benefactor from scientific studies is the public and, within a democratic society, it is for all of us to decide whether the benefits of those studies outweigh their costs.  Another reason is that scientists are generally sensitive and responsive to societal views, but feel an obligation to ensuring that these views are informed by facts as well as emotional appeals.  This is an issue that is not at all unique to animal research. It also appears in discussions of other topics that can elicit controversy, including for example: evolution, climate change, use of embryonic stem cells, and vaccines.

For animal research, the challenges inherent in serious evaluation of its costs and benefits are not trivial. Nor is it amendable to flashy, sensationalized, and emotion-evoking campaigns.  Simplistic approaches to this issue are not useful and do a disservice to all of us.

From our perspective, it is both disappointing and frustrating to find that understanding of the process by which science moves from idea, to the conducting of the study, to the dissemination of the findings, to the evaluation of those findings receives far less attention than would be needed in order to rationally discuss the research.  Why?  Because the reality of how science is actually conducted is centrally relevant to conversations about science.  And while this is an obvious statement, it is also clear from many portrayals of science by opposing groups that the basics of scientific process and conduct are often missed in the discussion.

In the case of laboratory animal research, the starting point of many opponents is an absolutist position in which the conditions for animals, the ultimate outcome of the research, and its benefits, are irrelevant. They are irrelevant because the starting assumption is that the use of animals is morally unacceptable. For those who hold this view, there is no benefit that would justify the animal use.  There are others who hold a less absolute view and, like us, believe that the use of animals in research begins with moral and ethical consideration that requires thoughtful, fact-based weighing of both relative harm and benefit.  One major part of this evaluation is identifying whether alternatives exist to meet the same goal.  Another is identifying as closely as possible what harm may be incurred, the probability and extent of benefits. Each of these considerations is integral to regulation of animal research in the U.S. and elsewhere. They are also considerations that are so integral to the scientific process that they operate far beyond those stages typically identified as the “checks” for ethical and humane conduct of animal research (e.g., IACUC review, federal oversight).

long haul slide

How scientific research moves from idea stage, to conducting a study, to success or failure, to critical review, to dissemination and use of findings is a process that can appear somewhat opaque to public view.  The pieces of information required to construct the general pathways are publicly available.  Putting them together, however, is not necessarily straightforward for those without immediate interest, expertise, or engagement.  So while the information is neither hidden nor made secret, it is of the type that can be easily misunderstood or misrepresented.

Should this gap in basic understanding and perspectives on how scientists’ ideas move from thinking to reality concern us?  The answer is yes.  Among other reasons, the gap serves as an impediment to an informed evaluation of science.  It also weighs heavily against productive dialogue about core issues of public interest.

How does an animal research project move from scientist’s idea to finished study?

In general, the process looks like this:  Scientists generate ideas that are based in careful study of what is known, what is not known, what methods already exist, what facts we have.  They next critically evaluate and review relevant previous literature and data–  often soliciting others’ expert knowledge–  to determine whether the idea is novel (has not already been tested),  of potential importance or significance, and feasible.

Thus, while some may have the impression that scientists roll out of bed in the morning, or have an aha-moment- then  move straight to the lab to conduct whatever study occurred to them via dream – this is not the way it typically works.

As illustrated, deciding on whether an idea is worth pursuing or not is driven by many factors. If the resulting data would have little potential benefit, few scientists are likely to pursue it. Why?  Because scientists have a lot of ideas and it makes no sense to expend energy on one that won’t be useful in terms of providing significant new knowledge or understanding.  It is also true that such ideas are unlikely to compete successfully in the different arenas of expert scientific review, including review for funding, publication, and citation.

research process

If a scientist judges his/her idea worth pursuing, the next step is likely to decide whether the study is feasible or practical. What does this mean?  In short, this is a question that revolves around ethical, economic, and practical issues.  On the ethical side, for animal research the scientist will consider animal welfare and treatment, any potential for harm.  Next, on the financial and practical sides, the scientist will consider how much the study will cost and whether the necessary work can even be done. During this initial stage the scientist will also critically evaluate whether the existing literature and facts provide adequate and strong platforms for the proposed study, or whether more basic and background data are needed to guide decisions before moving forward.

For that fraction of studies that survive the scientist’s own critical examination—and likely that of his/her collaborative group and colleagues—the scientist may decide to pursue the work. If so, for animal research the next step will be to write a proposal to the Institutional Animal Care and Use Committee (IACUC) in order to conduct a study.  In the U.S., IACUSs are among the main venues for thorough review of animal studies.  We have written previously about IACUCs and there is more information here.

In brief, the IACUC is comprised of individuals with veterinary and scientific expertise, as well as a public representative.  Animal studies do not proceed until the IACUC has reviewed and approved a proposal.  What do these protocols contain?  You can see some here, this site contains links to protocol forms from a range of institutions.  Although institutions vary in the format of applications, among other things, they include: information about what the study is designed to test, why it should be conducted, the literature review and strategies used to ensure that it is not unnecessarily duplicative, that alternatives do not exist, the number of animals proposed and justification for both the number and the species,  detailed description of all procedures,  and other details about the animals’ care and treatment.  In other words, the full range of information that the review committee will need in order to evaluate whether the study meets standards.

