Bad scientific arguments in the service of "animal rights" activism

One of the greatest threats to the preclinical research necessary for science-based medicine today is animal rights activism. The magnitude of the problem came to the forefront again last month with the news that animal rights terrorists tried to enter the home of a researcher at the University of California Santa Cruz (UCSC) whose research uses mice to study breast cancer and neurologic disease while she and her husband were having a birthday party for one of their children and assaulted her husband, who had gone to the front of the house to confront them. This unrelenting attack on the use of animals in research is primarily based on a belief that animals and humans should have equal rights and that eating meat or even having pets is viewed as immoral. However, increasingly, I seem to notice animal rights activists trying to use science to justify their beliefs. In other words, it is not enough to use ethical arguments; they feel they must argue that animal research is bad science.

What I am going to discuss is the seemingly scientific arguments that some opponents of animal research and animal rights activists like to invoke, arguments increasingly used in addition to the moral arguments that extremists use to justify their actions. If the arguments of opponents of animal rights research were indeed good science, then their appropriation by extremists would not allow me to do much other than bemoan the misuse of valid science as a justification for extremism. Unfortunately, such is not the case, and the bad scientific arguments used by opponents of animal research are often piled onto the extreme moral arguments that fuel actions such as those last month at UCSC. Consequently, given the events of the last month or so, I thought I would take this opportunity to look at some of the common scientific indictments of animal research by its opponents.

If you examine various websites or literature from animal rights extremists looking at the issue of animal use in medical research, the forms of the scientific arguments tend, when you boil them down to the very core of their essence, to take three main forms, which are related:

  1. Animal research doesn't teach us anything of value or even misleads us (i.e., it is bad science).
  2. Animal research does not predict human physiology or response to disease, or animals are "just too different from humans to give reliable results" (i.e., it is bad science).
  3. There are better ways of getting the information that do not use animals (i.e., there is better science available than using animals.)

I tend to look at these arguments as three faces of what is in essence the same argument, specifically what I like to call an "argument from imperfection." In other words, because animal models have many difficulties and flaws and all too often don't predict human physiology or drug response as well as the critics think that they should, then by implication all animal research is bad science. It is an example of demanding 100% perfection or certainty, a bar that no science can ever meet and of concrete thinking typical of extremists and/or pseudoscientists. (Creationists and "alternative" medicine mavens are particularly fond of this sort of argument against their hated "Darwinism" or "allopathic medicine," respectively.) In its most ridiculous form, this argument takes the form of claiming that cell culture and computer models, among other modalities, can give us the same information without animals. The first reason that this argument is ridiculous is that cell culture models tend to be even less predictive of many responses than animal models for many questions and because much physiology depends upon the interaction of different cell types in their native three dimensional matrix. The second reason is that, for a computer model to be adequately predictive, it needs (1) sufficient information to input and (2) sufficient understanding of the intricacies of the physiology and biochemistry. We don't have either. Finally, physiology requires understanding at the macroscopic level of how organs interact. Of course, these arguments are often made in less extreme forms, and I will discuss a some of these shortly. Keep in mind as I do, though, that the problem inherent in this sort of argument is that one has to look at what the alternatives to animal research are and compare their usefulness, accuracy, and reliability. If one can't show that one's alternative is better than animal research, then all the complaints about the imperfections of animal research don't amount to much. It's still the best that we have, and, as such, it's bad science (and unethical, to boot) not to use it before trying therapies in humans. I have yet to see a compelling argument that any alternative modality predicts human response to disease and treatment well enough that we should rely on it instead of animal models.

The first of the three arguments, namely that animal research doesn't teach us anything of value or even misleads us, is the easiest to deal with. Keep in mind that I am a cancer researcher and surgeon; consequently, my knowledge of applying animal research to cancer is stronger than for the use of animals in other fields. For example, when I see animal rights activists claim that human stem cells can be used instead of various animal models of cancer, it's hard for me not to want to grab them by the lapels, shake them, and point out that cancer stem cells were first discovered by a researcher who observed that only a small fraction of leukemic cells in a mouse--yes, mouse!--model of leukemia could transmit the cancer from one experimental model to another. Since it is not currently possible to transmit leukemia from one person to another and would be incredibly unethical to try, the conclusion I draw from this is that whoever wrote that FAQ is ignorant of recent medical history. Indeed, Americans for Medical Progress is quite correct in pointing out how the judicious use of animal models has led to improvements in understanding and treatment of a number of diseases, such as cancer, asthma, HIV/AIDs, antibiotics, organ transplantation, and far more.

My favorite example to cite when I hear the argument that other methods besides animal research can do better than animal research in helping us understand disease (or, in its more sophisticated form, that animals may have been needed a few decades ago to discover, say, insulin, but our understanding has advanced to the point where they are no longer needed) comes from my field and my area of research interest. It also happens to come from my scientific hero, Dr. Judah Folkman, who passed away suddenly in January. It shows an area of cancer biology whose importance would have been incredibly difficult to model, appreciate, or target for therapy without mouse models of cancer. That area, of course, is tumor angiogenesis, and Dr. Folkman did his pioneering work that has now resulted in drugs like Avastin and other antiangiogenic drugs that are making it to market now and making a real impact on cancer. Dr. Folkman did it through an ingenious strategy that began from the clinical observation that sometimes tumor metastases appear shortly after the operation to remove the primary tumor.

Folkman found a mouse tumor model that mimicked this behavior and in the early 1990s did a series of pioneering experiments. In a strain Lewis lung carcinoma cells of low metastatic potential (LLC-LM), when cells are injected into C57BL/6 mice and allowed to grow subcutaneously, if the tumor is left alone, mice develop only microscopic lung metastases. These metastases do not grow and kill the mouse. If, however, the primary cancer is removed, then many large lung metastases grow rapidly. The results of the experiment above strongly implied that the primary tumor is secreting something that suppresses the growth of microscopic metastases. After this, the Folkman group did what we like to call "brute force" science, collecting mouse urine and analyzing it for tumor suppressive activity until they were able to purify a single 38 kDa peptide, which they designated angiostatin. This involved analyzing literally gallons of mouse urine. (Who said science isn't glamorous?) Once Folkman's group had a bunch of angiostatin on hand, it peformed the following experiment. Two groups of mice were injected with LLC-LM and the tumors allowed to grow to a certain size, after which they were surgically removed. One group was treated with angiostatin, and the control group with saline. The result was that the control group developed massive lung metastases and died, while the group treated with angiostatin had microsocopic lung metastases that never grew beyond a ball of cells. Dr. Folkman then demonstrated that it was the inhibition of angiogenesis by the angiostatin that kept these tumors in check. Ultimately, he used a similar method to discover endostatin, and later he demonstrated that endostatin could induced tumor dormancy in mice. I trust that the reader can see how these seminal preclinical observations about angiogenesis would have been virtually impossible without animal models, given that angiogenesis requires the interaction between tumor cells, cells in blood vessels, and the surrounding tissue stroma to occur.

There are numerous other examples of how animal research allows us to do things that we can't do in humans and discover things that can't be discovered using just cell culture or human experimentation. Angiogenesis couldn't have been discovered through tissue culture, and computer models need the concept and measurements of a pheneomenon's behavior to be useful. Before Folkman, although angiogenesis was suspected to be important in tumor growth, it wasn't known to be so. My favorite other example is transgenic mice. The technology of making transgenic mice allows scientists to selectively delete a single gene (or multiple genes) and observe the effects that occur in the animal when this happens. P.Z. Myers at Pharyngula has written extensively of one class of genes whose functions in guiding vertebrate development and pattern formation were dissected largely through the use of both Drosophila models and transgenic mouse models, the homeobox genes, and indeed one of my two major areas of research interest involves the study of a diverged homeobox gene. Through these models, we have been able to study not only the structure and function of HOX genes in a manner not possible without animal models, but we've been able to trace the evolution of the genes all the way from worms, to fruit flies, to mice, to humans, even to the point of studying how plants and animals are related at a genetic level. These sorts of studies allow us to examine the effect of genes at the whole organism level in a manner that is not possible any other way, and, indeed, sometimes produce strikingly surprising results that lead to new avenues of research.

