Tag Archives: primate research

Animal research: Why are we still using monkeys?

A common argument from animal rights organizations is that animal models cannot tell us anything useful about human medicine, that animal research is outdated, and should be replaced with other methods. But in a recent article, a group of leading scientists argues that “Primate models still matter” — with the right attention to the animals’ social needs and welfare.

The mantra of “Replace, Reduce, Refine” is a common place in the animal research community — with an emphasis on replacing animal models where possible. Yet while most research with vertebrates involves rodents and fish, non-human primates (principally rhesus monkeys) remain a vital model for studying many diseases and conditions. A recent article in the American Journal of Primatology sets out the issues around research with non-human primates.

Research involving nonhuman primates (NHPs) has played a vital role in many of the medical and scientific advances of the past century. NHPs are used because of their similarity to humans in physiology, neuroanatomy, reproduction, development, cognition, and social complexity-yet it is these very similarities that make the use of NHPs in biomedical research a considered decision. As primate researchers, we feel an obligation and responsibility to present the facts concerning why primates are used in various areas of biomedical research. Recent decisions in the United States, including the phasing out of chimpanzees in research by the National Institutes of Health and the pending closure of the New England Primate Research Center, illustrate to us the critical importance of conveying why continued research with primates is needed. Here, we review key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research
http://www.ncbi.nlm.nih.gov/pubmed/24723482

Kimberley Phillips of Trinity University, San Antonio, Texas and co-authors discuss how non-human primate models are ideal for studying heart and respiratory disease; reproduction and pharmacology; immunology and infectious disease, including vaccines and treatments for HIV/AIDS; behavior, cognition and neuroscience, among many other topics.

primate monkey animal testing

Image Credit: CNPRC/Speaking of Research

Primate and monkey models have contributed to the fight against polio, typhoid and yellow fever, and have made possible advances in treating heart disease, AIDS, cancer, diabetes, asthma, and malaria. Efforts are under way to develop treatments for emerging diseases such as Ebola and avian influenza, and conditions that becoming more common, for example Parkinson’s disease, Alzheimer’s, obesity, arthritis, infertility, and aging.

Nonhuman primates provide unique opportunities for scientists and physicians to study human disease, because while we have important differences, their biology is similar to ours in many ways. Yet this similarity also raises ethical issues, especially with the great apes, according to Phillips et al.

The recent decision by the National Institutes of Health to end support for some forms of invasive biomedical research with chimpanzees reflects the development, by scientists, of alternative models for some types of research as well as reflecting a collective desire to involve chimpanzees only in research that is either noninvasive or otherwise essential to scientific progress.

The use of these animals in research must be carefully considered and conducted in a controlled and thoughtful manner, the authors write. They advocate standards of care that consider not just food, housing and veterinary care, but pay attention to the animals’ cognitive, social and psychological needs.

“Efforts are now made to enhance psychological well‐ being through social housing, addressing the specific social and development needs of infants and aged individuals, and providing environmental enrichment,” they write.

“We are at a critical crossroads in our society and unless NHP research is given the philosophical, emotional, and financial support and infrastructure that is needed to sustain it and grow, we are in danger of losing irreplaceable unique models and thus, our ability to continue to explore and understand, and develop preventions and treatments for numerous conditions that inflict great suffering on humans.”

Andy Fell

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Not Difficult To Grasp

Paralysis can have tremendous negative consequences for a person’s quality of life.  In the US alone, there are more than 200 thousand people living with chronic spinal cord injury, which is a cause of immense suffering to them and their families.  The disease generates economic burden for society as well.   Thus, there has been a lot of interest in using our knowledge of how movement is coded in the brain to allow patients to bypass nerve injuries and communicate directly with the environment.  Moreover, when asked about their priorities in terms of regaining motor function the vast majority of patients rank regaining arm and hand function as most important.

It is thus encouraging to read in Nature today an update on how these efforts by scientists have allowed a paralyzed patient to reach for a cup, bring it to her lips, and drink from it.

Critical milestones in the development of motor prosthesis for paralyzed patients

As explained in a nice News and Views piece by Andrew Jackson that accompanies the article, this type of work builds on decades of previous research on the neural mechanisms that control arm movements (here, here and here) (blue on the Fig above), on the development of chronic multi-electrode arrays (orange), their recording properties in animals, and on feasibility studies of neural interfaces in monkeys (here, here, here and here) (green), which opened the way to clinical studies in humans (here and here) (purple).

The value of animal research should not be difficult to grasp. The knowledge that allows us to “read out” the planned movements of the patient from different brain regions in order to guide the movement of the robot is critical in the design of the system.  And it is an indisputable fact that such knowledge has been (and continues to be) obtained by experiments in awake, behaving monkeys.

