Respectful Insolence

I spent a lot of time writing about animal rights extremists who have threatened to harass the children of an investigator whom they view as a “vivisector” and how they fetishize the very violence they decry. Unfortunately, I was disappointed to see that a fellow ScienceBlogger, namely Eric Michael Johnson of The Primate Diaries, appears to share some of the scientific misconceptions that the animal rights extremists when he prefaces an Open Letter to the Animal Liberation Front with:

Vivisection, or what in polite society is merely called animal experimentation, is a barbaric practice that has led to some necessary medical breakthroughs but has mostly served to profit multinational pharmaceutical and cosmetic corporations. I agree with the researchers who published in the British Medical Journal in 2004 that:

Clinicians and the public often consider it axiomatic that animal research has contributed to the treatment of human disease, yet little evidence is available to support this view.

I am also sympathetic to your frustration that, despite mounting evidence that little is gained from this research, its use continues and even grows.

As was pointed out in many of the rapid responses to this BMJ review article, the analysis was poorly conducted and selective. Many of the rapid response letters show the problems with the review Eric cited point out its failure to address any but a subset of the very broad questions it asks. As for benefits to humans from animal research, my field of surgery is chock full of them. Virtually every major surgical advance in the last 100 years was developed first in animal models: transplantation, heart surgery and cardiopulmonary bypass, testing of medical devices, the list goes on and on. One very good portrayal of how animal research led to a major advance in surgery is actually very well portrayed in, believe it or not, a movie. The name of the movie is Something The Lord Made. To put it briefly, it is the story of Dr. Alfred Blaylock, a giant of American surgery, and the unlikely friendship he shared with an African American technician who worked in his lab named Vivien Thomas. The movie is primarily about the pair’s unlikely friendship and the racism of the time. However, it examines their friendship in the context of showing how Blaylock, along with Dr. Helen Taussig, conceived an operation that might alleviate the hypoxia due to the Tetralogy of Fallot, which caused what was termed the “blue baby syndrome,” a universally fatal congenital anomaly. First, they developed a model for blue baby syndrome in dogs. Then they developed an operation to correct the syndrome, again in dogs. Finally, after many experiments, Dr. Blaylock was ready to test the operation on a baby. It was successful, and Blaylock taught it to other surgeons. The Blaylock-Taussig shunt became the standard of care for many years to treat the Tetralogy of Fallot until cardiopulmonary bypass and the development of new surgical techniques allowed the development of a more definitive surgical repair.

No animal model, no Blaylock-Taussig shunt. No testing on animals, no Blaylock-Taussig shunt. No practicing the surgical technique over and over in dogs, no Blaylock-Taussig shunt. And that’s just one example. There are many, many more, particularly in surgery, but I would also point out that virtually all of our current curative chemotherapy for leukemia and lymphoma was developed using animal testing. Moreover, as was pointed out on DrugMonkey, Eric’s likening primate research to the highly unethical Tuskegee syphilis experiment was uncomfortably close to blatant racism.

That’s why I felt obligated to resuscitate a post I wrote about this very topic a couple of years ago and, to some extent, update it by, for instance, pointing out that Camille Marino’s nonsense about the discovery of insulin is just that, nonsense. In any case, if you’ve seen the parts of this post I’ve appropriated to my end of educating Eric and making a futile attempt to educate Camille, I think they’re worth reading again; if you’ve only been reading for less than two years, it’ll be all new to you. So let’s begin with the rehashed, rewarmed, and updated but still hopefully informative and entertaining discussion from a couple of years ago. I wish I could say that a lot has changed since chunks of this first saw print, but it hasn’t. If it had, I would have had to write a whole new article.

I’ll begin by reiterating that 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 week with the news that animal rights terrorists had resumed their threats against investigator Dario Ringach, a researcher who had been forced back in 2006 to stop doing primate research because the animal rights extremists targeted his family for harassment. This continued a string of acts that included when animal rights extremists 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. Fortunately, the license plate number of the car fleeing the scene was reported to police, leading to a raid on a house by police and the confiscation of computers and other materials. This attack appeared to be the latest crescendo in an increasing campaign of harrassment and intimidation by animal rights “activists” that has also been observed in nearby Berkeley.

This sort of threat to researchers is not a problem just in Santa Cruz and the Bay area, but in particular has been a problem in southern California. In 2008, the University of California Los Angeles announced that it was suing several animal rights groups and individuals suspected of attacks on researchers who use animals, including UCLA Primate Freedom Project, the Animal Liberation Front (ALF), and the Animal Liberation Brigade (ALB), as well as several individuals believed to affiliate with these groups. The inciting event for this action was the second attack on the home of Edythe London, Professor of Psychiatry and Bio-behavioral Sciences and of Molecular and Medical Pharmacology at the David Geffen School of Medicine at UCLA, in early February 2008, and I note that animal rights extremists targeted London again a couple of weeks ago. Although, fortunately, no one was hurt in the “actions” mentioned above, I caution taht we in the U.S. often forget how much more radical animal rights extremists are in the U.K., where the campaign of intimidation takes the form of death threats, intimidation of personnel of companies that supply researchers, and even in one case digging up the grave of Gladys Hammond, whose family ran a farm that raised Guinea pigs for use in medical research, and stealing her remains.

Make no mistake, the aim of the most radical of these activists is nothing short of the cessation of the use of all animals in biomedical research. Second, sooner or later, someone will be hurt or killed. As a researcher who on occasion uses mouse models of cancer myself, I state up front that I could be on the firing line just as much as the UCSC researcher or others and am justifiably disturbed when I hear spokesperson for the ALF Dr. Jerry Vlasak, for example, repeatedly advocate violence against researchers who use animals. In this article, I am not going to discuss the moral issues involved in animal research. 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 earlier this week 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. (Creationists and “alternative” medicine mavens are particularly fond of this sort of argument against their hated “Darwinism” or “allopathic” or “conventional” medicine–usually said with a sneer–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. One example of this type of argument I’ve seen comes from, of all places, a 2008 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? 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) is a not-for-profit organization that promotes biomedical research and the practice of medicine based on critical thinking and our current understanding of evolutionary and developmental biology, complex systems and genomics.