Another common argument of animal rights activists is that "animal testing" is a very poor means of predicting human response to drugs or other therapies. This argument is closer to the true situation than the first one, and no scientist involved in animal research would deny that there are all too often serious problems in using animal models this way. The problem is, there are even more serious problems using other methods to predict toxicity, drug response, and other parameters in human beings. The most recent example of this type of argument I've seen comes from, of all places, a recent issue of Skeptic, in which animal research opponents Niall Shank (a professor of philosophy who, oddly enough, authored a book critiquing intelligent design), Dr. Ray Greek (an anaesthesiologist and President of Americans for Medical Advancement, Europeans for Medical Advancement, and Japanese for Medical Advancement, all facets of a single group that appears to be totally opposed to animal research in medicine), Nathan Nobis (another philosopher), and Jean Swingle-Greek (a veterinarian) authored an article entitled Animals and Medicine: Do Animal Experiments Predict Human Responses? Unfortunately, the text is not available online, but, given that it is a fairly long article, I will summarize and excerpt judiciously to give you a flavor of their thesis and trust my readers who may have read the article to keep me honest. I will also, when I deem appropriate, include statements from Dr. Greek's organization in my discussion, given that the Skeptic article clearly flows from the same sorts of rationales found there. In essence, the article consists of arguments #2 and #3 above writ large, with a the additional tactic of setting impossible standards for animal research to meet before they would concede that it is necessary.

First, it should be pointed out that the authors concede that "fundamental biological discoveries in the past three centuries were made by studying animals" and that "animal studies continue to be of important scientific value in the context of basic biological and biomedical research." Of course, given that they make this concession, it's odd that the authors can then argue that animal research is so useless in understanding human physiology and designing drug therapies, and they can't resist disingenuously adding later something that makes me wonder if they truly understand clinical research:

Animal models claimed to be predictive of human responses are widely used in drug testing, environmental toxicology and disease research. Animals, in the case of predictive models, are clearly used as substitutes for human subjects. Unless researchers believed that such models were causally analogous to humans in relevant respects, there would be no rational basis for their use as predictive models.

Yes, and no. Yes, we consider animal models to be somewhat predictive of human responses, but, no, we do not use animals as a substitute for human subjects. If that were the case and animals were viewed as substitutes for humans in testing drugs, then there would be no need for such extensive clinical trials after animal studies were completed. Rather, animal studies should be best viewed as the first test of a new drug or treatment on a whole-organism level in order to look for unexpected, toxic, or other effects that might not be apparent in cell culture. In other words, animal tests are a screening process, not a substitute for human studies. They are also a convenient tool that allows us to test hypotheses that we cannot test in humans, either for reasons of practicality or ethics. We can certainly argue about how good a tool or screening test animal studies can be, but it is disingenuous and incorrect to argue so strongly that animals are meant to be "substitutes" for human subjects. In fact, the argument above is consistent with, albeit a weaker statement of, part of the manifesto of Dr. Greek's organization, as stated on its website:

Americans For Medical Advancement (AFMA)/ Europeans For Medical Advancement (EFMA)/ Japanese For Medical Advancement (JFMA) is a mainstream science-based research and educational institute dedicated to improving policy and decision-making regarding the use of the animal model in biomedical research.

AFMA/EFMA/JFMA opposes animal-modeled research as a modality for seeking cures and treatments for human disease based on overwhelming scientific evidence that findings from animal models cannot be reliably extrapolated to humans. We seek to demonstrate, through rigorous research and analysis, that the reliance on animal-modeled research, as well as other pseudoscientific endeavors, harms rather than helps humans, and prolongs human suffering by inhibiting medical progress.

If this isn't dogmatic, I don't know what is, particularly the implied claim that all animal-modeled research is "pseudoscientific." Continuing in the Skeptic article, the authors then go on to list a number of references that supposedly show how horrible a tool animal studies are in terms of predicting human response. They tend to pick the worst examples and put even examples that are not so bad in the worst possible light, arguing that animal studies are so inaccurate that they cause more harm than good. That is a tenuous argument based on claims that false negatives and false positives generated by some animal research cause more harm than good by "misleading" researchers and that they "directly" harm patients by allowing harmful treatments to be tried on humans because they supposedly were found safe in animals, so much so that the whole enterprise should be scrapped as hopelessly irredeemable. The latter claim is such a mischaracterization of clinical drug development that it makes me wonder if the authors honestly believe that drugs are approved for general use after only animal trials. Apparently, they have never heard of a phase I clinical trial, where the goal is to give human volunteers increasing amounts of a new drug until toxicities are observed. Animal studies serve, until more predictive studies are found, as a rough guide for (1) dosage and (2) possible toxicities. Moreover, a logical consequence of another part of their complaint, namely that compounds that were found to be harmful in animals and therefore were not taken to clinical trials, is that we should test in humans therapies whose development stopped because of animal testing. After all, if animals and humans are so different that the animal results must be viewed as meaningless, then how else would we identify potentially life saving drugs that were missed? Again, if we as medical scientists actually operated under the straw man assumption that the authors attack (that animal models are such accurate predictors of human response), then we wouldn't bother to do phase I clinical trials at all! We could just test a new drug in animal models and then go straight to phase II trials of efficacy in humans. Indeed, Niall et al are not only attacking a straw man argument here but dubiously conflating toxicity testing and the recommendations made from it. Health policymakers, many of them unfortunately physicians, often err on the side of extreme caution when an animal experiment using even doses much higher than any human could ever encounter, shows that compound A causes cancer in mice, even as scientists point out the disconnect.

Another oddity is that the authors couch much of their arguments in evolutionary terms. Indeed, they more or less claim that evolutionary considerations are why one absolutely can't extrapolate responses in one animal to those of humans. Consistent with this article, the website of Dr. Greek's group, there is a bold claim rejecting the contention that we should, as most scientists would advocate, apply the "three Rs" ("Reduce, Refine, and Replace") to animal models:

  • Applying knowledge gained from animals to humans harms humans most of the time (see A Critical Look at Animal Experimentation for many examples)
  • Intractable differences between species mean that animals cannot 'predict' how the human body will respond to a disease or a drug. Their use violates the most fundamental principle of biology: evolution. Therefore the 'animal model' paradigm should be rejected as unscientific.

And:

Science already has a wealth of superior (not 'alternative'!) human-based methods at its disposal. They are responsible for the medical care we enjoy today and are the only way to prevent, cure and treat human illness - yet many are starved of funds while animal experimentation is highly funded. The animal experiment lobby maintains that animal experimentation is an expensive business - it is. But it is not just costing society enormous sums of money, it is costing us far more in terms of human health.

The authors use these same arguments in a weaker form in their article for Skeptic, but not once do they show a concrete example illustrating how and why one of these methods is so "superior" to animal experiments--and by how much. One would think, if these methods were so obviously superior and already available, that it would be child's play for the authors to spell out one or two specific examples in detail, with references from the peer-reviewed literature and concrete numbers, given how much verbiage they devoted to the deficiencies of animal testing. (More on that later,) As for evolutionary considerations, contrary to the fallacious arguments made by Niall et al, appeals to evolution do not tell us that animal models are useless, only whether one model is more likely to be useful than another. There's a reason why there are no good mouse models of HIV in rodents, while there are useful, albeit imperfect, primate models (some imperfections of which our always-intrepid critics of animal research point out gleefully in the article). Some physiological mechanisms are more highly conserved across species than others, and some animal tumor models, such as lung carcinogenesis due to carcinogens from cigarette smoke, actually recapitulate the genetic changes observed in human tumors pretty well, suggesting common, evolutionarily conserved mechanisms of carcinogenesis, as do some rodent models of human colon cancer, where chemoprevention trials in special strains of mice and rats actually line up fairly well with human trials. Although Niall et al correctly point out that modern medicine is moving towards personalized treatments based on gene expression profiles, we are not there yet.