And for those that doubt the true motivation of scientists for doing their work, it is worth noting what Dr. Leigh Hochberg (one of the leading authors of the study) had to say about their results — “The smile on her face … was just a wonderful thing to see.”   Do you want to see her smile too?  Watch this:

Of course the BrainGate system used by Dr. Hochberg and Dr. John Donoghue – director of the Institute for Brain Science at Brown University – is not the only brain-machine interface system under development to restore function in paralysis. In 2008 we wrote about a similar brain implant developed by Dr. Andy Schwartz at the University of Pittsburgh which enabled monkeys to manipulate robotic hands with unprecedented dexterity. Last year we wrote about how Dr. Schwartz’s team had used a different technology known as electrocorticography to enable a paralysed man to manipulate a robotic arm, while Dr. Chet Moritz and colleagues at Wachington National Primate Research Centre, have coupled readings from individual nerve cells to a technology called functional electrical stimulation to restore control to temporarily paralysed muscles in monkeys, an approach that may eventually supersede the use of robotic arms in some patients. It will be fascinating to watch this technology progress into more widespread clinical use over the next decade, and thrilling to think that, impressive as it appears today, we have barely begun to tap the potential of brain-machine interface technology to change lives.

Part 2: University of Toronto ends live primate research – Outsourcing Controversy

 Earlier this week we wrote about the University of Toronto’s public statements concerning the end of their on-site primate research. A number of broader questions were raised by considering similar cases and articles.  Among them, what does it mean for a university to claim that it does not engage in a particular type of research?  In the case of the University of Toronto, the same article announcing the end of their primate research indicated that Univesity of Toronto researchers will continue primate studies at other institutions. 

Although this seems like a small point that concerns only a single animal research program, it is illustrative of larger questions and issues that deserve more thoughtful consideration.  One is what it means to say that a researcher, institution, or nation does or does not conduct a particular type of research. It is not at all obvious, and thus is an easy thing to manipulate in public presentation. For example, ask the following questions:

  1. Does that mean only that they do not house animals and conduct studies, or do not conduct that work independently on their own campus or within their own borders?
  2. Or does it mean that they not only do not conduct the work, but also do not support the work in any way, with collaborative effort, resources, or their approval? 
  3. Or does it mean that they not only do not conduct the work, but also do not support the work and would refuse any benefit arising from the work?

It is not only the University of Toronto ending its housing of monkeys and instead relying on collaborative opportunities in the U.S.that raises these questions. The point is also well illustrated in considering whether Canada and other countries are, or are not, involved in biomedical research with chimpanzees. One of the frequently raised points used to argue against ape research is that biomedical research with chimpanzees is conducted in only two countries — the U.S. and Gabon.  But what does that mean? And is that really true?

In fact, a recent CTV news show highlighted the fact that studies for Canadians are performed at a U.S. chimpanzee research facility funded largely by a federal grant to maintain national research resources in the U.S.  The fact that Canadians are involved in chimpanzee research is not hidden in any way, but is easy to misconstrue.

In Canada, there’s no outright ban, but no one is actually doing it.

Instead, Canadians commission studies at research facilities like the New Iberia Research Center in Louisiana, the largest facility of its type in the world. It’s home to nearly 7,000 primates, 360 of them chimpanzees.”

It is not only Canadians. Scientists from a number of other countries engage in behavioral and biomedical research collaboration involving chimpanzees housed in U.S. research institutions. Furthermore, when the Netherlands became the last European country to ban chimpanzee research almost a decade ago, it was acknowledged that because the opportunity for chimpanzee research remained in the U.S.everyone could be assured of continuation of the work without the cost, controversy, or responsibility of having to maintain the possibility within their own country.  A 2003 article highlights this point:

The end of European ape research, long sought by animal rights activists, was accelerated by a report published in 2001 by the Royal Netherlands Academy of Sciences (KNAW). It concluded that high costs and decreasing scientific need had made chimp studies all but superfluous. In rare instances where ape research will be crucial to combat a human disease, the panel said, large colonies funded by the National Institutes of Health (NIH) in the U.S. would be better equipped.

However, even in parliament itself some hypocrisy was acknowledged. Because ‘if the occasion arises’, the government quoted the KNAW report, Dutch researchers would still be free to do experiments abroad. Observed House member Bas van der Vlies (SGP): ‘Since through a back door [the Netherlands will profit from [ape research elsewhere, I see no reason for us to start beating our chests like gorillas.’”