Our primary concern is the advancement of investigative methodologies that lead to effective cures and treatments for human diseases. As such, AFMA is opposed to research modalities that have been shown to be scientifically invalid–specifically, the use of animals as predictive models (also known as causal analogical models) for humans relative to drug and disease response.

While an immense body of empirical evidence has supported this conclusion for decades, new knowledge about genes, gene regulation, gene expression and gene networks–gained in large part as a result of the Human Genome Project–has significantly increased our understanding of why animals cannot be used to predict human response to drugs or the pathophysiology of human diseases.

Despite the development of an all-encompassing theory as to why animals are not predictive, there remains–much to the detriment of human health and medical progress–extraordinary resistance to abandoning the use of animals as predictive models.

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 (also known as the “Nirvana fallacy,” which I’ve discussed in the context of arguments of the anti-vaccine movement), 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 testing drugs on humans 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 almost always far more ideological than 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.

Comments

  1. #1 Vet Student
    March 1, 2010

    I’d also like to add that the Blaylock-Taussig procedure is still the standard of care for dogs with Tetrology of Fallot (English Bulldogs, often, but occasionally others).

    So in that case (as well as many others), the research done on dogs came around to provide some benefit to other dogs in the end. Veterinary medicine often takes advances in human medicine that were developed using animal models and brings them back to treat animals.

  2. #2 Tom Bloom
    March 1, 2010

    I agree that some animal models are necessary, but some animal experiments I have witnessed were pointless, and once a prof admitted he regularly did one (a demonstration that could have been videotaped once) just to demonstrate his right to. In med school, pharmacology and physiology labs used “prepared” dogs. One involved identifying drugs by responses. I argued that I could identify all the drugs without hurting (cutting its throat) the dog, and outlined tests for each that would be far more clinically realistic (treatment plans that start with cutting the patient’s throat violate some oath or another). I was told I would kill the dog in the prescribed manner or not graduate.

    It might be an interesting psych study to follow the careers of the two roughly equal divisions of the class: those who were disgusted, and those who thought it was great fun.

  3. #3 Brachychiton
    March 1, 2010

    those who were disgusted, and those who thought it was great fun.

    I expect it did occur to you that most people would be somewhere in the middle, but the temptation to indulge in a fallacy was far too strong to resist.

  4. #4 daedalus2u
    March 1, 2010

    Wow, I didn’t appreciate just how intellectually dishonest the ARA are. To say the treatment of diabetes didn’t require the use of animals sets a new standard for dishonesty. For 60 years, from 1922 until 1982 when human insulin was produced through recombinant techniques in bacteria, the only insulin available was from animals. Pancreases were recovered from slaughter houses and processed for their insulin.

  5. Thank you for such a clarifying and detailed post, Orac!

    A bit of history for those who may be scratching their heads about the similarity in names: the truly pro-research group Americans for Medical Progress, which Orac mentions above, was founded in 1991. About a decade later, in an not so obscure attempt to confuse, Ray Greek named his new organization Americans for Medical Advancement. He had also hoped to use the acronym AMA to further murk the issue, but a lawyer letter from the American Medical Association stopped that – Dr. Greek had to go with AfMA.

    Americans for Medical Progress stands ready to assist individuals and institutions in mitigating challenges to research by animal rights activists. http://www.amprogress.org

  6. #6 Speaking of Research
    March 1, 2010

    Excellent post Orac!

    Orac “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.”

    It’s not just cancer stem cells, the AR activists claims also show a shocking degree og ignorance of the history of embryonic stem cell research, which began with basic research in mice by scientists such as Sir Martin Evans and Prof. Matthew Kaufman, and Prof. Gail Martin.

    http://nobelprize.org/nobel_prizes/medicine/laureates/2007/evans_lecture.pdf
    http://immortalcell.com/Institute.html

    Of course their work built on the discovery of mouse embryonic carcinoma cells by Lewis Kleinsmith and Barry Pierce back in the 1960′s.

    The discovery of ESCs of course fuelled research on other stem cell (and related) technologies such as iPS cells, with animal research again being key to important advances.

    http://www.pro-test.org.uk/b2evo/index.php?blog=7&title=miracle_in_a_test_tube_thanks_to_animal_&more=1&c=1&tb=1&pb=1
    http://www.pro-test.org.uk/b2evo/index.php?blog=7&title=mice_show_the_way_to_safer_stem_cells&more=1&c=1&tb=1&pb=1
    http://speakingofresearch.com/2008/09/01/changing-cellular-career-paths/

    Of course animals are also important to the development and evaluation of stem cell therapies before they can be taken into human trials.
    http://speakingofresearch.com/2009/08/31/mending-a-broken-heart/
    http://speakingofresearch.com/2009/11/16/gene-therapy-on-the-brain/
    http://speakingofresearch.com/2010/02/15/mice-pave-the-way-to-a-cord-blood-transplant-advance/

    you mentioned the work of Dr. Judah Folkman and it’s important to remember that the development of anti-angiogenic therapies did not end with his discoveries either, it has contributed to the development of several treatments not in clinical use, including Lucentis and Avastin.

    http://www.pro-test.org.uk/b2evo/index.php?blog=7&title=the_long_road_to_lucentis&more=1&c=1&tb=1&pb=1

  7. #7 Obvious
    March 1, 2010

    Great post…if I had felt Oracian-level verbosity was appropriate for the comment section, this post encompasses many of the extensions I would have pursued in a previous comment that has been seemingly ignored (dead thread? ARAs stunned into silence by my cogent arguments?).