In some cases the authors also appear to exaggerate just how bad the situation is, even when it comes to references that they themselves cite. One example is a recent BMJ systematic review that--big surprise--found that animal models were good predictors for some conditions and poor predictors for others and was in fact more of a criticism of the quality of published animal studies than the utility of animal studies. It concluded:

Systematic reviews can provide insights into the limitations of animal models. For example, the animal models for stroke, where there was agreement with the results from clinical trials, seemed more representative of the condition in humans than the animal models for head injury, where there were differences in the results. In stroke, the time from the occlusive event to the start of treatment was similar in animal and human studies. In head injury, treatment was given within five minutes of injury in the animal models but up to eight hours after injury in the clinical trials. None of the animal experiments used models that mimic the complex situations that usually follow traumatic head injury. Comorbidities are clearly relevant in stroke, which occurs in older people with hypertension and diabetes but also in people with head injuries, often accompanied by other injuries and by hypotension and hypothermia. Comorbidities were examined in the stroke models but not in the head injury models.

That there is a gap between clinical research and clinical practice is well established. Our work highlights another gap--specifically the lack of communication between those involved in animal research and clinical trialists. Systematic reviews of animal experiments could promote closer collaboration between the research communities and encourage an iterative approach to improving the relevance of animal models to clinical trial design. When models do not represent the clinical context they could be adapted accordingly. Furthermore, as is the case for human research, systematic reviews could help identify and improve deficiencies in the conduct and reporting of animal research.

In other words, according to this article animal models of stroke, for example, are actually pretty good at predicting human response to ischemic brain injury. At the risk of injecting anecdotal evidence, I'll also point out that research using mouse tumor models that I did 10 years ago and that colleagues with whom I worked until 1999 did shortly after I left their laboratory showing that combining antiangiogenic therapy with either radiation or chemotherapy produces a synergistic antitumor effect has been validated in humans. Indeed, that is now how antiangiogenic therapies are generally used, as combination therapy. I could also point out a number of other reviews that find that animal models can be useful and predictive for cancer chemoprevention treatments, antibiotics, and neuroscience. In rabbits, for instance, evidence for a preclinical effect of drugs against fungal infections can be translated into humans if toxicity and pharmacology can be optimized in humans. In cancer, the use of mouse tumor models is more problematic in that single tumor models tend to have a fairly poor predictive value of human response. However, results are much better when a panel of in vitro and in vivo tumor models are used.

The most pervasive problematic aspect of the Skeptic article (and, indeed, all arguments of this type advanced by opponents of animal research) is the utopian "impossible dream" fallacy coupled with differential standards, in which they demand standards of accuracy of animal research that are impractical or even unobtainable for nearly any disease model, while failing to make the case that the substitutes proposed will yield results at least as accurate and useful or preferably more so. This is very much like the tactics of advocates of "alternative medicine," who are prone to demanding a utopian standard of perfection for what they perceive to be "conventional" therapies while asserting without good evidence that their therapies are better or expecting us to accept their speculations that they are. The authors of this Skeptic article do in essence the same thing, detailing the problems with animal models while making overblown claims for potential replacements. For example, here is part of their section What Will We Use If We Don't Experiment On Animals?:

There are two answers to this question.

1. If a test or research method does not accomplish the purpose for which it is used, it should be abandoned. If testing drugs for liver toxicity in animals does not predict liver toxicity in humans, then the test is a waste of resources and, moreover, can be dangerous since the results cannot be counted on to reflect the human condition. So, even if no other testing and research modalities existed, the animal model should still be abandoned. By analogy, there is no cure for AIDS but (hopefully) we would not treat AIDS patients with trephination--drilling holes in the skull--even if trephination happened to be the only available procedure.

This argument sounds seductive on its surface but greatly exaggerates the lack of utility of animal testing. Trephination is indeed utterly useless. Even the worst description of animal testing as made by these authors does not render it the equivalent of trephination, and their comparing it to trephination is clearly a huge exaggeration. The authors then propose a second answer:

2. In the case of human medicine, there are myriad research and testing modalities that are scientifically productive. Anything that is humanbased is, ipso facto, going to be more reliable than anything animal-based. Examples include human embryonic stem cell research; epidemiological studies of patterns of human disease and their associations with environmental causes; in vitro research using human cells and tissues; the use of gene chips or microarrays to study patterns of gene expression in humans; clinical research; autopsies; mathematical and computer modeling; post-marketing drug surveillance; basic scientific research in the fields of biology, physics and chemistry; and technology-based research methods such as those using positron emission tomography, functional magnetic resonance imaging, and others; these are viable means for discovering truths about human disease and drugs.

Here's where the authors' double standard towards animal research starts to become obvious. I note that in the several pages of prose leading up to this statement, the authors list and reference many, many problems with animal research. They provide citations for these problems and, when possible, provide numbers for the poor predictive value of some animal models of some diseases. Yet, when they describe their preferred models and tests, suddenly there is not a single reference to tell us how predictive these other methods are, not a single concrete number to show that these tests, or combinations thereof, can predict human response better than the animal models that the authors would like to see replaced by them. Instead, we are told the authors' preferred methods are "scientifically productive." No kidding! I wouldn't argue with the contention that they can be scientifically productive; what I'd argue with is whether the authors' preferred methods can presently predict human responses better than our current tools that include animal research. If they can't, then what the authors are proposing is that we throw out a useful (albeit flawed) tool (animal studies) in favor of either unproven techniques with a lot of promise that has not yet been realized (genomics and proteomics, functional MRI), known methods that study human response after the fact, given that they are done after a drug is in release (post-release surveillance, epidemiology), or methods that are clearly no better and probably worse at prediction than animal models (cell culture and computer models), all of which are also being used in addition to animals anyway. I would be more than happy to replace my animal tumor models with a combination of the above--when it can be shown that the above tests do an equivalent or better job of modeling human physiology, biochemistry, and pharmacology. The authors fail to show that they can, preferring argument by assertion rather than by evidence. Indeed, I'm not sure that they can ever show that some aspects of whole-organ physiology can ever be modeled that way, but I'll never know because they didn't try. Yet such complexities do not disturb the authors of this article:

We agree that life processes are interdependent; for example, the liver influences the heart, which in turn influences the brain, which in turn influences the kidneys and so on. Thus, the response of an isolated heart cell to a medication does not confirm that the intact human heart will respond as predicted by the isolated heart cell. The liver may metabolize a drug to a new chemical that is toxic to the heart whereas the original chemical was not toxic.

We also concede that cell cultures, computer modeling, in vitro research etc., cannot replace the living intact system of a human being. But while animal models may be intact systems, are they intact systems in ways that are causally relevant to human intact systems? Shifting the focus from genes, cells and tissues to intact animal systems does not evade the long reach of our concerns about causal disanalogy.

This, and their comment about how anything "human-based is, ipso facto, going to be more reliable than anything animal-based" also betrays their agenda. (It also makes me wonder if they think that a study of cultured human cells would be superior in figuring out the effects of hemorrhagic shock on cardiac pumping capacity than the use of a well-designed animal model. Hint: It would be highly unlikely to.) They seem to think that scientists use animal models because we don't realize that it would be better to do research whenever possible on human cells and human tissue. The reason we do not is that most of the time it is neither practical nor ethical to do such research on humans, particularly research involving what we most want to know about these days, macroscopic responses to genetic and biochemical signals and changes.

