Dr Ringach writing a response under the title “Predicting the Past” stated:
First, he [Ray Greek] states nobody knows where the next big breakthrough will come from. Then, he claims to know the probability of medical discoveries for various research areas.
Actually what I said was that “ . . . no one knows where the next big scientific breakthrough will come from.” Emphasis in the original as I anticipated Dr Ringach would attempt to obfuscate scientific and medical. I then explained that the probabilities for animal models predicting human response to drugs and disease have been studied and are too low to qualify as a predictive modality for medical science. As I pointed out in the blog there is a difference between a scientific breakthrough, regardless of how impressive and a medically important breakthrough. For example, to the best of my knowledge the study of string theory has of yet not yielded any medical breakthroughs despite leading to some very interesting science.
Read the blog in question and you will find that is exactly what I said. This is why my discussion with Dr Ringach last only about two or three exchanges. You really have to question the intent of someone who so blatantly misrepresents my words and does so when the original is so easy to check.
Perhaps I should clarify my statement that no one knows where the next scientific breakthrough will come from. In fact, we do know where the next big scientific breakthrough will not come from. Just as animals cannot predict human response to drugs and disease, neither homeopathy nor psychic phenomenon will give us the next scientific breakthrough. They will not give us the next medical breakthrough either. I base that on the same science, scientific method, and critical thinking that leads me to conclude that animal models are not predictive for human response to drugs and disease.
Dr Ringach then states:
Despite his claim, there is no calculation of the probability of yielding new therapies and cures for the different fields of research in Dr. Greek’s book. If I am mistaken, I’d like to be provided the page number in the book so we can all look at these data.
Data is exactly what we provide. We reference numerous studies where sensitivity, specificity, positive predictive value and negative predictive value have either been calculated or can be calculated. We did not expend countless pages doing the simple math that these calculations require. The data speaks for itself and people can plug in the numbers if they so wish. We give the data and the formulas. We list, twice, a table that illustrates how to calculate these values. There are also graphs in the book illustrating the principle. For the studies where such calculations can be made or have been made in the original source, I refer the reader to: Part IV in its entirety; pages 120—123; page 224 contains a list of studies that contain animal to human comparisons; pages 267—272; pages 275—279; pages 281—292; pages 294—302, where we discuss, among other things, the Olson study; and pages 303-306.
But this will not satisfy Dr Ringach. Dr Ringach is looking for a sentence in the book that says: “Here is the probability of calculating cures from animals-based research” and he will not find it. That is what the entire book is about. If we could have reduced the book down to a paragraph there would have been no need to write the entire thing. That is how science works. If Dr Ringach finds the actual calculations challenging, I will provide some in this blog.
I have provided the calculations and cited references with more calculations supporting my position that animal-based basic and applied research has a very low probability of resulting in treatments.
Shanks and I did exactly this in Animal Models in Light of Evolutionbut I also have done it in these blogs. Consider Response to Dr Ringach re: AFMA and Basic Science where I cited W. F. Crowley, Jr., Am J Med 114, 503 (Apr 15, 2003):
The article by Contopoulos-Ioannidis et al. in this issue of the journal addresses a much-discussed but rarely quantified issue: the frequency with which basic research findings translate into clinical utility. The authors performed an algorithmic computer search of all articles published in six leading basic science journals (Nature, Cell, Science, the Journal of Biological Chemistry, the Journal of Clinical Investigation, the Journal Experimental Medicine) from 1979 to 1983. Of the 25,000 articles searched, about 500 (2%) contained some potential claim to future applicability in humans, about 100 (0.4%) resulted in a clinical trial, and, according to the authors, only 1 (0.004%) led to the development of a clinically useful class of drugs (angiotensin-converting enzyme inhibitors) in the 30 years following their publication of the basic science finding. They also found that the presence of industrial support increased the likelihood of translating a basic finding into a clinical trial by eightfold. Still, regardless of the study's limitations, and even if the authors were to underestimate the frequency of successful translation into clinical use by 10-fold, their findings strongly suggest that, as most observers suspected, the transfer rate of basic research into clinical use is very low.
Even if one assumes that the one basic research study that successfully translated to clinical utility was from animals (it was not, the ACE-inhibitors came from a pencil and paper diagram) and even if we further assume that a majority of the basic research cited did not involve animals (a very unlikely assumption considering the percent of animal-based grants in basic research that come from the NIH and the fact that in the US basic biomedical research is almost synonymous for animal-based research) that still leaves the a very impressive calculation that “strongly suggest[s] that, as most observers suspected, the transfer rate of basic research into clinical use is very low.”
(We also cite Contopoulos-Ioannidis in Animal Models in Light of Evolution(p384).)
Dr Ringach continues:
Dr. Greek states learning how the brain works has no relevance to addressing disease. We disagree. If you want to fix your car or television, you are in a much better position if you know how they work to begin with. The same is true for the brain or any other organ.
This is another example of Dr Ringach resorting to flagrantly misrepresenting my words in order to refute my position. What I actually said was:
It is quite possible that we will answer the hard problem of consciousness and other fascinating questions about the brain and that such knowledge will impact not one iota on how we treat neurological illnesses.
It is true that advances in science do not necessarily lead to advances in medicine and this has been proven true many times. (See the above-mentioned Contopoulos-Ioannidis and Crowley articles.) But I agree that if scientists could learn more about the human brain then that knowledge certainly might lead to treatments. Learning about the brain of monkeys does not imply the same will be true in humans. And that is the essence of our disagreement. Spin it anyway you want, humans are always going to be differently complex from monkeys
Dr. Greek argues imaging technologies such as PET and MRI (actually developed with the help of animal research) . . .
I once again state that the basic sciences of chemistry and physics allowed the development of the MRI and CT. I am sure they were, at some point, tested on animals but then I am also sure that water was so tested but that does mean that before we tested water on mice we did not know whether we needed it to avoid dehydration. Post hoc ergo propter hocis a fallacy.
Dr Ringach then lists many discoveries that involved animals. I have stated many times, not enough apparently, that animals were used, especially in the distant past to illuminate commonalties between humans and animals. This fact does not change the equally important fact that Dr Ringach has not written any papers describing why even one of the breakthroughs could have happened only by using animals. That is the rub. I will even grant him the claim that some of those discoveries from the past probably could not have happened at that particular time without using animals. (I have no idea which ones as that would require a great amount of study and the results are simply not relevant to my position.) If he is going to claim that animals were necessary, science requires proof.
Regardless, that was then and this is now. I am arguing about the predictive ability of using animals in drug and disease research not the ability of animals to shed light on mammalian physiology. The knowledge we seek does not lie in the 1800s nor will the research modalities used then provide us with cures for Alzheimer’s, cancer, paralysis and so forth.
Another more general fallacy that Dr Ringach employs is the argument from repetition (argumentum ad nauseam). This fallacy is seen when someone perseverates a point until everyone who would argue with him is simply sick and tired of saying the same things over and over and hearing the same fallacies or otherwise false response and hence does not want to discuss it anymore. I have simply refused to continue numerous discussions with Dr Ringach for this reason. I can only answer the same question so many times before it should be obvious to everyone that my opponent is not seriously engaging in a debate. Think of the shouting matches that pass for news analysis on the 24-hour cable networks. No matter what a protagonist for issue X says, the antagonist is going to disagree and fallacious reasoning and outright lies abound. This is sales not science.
The blatant misrepresentations I have quoted above call into question everything Dr Ringach states.