Tag Archives: non-human primate

Speaking of Research welcomes 2011 UK statistics for animal use in scientific research

The UK Home Office has released the animal research statistics for 2011, which show a 2% increase overall in procedures compared to 2010 figures. A summary of the report is available here, while the full report can be downloaded here.  Once again basic research and breeding of GM animals accounted for the lions share – 88% – of the total number of procedures, with mice being the most commonly used animal, bring used in 71 % of procedures.

Some other interesting trends, the number of procedures involving fish increased again, reflecting a trend over the past decade as the importance of the Zebrafish in scientific research increases. The number of procedures involving non-human primates – both new world and old world – fell substantially in 2011 compared to 2010, but the number of procedures using non-human primates tends to vary quite a lot from year to year because of the small number used overall, so it’s too early to say whether or not this is part of an overall trend.

Another interesting fact to note is that over 7o% of procedures did not require anaesthesia, and as Understanding Animal Research point out in their commentary a procedure under the Home Office regulations can be as mild as a blood draw, or indeed breeding in the case of GM animals.

There’s some useful commentary in the Guardian, and the Association of Medical Research Charities blog also provides some insightful analysis of what the figures mean.

Speaking of Research welcomes these figures as evidence that the biomedical research in the UK remains a vibrant despite the tough economic climate, and as evidence that scientists in the UK continue to adopt the most up-to-date animal research techniques as they further understanding of biological systems and develop new therapies for human and animal disease.

Speaking of Research

The new face of transplant surgery, thanks to animal research

Yesterday the University of Maryland Medical Center (UMM) announced most extensive full face transplant completed to date, including both jaws, teeth, and tongue. In a marathon 36-hour operation the surgical team led by Professor Eduardo Rodriguez were able to transplant a face of an anonymous donor onto their patient Richard Lee Norris, who had been injured in a gun accident 15 years ago.  The operation was the culmination of years of clinical and animal research undertaken at UMM under the leadership of Professor Stephen Bartlett, and funded by the Department of Defense and  Office of Naval Research due to its potential to help war veterans who have received serious facial injuries.

This successful operation, termed a vascularized composite allograft, was made possible not only by the selflessness of the family of the anonymous donor, but also by the years of animal research undertaken by Professors Rodriguez and Bartlett and colleagues. For example, a key factor in the success of this operation was that they transplanted high amounts of vascularized bone marrow (VBM), which came inside the transplanted jaw, a technique that was developed by the team after observing that tissue rejection following composite tissue allotransplantation in a cynomolgus monkeys was greatly reduced when VBM was included in the transplant. This discovery will also help to reduce the amount of immunosuppression that Mr. Norris and future patients require following facial transplants.

Of course this is far from the first contribution that animal research has made to transplant surgery, from the development of the techniques of kidney transplant through research in dogs by Joseph Murray and colleagues, to the careful experiments in dogs conducted by Norman Schumway and Richard Lower that led to the first successful heart transplants, to the studies in mice and rats that identified the immunosuppressive properties of the drug cyclosporin that transformed the transplantation field in the 1980’s, animal research has made a crucial contribution to this field. Indeed, in his 1990 Nobel Lecture Edward Donnall Thomas stressed the importance of animal research to his Nobel prize winning discoveries concerning bone marrow transplantation.

Finally, it should be noted that marrow grafting could not have reached clinical application without animal research, first in inbred rodents and then in outbred species, particularly the dog.”

Animal research continues to make key contributions to transplant science, and we have had several opportunities to discuss its role in the development of lab-engineered tissues for transplant, such as the artificial trachea and bladder, on this blog.

Yesterday’s news from the University of Maryland is another reminder that animal research is still crucial to advances in transplant surgery. It is also worth remembering that when animal rights groups attack animal research conducted by the Department of Defense, it is work such as that which led to yesterday’s breakthrough that they are attacking.

Paul Browne

Professor Doudet vindicated as investigation rejects animal rights allegations.

Two weeks ago we discussed the targeting by Canadian animal rights group Stop UBC Animal Research (STOP) of University of British Columbia scientist Professor Doris Doudet. STOP alleged that Prof. Doudet had performed experiments on monkeys without the approval of the UBC Animal Care Committee, and then lied in a scientific paper to cover her tracks, though as we reported at the time their allegations of professional misconduct against her were based on a deliberate misrepresentation of the facts. We are now happy – though in the circumstances not very surprised – to learn that an independent investigation of Prof. Doudet’s work has dismissed the allegations made against her.

