Animal Rights
Animal Rights

Response to Dr Ringach re: AFMA and Basic Science

| by Dr Ray Greek

Dr Dario Ringach wrote:

"Animal experiments will not help humans"

A rather categorical statement, don’t you think?

This was the title of an OpEd published in the LA Times by Dr. Lawrence Hansen, one of Americans for Medical Advancement's officers.

Actually it wasn’t. Dr Ringach wrote this in response to my blog titled Where Are The Skeptics? The real title of the op-ed was  “Leading Alzheimer's researcher: Animal experiments will not help humans.” Dr Ringach is implying that Dr Hansen wrote the title to the op-ed and hence has made a sweeping generalization of the kind that I have often criticized. I feel I must here point out that Dr Ringach did not include the entire quote. Given his concern with quoting out of context this seems odd as the first part of the title certainly seems to influence the interpretation of the latter part.

I am suspicious Dr Hansen did not write the title, as number one, it is self-referring, number two, Dr. Ringach may not be aware of the fact that editors, not authors, generally provide the titles for op-ed pieces and number three, no where in the actual op-ed does Dr Hansen make that statement. Nevertheless, I am awaiting confirmation from Dr Hansen as to the origin of the title. Regardless of who wrote the title, if Dr Hansen, or anyone else for that matter, writes or endorses such a blanket statement then I must state that I disagree with it. Again, I seriously doubt this is the case with Dr Hansen, but will I communicate more on this as I receive more information from him. (I am awaiting an email response.)

The essay by Dr Ringach implies that the board of AFMA either speaks for AFMA, they do not, or that the board is of one voice in all things science, again they are not, or that inconsistency between a board member and AFMA invalidates the position of the organization, it does not. In a related item, Dr Ringach also asks whether AFMA and I support the basic research in neuroscience that he and others perform. I have addressed this in several blogs and at the panel discussion at UCLA. Nevertheless, I will attempt to spell it out one more time and simultaneously address the function of AFMA and the board in general.

I will begin by contrasting AFMA the organization with me as an individual.

1. AFMA is, for all intents and purposes, concerned only with the issue of prediction in biomedical research. AFMA acknowledges that animals can successfully be used in science in many other ways including basic research but not for predicting human response to drugs and disease. AFMA strongly denies that the research being performed by Dr Ringach is predictive for humans. It is basic research as I, and others, have defined basic research in past essays. It is important to note, as I have in the past, that basic research can result in knowledge that might someday be used to find cures or treatments. That is as far as AFMA goes. We try very hard to neither endorse nor condemn such research as that implies a moral evaluation and AFMA does not do ethics, only science. Let me be clear: using animals in basic research is scientifically viable when defined as knowledge for knowledge sake. In so far as the question relates to the scientific viability of using animals in basic research; AFMA supports it. That is all anyone is going to get from AFMA, as that is all we do: scientific evaluations.

2. My personal position on basic research differs somewhat from AFMA’s. First some background.

My wife Jean and I founded AFMA to do one thing and one thing only; provide an organization where those who support animal experiments and those opposed to animal experiments could join forces and agree on what is and is not scientifically viable in terms of using animals in research and in science in general. There was and is far too much propaganda and nonsense from both sides of the issue. We have been very minimally successful in our mission. Currently, the board is composed of one vegan (me), one vegetarian/vegan (Hansen), and two meat eaters (Rice and Shanks). (While one cannot guarantee an ethical position from an analysis of eating habits, it is not a bad prognosticator.) We have succeeded in forming a board that is not biased for or against experiments on animals in general and that agrees on the prediction position outlined above. But we have failed to recruit many doctors (scientists, veterinarians, or physicians), nonprofessionals, or other qualified people to support us. There are two reasons for this failure.

            i. The animal experimentation community, as exemplified by Dr Ringach, steadfastly refuses to acknowledge that using animals to predict human response is scientifically inviable. As I have written, the reason for this revolves around the fact that, as Dr Hansen stated in his OpEd, if society knew just how little chance there is of basic resarch using animals actually resulting in cures/being predictive for humans, they would not allow it. (I have a paper under review that goes into much more detail on this. For more, that is currently available, on my position please view my portion of the UCLA panel discussion.) In a related area, supporters of AFMA who occupy positions in other academic/research institutions or departments, will not publicly acknowledge their support of AFMA on the prediction issue, as they fear for their jobs. As I said in my last blog, the animal-based researchers brings in the money, they do not.

