Dr Ringach has stated that the development of Herceptin was due to animal-based research, so let’s examine how to analyze claims like that in general.
Almost every time I say “human-based research led to X” some one will pipe up and claim that if you go far enough back there will be an animal experiment that laid the basis for the discovery. In some ways, this is true. In the 18th and 19th centuries, scientists did learn many things from studying animals. So in a sense, almost all current discoveries relied on past breakthroughs that involved animals. Of course, by this line of reasoning almost all breakthroughs relied on slavery as the scientists of the past either lived in a society that depended on slaves, thus profiting directly or indirectly from that practice, or were slave owners themselves or descendants of slave owners or had some other connection. What would the history of medical science look like had slavery never existed? This brings me to the question of how to judge claims like the one Dr Ringach made about Herceptin.
Invariably, scientists wishing to justify current use of sentient animals in research point to past uses where great gains were accomplished, presumably, secondary to such use. Proving a medical science discovery could only have been made by using animals, that animals were necessary not merely sufficient, is problematic. First the claimant must show that the knowledge in question was absent prior to the discovery. For example, there was no effective polio vaccine until those provided by Salk and Sabin.
Second, the claimant must show that the discovery and use of animals were related temporally. Evidence would include published papers in the scientific literature outlining how the scientist was using animals to search for this particular discovery or was using animals in a fashion that led to this discovery serendipitously. Many animals were being used in the pursuit of a polio vaccine as can be seen from a study of the literature, but it is not clear how useful they were for actually making the discoveries that led to the vaccines. A temporal relationship does not prove a causal relationship, but it is difficult to have a causal relationship without a temporal one.
Third, the claimant must show how using animals contributed to the discovery. The polio vaccine for example was invented, in part, by using poliovirus that was incubated in nonhuman primates. The animals were not being used as predictive models or even heuristic devices but merely as incubators. So the claimant could not claim, on that basis, that the nonhuman primates were useful for gaining a knowledge of what the disease did in humans. Their use would fall under the use of animals as bioreactors, which is a scientifically legitimate use of animals (Paul 1971).
Fourth, if the above are fulfilled then the claimant must essentially prove a negative; that the discovery could not have been made any other way. Although difficult, this can be done and indeed must be done for the claimant to say the discovery was dependent on animal use. (Proving a negative is done every day since most negative statements contain an element of a positive which can be proved. (Wilkins 2008; Hales 2005))
For example, the discovery of the mechanism of the action potential by Hodgkin and Huxley (Hodgkin and Huxley 1952) was made possible because they conducted experiments on the axon of squid in the 1940s. The large diameter of the axon (squid reportedly have the largest nerves in the animal kingdom) allowed Hodgkin and Huxley to insert voltage clamp electrodes inside the lumen of the axon. Supposedly, to this day, no experimental preparation yields greater accuracy in the measurement of action potential characteristics, and thus squid are still widely used.
In order to prove Hodgkin and Huxley could not have made their discovery without using such animals, we would need to know why smaller axons could not be used. Are there limits to the mechanical engineering of the instruments? Or, is it just the case that no one had tried to change things since this preparation was adequate? The burden of proof for stating that such use of squid is the only way these discoveries could have been made falls to the claimant, not to others to refute the claim.
Fifth, if the proponent is claiming the breakthrough was instrumental in developing a treatment or cure, or in revealing important aspects of the mechanism of disease in humans, he would need to show specifically and in detail just how the discovery was used in the cure of diseases or the study of diseases as opposed to just increasing the amount of knowledge in the world.
In terms of Herceptin, the main question is number four above. Clearly, many of the initial finding about cancer and monoclonal antibodies came from animal-based research. This should come as no surprise as a vast majority of research funds go to animal-based research and animals and human share traits. (This does not mean that animal-based research is the best way to make discoveries, merely that if you do something millions of times, you might eventually find something new. More on that in a later blog.) If Dr Ringach wishes to justify animal-based research as opposed to human-based then he must show how these discoveries would not have been possible using humans and human tissues. Since all the discoveries were replicated in humans, this is not going to be possible. All this raises the question: “Why were animal used in the first place?” Why not just go directly to human tissues? The answers are not flattering to the animal-based research community.
Lastly, the benefits gained for using animals when humans and human tissue would have sufficed must be weighed against all the time humans were killed or otherwise harmed because of extrapolating results from animals to humans. The use of animals as predictive models fails no matter how you analyze it and using animals as heuristics is scientifically and ethically controversial in light the availability human tissue.
Finally, let me address Dr Weinberg’s comment:
Dr. Greek says the silliest things, [..] implying that people are not studying human tumors, and implying that the kinds of experiments that one can do in mice can be done as well in humans -- truly mindless!