  8. #8 di
    March 1, 2010

    “One of the chapters in this book, “The Exploitation of Non-Human Animals”, addresses the issues concerning animals being used for science and the conditions for which they are being housed and experimented upon. The conditions of these poor animals are often beyond inhumane and are sometimes unnecessary as many research studies duplicate previously researched data, and some research is simply for the sake of gaining knowledge and not intending to be used specifically for a purpose, such as working towards curing a disease. The growth of science is necessary, however, with the rapidly growing advancements in the developments of techniques used for research, in vitro testing, tissue culture, computer simulation, etc., alternatives for animals and their inhumane treatment within laboratories is obviously a cruelty in which humanity can easily correct if we decide to take action and show our compassion and concern for these issues and their importance. In one section of the book she approaches the complaint about the costs of introducing humane living conditions to those animals being used for medical research or research studies.”

    http://underbite.blogspot.com/2010/02/jane-goodall-institute.html

  9. #9 Paul Browne
    March 1, 2010

    Orac “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.”

    An interesting aspect of that study was that the 3 cases, Bisphosphonates to treat osteoporosis, Antenatal corticosteroids to prevent neonatal respiratory distress syndrome and Thrombolysis in acute ischaemic stroke, where the disease/injury and subsequent treatment most closely matched what happened (time to treatment, dose etc) in the subsequent clinical trials were also the ones where results of the animal studies agreed with those of the clinical trials.

    In the 3 cases where the results did not agree, in least one, Tirilazad in acute ischaemic stroke the treatment, regime differed so much between the animal studies and human trials that it is far from clear that they do actually disagree. In fact at the Authors of the BMJ review point out a proper analysis of the results of the animal tests of Tirilazad indicated that it would not work in the human trials, at least not with the doses and time to treatment actually used in the clinical trials. In another example they give as discordance between the animal and human outcomes, Antifibrinolytics in haemorrhage, the BMJ authors state that the antifibrinolytuics successfully reduce bleeding in humans and animal models, but that the evidence from the animal studies was not strong enough to support proceeding. I wonder if their analysis missed other evidence supporting that decision, or even data not published in the scientific literature that was however made available to those deciding on whether to approve a clinical trial…this is quite often the case with new drugs. The final outcome of discordance between the animal and human outcomes is the use of corticosteroids for traumatic head injury, and is the only example where the animal studies do appear to have been genuinely non-predictive, and in that case the problem may have been that the head injury model was overly simplified and didn’t accuartely represent the clinical situation where it would often be accompanied by other injuries and illnesses. This is a legitimate limitation of the experiment rather than a design flaw, an example of where it is not always possible to account for every real life possibility in laboratory experiments.

    It’s odd that this study is BMJ review is touted as evidence of animal research not working, when it shows that 4 out of 6 therapies the animal studies predicted the outcome in the human trials, and in the other two cases the differences appear to be more to do with flaws or legitimate limitations in the experimental design rather than species differences.

    However this is no reason for those of us who support animal research to rest on our laurals. The BMJ study does show that poorly designed animal studies, possibly due to poor communication between clinical and laboratory scientists, can lead to treatments entering clinical trials whose development should have been halted (or redirected tt other therapeutic areas) on the basis of the animal study results before they got to clinical trials. They also correctly highlight the need for better reporting of the details of animal studies such as the number of animals used, randomization and blinding methods, statistical analysis etc. that Ben Goldacre also noted in a recent post http://www.badscience.net/2010/01/12-monkeys-no-8-wait-sorry-i-meant-14/ *

    For me the message is clear, animal research is crucial to modern medicine, but it can and should be done better.

    * before anyone brings it up I know that it is unrealistic to require the same standards for animal studies as for clinical trials, though for the more immediately pre-clinical studies standards more akin to clinical trials would help. Improvements on reporting of experimental design are something that funders and journals should demand, with the availibility of supplimentary online information lack of space is not an excuse…needless to say this applies to all basic and a lot of clinical science, not just animal research.

  10. #10 BB
    March 1, 2010

    @di; You obviously have never visited a vivarium in the US, where animals are cared for better than most US pets.

  11. #11 Speaking of Research
    March 1, 2010

    Di “some research is simply for the sake of gaining knowledge and not intending to be used specifically for a purpose, such as working towards curing a disease.”

    Congratulations, you’ve just described the sequencing of the human genome!

    Thirty years ago stem cell research was “for the sake of gaining knowledge and not intending to be used specifically for a purpose”, now it’s one of the hottest areas of medical research.

    Go figure!

  12. #12 nat
    March 1, 2010

    Not only cell lines models are far from perfect but most of the cell lines are grown in media supplemented by fetal bovine serum. Whatever the way fetal blood is collected I suppose the fetuses do not survive…

  13. #13 Douglas Watts
    March 1, 2010

    Make no mistake, the aim of the most radical of these activists is nothing short of the cessation of the use of all animals in biomedical research.

    This aim is shared by all laws on the books prohibiting animal abuse and granting a narrow, tightly-controlled exemption for certain animal research projects. The implicit and explicit goal of these statutes is to encourage and require the most human and non-invasive treatment of animals possible in a research setting. By tautology, the most humane and non-invasive treatment is to adopt and use techniques which do not require the sacrifice of animals. The goals of humane activists are identical to the goals and intent of the underlying statutes which create the narrow exemptions which now allow any research at all to be conducted. The logical end point of the “most humane” approach is one that does not involve animals.

    What is, or should be, under discussion now is a program to phase out and eliminate the most invasive, non-humane research types by aggressively developing less invasive and more humane alternatives and to continue this process step-wise over time.

  14. #14 Katharine
    March 1, 2010

    Dudes, Eric Johnson is an anthropologist. I would no more trust him on animal experimentation more than people who have experience in it, either as users or as overseers, than I would trust Orac more than Ethan Siegel on particle physics.

    … and I’m generally less inclined to trust biological anthropologists than actual experimental biologists on just about anything related to biology, really.

  15. #15 Katharine
    March 1, 2010

    A gigantic part of America seems to be obsessed with the Galileo gambit. It’s sad.