Finally, let me show you an example of what I referred to earlier as the "impossible dream" fallacy, namely the impossible standard to which the authors demand that animal research be held:

We realize that our claims are controversial, but our arguments are straightforward. If our arguments are unsound, they should be easy to refute. Here is how:

1. Explain why animals, when used as predictive models for the study of human disease and to test drugs, are not used as CAMs ["causal analogical models."] (Remember, we fully accept that animal studies can yield fruitful insights in the context of basic biological research. If you want to know about rat biology, you must study rats. The issue here is whether you can study humans in ways that are predictively efficacious by studying rats).

2. Show that animal models, when used as CAMs, are successful far more often than not. This can be accomplished by comparing the results of drug toxicity studies in animals with studies in humans or by comparing the results of induced diseases in animals with the same disease in humans.

The first one is more a game of semantics than any substantive criticism in that animals don't have to be "causal analogical models" to be useful to biological research or predictive enough of human responses to remain useful. It is in essence defining the use of animals in such a way that one could never demonstrate sufficient accuracy to satisfy the authors, namely as a true predictive surrogate for human beings. The second one, however, is the "Bingo!" of double standards. The authors demand that animal models must be successful predictors "far more often than not," a standard to which they do not even try to hold their preferred methodologies or even claim that they can achieve. Remember, epidemiology is prone to all sorts of confounding factors that make incorrect conclusions very easy, as we discuss quite frequently on this blog. Do they honestly claim that epidemiological studies are accurate "far more likely than not"? Post-marketing surveillance is not predictive; it is after the fact. Genomic approaches, although promising, are very expensive (although they are decreasing in cost). They are also computationally intense, require many human tissue samples to produce statistically valid patterns that must then be validated as predictors, and require very sophisticated statistics and rigorous methodology, without which they are extremely prone to false positive results, something that occurred time and time again early on in such studies. Finally, computer models, as sophisticated as they are becoming, are still too unreliable to trust as a primary modality for preclinical drug testing.

The authors give another indication of where they're coming from near the very end of the article. First they crow about how none of their critics have been able to meet their intentionally impossible standards, while neglecting to recognize that they can't meet their own standards, and then they bring out a dread accusation:

Thus far, we have not been able to find such data contradicting our arguments; more importantly, none of our critics have been able to present this data either. One hypothesis that explains this is that there are no such data. Either no one has compiled it, or it simply doesn't exist. We suspect that these are hypotheses worthy of further research. Until such data can be found, analyzed, and interpreted we must tentatively conclude that the use of allegedly predictive animal models remains in vogue not for scientific reasons but for non-scientific reasons. Those who have an interest in social policy being guided by science should demand that good science prevail and, thus, that society turn its attention to more fruitful methods of biomedical research.

Actually, we are trying to use methods that use fewer or no animals. There isn't a biomedical researcher alive that I'm aware of who doesn't wish that there were another way to get the answers we seek. Animal research is expensive, messy, labor- and time-intensive, and falling under increasingly onerous federal regulations. As for the claim that animal models remain in vogue for non-scientific reasons, that's about as good a case of the pot calling the kettle black as I've seen in a long time. Here's why. Most responsible animal researchers actually do subscribe to the "3 Rs" mentioned earlier. It's a reasonable strategy for minimizing the use of animals now while still using them to study diseases where they have relevance, all with the the long term goal of eventually rendering animal models unnecessary, particularly if we regulatory bodies approve only high quality studies. Unfortunately, that reasonable strategy is not enough for the authors of this article, however, at least not for Dr. Greek as evidenced on his group's website. He considers animal research to be so rotten and useless that it should be stopped now, even though he can't show that there are other methods, whether they are "alternatives" or mainstream, that can do the job even as well as (according to the article) the poor standard animal research presently shows. He comes to that conclusion through straw man arguments about how animals are actually used and defining the bar for success so high that few imaginable modalities could reach it while excusing his "alternatives" from the same bar. His vision, if it came to pass, would be a disaster for biomedical research. His arguments, as embodied in the Skeptic article, are the real pseudoscience.

When it comes down to it, opposition to animal research is ideological, not scientific, in nature. I purposely did not go into the moral issues involved with animal research because such issues depend very much upon the background and moral framework from which each of us proceeds. Animal rights extremists, such as those described at the beginning of this post, tend to emphasize their moral objection to such research above all, or how they view animals as being equal to humans and deserving of the same rights. That is how they justify their campaigns of harrassment and even violence against medical researchers. Indeed, some of them argue that even in the hypothetical case in which animal research would definitely result in a cure for AIDS or cancer, they would still oppose it. Other opponents of animal research, such as authors of the Skeptic article, differ from the extremists in that they are not violent, will acknowledge when pushed that animal research has produced useful scientific discoveries, and do not make arguments that animals are morally equal to humans or that we should therefore not eat them, experiment on them, or keep them as pets. However, in their seeming reasonableness, their opposition to animal research is not, their claims otherwise notwithstanding, based any more on science than that of the animal rights extremists. That they would apply such a double standard to animal research compared to their favored non-animal research modalities, coupled with their absolutist language and cherry picking of studies, show this quite conclusively. Just remember, whenever you hear seemingly "scientific" arguments against animal research that emphasize how bad and inaccurate it is, ask for concrete examples from the peer-reviewed literature that show that non-animal modalities are consistently equal to or better than animal experiments to answer the question being asked. You'll be hard-pressed to find them.

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Wow! What a takedown! Thank you for this.
I was astonished when Skeptic chose to publish that article and have to conclude that Michael Shermer either was taken in by the argument (he doesn't have a background in scientific research), or he put it out there to provoke a discussion.
I urge you to submit this piece as a letter to Skeptic. They appear to publish detailed letters commenting on their articles, and Greek et al deserve a rebuttal like yours.

By T. Bruce McNeely (not verified) on 17 Mar 2008 #permalink

Wow! What a takedown! Thank you for this.
I was astonished when Skeptic chose to publish that article and have to conclude that Michael Shermer either was taken in by the argument (he doesn't have a background in scientific research), or he put it out there to provoke a discussion.
I urge you to submit this piece as a letter to Skeptic. They appear to publish detailed letters commenting on their articles, and Greek et al deserve a rebuttal like yours.

By T. Bruce McNeely (not verified) on 17 Mar 2008 #permalink

By switching to these "science" arguments they contradict themselves: their main argument is that there is no difference between humans and other animals, thus other animals deserve the same rights. But these new arguments try to do the opposite - argue that humans are very different from other animals. They need to choose either to blur the line between humans and others or to make this line sharper - they cannot do both (if they have any trace of logic and rationality still intact in their minds).

Thank you for that cogent post. You are now one of my heroes Orac.

I'm going to have to disagree with you there, Coturnix. It does not follow that two organisms that are biologically dissimilar differ in moral standing. The question of whether these animals are biologically relevant models for human disease is not relevant to the question of whether they have rights or what sorts of rights they have. The usefulness of animal models only matters after parties have agreed that the animals have at least some rights. The extremists are not contradicting themselves; they're trying to skip an argument they're losing.

I never actually got around to reading Dr. Folkman's papers on angiogenesis, but the LLC-LM experiment you described was a fantastic example of animal research. An observation, a simple theory, very labor intensive (and at times disgusting) work, and phenomenal results that single-handedly push human knowledge to heights. Absolutely amazing, and impossible without the animal model involved.

I find it astonishing that Skeptic would publish something like that. It's rather similar to the tactics employed by politicians attempting to defeat their opponents -- smear the opposition, hoping to trick the audience into assuming that you must be right if the opposition is wrong.