The point made by Bas van der Vlies is a good one and one especially relevant now as the U.S. weighs legislation to end invasive chimpanzee research.  It is also more broadly relevant because it underscores why the decision of single entity, institution or nation, to end a particular type of research must be viewed within the context of the range of alternative opportunities and avenues that will serve the overall goal.  In other words, the decision to ban an avenue of research means one thing if that choice will result in a true end to the work. The same decision is inherently less risky if it is cushioned by knowledge that another institution or another country is committed to maintaining that research avenue and shouldering the accompanying burdens.

It is also true that the decision to “end” a particular kind of work is often more reflective of different types of cost considerations.  For example, note increasing outsourcing of animal research to other countries with less developed regulatory structure and lower costs. Whether that is good for animal welfare, science, research institutions, and the public is a topic of discussion among scientists and is one that should be given more thoughtful public consideration. We believe the US public is better served by advocating for reasonable improvements in animal welfare while keeping important medical research at home. The adoption of unrealistic policies and regulations that dramatically increase the cost of the work, while not significantly impacting on the well-being of the animals, will help drive the research overseas, with negative consequences on the biomedical leadership of our country and uncertain consequences for the well-being of the animals.  

So how do we tell the difference between individuals, institutions, and countries genuinely committed on moral or ethical grounds to ending particular types of research, rather than in only displacing it to others?  One piece of evidence would be for those claiming that the work is either unnecessary or unethical to also make clear that they do not simply outsource the work to other institutions or countries. 

Another would be for them to decline any benefits from the work.  For example, although we are aware of no efforts underway to preclude citizens of countries that disallowed such work to benefit from the findings or any advances made through chimpanzee biomedical research, for example hepatitis C vaccines currently under development, it would seem that this would be an easy way for people to affirm their commitment to the global picture. (Whether it should be habitat countries or a world-wide body who provides consent on behalf of the wild apes for whom conservationists are arguing should benefit from vaccines developed from research in laboratory studies of nonhuman primates might be a separate issue.)

What is gained from considering this more complicated picture?  In the case of the recent University of Toronto press coverage, a reminder that it is disingenuous at best to solicit public approval by disavowing research that the institution has conducted, has benefited from, and will continue to be involved in — albeit with the majority of risk and cost assumed by other institutions. In the case of chimpanzee research, a reminder that as long as non-U.S. interests benefit from and participate in studies conducted in the U.S., it is not accurate to claim that it is only the U.S.that sanctioned and benefited from such work.  And that includes the apes in Africa who could benefit from the vaccines developed via laboratory research in theU.S. and elsewhere.

Finally, we would advise a critical eye towards any articles in which universities, pharmaceutical companies, or countries claim that they are not engaged in primate or other animal research.  Those who have simply chosen to do the same work elsewhere or via collaboration should be clear about their involvement. Similarly, those whose work depends on data, tissues, or animal models developed by others, or at other institutions, should acknowledge a responsibility and involvement in the live animal work as well. 

Allyson J. Bennett

Interview with a Primate Researcher

Wisconsin National Primate Research Center Director Jon Levine has kindly allowed us to reproduce a piece previously posted in On Wisconsin.

Question and Answer with Wisconsin National Primate Research Center Director Jon Levine

Work flows from “the best of reasons,” says new director of primate research center.

Administering a big research center at the forefront of biomedical science is challenge enough. Running one with 1,500 monkeys is the test of a lifetime. But that is exactly the matchup for Jon Levine, the Northwestern University neuroscientist recruited to UW–Madison in late 2010 to run the Wisconsin National Primate Research Center (WNPRC). For Levine, leading one of the nation’s eight national primate centers is an opportunity to promote the kind of science that led to human embryonic stem cells and remains our best hope for beating diseases such as Parkinson’s and AIDS. At the same time, the center is a magnet for controversy, as the use of monkeys in biomedical research is contentious.

Q: Many people hear about the Primate Center only when there is an issue — or a perceived issue. If there is one thing people should know about the center, what would that be?

A: That researchers and staff are passionate about their work, and that they are wonderful, caring people committed to advancing the cause of human and animal health. The average person knows very well the suffering a family member or friend may endure in disease or injury; unfortunately, few are aware of the importance of biomedical research with non-human primates in developing therapies and strategies for preventing these conditions. I want everyone to know why we do what we do — because we are deeply committed to bringing about a future in which HIV can be prevented, the ravages of Parkinson’s disease can be stalled or reversed, and infertility, complications of pregnancy, and metabolic diseases such as diabetes can be successfully treated.

Q: What do you tell someone — a child, for example — who asks you about the use of monkeys for biomedical research?