  16. #16 anon
    March 1, 2010

    Hmmm, to remain true to their principles, they should not take any drugs where animal testing was used in development.

    I remember my husbands response to his daughter when they were in a store where cosmetics advertised that they hadn’t used animal testing and the daughter was pleased by this– my husband who directed a large in vivo lab gasped in mock horror and said he would refuse to pay for any cosmetics for her in this store because he didn’t want her to be the guinea pig!

  17. #17 symball
    March 1, 2010

    Di, You have obviously never actually looked into this, the pamphlets are not very accurate. I can’t comment for the US, but in the UK the conditions of all laboratory animals is mandated by the government. every establishment who perform testing is licensed, and there is a government department who have a group of vets who inspect the conditions of the animal testing centres, and who perform routine un-announced inspections. They have the power to enter any licensed facility and inspect wherever they like without any form of warrant, and they have the power to shut down an animal house or facility if it is not up to their standards.

    The government also license all of the people involved in the handling of animals, from study director to animal tech, Loss of a licence would render that person unemployable, and there are further punishments up to 3 years in prison for breaking the laws on animal testing.

    Finally each project must also be approved by the government- the person wanting to test on animals must justify why they need to test, how they have minimised the number of animals required and refined the procedure to cause the minimum distress. This must be approved before the tests can start, and then the tests can be inspected as stated above.

    If pet animals were given even 1% of this protection there would be such a huge improvement in the animal welfare standards in this country- and we are a ‘nation of pet lovers’ apparently.

  18. #18 symball
    March 1, 2010

    What is, or should be, under discussion now is a program to phase out and eliminate the most invasive, non-humane research types by aggressively developing less invasive and more humane alternatives and to continue this process step-wise over time.

    Douglas- this is very much the case- most developed countries have centres looking into this- eg. EVCAM in Europe.

  19. #19 Phoenix Woman
    March 1, 2010

    Thanks for this, Orac. The angiostatin passages are particularly compelling to me. It must have been incredibly frustrating, pre-angiostatin, to know that there were tumors that a doctor didn’t dare try to remove surgically and yet not know why.

  20. #20 BB
    March 1, 2010

    @Symball, except that EVCAM is a HUGE fail since the EU has instituted more stringent testing of consumer products for toxcity, leading to more animal testing, not less.

  21. #21 Scott
    March 1, 2010

    except that EVCAM is a HUGE fail since the EU has instituted more stringent testing of consumer products for toxcity, leading to more animal testing, not less.

    You’re inappropriately conflating the distinct issues of (a) developing methods to replace animal research and (b) what research is important. (a) can be being aggressively pursued, yet still have the number of animals used increase, if (b) changes. Symball’s point is with regard to (a); you’re claiming that it’s a failure due to (b). That’s not good thinking.

  22. #22 Paul Browne
    March 1, 2010

    BB “except that EVCAM is a HUGE fail since the EU has instituted more stringent testing of consumer products for toxcity, leading to more animal testing, not less.”

    An odd claim, since it pre-supposes that without ECVAM the EU would not have introduced its more stringent REACH regulations for the testing of chemicals for industrial and consumer use. As it stands less animals will probably be used in REACH testing might otherwise have been the case because of the work done by ECVAM.

    It’s also worth noting that the main drivers of the REACH legislation were environmental and consumer protection groups, and certainly not industry who didn’t appreciate the extra expense and red tape. The regulations agreed to are pretty sensible overall, though the deadline is probably too tight and may well be missed. Rather ironically given their outspoken opposition to animal rights if the Campaign for Consumer Freedom had a European branch they would almost certainly have opposed REACH!

  23. #23 rob
    March 1, 2010

    orac is obvously a shill for Big Animal Experimenta.

    p.s. good post.

  24. #24 Camille Marino
    March 1, 2010

    BOO! haha (just playing)

    You’re precious, ORAC!

    I see you enjoyed my analysis about insulin. Please be sure to cite my research properly in your journals. Attention to detail ORAC… hallmark of competent researchers.

    And, of course, truth! Another hallmark of competent scientists…

    I had no idea that Vlasak was the official doctor of the ALF. Is his office in the ALF batcave? Is there a batpole that Dr. Vlasak jumps on … and by the time he slides down he’s wearing a cape and a balaclava?

    Can you please upgrade me from “terrorist wannabe” to “domestic terrorist,” tell me where I can get my ALF ID card, and schedule an appt. for me? I have a torn rotator cuff and I’m very concerned that I don’t have the proper range of motion to toss a molotav. My redphone is out of service. I would really appreciate your help.

    I know that “proper” animal rights activists care about the rest of your post and will do the necessary deconstructions. Eh, not me so much… The discussion has changed. It’s not about trading PCRM links for FBR links (btw, Frankie Trull — she’s hideously ugly; can’t any of you “scientists” do anything to help the poor woman?).

    I couldn’t care less if you stand on your desk with a bullhorn, jump up and down, and scream about medical progress.

    It’s now about WHAT you do inside of your dungeons of death. That’s all I care about. And, newsflash ORAC, that’s all the public will care about too when they realize what heartless deviants their friendly neighborhood “researchers” are.

    But you knew that already, didn’t you? ;)

    Oh well, just wanted to tell you that I’m becoming a big fan of your work. You espouse the same drivel as the Speaking of Research mascot… but you’re so much more creative…

    I appreciate that! :D

  25. #25 Scott
    March 1, 2010

    Uh, yeah. Nice pile of incoherent drek there. If there was an actual point, it’s very well obscured.

  26. #26 Todd W.
    March 1, 2010

    @Camille Marino

    Did you have anything substantive to say regarding Orac’s post?

  27. #27 John
    March 1, 2010

    Orac:
    “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…”

    Forget about that. Concentrate on the fact that cell culture models, even when the cells are human, are human/animal hybrids to begin with. The leaders of the AR movement clearly know this, as the term they use has been changed to “human-based” lately.