Astonishing. Truly astonishing. And definitely not skeptical or scientific. I can only hope that it was published with the intention of sparking discussion, as Mr McNeely suggested.

By Calli Arcale (not verified) on 17 Mar 2008 #permalink

Wow! A brilliant post Orac.

I think a point worth making is that in many cases where animal tests apparently fail to predict the effects of a treatment in humans the problem is not the animal used but the design of the experiment and the way in which the results have been interpreted. Any of us who've been following the development of HIV vaccines over the past few years are aware of how the interpretations of the monkey studies got wildly over-optimistic at times. The BMJ paper includes a good example of poor design and communication in the use of tirilazad for stroke, where in animal tests treatment was usually started within 10 minutes of stroke onset while in human trials it did not commence until 5 hours after stroke onset, which probably accounts for the difference between human and animal results. Indeed a longer version of the BMJ Perel et al paper that was available online but has now disappeared referred to animal tests indicating that the efficacy of tirilazad decreased rapidly as time after stroke onset increased.

There's an old saying that a bad workman blames his tools, Dr. Greek and his colleagues (mainstream? don't make me laugh!) would have us abandon our tools because of some peoples bad work*.

* Of course not all of it is bad, and it's easy to criticize somebody else's judgment call with the benefit of hindsight.

By Paul Browne (not verified) on 17 Mar 2008 #permalink

Awesome and timely post. As a neuroscientist, I work with published animal data all the time and I have several friends who work in animal testing. Just last night I was debating animal rights with a good friend who is anti any kind of animal testing. We focused more on the moral and ethical arguments than the scientific ones, and we both (IMO) had some very good points, and in the end we agreed to disagree.

I think we're going to do it again formally online though. In the mean time, I might well send him this article.

I think taking the scientific efficacy argument in isolation from the ethical argument makes it look worse than it is. As Orac notes, there are experiments done on animals which would be unethical if done on humans: a direct comparison of the two modalities, then, can't be done assuming different ethical foundations. What this article seems to be saying is "put up or shut up: attempt these methods on humans, where you'll get better results, or admit that these methods are unethical when applied to sentient beings (and, by the way, we think mice, etc., are sentient beings, but that's something we'll talk about later)."

Just a comment to those people who appear to be disappointed that an article was published in Skeptic arguing that animal experimentation was unnecessary.

Skeptic does have a history of publishing controversial, and even at times poorly thought out articles. While they detract from the general tone of the magazine, they do serve the purpose of inciting discussion about the topic. For example, the essay in question was in Vol. 13, No. 3, 2007, and in the following issue Vol. 12, No. 4, 2008, a rebuttal mentioning several of the points Orac does appeared in the Forum section of the magazine.

FWIW, the issue where the original essay was published was focued on medical controversies. While it may be true that animal research is still, in many cases, the best tool to use, it's hard to argue that the use of animal research is controversial.

There has been historically a willingness in Skeptic to publish controversial articles even if they have little evidence to support them. Which is a reason to be a little wary of relying on the Skeptic for data to support your arguments.

For what it's worth, I do subscribe and enjoy reading Skeptic.

And I would recommend Orac inquire whether Skeptic would be interested in this well-written essay as a article. (Although it may need to be trimmed a bit as a letter; oh prolix one!)

Superb post Orac, well done.

So far as computer modelling goes, the sheer complexity of any animal system is impossible to model on current computing platforms. Areas like turbulence in fluid flow absorb vast amounts of computing power, so a rat is likely to give us a better model than any computer for the next twenty years or so. And as you say, it's impossible to model what you don't know.

Many thanks

Kevin Elliott

By Kevin Elliott (not verified) on 17 Mar 2008 #permalink

"By analogy, there is no cure for AIDS but (hopefully) we would not treat AIDS patients with trephination--drilling holes in the skull--even if trephination happened to be the only available procedure."

We wouldn't? Huh? If it somehow worked, trephination would be a fairly unobjectionable procedure, so why wouldn't we? It seems far less severe than, say, cracking open the sternum and operating on the heart or lungs, which is done regularly. Or the treatment for shortness which involves breaking the legs and putting the long bones of the leg into external fixation, and turning screws every day so that, each day's bone healing is re-broken, so the leg bones gradually lengthen.

Hell, people with head injuries have plates of skull removed long-term while the swelling goes down, with the removed skull tissue implanted elsewhere to keep it alive. One girl had this done, but then couldn't get anyone to pay for the removed skull to be put back!

Embryonic stem cell models for researching human diseases, hmmmm.

Why don't the animal rights people go over and fight with the right-to-life people to see who gets to oppose research. I hope the fight is protractred and debilitating.

By natural cynic (not verified) on 17 Mar 2008 #permalink

Embryonic stem cell models for researching human diseases, hmmmm.

Why don't the animal rights people go over and fight with the right-to-life people to see who gets to oppose research. I hope the fight is protractred and debilitating.

By natural cynic (not verified) on 17 Mar 2008 #permalink

Implicit in this kind of criticism is the assumption that biomedical researchers want to work with animals, and need outsiders urging them to find alternatives. In my experience as a biologist, pretty much every researcher I know would leap at the chance to do his studies in a non-animal model if he could obtain equally valid results. Animals are expensive, disease-prone, time-consuming, and entail a substantial regulatory burden. Even the smallest, most benign change in research protocol requires outside approval. They are space intensive, both for maintenance and for laboratory equipment.

And in fact, one of the biggest weaknesses of the biomedical literature is that it is loaded with studies that have been carried out on cell culture or in vitro systems, and where there is no way to determine to what extent the results are meaningful in terms of the function of the intact animal.

As for the argument that the species are too different, I used to work on chicken cells. When I first started, I worried constantly that my results might not be relevant to mammals. As far as I can recall, every single result ultimately held up in mammals, so it is hard for me to take it very seriously when people try to argue that results in one mammalian species might not be relevant to another. There are certainly areas where divergences can be found, particularly when you start dealing with the complexities of multiple interacting systems (e.g. pharmacokinetics). But when it comes to fundamental mechanisms, they seem to be remarkably well conserved.

Thanks for this article.
I`m just an ordinary person who has had both family members and pets with Cancer.
Most recently a dog treated for Primary lung Cancer,who had a lobectomy and follow up chemotherapy.

So this research is not only benefiting humans,it is also benefiting our pets.
Of course anyone involved with animal welfare issues knows that the AR agenda is to end the whole concept of pets.

This really summed it up for me.
[quote]Actually, we are trying to use methods that use fewer or no animals. There isn't a biomedical researcher alive that I'm aware of who doesn't wish that there were another way to get the answers we seek.[/quote]

I`m sure there isn`t a human alive who doesn`t wish there was another way and maybe someday that will come to pass but that day is obviously not here.

I find this extremely bothersome that Researchers have to waste their time defending their work against AR activists.

Thanks for that post,

I am a vegetarian and animal rights activist, as far as that goes, but I think it's silly to say that we can find out the answers to the kind of scientific questions we're asking without using real, living systems. There is no easy way out of the moral problem by claiming the inefficacy of animal testing. It's simply not true. This raises all sorts of lively discussions between me and my girlfriend, who does behavioral research on mice and rats. One question I ask myself is "Do we really need to know this information so badly that we are willing to kill another reasonably sentient creature to find out?" I usually answer yes to this question, being a good child of the techno-science era who buys into the "science as salvation" idea. The second question is "Would I be willing to put my dog up for this experiment?" I usually answer "Hell No!" as would most scientists, I believe, who are willing (but not happy) to test on lab animals. There really is a hint of truth in the phrase "meat is murder," and the same holds true for animal testing, especially on primates.
Maybe the way out is to abandon the science-as-salvation myth itself; too bad it's so damn fruitful and useful in raising standards of living and saving lives. No matter how you spin it, hugs don't cure cancer.
Bohr said that the opposite of a profound truth is a profound truth.
1. I love my dog, and don't see any essential difference between her and lab animals.
2. I believe that scientific research is the best way forward, and is irreplaceable.

