Where Are The Skeptics?
My concern with using animals in research primarily revolves around using them as predictive models for human response to drugs and disease. AIDS vaccines have succeeded in monkeys but harmed humans. Countless drugs that have helped humans would have been lost had animal studies been believed. Animal models are simply not predictive for human response. The sensitivity, specificity, negative and positive predictive values for touting animal models as predictive is simply inadequate. (See Animal Models in Light of Evolution for an in depth analysis of the prediction issue).
Despite my preference to stick with the science, the question I am most often asked is “Why does such use continue?” This lies outside my comfort zone. However, as this is so frequently asked, I usually attempt to shed some light, based on my experiences and an analysis of similar situations. My explanation infuriates those with a vested interest in using animals as I almost always point out the money connection. But another reason such use persists is, to paraphrase Edmund Burke: all that is needed for nonsense to continue is for skeptics to do nothing. In this blog, I ask skeptics to consider the following three examples.
1. Recently, Dr Dario Ringach said in a blog:
Now think... ask yourself: in what version of evolutionary biology can one expect studies with flowers to save lives, while studies with animals be guaranteed to fail? (Hint: None.)
This is classic fallacious reasoning, as I know of no scientist who has said that studies with animals are guaranteed to fail. Animals cannot predict human response but they can be used for many other scientific endeavors, as I have repeatedly said. Dr Ringach is again setting up a straw man. Fallacies like this are the bread and butter of vested interest groups in general, thus Dr Ringach’s statement does not surprise me. What I would like to know however is where are all the skeptics and critical thinkers who would, were the subject matter different, be all over such fallacious reasoning? Even a superficial reading of Dr Ringach’s blogs will reveal numerous fallacies. Where is the outcry from skeptics? The use of animals as predictive models in research has more far reaching ramifications than homeopathy, which is routinely (and rightly) attacked by skeptics.
2. Outspoken supporter of using animals in research Dr David Gorski wrote in his blog on May 10, 2010:
Another good part of the report [from the President’s Cancer Panel] is its emphasis on the deficiencies in our current technology and tools for assessing the carcinogenic potential of various chemicals. Related to the report’s emphasis on how little we know about carcinogenesis in children, the report criticizes current animal models because they fail to capture the impacts of early exposures and miss the late effects of such exposures. Also problematic is that most animal studies use long-term, high-dose exposures that may have little relation to humans. Consequently, the report urges the development of alternatives to animal testing involving testing in human cells in vitro. I’m rather skeptical that this recommendation will produce much benefit very fast. After all, one reason we use animals is because, as imperfect as animal carcinogenesis studies are, the correlation between cell culture studies is even more unreliable than that of animal studies. (1) (Emphasis added.)
His statement seems to be at odds with the following from Salen in 1994 in the Handbook of Laboratory Science Volume II:
The case of the huge 25-year screening program, undertaken by the prestigious U.S. National Cancer Institute, illustrates the kinds of dilemma possible: in this program 40,000 plant species were tested for anti-tumor activity. Several of the plants proved effective and safe enough in the chosen animal model to justify clinical trials in humans. In the end, none of these drugs was found useful for therapy because of too high toxicity or ineffectivity in humans. This means despite 25 years of intensive research and positive results in animal models, not a single antitumor drug emerged from this work. As a consequence, the NCI now uses human cancer cell lines for the screening of cytotoxics. (2)
I asked Gorski to provide references for this position on May 11 but he has not replied.
The website where Gorski posts is called Science-Based Medicine and I highly recommend it! It is a very good source for learning about what does and what does not work in medicine. But the strengths of the website are that it is science-based, adheres to the rules of the scientific method and scientific evaluations including citing references, and does not allow unsubstantiated nonsense. Maybe Gorski has substantiation for his comment but he has not provided it. Sadly, this lack of response is common when asking questions of the vested interest groups, including the animal-based research community. Maybe Gorski is on vacation or otherwise unavailable. If so, I look forward to hearing from him when he is available. (For the record, Gorski declined my previous invitation to discuss the use of animals as predictive models in an indexed peer reviewed science journal that was seeking a Point Counter Point-style debate. For more on statements by Dr Gorski see Response to Orac.)