    They are blatant hypocrites in both their scientific and moral arguments.

    Nat:
    “Not only cell lines models are far from perfect but most of the cell lines are grown in media supplemented by fetal bovine serum. Whatever the way fetal blood is collected I suppose the fetuses do not survive…”

    It’s worse than that. First, the calves have been removed from the mother, which means that ethically they are no longer fetuses. Second, the blood is collected by cardiac puncture without anesthesia, which causes more suffering than 99% of the experiments done on animal subjects.

  28. #28 Orac
    March 1, 2010

    I don’t know if I should be “honored” or appalled by Camille’s attention.

    Of course, her “analysis” of the discovery in insulin is still a pack of lies. Much like much of the rest of the NIO website and blog.

    As for Jerry Vlasak, I’ve said it before and I’ll say it again. He’s a disgrace to the profession of surgery.

  29. #29 Todd W.
    March 1, 2010

    @Orac

    I don’t know if I should be “honored” or appalled by Camille’s attention.

    Well, if honored, temper that with the fact that it took her so long to post (4 posts before you got a response).

    If appalled, then think that it at least took some time before she deigned appear in the comments.

  30. #30 Camille Marino
    March 1, 2010

    Brilliant post ORAC!

    I see you enjoyed my analysis about insulin. Please be sure to cite my work properly in your journals. Attention to detail… hallmark of competent researchers.

    And, of course, truth! Another hallmark of competent scientists…

    I had no idea that Vlasak was the official doctor of the ALF. Is his office in the ALF batcave? Is there a batpole that Dr. Vlasak jumps on and by the time he slides down he’s wearing a cape and a balaclava?

    Can you please upgrade me from “terrorist wannabe” to “domestic terrorist,” tell me where I can get my ALF ID card, and schedule an appt. for me? I have a torn rotator cuff and I’m very concerned that I don’t have the proper range of motion to toss a molotav. My redphone is out of service. I would really appreciate your help. Thanks!

    Trading PCRM links for FBR links is pointless. Let’s try to elevate the level of discourse… maybe you could stand on your desk in your underwear, grab a bullhorn, jump up and down, and scream about medical progress.

    It’s now about WHAT you do inside of your dungeons of death. That’s all I care about. And, newsflash ORAC, that’s all the public will care about too when they realize what heartless deviants their friendly neighborhood “researchers” are.

    But you knew that already, didn’t you? ;)

    Oh well, just wanted to tell you that I’m becoming a big fan of your work. You espouse the same drivel as the Speaking of Research mascot (is everyone else as impressed as I am with his proficiency at posting links?!)… but he’s not very bright… you’re so much more creative…

    I appreciate that! :D

  31. #31 The Panic Man
    March 1, 2010

    Don’t worry, Camille, your mindless blather won’t distract us from being evil puppy-torturers. We’ll just get your IP address, send the authorities to your house to have you hauled off for terrorism, and laugh it up.

    Or we’ll just ignore you since you’re obviously a troll trying to be funny (and failing miserably), and go about our lives where we, you know, support ways to save your pathetic existence from being ended early by disease.

  32. #32 Paul Browne
    March 1, 2010

    Camille, rubbish posted twice is still rubbish. I’m kinda glad you didn’t include the comment “btw, Frankie Trull — she’s hideously ugly; can’t any of you “scientists” do anything to help the poor woman?” the second time though, it blew my irony meter first time around and those things are expensive;-)

    By the way how does “spokesperson for the ALF” become “official doctor of the ALF”? Did you have to take lessons in crude misrepresentation or does it just come naturally?

  33. Camille sounds like the village idiot of old, spouting off on a megaphone about how “They” are coming to get you. She strikes me as just another one of those people who are full of themselves, and despirate to garner attention.

    It might annoy Camille to know that I learned surgical airways on pigs – a procedure that I later used to save the life of a person. But, of course, animal training doesn’t benefit medicine at all!

  34. #34 Jack Demolay
    March 1, 2010

    Ah Camille, predictably idiotic. It’s comforting to know that, in the world of constant change and advancement, you’re still a troglodyte. I loved the comment about Frankie Trull though. Hello kettle? This is the pot…you’re black.

  35. #35 The Panic Man
    March 1, 2010

    I’m still dead-set in my belief that “Camille” up there is a fake. The Real McCoy wouldn’t dare approach us out of sheer cowardice.

  36. #36 Paul Browne
    March 1, 2010

    The Panic Man “I’m still dead-set in my belief that “Camille” up there is a fake. The Real McCoy wouldn’t dare approach us out of sheer cowardice.”

    Nah, it’s her all right. The signs are all there.

    I can understand your confusion though, when somebody first showed me the NIO website I honestly thought it was a spoof set up by CCF, but after a couple of minutes I concluded that no parody would be so pathologically unpleasant in tone and downright sociopathic in message.

  37. #37 Andrew S.
    March 1, 2010

    I actually pity Camille. It’s fairly obvious she has an extreme, undiagnosed, personality disorder. I hope for her sake, her family’s sake, and for the sake of people around her that she gets whatever help she needs, and soon.

  38. #38 DuWayne
    March 1, 2010

    I don’t know if I should be “honored” or appalled by Camille’s attention.

    I think the “honor” comes when she actually posts your personal information on her hatesite…

  39. #39 Pareidolius
    March 1, 2010

    Paul Browne and Andrew S.,
    Oh, it’s her alright. Having a cousin who suffers from Borderline Personality Disorder and reading Camille’s site gives me the willies. Her description of her “transformation” reminds me of when my cousin decompensated, and went from a high-functioning (six figure income) BPD sufferer (which was hard enough to deal with) to a low-functioning one. The mood swings intensified, paranoia became intolerable, everything became black and white (no grays) and ultimately violence followed. He’s landed in jail on several occasions, lost his family and joined a very intense, rigid religious community where at least he feels a sense of boundaries. The world that we are privy to when we read Camille’s blog sounds like the letters I get from my cousin.