According to today’s report in the Vancouver Sun, the Canadian Council on Animal Care (CCAC) carried out a detailed review of the research undertaken by Prof. Doudet’s team, and found:

no evidence to support allegations of animal cruelty against a University of British Columbia research team related to the deaths of four macaque monkeys.”

An earlier report on CTV news adds that the CCAC investigation:

found no evidence to support allegations that UBC was subjecting monkeys to cruel research experiments that were not overseen by the UBC Animal Care Committee.”

The letter from the CCAC to STOP detailing the conclusions of their investigation can be read here.

We asked Prof Doudet her views about this week’s developments, welcoming the news she said:

It is distressing to be wrongly accused, but the truth prevailed and we are all grateful for it.  MPTP always had unexpected effects, not only in monkeys but in the humans who unknowingly injected themselves with it: Out of the more than 100 people who were exposed to the drug in the early 80s, only a handful developed severe parkinsonism and there is no way to predict who will have such a severe negative response. But the MPTP primate model and the knowledge gained from it have played an important part in the basic understanding of physiological mechanisms involved in the disease, and this has been key to the development of many therapies for Parkinson’s disease, including DBS and the current testing of many gene therapies.”

We too welcome this news, though we wonder whether a formal investigation was really required to confirm what had been patently obvious right from the start.

Speaking of Research

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

Open Letter to Dr. Greek

This is a copy of a letter written to Dr. Greek long ago (July 2003) in response to his request for a written contribution from me.  Everything I say in this letter is the honest truth of what I think now, as I did then, with regard to cognitive neuroscience in the non-human primate.  At the foot of the letter I add a glossary of terms unfamiliar to other readers.

Dear Dr. Greek,

Thank you for your letter of July 8 inviting me to contribute a chapter to your new book on the scientific evaluation of the animal model in science and medicine.  It seems a highly worthwhile and timely project.  Unfortunately, because of my–deserved or undeserved–reputation, to which you kindly refer, I am unable to contribute the chapter that you solicit.  I have a very active research program, a splendid group of graduate and undergraduate students to teach, and an apparently never-ending list of meetings and writing commitments.  In a word, I’m swamped.

However, because I think the issue is legitimate and important, and you are interested in hearing both sides of the controversy, I cannot refrain from addressing it here with a few words, although only sketchily.  Of course, I presume you see me, correctly, on the side of those who believe that the animal model is extremely useful, at least for some aspects of neuroscience.  Indeed, I firmly believe that, with regard to the cerebral cortex, there is no adequate substitute for the non-human primate model (no set of algorithms, no computer simulations, no inferences from human imaging or scalp electrophysiology).  The value of the primate model, in what pertains to cognitive functions and the role of the cortex in the human, rests in the homology between the cortex of the non-human primate and that of the human.

That homology is structural as well as functional.  As you probably know, the cytoarchitectonic structures of the two cortices are very similar, almost indistinguishable from each other.  Functionally, the homology is just as striking.  Here I am referring to the physiological mechanisms and principles of operation of the principal cognitive functions (perception, attention, memory, intelligence); not language, of course, which is exclusive patrimony of our species.  Certainly, human cognition is immensely richer than monkey cognition, but the same essential network structure and dynamics can be recognized in the cortex of the two species.  I do not need to explain to you the implications of the similarities in cortical structure and function for the pathogenesis, etiology, diagnosis, and treatment of certain nervous and mental disorders, even though some of those implications may not be direct or immediate (“lifesaving”).

To be sure, we have to be aware of the limits of the homology and of the important and undeniable inter-species differences.   We have to also avoid the simplistic, indeed silly, assumption that homology is reducible to genetic identity.  In the cortex, as in genetics, relationship is what really matters.  Relationship–between cortical cell assemblies or between genes–is what ultimately defines the cognitive structure (percept, memory, etc.) or the phenotype.  In the 21st century, as I see it, both cognitive neuroscience and genetics will finally make the much-needed Copernican shift from the sterile down-spiral of reductionism into molecules to the more holistic view of how biological systems operate  (I recommend to you Hayek’s Sensory Order, U. Chicago, 1952 and my Cortex and Mind, Oxford, 2003, sorry I have no extra copy at hand to give you).  For that crucial shift, the primate cortical network model is going to be pivotal.