No way out of that one.

Thanks for a very impressive scientific case for the use of animals --- humane, compassionate and in accordance with regulations and stipulations of the law --- in health research.

Scientist P. Michael Conn and I, a colleague but not a scientist, have authored a similar case for animal research but one that is aimed at the general public. The book, The Animal Research War, will appear in bookstores in May.

By James V. Parker (not verified) on 17 Mar 2008 #permalink

As an addendum, I thought this would be interesting. Found it writing a paper on this topic.

"The fact is that there is in our nation still a small body of apparently sane men and women, so poorly informed that they deny the value of animal experimentation for human health and human understanding, men and women so misled that they would, if they could, stop by law the humane use of animals by us in our perpetual labor towards understanding and controlling life and death processes."
-Address in the Symposium on Animal Experimentation,
Pacific Division of the American Association for the
Advancement of Science, San Diego, Calif., June, 1938

The more things change...

"Embryonic stem cell models for researching human diseases, hmmmm."

It gets even better for two reasons:

1) Assuming that human embryonic stem cells even exist is an extrapolation from animal research, as the test for pluripotency is to make a chimera that transmits the stem cells through its germline, something that has never been done with humans.

2) Embryonic stem cells are typically grown in 15-17% fetal calf serum. The calf is no longer ethically fetal, as it has been removed from its mother, and the serum is obtained by direct cardiac puncture without anesthetic. The lying AR movement then calls cell culture "non-animal," when in fact the production of the serum causes far more animal suffering than the typical experiment on an animal subject. The same fallacy underlies "ethical" veg*nism and racism.

At the biological level of the gene there exist such irreducibly complex differences between species that it is impossible for one to act as a reliably predictive model for another. Sounds familiar, doesn't it?

Jean Swingle-Greek is on the board of AVAR - recently conjoined to HSUS.

"The Association of Veterinarians for Animal Rights actively works toward the acquisition of rights for all nonhuman animals by educating the public and the veterinary profession about a variety of issues concerning nonhuman animal use. The AVAR is actively seeking reformation of the way society treats all nonhumans and an increase in environmental awareness, as well.

AVAR operates under the premise that all nonhuman animals have value and interests independent of the values and interests of other animals, including humans. As physicians protect the interests and needs of their patients, so should veterinarians."

"Whereas the AVAR recognizes that there may be benefits from using nonhuman animals in research, we do not believe that the end justifies the means. We do not believe that the utilitarian philosophy of 'sacrificing' a few for the benefit of many is morally defensible regardless of the species in question. There are no morally relevant differences between human and nonhuman animals that would justify treating the latter group in such a radically different manner from the former."
http://www.hsus.org/press_and_publications/press_releases/hsvma_011408…
http://www.avar.org/default.asp
http://www.avar.org/about_position.asp#p15
http://www.avar.org/about_difference.asp

The article in Skeptic is just anti-vivisection/animal rights dressed in a cheap tuxedo.

By Leigh Jackson (not verified) on 17 Mar 2008 #permalink

I`m sure there are reasonable animal rights activists and I didn`t mean or intend to insult all.
I was thinking of certain groups that openly state that they want an end to companion animals and they support breed bans(BSL) and they attack researchers.
I also don`t see any essential difference between my dog and one in a lab and I do struggle with that aspect.
I`m sure the Researchers also struggle with it.
I have no solutions,I am grateful for the research and hopeful for the future that fewer and fewer animals will be used.
Interestingly enough,another cancer did appear in my dog.
The prognosis was not good.
There was an option for my dog to go to either Cornell or Guelph for surgery and intensive daily radiation for a month.
I had promised myself that my decisions would always be based on what was best for my dog.
The Cancer specialist explained that the median survival rate was 10 months.
I asked him what he would do if this was his dog.
He said "You would basically be contributing to research and I personally wouldn`t do it."
I appreciated his honesty.
So that goes back to the question you asked
[quote]"Would I be willing to put my dog up for this experiment?" [/quote]
My answer was no and I did what was best for my dog.
So I see no "essential" differences but I obviously see a difference.
I felt somewhat selfish knowing that other dogs had died to help my dog with his first surgery and treatment but I wasn`t willing to contribute to the research to help future dogs.
I feel queasy even writing about it now.
I just don`t have any answers.
But I do believe the medical research must go on.

Scientist P. Michael Conn and I, a colleague but not a scientist, have authored a similar case for animal research but one that is aimed at the general public. The book, The Animal Research War, will appear in bookstores in May.

Thanks for the kind words.

You could always send me a review copy of your book before it comes out as a show of gratitude. ;-)

Thanks for debunking some of the extremists' claims, but I wish you had used a tone that showed more appreciation for the fact that not everyone who supports animal welfare is an extremist. For example,

This unrelenting attack on the use of animals in research is primarily based on a belief that animals and humans should have equal rights and that eating meat or even having pets is viewed as immoral.

If that's not a strawman, I don't know what is. I'm sure there are some out there who agree with every word you're putting in their mouths, but you didn't quote them, so I can't tell if you even bothered to look into it in the first place. The people your message needs to reach are the moderates, but you've just told them they don't exist. What an unfortunate and counterproductive combination of good science with lazy political ignorance.

I would also like to add that the Surgeon who operated is a very well known,respected,published Surgical Oncologist so I appreciated his willingness to be perfectly honest with me, even more.
I`ve read some of his original research reports on his site so he must have struggled to answer my "What would you do?"
question.
My dog was anesthetized when I had to make this decision
and I was told the dog could be moved and I could take my time to decide.
It only took me 5 secs to decide what was best for my dog but it did take me longer to decide if I could allow my dog to wake up and be put through further treatment in order to possibly give him 10 months and contribute to research.
My answer to the latter was no.
This surgeon made me feel very differently about those that do research that needs to be done.
They`re not monsters that take delight in having to use animals.
I will never forget what he did for me that day.

f that's not a strawman, I don't know what is. I'm sure there are some out there who agree with every word you're putting in their mouths, but you didn't quote them, so I can't tell if you even bothered to look into it in the first place. The people your message needs to reach are the moderates, but you've just told them they don't exist. What an unfortunate and counterproductive combination of good science with lazy political ignorance.

Define "moderate."

Also show me the "moderate" animal rights activists who do a damned thing about people like Ingrid Newkirk or the Jerry Vlasaks of the world. When Vlasak is calling for the assassination of "vivisectionists" (as he has on many occasions, his rhetoric becoming more violent when he is at meetings where outsiders won't hear him), the silence from the "moderates" is deafening.

Actually, though, you appear to be confusing the concept of animal welfare with the concept of animal rights. I could be wrong, but I strongly suspect that what you would define as a "moderate" animal rights believer is in fact someone who believes in animal welfare and humane animal husbandry, not animal rights. Animal rights activists are of a different cloth altogether. Brian O'Connor put it well when he said that animal rights activism "is not, repeat NOT, simply animal welfare on steroids," and his series of posts on the topic are well worth reading to gain an insight into the animal rights philosophy. It's a good primer, and there's lots of other good stuff on his blog about this very topic and how animal rights activists take advantage of the confusion many people have about what animal rights activism really is. There are also lots of good quotes by animal rights activists in that series and on Brian's blog.

So, to answer your question, I was not attacking a straw man at all. The concept of animal rights as enumerated by groups like ALF or PETA is that animals should have rights that preclude their being used for meat, research, or pets. Reasonable people have a hard time believing that this is what the philosophy behind the movement says, but that's because they're reasonable people.

i always appreciate your posts, orac, but i wanted to link (here) to what i believe is the real reason researchers experiment on animals, courtesy of America's Finest News Sourceâ¢.