  40. #40 Douglas Watts
    March 1, 2010

    Douglas- this is very much the case- most developed countries have centres looking into this- eg. EVCAM in Europe.

    Thanks, Symball.

    What is missing from Orac’s post and others similar at scienceblogs is a good outline of what steps the US research community is taking right now to phase out and end its use of invasive and lethal experimentation, esp. on primates.

    Ball’s in your court, folks.

  41. #41 Vicki
    March 1, 2010

    Douglas, That is an impressive example of ignoring what someone actually said. Orac explains why something isn’t possible, and your reply is that the ball is in his court to explain how he is doing it?!

    If two people disagree about whether something is possible, the one who thinks it is possible is the one who should be trying to do it, or at least explaining how it can be done. Not just asserting “Yes, it is possible,” but saying how. If I had argued in 1500 CE that humans could fly, you’d have been entitled to say “show me.” And if I said “by pasting feathers to my shirt and praying,” you would have either said “I’m watching” or sensibly have gotten into your boat and gone on about your business. You wouldn’t have decided we could stop building boats and wagons, because we don’t need them now that we know it’s possible to fly.

    Maybe, in a century or four, we’ll be able to do entirely without animal models in medicine. Maybe it will happen sooner. Maybe it will never happen.

    Here and now, the choice is to use animal models or give up on life-saving research.

  42. #42 Jody
    March 1, 2010

    Reading Camile’s post is illustrative of a mindset, if no the mindset, of ARAs: “We don’t care about how wrong we are about the science, we just want you to die.”

    To be fair, I’m sure there are many ARAs who are honestly in it because they believe animals are being abused; however, the groups mentioned here who are threatening researchers are more about inflicting pain on the scientists than anything else.

    That’s the scary part. The bloodlust that they accuse researchers of is a projection of what drives their hatred.

  43. #43 synapse
    March 1, 2010

    @nat: Fetal bovine serum is collected from fetuses that happen to be in cows that are being slaughtered for meat.

    @di: When I look at those pamphlets, the first thing that strikes me is how old a lot of those pictures must be. Conditions in vivariums today are a lot better than they were even 10 years ago. However, none of the research institutions I’ve been associated with recently allows photos to be taken of the vivaria or animal experiments for public consumption because of animal rights extremism, so the public literally can’t see the improvement.

  44. #44 Sean O'Doherty
    March 1, 2010

    Posted by: Camille Marino | March 1, 2010 1:00 PM

    Someone get the Lysole…

  45. #45 DLC
    March 1, 2010

    Orac: thanks for posting on this again.

    Camile: if you lie twice it doesn’t make it truth.
    Perhaps if you turn it up to 11 . . .
    no, that doesn’t work either.

  46. #46 kb
    March 1, 2010

    But, you don’t understand, vivisection is a really gruesome thing. There’s one experiment where they slice up the animal’s stomach, rip out some bowel that the scientists decide they “need,” and 20% of the time the entire procedure is worthless. How can you support the continued disembowelment of animals?

    Oh, that’s right, because we do it to *people* when they need an appendectomy. And after decades of work with anesthesia, we can do things like this to ourselves and other mammals with a minimum of pain, no matter how brutal the procedure sounds. But I guess it’s harder to rail against mice dying peacefully before their time (from their point of view, which is what we care about, right?) than it is to gross people out with mice-surgery. (Or other mammals, animals, etc.)

  47. #47 Douglas Watts
    March 1, 2010

    Vicki —

    If Orac is truly saying that there is absolutely no possible way to improve or phase out or eliminate the type and extent of existing invasive and lethal experimentation on endangered primates like chimpanzees and bonobos, then that admission proves my point: researchers cannot be trusted to police themselves and the public must intervene on behalf of settled law and the animals who are being harmed.

    The default option is for researchers to stop using these animals and these lethal and harmful techniques. Nobody is forcing them to do this stuff. They are doing it electively. There is no inherent “right” for them to do it.

    I am asking the researchers themselves, or those close to them, to make their best case. These animals are quickly going extinct. If chimps and bonobos were native to the U.S. you could not even touch them without an Incidental Take Permit issued under the U.S. Endangered Species Act and getting one of those for lethal medical experiments would be impossible (try it with Right Whales). It is only through a perverse loophole that U.S. researchers even have access to these animals, which is because the countries where chimps and bonobos are native do not have, in many cases, any functioning governments, and have no enforceable analog to the ESA.

    For the moment I am trying to keep my comments focussed on invasive research using primates, esp. chimps and bonobos and great apes. This is where folks like Orac have their hardest case to make. But as a good scientist and researcher, I’m sure Orac is up to the challenge.

  48. #48 anonymous
    March 1, 2010

    “I am not going to discuss the moral issues involved in animal research.”

    OK. Discussion over. Nothing to see here.

  49. #49 Todd W.
    March 1, 2010

    @Douglass Watts

    The default option is for researchers to stop using these animals and these lethal and harmful techniques.

    I’m curious. What do you propose researchers use in place of animals? Please support your answer with scientific evidence showing that the replacement option is at least as good as, if not better than, using animals.

  50. #50 Bill
    March 1, 2010

    @Todd – it seems to me that Douglass is saying that if there is no replacement option at least as good, then the research should be done (for example, he says ‘nobody is forcing them to do this stuff. They are doing it electively’).

    Is this indeed your assertion, Douglass, that if there are no reasonable replacement options and the research involves the use of apes, then the research should not be done, regardless of the flow on benefits that may accrue?

  51. #51 Douglas Watts
    March 2, 2010

    Hi Todd –

    You asked, “What do you propose researchers use in place of animals? Please support your answer with scientific evidence showing that the replacement option is at least as good as, if not better than, using animals?”