3. Scientists who are not animal-based researchers themselves but who are in universities that are dependent upon money from animal-based research uncritically support animal-based researchers. For example, The Oxford Student (the student paper at Oxford) published an article by Rachel Bennett about Dr Macleod and animal-based researcher Dr Tipu Aziz:
Malcolm Macleod, a clinical neuroscientist, was asked by Animal Aid to conduct a systemic review into Aziz’s research. Macleod accidentally sent an email intended for a colleague to animal rights group Animal Aid. The e-mail stated he felt that Deep Brain Stimulation [the area of Aziz’s research] was an “area of weakness often trumpeted as a success, but which in reality is probably a failure”. He asked for “advice” and suggested he would "avoid, play a straight bat or price [himself] out of the market” for the review requested. Animal Aid said about the e-mail “He [Dr Macleod] feared that an objective investigation of the associated animal research would expose the treatment's shortcomings. He was determined to avoid being drawn into the front line of the vivisection debate.” Dr Macleod claimed that he stood by his choice not to do the review “I was not comfortable taking part in a study which was motivated by a desire to undermine Aziz.” (My additions are in bold.)
The skeptic community has contributed and is contributing greatly to debunking nonsense. But with the exception of Skeptic magazine (see 2007;13(3):44-51) the community has been very silent or even hostile (see transcript and video of debate with Andrew Skolnick) on this issue. Why are they allowing to go unchallenged the position that animals can be used as predictive models for humans? If animal models are not predictive, then the FDA and EPA should vastly change their rules and regulations. (NIH would also need to change some of their funding assumptions but the FDA and EPA would have to more or less start over.)
I will accept from any organization that stands for critical thought and science any invitation to engage in public dialogue on this issue.
(For more on fallacious reasoning and animal models, please read FAQs About the Use of Animals in Science: A handbook for the scientifically perplexed.)
References
1. D. Gorski. (Science-Based Medicine, 2010), vol. 2010. http://www.sciencebasedmedicine.org/?p=5045#more-5045.
2. J. C. W. Salén, in Handbook of Laboratory Science Volume II. Animal Models. 1st edition., P. Svendsen, J. Hau, Eds. (CRC Press, Boca Raton, 1994), pp. 1-6.
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"Systematic Reviews of Animal Experiments Demonstrate Poor Human Clinical and Toxicological Utility" by Andrew Knight.
ATLA 35, 641–659, 2007 641.
http://tinyurl.com/23pq835 for article
Abstract:
"The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive Scopus biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. In 20 reviews in which clinical utility was examined, the authors concluded that animal models were either significantly useful in contributing to the development of clinical interventions, or were substantially consistent with clinical outcomes, in only two cases, one of which was contentious. These included reviews of the clinical utility of experiments expected by ethics committees to lead to medical advances, of highly-cited experiments published in major journals, and of chimpanzee experiments — those involving the species considered most likely to be predictive of human outcomes. Seven additional reviews failed to clearly demonstrate utility in predicting human toxicological outcomes, such as carcinogenicity and teratogenicity. Consequently, animal data may not generally be assumed to be substantially useful for these purposes. Possible causes include interspecies differences, the distortion of outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments, which was evident in at least 11 reviews. No reviews existed in which the majority of animal experiments were of good methodological quality. Whilst the effects of some of these problems might be minimised with concerted effort (given their widespread prevalence), the limitations resulting from interspecies differences are likely to be technically and theoretically impossible to overcome. Non-animal models are generally required to pass formal scientific validation prior to their regulatory acceptance. In contrast, animal models are simply assumed to be predictive of human outcomes. These results demonstrate the invalidity of such assumptions. The consistent application of formal validation studies to all test models is clearly warranted, regardless of their animal, non-animal, historical, contemporary or possible future status. Likely benefits would include, the greater selection of models truly predictive of human outcomes, increased safety of people exposed to chemicals that have passed toxicity tests, increased efficiency during the development of human pharmaceuticals and other therapeutic interventions, and decreased wastage of animal, personnel and financial resources. The poor human clinical and toxicological utility of most animal models for which data exists, in conjunction with their generally substantial animal welfare and economic costs, justify a ban on animal models lacking scientific data clearly establishing their human predictivity or utility."
See also Thomas Hartung's article entitled "Toxicology for the Twenty-First Century" in Nature, Vol. 460, July 2009. He earned a PhD in biochemical pharmacology and an MD in toxicology. Hartung also made this easy to comprehend presentation http://tinyurl.com/25a8mfa “Towards a New Toxicology – Evolution or Revolution?"
See, for instance, this UK report:
http://www.publications.parliament.uk/pa/ld200102/ldselect/ldanimal/150/15007.htm #a19
http://tinyurl.com/2wksdub
Here's the first chapter.
Replacing the Animal Model in Biomedical Research and Education
http://tinyurl.com/372x2ag
Well, here is hoping my link will work .