Is the IACUC process perfect in evaluating study protocols? No.  It is, however, the current system mandated by federal law and it is one that generally functions well to protect animal welfare.  It is also an evolving system, with scientists, veterinarians, federal agencies, science and animal welfare advocates engaged in its ongoing evaluation and improvement. Some of the criticisms of the existing system, however, neglect consideration of the larger context, the process by which research unfolds. For example, critics point to the fact that IACUCs approve the majority of studies put before them as evidence that “almost anything” a scientist could dream up receives approval.  In reality, IACUCs only review proposals that scientists write and submit. This means that the IACUC only sees study proposals that have already received some critical evaluation and that likely already fall within the constraints of current guidelines, practices, and norms.  Scientists, like others involved in animal research, take part in training and education about the range of issues related to animal welfare, humane treatment, and regulatory requirements.  As a result, they are generally not likely to write protocols that diverge from acceptable practices.

Following IACUC approval, the scientist may then begin conducting the study. It is often the case however, that IACUC approval is not the final step between idea and study.  Instead, for a new project, the scientist must also write a proposal to a funding agency in order to secure financial support for the research. In many cases in academic research, funding for these studies comes from federal agencies such as the National Institutes of Health or the National Science Foundation.  Competition for these funds is high and the majority of applications are not successful.  Those proposals that are funded have undergone rigorous review by a panel of scientists whose expertise is within the area of the proposal.  The criteria for review vary by agencies, but include very close examination of the significance of the research question, evaluation of its potential for success, scrutiny of the methods, expertise of the investigator, and quality of the facilities in which the research will be conducted.  The appropriateness of the animals chosen for study, their number, and their treatment are also subject to critical evaluation and discussion.  In sum, beyond IACUC review, many animal studies—including all of those funded by NIH, NSF, and other agencies— undergo another level of external expert scientific review.

Take-home message?  The evaluative process between a scientific idea, the conduct of a study, the results, and their evaluation, use, and further discovery is one with many steps and significant consideration.  The potential harm and benefit of each study receives review at each stage as well, both within and outside.

Research aimed at addressing basic, translational, or clinical questions relevant to advancing our scientific understanding and medical progress for humans and other animals is ultimately all aimed at questions with significance to many.  At the same time, it is also absolutely true that the benefits of research are not always directly or immediately apparent.  We simply do not know the answers before we conduct the work.  Furthermore, we can be confident—drawing from real conclusions from the history of science – that important, meaningful, generative breakthroughs are not entirely predictable.  As a result, it is no easy task to construct a metric by which to evaluate the potential benefit of research and to weigh that against any harm incurred during its conduct.

Considered carefully, the history of animal research and animal welfare are quite clear with respect to how the accomplishments of research and consideration of mutual interests in animal welfare provide the basis for progress in ethical and humanely-conducted animal research.   Public interests are served by dialogue based in fact and in clear accurate articulation of ethical frameworks from which animal research is considered.  Understanding the multiple levels at which research projects are evaluated from scientific and ethical perspectives is an integral starting point for this discussion.  Science doesn’t occur through simple processes or via a single stage of evaluation; nor should public dialogue about this complex issue.

Allyson J. Bennett

The Golden Goose Awards

Politicians sometimes deride research based on the what they perceive as being “silly” titles of federal funded grants.  If they spot a title that deals with “games”, for example, they may assume it deals with some sort of amusement of little value to society, instead of a deep, powerful branch of mathematics that describes the behavior of competing rational agents with much relevance to voting, economics, cooperation, and so on.  Animal rights activists also enjoy the hobby.  The latest example is IDA’s list of “ridiculous research” ,whose claims were sadly repeated by far too many news journalists who were clearly too lazy check if they were accurate.  There were some honorable exceptions, notably an excellent editorial entitled “When the facts ruin a good spin” in the Times Union, which discusses a project on the role of music as a conditioning stimulus for drug use ends with a statement with which we heartily agree:

What’s “ridiculous,” to borrow the press release’s language, is that we fall for it, over and over, egged on by politicians eager to score easy points. And what’s “wasteful” is the time and energy that could be so much better spent on something other than a cheap shot.”

Back in 1976 the House Committee on Appropriations asked the National Science Foundation “Why does the Foundation persist in supporting research whose results have no apparent value to the American people?”  The NSF responded in part that:

Basic research seeks an understanding  of the laws of nature  without  initial  regard  for specific  utilitarian  value. Ultimately, however, it  is of the  most important  practical significance, because in a broad sense it is the foundation upon  which rests  all technological development.  Applied research builds on the results of basic research, seeking detailed  information  about  a specific situation  whose general laws have  been  discovered by  basic  research.  The  final step  toward  utilization  of research-development is  the systematic  application  of knowledge to  the  design  of  end products. [...]