    As someone who is not a clinical researcher using animals as test subjects, that is outside my expertise. Animal researchers are best qualified to answer that question and I would like to hear what they have to say. The universe of animal experimentation is a continuum. In any and every case, there is a trade-off between the real cost to the animal and the potential benefit in knowledge. In this trade-off, the animals have no rights, have no spokespeople, have no advocates and have no defenders. The power balance is asymmetric in the extreme. Researchers basically do whatever the existing laws let them get away with. That is not a system based on ethics or shared cost and benefit. It is a system based solely on an asymmetry of power. The subject animals receive no benefit from any of this, nor is it even assumed they should or would. It’s not like sticking electrodes in bonobos’ brains help keeps bonobos from going extinct. Their welfare, even as a species, is not included in the calculus. They are basically considered as human-like brains which can be exploited without running into the legal barbed-wire which would occur if we did the same thing with prisoners’ brains. They are human proxies, without the threat of a lawsuit.

    Since I do not do animal experimentation, I don’t have the solutions you seek. These solutions must come from the experimenters and their funders and supporters. I don’t support this research. I believe it should end. If the laws allowed human subjects to be used, like death row inmates, we could get even better results than from primates. It would not surprise me if in the next few years this came to pass, and it would not surprise me if some researchers adopted this, so long as they were free from legal liability. The arguments now than then (the ends justify the means) are identical. Ethics are artificial constructs. Only power is real and only when it comes equipped with straps and sedatives.

  52. #52 Douglas Watts
    March 2, 2010

    Is this indeed your assertion, Douglass, that if there are no reasonable replacement options and the research involves the use of apes, then the research should not be done, regardless of the flow on benefits that may accrue? — Bill.

    Bill –

    Correct. We are talking here about several species, chimpanzees and bonobos, and the great apes, all of which are now going extinct before our eyes and may be fully extinct in their only habitat in 20-50 years based on how things are going in the Congo and Virunga. The idea that anyone would do lethal experimentation on endangered primates, the species closest to humans in all aspects, needs to have their head and heart examined.

  53. #53 bellastarkey
    March 2, 2010

    “It’s now about WHAT you do inside of your dungeons of death. That’s all I care about. And, newsflash ORAC, that’s all the public will care about too when they realize what heartless deviants their friendly neighborhood “researchers” are.”

    Yeah I’m pretty sure they will be more concerned about not dying of cancer and what to marinate thier steak in instead.

  54. #54 Bill
    March 2, 2010

    @Douglass, I can understand your position, Even though we were not talking about that specific case. I assume from your response that therefore you support the use of other species (non-endangered)in animal research because, for the time being, there is no reasonable alternative?

    Another question, let’s assume that research on apes ceased; and 100 years from now, we had ‘saved’ the great apes – they are no longer endangered, populations are robust and healthy, they are no longer at risk. Under those conditions, and in the absence of alternative approaches that would reveal useful information, would you support the resumption of research involving apes?

  55. #55 SkydiverIm
    March 2, 2010

    Douglas
    You should not drive a car to work.
    Why?
    As someone who is not a car user, that is outside my expertise. Car drivers are best qualified to answer that question, and I would like to hear what they have to say!
    Even if you do not drive a car, do you still see how that argument doesn’t work?

  56. #56 Paul Browne
    March 2, 2010

    Douglas, since you ask about what is being done about finding replacements for animal research I’m going to have to be link man again.

    http://www.nc3rs.org.uk/
    http://altweb.jhsph.edu/
    http://ecvam.jrc.ec.europa.eu/
    http://iccvam.niehs.nih.gov/home.htm

    Of course these are only the big players, and are as much if not more concerned with co-ordinating efforts of industry and academia as with directly funding their own research.

    I also don’t see the relevence of your point about chimpanzees being an endangered species. Does anyone who knows about the issue really believe that the use of chimpanzees in medical research has any significant impact on their conservation status? If they were not endangered would it change your views on the subject? Oddly enough with the discovery that chimpanzees in the wild suffer from AIDS chimpanzees may end up benefiting from vaccine research on monkeys and humans (invasive HIV research in chimpanzees all but ended over a decade ago).

    http://speakingofresearch.com/2009/07/25/scientists-discover-aids-in-chimpanzees/

  57. #57 Todd W.
    March 2, 2010

    @Douglas Watts

    As someone who is not a clinical researcher using animals as test subjects, that is outside my expertise. Animal researchers are best qualified to answer that question and I would like to hear what they have to say.

    SkydiverIm already pointed out why this argument doesn’t work. If you come in saying “The default option is for researchers to stop using these animals and these lethal and harmful techniques”, then you need to back up why that is the case, showing that such a position is at least as good as, if not better than, a default option that animals should be used in the absence of other alternatives.

    The subject animals receive no benefit from any of this, nor is it even assumed they should or would.

    Wrong! While there may be some instances where no benefit to animals is derived from the research, or where no thought is given to animal benefit, there are numerous accounts of animals profiting from research that was done on them for pre-clinical trials. In the thread on computer modeling, there is the example of advances in skin replacement for burn victims coming back around to benefit animals. There are numerous drugs that were developed for humans which are now also used to treat animals.

    If the laws allowed human subjects to be used, like death row inmates, we could get even better results than from primates.

    Why death row inmates (who actually are allowed to participate in human research, though the ethics approvals for such are a bit tricky, what with concerns about coercion and undue influence)? Do you mean using death row inmates without getting their consent? And what about those individuals who were wrongfully convicted and are actually innocent? Your comment suggests that you know very little about the field of live subject research and even less about human subjects research. I strongly recommend reading the Belmont Report and learning about Tuskegee. In fact, pay a visit to the Office for Human Research Protections web site and read their materials.

    Your comments also suggest that researchers view animals as a replacement for humans. They don’t, or else they wouldn’t bother moving on to humans after testing in animals. My assessment may be wrong, but that’s the kind of vibe I get from some of the things that you say.

  58. #58 Maria
    March 2, 2010

    “If the laws allowed human subjects to be used, like death row inmates, we could get even better results than from primates.”