Define "moderate."

I could be wrong, but I strongly suspect that what you would define as a "moderate" animal rights believer is in fact someone who believes in animal welfare and humane animal husbandry, not animal rights.

I can put words in my own mouth. I would define a moderate as someone who feels that there is a legitimate ethical conflict between the well-being of laboratory animals and the well-being of the people whose lives or quality of life may depend on the research being done. Moderates have reservations about things like the Draize test, LD50, and vivisection - do you? The nature of the research - a lifesaving drug vs. a new mascara, for example - is an important factor, and so is the likelihood that it will produce a useful result. That's why I wish you hadn't prefaced your otherwise wonderful debunkathon with a tone-deaf slur that alienates the people who actually need to be reached.

Also show me the "moderate" animal rights activists who do a damned thing about people like Ingrid Newkirk or the Jerry Vlasaks of the world.

That's unfair. For one thing, the shrillest voices are the ones you're most likely to hear, especially if you don't actively research the issue before you start your tirade. For another, activists aren't moderate, by definition - that is, by my definition, which is the one you asked for (before you proceeded to tell it to me). But there are different flavors of activist. Some condone vandalism, terrorism, and so forth, and some don't. Ingrid Newkirk seems to be among the former, but Peter Singer is a prominent example of the latter.

So, to answer your question, I was not attacking a straw man at all.

Did you read my comment before you responded? It wasn't a question.

Even so, I don't understand how you've shown that you weren't attacking a strawman. I accused you of attributing extreme viewpoints to a large number of people without actually quoting anything they've said themselves. Your response to my comment was to attribute extreme viewpoints to a larger number of people, including me, still without referring to anything they've actually said. That isn't a rebuttal.

Epistaxis, Peter Singer is not a "moderate". I don't have the reference immediately at hand, but his writings on animal research take the same approach as Greek et al, slanted, exaggerated and at times just plain wrong. I understand that his stance on research is not so absolute now, so he may currently be a moderate. You also have not addressed Orac's point about the difference between animal welfare and animal rights. In my mind, the animal welfare position recognizes the indisputable difference in cognitive abilities between humans and all other animals. Animal rights ignores this, and thus by definition (in my opinion)becomes an extremist position. This also explains some of the absurd opinions and stances of the animal rights types (mandating universal vegan lifestyles, eliminating pets and guide dogs for the blind etc.)
I am too tired to explain this right now (it's after midnight here), but read Orac's links to Brian O'Connor. All will become clear.

By T. Bruce McNeely (not verified) on 17 Mar 2008 #permalink

Epistaxis, Peter Singer is not a "moderate".

Please re-read my comment. But I'll take a look at the reference when you find it.

You also have not addressed Orac's point about the difference between animal welfare and animal rights.

I think that's a separate issue, and purely semantic.

read Orac's links to Brian O'Connor. All will become clear.

Are you sure that's the right source? All O'Connor does is attack specific activists for their statements and actions. They deserve it, of course, for supporting terrorism. But one thing he does not do is explain a difference between the concepts of rights and welfare. It's a series of ad hominem denunciations, not a philosophical argument. Strange as it apparently sounds to many people, I submit that you can believe in extending rights to animals (for their welfare) without condoning the assassination of humans.

Epitaxis you may have a point about the overly broad brush, but I suspect that Orac would consider himself to be one of the "moderates " you describe (though I'm not sure precisely what you mean by "vivisection") since he has endorsed the principle of the 3Rs.

I actually have my own doubts about O'Conner, in an essay entitled "Reply to Peter Tatchell's: "Why Animal Research is Bad Science"" he discusses pre-clinical testing and clinical trials but needlessly concedes ground by apparently accepting Thatchell's claim that animal tests delayed the development of HIV protease inhibitors, when the facts show that animal testing enabled scientists to select from a panel of candidate drugs with good in vitro anti-viral activity those that were safe and had acceptable oral bioavailability and could be progressed to clinical trials. The Merck protease inhibitor that failed animal tests in 1989 was a very different beast to those designed after the crystal structure of HIV protease was published in 1989.

Animal studies played an important role in the development of Cirixivan/Indinavir. From a review on rational drug design in protease inhibitor design by Alaxander Wlodawer and Jiri Vondrase (1998) :
http://arjournals.annualreviews.org...iophys.27.1.249

"More than 150 compounds were described in several papers as intermediate steps in the design of Indinavir. The drug lead compound was L-685,434 (70, 120), a hydroxyethylene-based inhibitor with a benzocycloalkyl amine at the C terminus (Figure 5). The properties of this compound were improved by variation at the N terminus. Although very potent, the molecule lacked solubility in aqueous media and did not show an acceptable pharmacokinetic profile ( i.e. in animal studies, Visigoth). Incorporation of a basic amine into the backbone of the L-685,434 series provided antiviral potency combined with highly improved pharmacokinetic profiles in animal models. The design of L-735,524 (Figure 3) was guided by molecular modeling and X-ray crystal structure determination of the inhibited enzyme complex (24,119). The inhibitor was potent and competitively inhibited both HIV-1 and HIV-2 PRs with Ki values of 0.52 and 3.3 nM, respectively. This inhibitor, highly selective for retroviral proteases, showed no inhibition against a variety of mammalian proteases including human renin and cathepsin D, porcine pepsin, and bovine chymosin. It also was capable of preventing the growth of HIV-1-infected MT4 lymphoid cells at concentrations of 25-50 nM. L-735,524 was orally bioavailable in three animal models and therefore was tested as a promising drug in clinical trials. In early 1996, the compound (under the name Crixivan) was approved by the FDA as a drug against HIV infection."

I know this has all been a little long winded, what I'm trying to point out the danger of conceding points unnecessarily.

Strange as it apparently sounds to many people, I submit that you can believe in extending rights to animals (for their welfare) without condoning the assassination of humans.

Now there's attacking a straw man argument, as I never claimed that was the case, as you appear to be implying in your response to T. Bruce. And you still haven't addressed the entire issue of animal welfare versus animal rights. That is the core, and I still suspect that you are mixing the two up. As for O'Connor attacking specific activists, these aren't just any old activists. These are the "leadership" (such as it is) or the "thought leaders," if you will, of the animal rights movement.

I suspect that you're an advocate of the former, and good on ya for that. As for Ingrid Newkirk, she may not (at least as far as I know) advocate violence, but PETA does do a lot of truly radical (and idiotic) things in the cause of animal rights, likening it to the Holocaust for existence.

"As for O'Connor attacking specific activists, these aren't just any old activists. These are the "leadership" (such as it is) or the "thought leaders," if you will, of the animal rights movement."

You have a good point here, I believe that you can tell a lot about an ideology form the company it keeps. In particular where any kind of radical movement is concerned (and I first observed this growing up in Ireland during the bad old days of the troubles) the true beliefs of the movement are more often displayed in the character of its leaders and conduct of its adherents than in any statement issued to the press, or these days posted on its official webpage.

PETA do a lot of things without any large degree of thought for *actual* animal welfare. Like, say, releasing the contents of a mink farm into the wild, where most of them will die, but not before wiping out the local populations of endangered water voles.

Or, say, euthenising more companion animals than most state-run shelters (in fact, Newkirk is on record in multiple places as actively opposing no-kill shelters!).

They get no respect from me. None.

By Luna_the_cat (not verified) on 18 Mar 2008 #permalink

Newkirk may not openly advocate violence, but she doesn't condemn it. There's a money link among her group, PCRM, and ALF (Vlasak's group).

Speaking of which, why hasn't Vlasak's license been pulled in CA? He's a trauma surgeon, couldn't one view his call for violence as a way to give himself more patients?