As we  increase  our  knowledge  of nature  and  mankind,  in order  to adjust  nature  to our survival, safety,  comfort and convenience, we must  depend  upon  scientific research  to clarify the  relationships  of many, many things.  Thus,  we study  atoms,  even  though  they  will never  be seen  by an  unaided  human  eye.  We study  stars  too  faint  to  be  seen without  a  telescope  and  with  wavelengths  which  can  only be  detected  with  radio  receivers  or  photographic  plates. To  understand  geology, we must  look  at  geologic formations  and processes in many  parts  of the world where different  conditions have existed.  To understand  more about the  phenomena  of life, we must  study  the  behavior  of viruses,  single  cells,  plants,  and  animals  of  many  species.

A book was compiled covering various areas of research with Isaac Asimov writing an essay defending the value of basic research.

Thus, it was with some surprise and delight that we read in the news about Rep. Jim Cooper (D-Tenn) understanding the value of basic research.  The Washington Post reports that:

On Wednesday afternoon, Cooper rose to the defense of taxpayer-funded research into dog urine, guinea pig eardrums and, yes, the reproductive habits of the parasitic flies known as screwworms–all federally supported studies that have inspired major scientific breakthroughs.

Together with two colleagues he created the Annual Golden Goose Awards to honor federally funded research  “whose work may once have been viewed as unusual, odd, or obscure, but has produced important discoveries benefiting society in significant ways.”

Studying dog urine, among other stuff deem crazy by animal rights cranks, led to major medical discoveries

The article goes on to describe how research on dog urine led to an understanding of the effects of hormones on the human kidney, how studies in the guinea pig led to a treatment for hearing loss in infants, and how studies on the screwworm led to the effective control of the a deadly parasite that targets cattle.  All these provide additional examples refuting the notion that learning about life processes from animals cannot yield knowledge applicable to human health.

The Golden Goose Award has the backing of the American Association for the Advancement of ScienceAssociation of American Universities (who in 2011 published a series of “Scientific Inquirer” articles skewering dubious politically-motivated attacks on basic science) and the Progressive Policy Institute, who are to be congratulated for this excellent initiative to highlight the importance of basic research.

At the press conference to launch the award Rep. Robert Dold told reporters that “When we invest in science, we also invest in jobs. Research and development is a key part to any healthy economy,” while  Rep. Charlie Dent (R-Penn.) added “It’s critical, and the federal government has an important role to play,” who went on to describe how injecting horses with snake venom might “seem peculiar” but led to the discovery of the first anti-venom.

Taking us, once again, to the concluding words of Asimov’s essay:

Unless we continue with science and gather knowledge, whether or not it seems useful on the spot, we will be buried under our problems and find no way out.  Today’s science is tomorrow’s solution — and tomorrow’s problems , too — and, most of all, it is mankind’s greatest adventure, now and forever.

A welcome end to random-source dog and cat dealers

The National Institutes of Health has announced that starting October 1, 2012, NIH funds may no longer be used to buy cats from Class B dealers. A similar prohibition in the purchase of dogs from Class B dealers takes effect in 2015.

Although dogs and cats constitute only small percentage of research animals, they have been used in American biomedical research for over a century for studies of cardiovascular and neurological diseases, and for other areas of research including recent studies that led to a gene therapy for the eye disease Leber’s congenital amaurosis, whose success was reported widely last week.  The use of these animals is tightly regulated by the Animal Welfare Act, and they are only employed for studies where lower species do not provide adequate models.

Class B dealers are individuals licensed by the USDA under the Animal Welfare Act to resell animals they did not breed themselves. Class A dealers are breeders who do raise the animals themselves. Class B dealers may purchase dogs and cats from sources such as municipal pounds, from individuals who bred and raised the animals, and from other licensed dealers. They are required to keep records on where they got each animal and to hold pound animals for a minimum period so that if an unwanted animal was actually a stray, the owner has time to reclaim it.

Animal statistics in 2010 (US data) - Dogs account of 0.25% and cats 0.08% of the total number of animals used.

Class B dealers used to provide a large number of cats and dogs for research because they were virtually the only source for older animals and for some breeds. Regrettably, some Class B dealers used practices that violated the Animal Welfare Act both in terms of how they acquired animals and how they treated them.  The National Academies of Science studied the specific areas of science where Class B dogs and cats were being used and concluded that NIH could develop alternate supply mechanisms to replace them. NIH decided the best way to facilitate the transition was to provide an initial outlay of funds so that Class A dealers could begin raising older dogs of the breeds required for scientific research. It is expected that these breeders will be able to produce the necessary animals by 2015.

After October 1, 2012, NIH-grant supported research can only use cats from the following sources: Class A dealers, privately owned research colonies, or client owned animals, such as animals that participate in veterinary clinical trials.  The same policy will apply to dogs in 2015 when the Class A breeding program is in full swing.

The transition of NIH-funded research away from the use of Class B dogs and cats is an example of how measures can be taken to correct ethical problems regarding the treatment of animals.  When ethical concerns exist, thoughtful and deliberate steps can address those concerns, while preserving important biomedical research projects.

Bill Yates and Alice Ra’anan.

Bill Yates is the Chair of American Physiological Society Animal Care and Experimentation Committee. Alice Ra’anan is Director of Science Policy for the American Physiological Society. The views expressed above are exclusively those of Bill Yates and Alice Ra’anan and do not necessarily represent those of their employers.