Animal Rights

Yes, You Can Fool Some People But Its Not Nice

| by Dr Ray Greek

On July 31, 2013, Chris (that’s the name he posted under) AKA Blue Sky Science wrote an essay on the Speaking of Research site titled: “You can fool some of the MPs all of the time…”. As the essay criticizes some of my positions I will comment on it here.

Chris’s issue revolves around an Early Day Motion (EDM) in the UK parliament. As I am not an expert on UK politics and procedures, I will leave that aspect of the essay to others and simply address Chris’s criticism of my position. Before I do that however, I will state once again that the organization that apparently advocated for the EDM, Friends for Life on Earth (FLOE) is not associated with me despite the fact that they advocate for my position and use my articles and books to make their case. I know some of the people at FLOE but have no position or power in the organization. I appreciate their efforts and use of my publications but that is the extent of it.

The first specific point Chris takes issue with is my quoting the US National Cancer Institute regarding animal models. Here is the quote with the material before and after the relevant part:

Pharmaceutical companies often test drug candidates in animals carrying transplanted human tumors, a model called a xenograft. But not only have very few of the drugs that showed anticancer activity in xenografts made it into the clinic, a recent study conducted at the National Cancer Institute (NCI) also suggests that the xenograft models miss effective drugs. The animals apparently do not handle the drugs exactly the way the human body does. And attempts to use human cells in culture don't seem to be faring any better, partly because cell culture provides no information about whether a drug will make it to the tumor sites.

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The pressure is on to do better. So researchers are now trying to exploit recent discoveries about the subtle genetic and cellular changes that lead a cell toward cancer to create cultured cells or animal models that accurately reproduce these changes. "The real challenge for the 1990s is how to maximize our screening systems so that we are using the biological information that has accumulated," says Edward Sausville, associate director of the division of cancer treatment and diagnosis for the developmental therapeutics program at the NCI. "In short, we need to find faithful representations of carcinogenesis." [1]

A theme of Chris’s article is that because the quotes and or data (regarding either toxicity or anti-neoplastics) are old, they are therefore invalid. The age of data and quotes can be relevant, especially if new developments have occurred that invalidate the data or concept. But Chris offers no new data. This is because the positions he criticized have either no new data to refute the old or the new data supports the old. The reality of current cancer research is the same as it was in 1997 when the above was published by Science. Roughly 5% of new cancer drugs pass human clinical trials after passing safety and efficacy testing in animals.[2-4] This means the predictive value of animal models is nil. Whether a drug cures or kills an animal is immaterial to the safety and efficacy in humans. (There are exceptions to this, such as if the drug kills by means that are best described by physics or physicochemical properties. In other words sulfuric acid is bad for you.) Moreover, scientists continue to question whether society has lost cures and treatments because drugs from numerous categories failed animal tests.[5] The new animal models that have been used since 1997 have not been any better than the old ones. [3, 6-15] See [16-23] for support from theory on why this is the case. (I have made the same case regarding toxicity, Chris’s other issue in the essay, relying largely on studies still accepted by Pharma in addition to quotes from scientists directly involved with Pharma acknowledging that animal models are not predictive for toxicity. [3, 7, 16, 24-46].)

I have stated many times that Pharma needs predictive tools. This is the case for discovering cancer drugs as well. Neither in vitro nor in vivo qualifies as having predictive value for chemotherapies in terms of safet or efficacy. This lack of predictive value for in vitro and in silico does not justify using animal models. 1) Contrary to what Chris implies, vivisection activists base their justification for using animals on their predictive value.[26, 47-55] They just don’t know what the phrase means.[56] I do not know of any “in vitro activists” that do this. In fact, I don’t know of any in vitro activists. Vivisection activists lobby Congress, not scientists that use in vitro methods as they use in vitro as tool, not a method to pay their mortgage and fund the university. 2) A method or practice either has predictive value or it does not. Regardless of where one draws the line for predictive value, say a PPV and NPV of 0.9 or 0.8 or 0.75, animal models do not come anywhere close to this value and hence are not predictive and hence should not be sold to society as having predictive value.

I have provided references before regarding what constitutes predictive value in medical science.[17 ] I have stated that somewhere in the 0.9 neighborhood is needed and provided references supporting this. Granted, some tests in medicine are used despite not being that high. This is because these tests are the best we have and sick patients and their physicians are doing the best they can. Drug development is in a different category in terms of expediency and have more options—like human-based testing. There is no excuse for using animal models in drug development unless you are also advocating for using Ouija boards and a random number generator. Moreover, physicians fully realize the fact that some tests are not great and take this into consideration when determining care recommendations. One does not, however hear physicians advocating for tests that have a PPV of 0.5. Nevertheless, here [57-61] are some references comparing PPVs that support the 0.9 neighborhood value. Further, what constitutes predictive value will vary based on circumstances. Whether to operate on a potential hot appendix will require a different predictive value that whether to use drug-sniffing dogs in airports. Ask any physician if a PPV in the 0.3-0.5 (the numbers one sees with animal testing) area has predictive value and the answer will be no. Finally, regardless of what the exact number is for predictive value, most people actually involved in drug development agree that animal tests do not come close to that value. [3, 7, 16, 24-46]. (Interestingly, Chris refers to the fact that homeopathy is offered by the NHS as an example of why PPV is unimportant. NHS is a government agency not a scientific one and as such the fact that NHS offers voodoo is not relevant to the discussion.)

Finally, Chris’s criticisms, while disingenuous IMO, are good examples of what one should expect and not expect from reading a blog. I reference most of the controversial statements in my blog but do not usually reference noncontroversial statements. Therefore the vivisection activist must manufacture a controversy—such as the exact value for predictive value in medical science—or ignore the references that explain and prove the points in depth. The scientifically under-educated will not realize the difference between a manufactured controversy and a real one hence my position will be called into doubt. This brings me back to a theme in my blogs, articles, and interviews: if you want to discuss science intelligently, you must read the relevant material. There is far too much knowledge needed to participate in science discussions in general and animal model discussions specifically to rationally expect a 2000 word blog to provide enough of that data, education regarding science in general, and that degree of explanatory power. If a person does not have doctorate in science, it will be very difficult to become an expert in scientific areas like animal models. Even some with a doctorate fail to understand the relevant concepts, although how much of that failure is feigned is debatable. This is why I frequently reference books and articles I have written that go into more depth, along with article by others that support my position. However, even that is insufficient to convince a man whose livelihood and ego are wrapped up in animal models.

This is one reason I repeatedly request that vivisection activists debate me in the scientific literature. Referees from science journals would be asked to judge validity and fallacious reasoning and so forth. I have nothing to fear from a fair critique of my position. That is why I have over a dozen article published in peer-reviewed science journals that specifically address animal modeling theory. Most vivisection activists do not have this record. They say they rely on past article regarding the importance of animal models but this is unacceptable as 1) most of these articles have not been critiqued specifically for the value of the animal model in the development or discovery (for examples see [40, 43, 44, 62-64] and 2) the reasoning used by most articles supporting animal models is an example of post hoc ergo propter hoc. There are numerous on-line only, open access journals that would publish a lengthy debate between a vivisection activist and me, along with comments from the referees. The only reason such a debate does not happen is the lack of participation by a vivisection activist. A public debate could also easily involve a peer-review format with judges and a moderator with actual power to hold the participants accountable for fallacies, misleading or false statements, and lack of evidence.

I won’t be holding my breath waiting for this to happen.

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