    This kind of thing creeps me out. So AR activists think that it would be OK to do experimentation in inmates that they would not accept being done in other people? Their lack of respect for human life and dignity is scaring.

  59. #59 Lucy
    March 3, 2010

    @ Douglas Watts
    Regarding your post about extinction and permissions, I am afraid that you are severely misinformed. I used to do behavioral (emphasis, behavioral) research on Cotton Top Tamarins. As a quick back story, they were born an captivity, so the choice is either raise them as we did in an excellent environment with plenty of food and enrichment or release them in the wild where they would die promptly.
    Because Tamarins are endangered in their native habitat (South America), it is not legal to do any invasive research on them – in fact, we could do less than a veterinarian.
    So regarding permissions to use native/nonnative species and rules regarding treatment and research, you are flat out wrong.
    PS. I am a type I diabetic who is insulin dependent, and I used to take insulin collected from pig-pancreas. Invasive animal testing is the reason I did not die when I was 12 years old, so I would like to politely tell all of these idiots threatening the researchers who save lives like mine to go fuck themselves.

  60. #60 Vicki
    March 3, 2010

    Douglas–

    No, the question for researchers isn’t “You have to abandon the best techniques currently available, what would be second-best?” It’s “What are the best ways to do this research?” and they are in fact answering the question. They’re answering it by what they do, and a significant amount of the time, the answer is that the best way to save lives and improve human (and sometimes nonhuman animal) quality of life is animal research.

    If you want people to abandon the best techniques in any field, you need to make a much more convincing case than “I disapprove, and I have no idea of how to replace this, but that’s not my job.” If you want it changed, that is your job. Go back to school and study research methods. Find or invent techniques that are at least equal to what’s going on now.

    Or admit that you don’t care if humans die, as long as you can feel superior and make other people do the work.

  61. #61 MadScientist
    March 3, 2010

    @Tom Bloom: What era was that? For at least the past 30 years if anyone suggested some experiment with no clear benefit they’d be ripped a new one.

    The claims of ‘vivisection’ are simply ridiculous as well unless you’re willing to call all surgery ‘vivisection’. Nor do the majority of animals undergo any form of surgery at all. In many labs most animals live until they die of natural causes. About 10 years ago a lab was shut down and the folks who bred and took care of the animals (mostly mice) were looking for people who wanted the animals as pets. They were horrified when I said they’d be good for food for a number of animals such as snakes.

  62. #62 John
    March 3, 2010

    Camile wrote:
    “I see you enjoyed my analysis about insulin.”

    Why are you lying to conceal vivisection, Camile?

  63. #63 Mike
    March 4, 2010

    As long as people are eating meat, with the concomitant holocaust for the particular, individual animals involved, the ethics of animal experimentation seem like a non-starter.

  64. #64 Raging Bee
    March 4, 2010

    Watts trotts out another non-brilliant non-sequitur:

    If Orac is truly saying that there is absolutely no possible way to improve or phase out or eliminate the type and extent of existing invasive and lethal experimentation on endangered primates like chimpanzees and bonobos, then that admission proves my point: researchers cannot be trusted to police themselves…

    I guess that pretty much sums up the mentality of the AR fanatics: “If researchers don’t tell me what I want to hear, they can’t be trusted.” Sorry, Watts, you conclusion doesn’t follow from your premise.

  65. #65 Dan J
    March 4, 2010

    Douglas @51 said:

    As someone who is not a clinical researcher using animals as test subjects, that is outside my expertise.

    Shorter translation: “I don’t know.”

    For the foreseeable future, there will not be a time when we will be able to conduct all research without using live animals. Computer simulation will likely never be an option for testing (See Animal Experimentation and Simulation by MarkCC).

  66. #66 SmartDogs
    March 7, 2010

    I question the AR activists’ speciesist assumption that the only creatures who benefit from animal research are human.

    Comparative medicine has been an enormous boon to companion animals who now receive many of the same treatments we do. Because we’ve learned so much about them they can be treated with new medications, pain treatments, orthopedic surgeries – and even chiropractic care.

  67. #67 The Panic Man
    March 7, 2010

    Mike @#63: And as long as screaming militant veg-heads slam their fists into their chests and bellow about ZOMGZ TEH ANIMOOL HALOCOST! nobody will take you seriously.

    In short, go suck a bag of flaccid dongs.

  68. #68 NotAllAlike
    March 30, 2011

    Orac,

    First, the greatest threat to science isn’t the animal rights movement. It’s religion. Religiously driven anti-science legislation, rulings, and education is by far the greatest threat to science.

    Second, you complain of animal rights critics lumping together the worst case studies of vivisection, but then you do likewise with the animal rights movement. There are many disagreements within the animal rights movements in regards to its philosophy, tactics, and strategy. Many, for example, don’t condone threatening or harassing behavior. However, you prove yourself prone to the same fallacy as those you criticize, and don’t investigate to take a whole view of the matter.

    Third, just as one cannot discount vivisection entirely for a number of worst case studies, one cannot discount the animal rights movement philosophy and concerns entirely either for the arguments or behavior of the worst case examples. The latter may get more attention, but they aren’t representative of everybody.

    For instance, if you are ecologically or climate crisis concerned, a vegan diet is the most conscious diet when it comes to both of these factors. A study by the University of Chicago found this to be true: http://www-news.uchicago.edu/releases/06/060413.diet.shtml Not too mention that a vegan diet is healthier for people as well, and will reduce a long litany of health problems.

    The next time you sharpen your sword to stab at the animal rights movement, I only ask you pause for a moment and contemplate the possibility that the picture regarding them is not, in fact, black and white.

  69. #69 Chris
    March 30, 2011

    Excuse me, NotAllAlike the Necromancer, exactly why did you decide to post on a year old article and not the two on the same subject that are active today? Did you think you would get in a last word while there was a distraction elsewhere?

The site is currently under maintenance and will be back shortly. New comments have been disabled during this time, please check back soon.