For many years, in my laboratory, we have been working on the neuronal foundation of memory and the role of the cortex, especially the prefrontal cortex, in it.  It is difficult research, with its problems and limitations, like any research in complex systems.  It is also quite rewarding and productive.  Again, to a person like you I do not have to explain, because you will readily understand, that we study neural activity at the cellular level because we are interested in cortical systems and networks and in the functional relationships between neurons and between cortical areas.  Much of the knowledge we acquire in the monkey is undoubtedly transferable to the human.  Some of it is not.  On the whole, our work is not only consistent with, but also supports, the network model of cortical function.  Nowadays it gives me considerable satisfaction to see that model slowly but surely penetrating current thinking in cognitive neuroscience.

However, precisely because of the homology, indeed the unquestionable similarities, between human and monkey in cortex and cognition, we face some special problems.  In your letter you state that you are not interested in ethical or philosophical questions.  Yet, in our field, some of these questions are inextricable from scientific questions.  In the first place, on scientific grounds alone, we cannot tolerate that our monkeys experience stress or pain.  You know how detrimental both stress and pain can be for cognitive functions.  Stress and pain, even minimal, can be serious obstacles to the attainment of our scientific aims, especially when we have to use behavioral tests for cognitive assessment.  We have to avoid them in our monkeys at all costs. This is something that people in the animal rights movement do not seem–or want–to understand, even though I have no trouble understanding some of their ethical concerns.  (In fact, years ago, when we had a miserable regulatory climate, I was gladly one of their best allies.)

Then, of course, there are the very legitimate ethical and philosophical questions of experimenting on animals that are very much like us but lack one of our cognitive functions, namely (no pun intended), language; they cannot tell us what pleases or displeases them, even though they are fully sentient.  Fortunately, of course, they have emotional “language.” (I am sure you know it but, in case you don’t, I highly recommend to you Darwin’s wonderful book on emotional expression in man and animals, reedited by Eckman).  Thus, by vocal, facial and bodily signs, monkeys can indeed tell us how they feel.  (After almost half a century of working with macaques, I think I can proudly add “monkey language” to the list of the other six that I can understand reasonably well!)

So, the challenge in the study of primate cognitive neuroscience is to apply a judicious combination of scientific, ethical, and philosophical precepts.  The ideal balance is difficult to achieve, but the basic principles are simple enough:  (1) Impeccable scientific rationale toward practical and meaningful goals;  (2) Minimum number of animals to attain those goals;  (3) Exquisite care of the animals; and (4) Exhaustive analysis of the data to obtain maximum yield of information and to avoid duplication.

I’ll finish by going back to the scientific aspects, which are those that interest you.  Right now, we are investigating the coupling, in higher cognitive functions, between neural activity–as reflected by neuronal discharge and local field potentials–and hemodynamic change, something that cannot be done in the human.  The results of this exciting research, in my view, may have enormous implications for our understanding of the biophysics of functional imaging methods in the human and the dynamics of cortical networks.

Although I cannot write the article that you graciously invited me to write (it almost seems that this long letter ought to do!), you are naturally welcome to visit my website, where you can find the details of my use of the monkey model in cognitive neuroscience.  That would undoubtedly give you a better perspective of my views on the issue than I have been able to convey in these lines.

I wish you success with your book, which I look forward to reading after it appears in print.  I hope you will, indeed, cover both sides of a very important controversy.

Yours sincerely,
Joaquín M. Fuster, M.D., Ph.D.
Professor, UCLA School of Medicine

Glossary

Cognitive Neuroscience.  The neuroscience of knowledge and memory, that is, of what we know and remember (more).

Cytoarchitecture. Structural geometry of cells and fibers in the brain.

Etiology
.  The cause(s) of disease (more).

Genes
. Chemical substances inside cells that encode the hereditary characters of the organism (more).

Hemodynamic change
.  Change in blood flow in nerve tissue as a result of its nervous activation.  It is an indirect measure of brain activity currently used in hospitals, clinics, and laboratories.  Extremely useful in cognitive neuroscience to assess the cerebral foundation of higher cognitive functions, such as memory.

Homology
.  Equivalence of anatomical and physiological brain features across animal species.

Neural networks
.   Assemblies of interlinked cortical neurons (brain cells) that by their patterns of connectivity encode memories and actions.

Pathogenesis.  The anatomical and physiological foundations of disease.

Phenotype.  The physical manifestation of the developed hereditary traits (more).

Prefrontal cortex
.  The anterior cortex of the frontal lobe, essential for organizing behavior.  It plays a vital role in all the executive functions (working memory, decision-making, planning, etc.) that serve behavior organization (more).

Reductionism
.  The scientific search of ever-smaller physical elements (down to particular chemical molecules) in attempts to understand cause and effect in higher functions (for example, cognitive functions).