A: That we are the good guys. We play by the strictest of rules, intended to ensure the humane and careful utilization of a precious resource. And we have the best of reasons for the work we do. I do not hesitate to give children an explanation in terms they can appreciate. For example, many kids know someone who has been diagnosed with some form of leukemia. We are developing methods to take blood cells from cancer patients and reprogram them into “induced pluripotent stem cells” — make them younger versions of themselves, before they became cancerous. Those induced cells can lead us to an understanding of how blood cells become cancer cells and how we might better treat leukemia.

Q: What do you think we can look forward to in the way of scientific advances from the center in the next few years?

A: I could fill pages with advances I hope will be realized. I’ll mention one that I think could enable progress in many others: transgenesis. The ability to induce, block, or alter the expression of specific genes in the mouse is now routine and has made it the standard for most studies of the genetic mechanisms underlying human disease. However, there are many aspects of human physiology and disease that can only be faithfully reproduced in non-human primates. We are undertaking new approaches to manipulate gene expression in non-human primates. We hope to target genes involved in neurodegenerative diseases such as Parkinson’s, metabolic diseases such as type 2 diabetes, and developmental disorders such as autism.

Rhesus Monkeys are used to try to find treatments for illnesses like Parkinson’s

Q: What will be the greatest challenge for the Wisconsin National Primate Research Center over the next decade?

A: The major challenge for federally funded research institutions is to sustain funding from the National Institutes of Health (NIH) and other sources, especially through times of austerity, flat budgets, and increasing costs. I’m confident, however, that the talented researchers and staff at the WNPRC will keep us positioned to renew our base grant funding from the NIH. I am also certain that researchers who use non-human primates on campus will continue to successfully compete for individual research funding. Nevertheless, given the special costs of research with monkeys, and the preciousness of the resource, we will be looking at new sources of support. Over the longer term, the center’s biggest challenge will be to replace and/or renovate portions of our infrastructure. My vision for a new WNPRC building complex may have to wait until the economy recovers over the next few years — but it is a goal that I hope we can realize.

Article reprinted with permission from Jon Levine and On Wisconsin http://onwisconsin.uwalumni.com/departments/qa/jon-levine/

Photos courtesy of WNPRC

Lasker awards highlight the contribution of animal research to medical progress

Each September the Albert and Mary Lasker Foundation recognizes the contribution made by scientists and doctors to medicine by awarding prizes to those who have made outstanding contributions to our understanding of disease, and to its treatment and prevention. The list of past recipients of these awards reads as a veritable who’s who of the greatest minds in medical research over the past 65 years, so it’s not surprising that the Lasker prizes are often called the “American Nobels”, indeed many Lasker prize winners have gone on to pay a visit to Stockholm not long afterwards.

As one might expect the Lasker prizes have often been awarded for discoveries and medical advances that relied on animal research, and this year is no exception.

The Albert Lasker Basic Medical Research Award went to Douglas Coleman and Jeffrey M. Friedman for their work on the hormone leptin, work that has led to a revolution in our understanding of the regulation of appetite and metabolism.  The story of leptin is the story of how decades of careful research in mice led to an important discovery that is now helping to improve the lives of patients with rare genetic disorders, and more recently to help patients whose own leptin levels are too low as a result of HIV-related loss of fat tissue.

Napoleone Ferrara won the Lasker-DeBakey Clinical Medical Research Award for his discovery of the Vascular Endothelial Growth Factor (VEGF) and its role in regulating the growth of blood vessels.  The description of Dr. Ferrara’s  research on the Lasker website shows how Dr. Ferrara identified VEGF through research on cattle, and how his subsequent research using mice and rats ultimately resulted in the development of effective monoclonal antibody treatments for wet age related macular degeneration, a leading cause of blindness.

The third prize, the Lasker-Koshland Special Achievement Award in Medical Science, was awarded to Sir David Weatherall, a pioneer in the field of human genetics who has made invaluable contributions to our understanding of inherited blood disorders including α-or β-thalassemia and sickle cell anemia. His research laid the foundations for successful programs to reduce the incidence of these disorders, and of course to the development of treatments, some of which we discussed here just last week.  Sir David may not have performed any animal research in his own career, but he recently chaired the committee which wrote an influential report on the role of primates in medical research. The report concluded that primate research has made an important contribution to medical progress, and is still needed in several important areas of medical research including neuroscience and vaccine development.

The message from this year’s Lasker prizes is clear; for medicine to continue to advance many different approaches to research must be applied, and among the many techniques that are necessary to progress animal research has an honored place.

Addendum: Dario Ringach has written an excellent essay on the Opposing Views website of the process through which basic scientific discoveries about the function of VEGF were harnessed to yield new therapies for retinopathy.

Paul Browne