1. I never said that people are not studying human tumors. This is a straw man argument and is frequently made by people suffering from a lack of facts to support their position especially when their position justifies their income or their enormous ego.
2. Neither did I say that all the experiments that are done in mice could be done in humans, as the above implies. I said, and say again, that if an experiment is replicated in humans then it could have been performed in humans or human tissues to begin with. This is almost a tautology and I would love to hear Dr Weinberg refute it. He can’t!
3. If Dr Weinberg thinks such statements are silly and mindless perhaps he would like to defend his position in a public debate. I will save the reader the anticipation—this will never happen. Weinberg has a big mouth, contradicts himself, and likes to spout off when there are no consequences for his actions. He will not expose himself to the humiliation of being proven wrong in front of his peers. In the original article from which Shanks and I quote (Dennis 2006), Weinberg contradicted himself and we pointed this out. He reacted like a child. Again, I suggest people actually read the article we quoted from and decide for themselves. Weinberg is quoted in the article as stating the following:
It was in 1991 that Bob Weinberg first realized he had a problem with mice . . . "Up until then, I had always believed that all mammals were biologically equivalent," he says. "This planted the seeds of doubt in my mind."
This is a profoundly naïve statement for someone who claims to be an expert in biology. Being able to perform experiments, in other words acting as a technician, is not the same as being an expert scientist. Weinberg’s statement clearly puts him in the category of technician, not scientist. Technicians can make discoveries too! That does not make them experts. Believing that all mammals are biologically equivalent is a creationist position and is an implicit denial of evolution. Had Weinberg asked, my wife could have, when she was in vet school in 1990, explained to him that species differ, thus saving him this frustration. (So much for listening to people who were involved in discoveries.)
Dr Weinberg is not an MD. He has not taken care of patients or sat at the bedside and watched the harm from animal-based research. It is not surprising that he exhibits such a cavalier attitude about medical science.
As to Dr Ringach’s credibility, remember this is the same man that does not believe in the laws of physics.
References
Dennis, C. 2006. Cancer: off by a whisker. Nature 442 (7104):739-41.
Hales, Steven D. 2005. You can prove a negative. Think 10 (Summer):109-112.
Hodgkin, A. L., and A. F. Huxley. 1952. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117 (4):500-44.
Paul, J R. 1971. A History of Poliomyelitis. New Haven: Yale University Press.
Wilkins, John S. 2010. You can prove a negative. ScienceBlogs.com, June 25, 2008 2008 [cited Fevruary 27 2010].
First some technical details. I think you meant that squid have the largest neurons not nerves (just fyi there is a difference). And yes, there is a mechanical consideration when doing patch clamp. Neurons are small and squishy, it is difficult to get a good seal, the larger the neuron the easier. In those days, the electrodes were hand-made glass. There were very few people capable of making them small enough, even for the squid axon, using a smaller axon would have been practically impossible.
The second paragraph with the slavery comparison . . . speaks for itself (is Godwin's Law about to kick in?)
I know you like pointing out the fallacies of others, but after your comments here about Drs. Weinberg and Ringach I don't see how you could bring up ad hominem with a straight face.
On a more serious note, one of the real issues is that it seems unclear where the burden of proof lies. In other words who is really making the claims and who is refuting? Would you make the claim that animal research was not necessary to the development of Herceptin? How do you prove that?
Normally I do not rely to posts that use an alias, however Costaguana made some points that I need to address. 1. I want to thank you for the correction re nerves v neurons. What I actually was referring to was axons (I am writing to a mixed audience here), but you are correct in making the distinction between nerves and neurons. 2. I had heard your explanation re the patch clamp and believe it but would still like references and supporting evidence. I am not doubting the claim, that is just how science is done. 3. Goodwin’s law is not going to kick in from me as: a) I am aware of it and agree with it; and b) I was not comparing animal experimenters to slave owners (almost everyone in those days benefited from slavery, antivivisectionists included) but rather questioning what role the status quo of the era could be said to be responsible for current and even past events. 4. The burden of proof is clear in these cases. I am NOT claiming Herceptin came about without animals. I never said that. If the opposition wants to claim that any breakthrough relied on animals vis-a-vis that animals were necessary not merely sufficient (and that is what they routinely claim) the burden is squarely on them.
And finally, my comments about Ringach and Weinberg were in response to ad hominems from them. If my statements are true then they are true regardless of how insulting. I did not make their statements up out of thin air. There is no straw man here. I merely pointed out their ad hominems and or nonsense and defended myself. If you think my defense false, then you could certainly interpret it as an ad hominem. But, if it is true, would you still consider it an ad hominem? Self defense is not ipso facto an ad hominem. I let the Weinberg comments go unanswered several times in an attempt to elevate the conversation. I was alone in that attempt.