            ii. The animal rights community on the whole equally steadfastly refuses to acknowledge that using animals in dissection, as bioassays, as replacement parts and so forth is scientifically viable. They will go into great detail about all the alternatives that exist to these uses (and some alternatives do exist) but they will not admit the scientifically obvious. Many become apoplectic if pushed on this issue and some do not speak to me anymore. Note that whether a practice is scientifically viable does not influence whether it is ethical. (For example, some (very few actually) experiments on Jews in Nazi Germany did advance knowledge but were by no means ethical.) The inability of the animal rights movement, as a whole, to distinguish between these two issues does not speak well of its intellectual competence. Then again, neither does the fact that basic researchers cannot acknowledge that animal models are incapable of predicting human response to drugs and disease. But there we are.

On to the question at hand. When Dr Ringach asks: “So, are you against basic research that leads to therapies... such as basic research with flowers that led to chemotherapy based on vincristine?” he is assuming: 1) that basic research exists for such outcomes, it does not; 2) that such outcomes are the rule not the exception, they are not; and 3) that such research is not stealing money from research modalities better suited to find cures for humans e.g., human-based research. Such a presentation is pure fallacious reasoning.

Isolated cases of productive outcomes do not make a modality predictive nor do they justify research grants. If they did, the NIH should be sending researchers money: to dream, as that is how Kekulé said he discovered the benzene ring; to watch sailboats, as that is how Dr Swan thought of adding a balloon onto to the tip of a catheter so it would go with the flow into the heart; and so forth. There are many such examples.

When evaluating a research method, one must look at the track record before deciding usefulness or viability. In this case, modern day basic research that uses animals (purportedly for drug and disease research) has a very poor track record of leading to cures for human disease. (I will reference my article on this when/if it comes out, but for now see my comments at the UCLA panel discussion.)

There is no doubt that current basic research using animals produces papers but it just as clearly only very rarely produce cures. Boat 2010:

As Dorsey et al (1) point out, broader measures are needed to adequately judge return on the substantial biomedical research investment. Ultimately, biomedical research productivity must be assessed against individual and population health. (2)

From Nature 2008:

There is a growing disparity at the heart of biomedicine. In some ways, the field is experiencing a golden age: the quantity of basic research is shooting off the charts and budgets are far higher than they were two decades ago. Yet the impact of this research is growing at a much more modest rate: new cures and therapies are ever more expensive to develop and worryingly thin on the ground. (3)

Crowley 2003:

The article by Contopoulos-Ioannidis et al. in this issue of the journal addresses a much-discussed but rarely quantified issue: the frequency with which basic research findings translate into clinical utility. The authors performed an algorithmic computer search of all articles published in six leading basic science journals (Nature, Cell, Science, the Journal of Biological Chemistry, the Journal of Clinical Investigation, the Journal Experimental Medicine) from 1979 to 1983. Of the 25,000 articles searched, about 500 (2%) contained some potential claim to future applicability in humans, about 100 (0.4%) resulted in a clinical trial, and, according to the authors, only 1 (0.004%) led to the development of a clinically useful class of drugs (angiotensin-converting enzyme inhibitors) in the 30 years following their publication of the basic science finding. They also found that the presence of industrial support increased the likelihood of translating a basic finding into a clinical trial by eightfold. Still, regardless of the study's limitations, and even if the authors were to underestimate the frequency of successful translation into clinical use by 10-fold, their findings strongly suggest that, as most observers suspected, the transfer rate of basic research into clinical use is very low. (4)

Incidentally, the angiotensin converting enzyme inhibitors mentioned above were the result of human-based and in vitro research. The scientists who made the drugs possible, David W Cushman and Miguel A. Odentti wrote in Nature Medicine 1999:

The active site model that we described in our original studies used simple chemical concepts guided by a hypothetical ‘paper and pencil’ model of substrate and inhibitor binding to enzyme. This rational design approach led has led to a class of structurally simple compounds that can inhibit the action of the enzyme with great potency and specificity, properties that translate into in vivo into effective antihypertensive activity with a remarkably low level of unwanted side effects or toxicity . . . Clinical research and drug discovery have always been closely associated. (5)

My personal position aligns with Dr Hansen’s when he says in the aforementioned op-ed:

Contrived connections between cruelty-intensive basic neuroscience research and future human welfare is a tacit admission by neuroscientists the general public, which ultimately funds most research, would recoil in horror from their more grotesque monkey, dog or cat experiments and overwhelmingly condemn them if they knew they were not going to help humans.