The following excerpt discusses some of the reasons animal testing of drugs was first mandated by law , and gives numerous examples where the animal testing prevented harmful drugs from being put on the market:
http://books.google.ca/books?id=Rno1rYxR264C&pg=PA3&lpg=PA3&dq=predictive +value+of+animal+ research &source=bl&ots=OKYbhz9udw&sig=tmtfzb3MR4UCc25dM3AIlNiElQA&hl=en&ei=rZvxS9H6E4a2sgPB0Zi4Dw&sa=X&oi=book_result&ct=result&resnum=8&ved=0CDcQ6AEwBw#v=onepage&q=predictive%20value%20of%20animal%20research&f=false
Or, should the link fail, the actual title is:
Animal Models in Toxicology, 983 pp. CRC Press, Boca Raton, FL 2007. $169.95. ISBN 0-8247-. 5407-7. Animal Models in Toxicology edited by Shayne C. Gad
"Animal experiments will not help humans"
A rather categorical statement, don’t you think?
This was the title of an OpEd published in the LA Times by Dr. Lawrence Hansen, one of Americans for Medical Advancement's officers.
http://www.latimes.com/sns-200910230804mctnewsservbc-animaltesting-peta-m ,0,268252.story
AFMA is, of course, the organization you direct.
http://www.curedisease.com/directors.html
If you read the OpEd, Dr. Hansen's main complaint was the use of animals in neuroscience research . The kind of work I have been defending here.
I have already provided some examples of the relevance of such research to human health :
http://www.opposingviews.com/i/paralyzed-rats-walk-again
http://www.opposingviews.com/i/trying-to-help-patients-with-paralysis
http://www.opposingviews.com/p/explaining-my-work
...and I still cannot get a clear answer from you: do you and AFMA support such research or not?
All along you seem to imply such research is “basic research” that is done without goals and simply for “knowledge sake”.
But I have pointed out multiple times, much of this fundamental knowledge has produced the therapies, cures and medical devices of today, and will also produce the ones of tomorrow.
So, are you against basic research that leads to therapies... such as basic research with flowers that led to chemotherapy based on vincristine?
http://www.opposingviews.com/i/saved-by-a-flower-nature-as-the-neighborhood-pharmacy
Or, as I suspect, are you only against basic research if it involves animals?
Everybody's probably grown tired of having the same conversation with you. Dude, you want credibility, you know the bare minimum you have to do: take this whole dialogue to a peer-reviewed science journal. Then it'd be an actual dialogue. No way that's happening, even if hell froze today. You'd have to use precise references and directly address the science. You can't evade like you do here and make connections where, logically and sanely, there just are none. That you and Gorski both refuse to take on Dr. Greek in a legitimate scientific forum says it all.
Studying humans and human tissue often leads to accurate information about drugs and diseases in humans. No kidding. It's among the best modern methods. But you keep claiming that studying disease and drug efficacy in the biology of dogs and mice will give us more trustworthy information about human biology. Diseases and drugs affect each individual person in the same species quite differently. Your cross species approach fails in the most basic logic.
I'm not bothering with your delusional attempts to bait Dr. Greek. That speaks for itself. Let's just look at what you keep proposing we do as a society . You want us to look to animal research for answers to problems of human biology. It's like you're saying society should support this wrong way of doing research only because it's less wrong...than flipping a nickel and calling heads or tails. This is the logic you advocate, and it sucks. Lucky for you this isn't even close to a peer-reviewed situation. Your house of sand would have crumbled and washed away long ago.
Maybe NIH grant money and our taxes should go toward research on promising methods like personalized cell culture analogs, a.k.a. (Your) Body-on-a-Chip. One proposed application would be pretesting chemotherapy on a patient’s healthy cells as well as his/her tumor biopsy to determine the drugs most appropriate for that patient. The drugs would attack only the tumor and not the patient’s healthy tissues. PCCAs are the best representation of the effect of a drug on the entire human body, and they're a vital link between in vitro and clinical research. Sadly, NIH doesn't give grants to such work currently being done at Cornell University.
About 89% of the compounds (1) pharmaceutical companies test that enter clinical trials don't produce the wanted results in humans. But the tested compounds work in rats, mice, voles, and other animals you keep claiming are the hairy biological mini equivalents of humans. These testing failures prove human disease mechanisms and the basic metabolism of humans are very different from those of animals.
Words can be used to disguise, not to illuminate. Words can be used to confuse, so people vote against their own interests. Words must be twisted to justify an empire that has now ceased to exist, much less make sense. Gore Vidal said something along these lines. Your approach to setting up what you believe is a logical progression of thought remains embarrassing.
(1) Kola, I. and Landis, J. “Can the pharmaceutical industry reduce attrition rates?” Nature Reviews Drug Discovery. 2004, 3, pp. 711-715.