Singer is a nutball who advocates euthanasia of human infants born with congenital defects, an advocate of bestiality, and an eater of rare beefsteak when a reporter pays the tab (just ask Mother Jones magazine about it). He's no moderate.

animal rights terrorists

With that rhetorical flourish of politicized language, you expose yourself as a demagogue, too interested in incitement to pass up an opportunity for propagandizing. Now everything you say is suspect, and if you ever had a chance to reach people like me with your message, you just squandered it completely. I have no reason to listen to someone who I cannot trust. And I cannot trust you, Orac.

By Grammar RWA (not verified) on 18 Mar 2008 #permalink

Geez, what's with the sudden surge of trolls? Did Mr. "You're-All-Liberal-Sissies-Brainwashed-By-The-Big-Feminist-Conspiracy" invite them here or something?

By Laser Potato (not verified) on 18 Mar 2008 #permalink

And you still haven't addressed the entire issue of animal welfare versus animal rights.

Neither has O'Connor, as far I can tell. Why don't you just tell us what you mean?

Epistaxis, you're being bloody-minded (pun intended).

Go to the link that Orac provided, read down about 4 paragraphs, and look at the pages under the heading:

"Animal Rights: Its ideology, logic and how AR differs from Animal Welfare."

...and if you then tell me: "But he doesn't ADDRESS THE ISSUE!!11!!", then I don't know what else to do.

By T. Bruce McNeely (not verified) on 18 Mar 2008 #permalink

Laser Potato:

Geez, what's with the sudden surge of trolls? Did Mr. "You're-All-Liberal-Sissies-Brainwashed-By-The-Big-Feminist-Conspiracy" invite them here or something?

Try to think of it as a reprieve from the monotony of anti-vax trolls.

With each diverse topic we are treated to fresh wingnuttery, as they all appear to be one-trick ponies.

T. Bruce,

As I've said twice already, I did that. Simply putting it in the title doesn't make the content of the article relevant. I reacted to this a few comments ago.

As I've said once already, if there's something in there that I'm missing, maybe it would be easier if someone would just tell us what that is, instead of stalling.

T. Bruce, I didn't see your follow-up when I was writing that comment. Where I can find the rest of the article online?

Epistaxis, I said that I wouldn't know what to do, but what the hey, I'll give it a shot. I read those pages by O'Conner and they are entirely clear to me. Here is a useful quote:
"It (the "philosophy") is based squarely on the unsupported assertion that human life is of no greater value or consequence than non-human life. In short, if it's immoral or unethical to do something to a human, it is no less so to do it to a non-human.

Such equivalency is the very core -- the heart and soul, to use a misplaced analogy -- of the Animal Rights movement.

If you believe that human and non-human lives are equally worthy, then you believe in Animal Rights..."

Animal welfare does not make this assumption.

Here also is a quote from one of my earlier comments:
"In my mind, the animal welfare position recognizes the indisputable difference in cognitive abilities between humans and all other animals. Animal rights ignores this, and thus by definition (in my opinion)becomes an extremist position. "

Does that help?
And no, sorry, I didn't locate an on-line source of the full reference.

By T. Bruce McNeely (not verified) on 18 Mar 2008 #permalink

Regarding the difference between animal rights and animal welfare may I quote AVAR again:

"Whereas the AVAR recognizes that there may be benefits from using nonhuman animals in research, we do not believe that the end justifies the means. We do not believe that the utilitarian philosophy of 'sacrificing' a few for the benefit of many is morally defensible regardless of the species in question. There are no morally relevant differences between human and nonhuman animals that would justify treating the latter group in such a radically different manner from the former."

This is the form of animal rights which O'Connor opposes. The form which believes that it is not defensible to sacrifice the lives of animals in order to save the lives of humans, because there is little or nothing to morally distinguish between them.

The animal welfare position is that we should always endeavour to minimise animal suffering in any use that we make of them, and we are entitled to make use of non-human animals in ways which we are not entitled to make use of humans because of the moral gulf which separates humans from other animals.

By Leigh Jackson (not verified) on 18 Mar 2008 #permalink

ugh. I always wonder what these people will do if or when they get sick. Will they refuse any and all medication and procedures that are a result of animal research? Are they going to submit themselves as research tools for treatment before any animal testing was done?

Wasn't there a recent breakthrough in canine melanoma as a result of animal experimentation?

Real life and death situations may help them put things in perspective. As my husband was fighting melanoma, life and death made things clear. We were both ovo/lacto vegetarians. When he bleed internally and his counts dropped, it became clear that he NEEDED to eat meat (fish and poultry). It was him or them. We were always greatful to the animals and people who died so that he could live as long as he did.

As for the veterinarians in this, what did they do in school? I'm guessing they did disections, surgery for the first time, etc. Also, how do they think medical treatments for animals happen? I'm speculating, but I'd guess it came from animal research.

While working toward my philosophy degree, I spent a lot of time under the tutelage of a pretty well-known animal rights advocate. I bought into quite a bit of what I was told, and am now gradually balancing those concerns with the healthy critical analysis I should probably have been taught in the first place.

I don't think I'll give up vegetarianism anytime soon (though it's not a lifestyle I maintain for animal rights reasons anyway), but I've relaxed my views on vivisection and animal testing due in large part to level-headed, well-researched pieces like this. Thank you for helping me become a better critical thinker. It's nice to be digesting these rational arguments and not catchy counterculture aphorisms.

Katrina, I would like to make it clear that AVAR are a fringe group of animal rights vets (3,500 members). They parted company with the American Veterinary Medical Association (76,000 members)in 2004, and recently joined forces with HSUS ($100 million revenue per annum) under the title of the Humane Society Veterinary Medical Association. The HSUS were rebuffed a couple of years ago by AVMA.

The AVMA have recently been charting a route to the future based on the "one medicine" concept. This approach will bring veterinary and human medicine closer together - reflecting their common historical roots. Biological continuities between animal species are, of course, very relevant to the practice of human and animal medicine.

What we see is the moral equivalence of humans and animals as the guiding principle of AVAR. The essential continuities of animal life and medicine, guide the AVMA. AVAR are staking out the the position of animal guardians: vets should serve the interests of animals first. The AVMA seek to make the veterinary profession relevant to society's needs for the 21st century: vets should serve society first. AVAR want "to educate and reform society", not to serve it.

http://www.petconnection.com/blog/2008/01/15/hsvma-whats-in-a-name/
http://www.nature.com/labinvest/journal/v88/n1/full/3700695a.html
http://www.deliberate.ca/proj03.htm
http://www.avma.org/press/speeches/onehealth_mahr_070424.asp

By Leigh Jackson (not verified) on 19 Mar 2008 #permalink

"Wasn't there a recent breakthrough in canine melanoma as a result of animal experimentation?"

I guess this is a reference to the recently developed therapeutic vaccine.

http://www.amcny.org/technology/melanomavaccine.aspx

The technique they used, known as xenogeneic DNA vaccination, was studied in mouse melanoma models as described in "Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center." Bergman PJ et al. Vaccine. Vol. 24(21):4582-4585 (2006).

There are a couple of phase I clinical trials of this vaccination strategy currently underway in humans
http://www.cancer.gov/search/ResultsClinicalTrialsAdvanced.aspx?protoco….

"Wasn't there a recent breakthrough in canine melanoma as a result of animal experimentation?"

I guess this is a reference to the recently developed therapeutic vaccine.

http://www.amcny.org/technology/melanomavaccine.aspx

The technique they used, known as xenogeneic DNA vaccination, was studied in mouse melanoma models as described in "Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center." Bergman PJ et al. Vaccine. Vol. 24(21):4582-4585 (2006).

There are a couple of phase I clinical trials of this vaccination strategy currently underway in humans
http://www.cancer.gov/search/ResultsClinicalTrialsAdvanced.aspx?protoco….