I do not think such research is scientifically justified solely from the perspective of using scarce research funds in ways that are very unlikely to result in cures or treatments or from the ethical perspective of using animals in that fashion. In my opinion, the only way to justify such research scientifically is to admit that it is being done for the sake of generating new knowledge. Nothing more. James W. Hicks, PhD is Professor of Comparative and Evolutionary Physiology at the University of California-Irvine. Dr Hicks, in a debate with me at the University of California at Irvine in March 2, 2006 stated:

But what happens in terms of CAMs [causal analogical models which is a more technical way of saying predictive models] is that what -- what he's [RG] attacking is the way scientists talk to the public. And this is a problem. And so when you ask me does every experiment result in a benefit to humans, you know, every time I'm interviewed by reporters -- and I've done -- some of the research that I have done in my lab has had interest by the popular press. Every time they'll ask me that question, well, what benefit is it for humans? That's the common question. Well, do you ask that of a physicist who's studying black holes? . . . What motivates a lot of biomedical scientists is using animal models to generate novel and new ideas. However, what has happened -- and Dr. Greek is entirely correct -- is that to sell the idea, quote, unquote, sell it, I would -- I would agree that many biomedical scientists can be accused of over promising and under delivering.  But the over promising is what's required or the -- or is what they have to define why are you doing this research and how's it going to directly benefit humans? . . . And many experiments lead nowhere.  But in defending they're doing the experiments they often will tell the public or tell the granting agency or tell the Congressman the end point, "I'm doing -- I'm studying cell cycling because it's going to cure cancer."  Well, you know, cell cycling, how cells determine how they're going to divide, that is important to cancer biology.  But will that specific project cure cancer?  Well, probably not.  But it will -- might lead to some new insights into the cell cycle, which then later on might lead into some additional insights into the cell cycle, which then might lead on -- and this can take a long time . . . So I think it depends on the question.  I do agree with Dr. Greek that -- that if someone directly thinks that there is a -- that they're using a CAM -- a real model, that they're studying a rat, that's really going to cure hypertension, I think that that's bad science.

(View the complete transcript of the debate here.)

Dr Hicks gives a decent summary of my position that basic research can be justified scientifically by appealing to new knowledge for the sake of new knowledge but not on the basis of promising cures. No doubt he disagrees with my ethical stand, as do Drs Rice and Shanks. But that is why we formed AFMA; to allow disagreement on the emotional issue of ethics while encouraging agreement on the more objective science. I still think it is a good idea and, since both sides seem to hate me, there must be some truth to it.

I am the only official spokesperson for AFMA (there are some perks to being the founder). At the UCLA panel discussion, I discharged that duty to Dr Shanks so I could make the presentation that I made, which is in keeping with the above position on basic research using animals. As I said that evening, Dr Shanks was representing the official AFMA position. I, on the other hand, discussed the use of animals in basic research, something that included an evaluation of how society views the matter vis-à-vis the cost benefit ratio. That is something AFMA does not do as it touches on ethics. Hence I made it clear, as the video shows, that I was speaking only for myself. Likewise, board members of AFMA are free to speak their minds on whatever they wish. As long as they do not pretend to be representing AFMA, they can say whatever they want. If they endorse murder or other heinous acts then we will ask them to leave but their commitment to AFMA does not prevent them from having personal opinions.

As for my position that basic research is not performed with an end goal in mind, I will once again point out that I am merely quoting the researchers themselves, and some Nobel laureates at that. If members of a group have issues with the position of the group as a whole, there is nothing new about that. Such members should take up their issue with their group.

 

References

1.E. R. Dorsey et al., JAMA 303, 137 (Jan 13, 2010).

2. T. F. Boat, JAMA 303, 170 (Jan 13, 2010).

3. Nature 453, 839 (Jun 12, 2008).

4. W. F. Crowley, Jr., Am J Med 114, 503 (Apr 15, 2003).

5. D. W. Cushman, M. A. Ondetti, Nat Med 5, 1110 (Oct, 1999).

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