I frequently complain that animal modelers seek to justify the use of animals by promoting every use of animals as a cure or potential cure. The media is complicit in this as the stories help sell their newspapers, increase their ratings, increase the Internet traffic to their site, or whatever. Vivisection activists have assured me that such things no longer happen but then I continue to see headlines like the following.
In an article titled “Zebrafish used to find cures for human diseases” JoAnna Wendel states: "University scientists are using a seemingly unlikely animal to study development, cell function and the effects of debilitating human diseases." There is no doubt zebrafish can be used to study cell function but then so can human cells. But regardless of what you think of using intact zebrafish to study cell functions, they cannot be successfully used to study the effects of human disease. (See Animal Models in Light of Evolution for more.)
Wendel continues: “These shiny little fish, miles away from humans in terms of physical description, are remarkably similar to us in many ways.” This is also true but raises the question: similarity on what level? All life forms are similar on some level. For that matter all matter is similar on some level. The question is whether the similarities outweigh the differences in what is being studied or in the questions being asked.
Wendel’s interviewee then seeks to justify using zebrafish:
John Postlethwait, professor of biology and principle investigator at one of the zebrafish labs on campus, offered a good analogy for what investigating the effects of a mutation is like:
Suppose you're exploring the inner workings of your car and you find a mysterious wire that doesn't have an obvious function. How can you find out what that wire does? Cut it. Then do some testing. Do the brakes still work? The lights? The air conditioning? The engine? If all those answers are yes, than that wire doesn't affect those functions of the car. But if you discover that the windshield wipers are no longer wiping, it's very likely that was the wire's purpose. The same can be applied to genes. Mutate a gene in a growing zebrafish, and see how the embryo develops.
"Clearly that is something that you cannot do on intact people," said Postlethwait.
That is clearly the logic used by animal modelers. Find out what a gene does in an animal and you will know what it does in humans. This despite the known mechanisms of evolution and the fact that animal modelers themselves have stated such gene to gene comparisons are not sound. Van Zutphen states that animals can be used to find out which gene causes a disease in humans:
However, results to-date suggest that the predictive value of a candidate gene, established in such an animal model, is rather low: thus far only few genes have been allocated as causative factors for corresponding disorders in man. In fact, it can be questioned whether the use of animal models is the most effective way to detect candidate genes for complex human disorders. Due to the complexity of the genotype-environment interactions, the pathways that lead to an aberrant phenotype often differ between man and animal. (van Zutphen 2000) (Emphasis added.)
However, if the object of a project is to study the genetic causes and etiology of a particular disease, then comparable genomic segments involved in the etiology of the disorder ‑ construct validity ‑ is normally a requirement. It should be remembered, however, that an impaired gene or sequence of genes very often results in activation of other genes and mobilization of compensating metabolic processes. These compensatory mechanisms may of course differ between humans and the animal model species. [(Hau 2003) p4] (Emphasis added.)
From New Scientist:
One puzzling discovery is that several mutations that cause genetic diseases in humans - such as phenylketonuria and Sanfilippo syndrome, which lead to mental retardation - are the normal form in macaques and, presumably, our own ancestors. "How can genes that seem to be fine in one species give disease in another closely related one?" asks Richard Gibbs, a geneticist at Baylor College of Medicine in Houston, Texas, who led the consortium. (Holmes 2007)
NIH-supported mouse studies suggest treatment target for alcohol problems is a press release from NIH. It states:
A molecular pathway within the brain’s reward circuitry appears to contribute to alcohol abuse, according to laboratory mouse research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH) . . . "By advancing our understanding of the neuroscience and treatment of alcohol problems, these findings open new avenues for research and discovery," says NIAAA Acting Director Kenneth R. Warren, Ph.D.
I agree that by advancing our understanding of the neuroscience and treatment of alcohol problems, scientists can open new avenues for research and discovery, but I disagree that what happens in a mouse is evidence of what happens in the human brain. If scientists want to make such a statement they need to explain why the pathophysiology of alcohol-related problems in mice is the same as for humans then explain why they expect treatment mechanisms to be the same. A history of animal models being predictive would also be needed.
Finally, a press release from Tufts University was picked up by ScienceDaily:
A class of compounds that interferes with cell signaling pathways may provide a new approach to cancer treatment, according to a study published online in the Proceedings of the National Academy of Sciences (PNAS) Early Edition. The compounds, called PITs (non-phosphoinositide PIP3 inhibitors), limited tumor growth in mice by inducing cell death.
The researchers studied 50,000 molecules and found two that inhibited PIP3. Such research has not been particularly productive or predictive before.
To begin with, the National Cancer Institute believes society may have lost cures for cancers because the drugs failed animal tests. (Gura 1997)
In the 1970s, the National Cancer Institute also undertook a twenty-five-year screening program, testing 40,000 plant species on animals for anti-tumor activity. Out of this very expensive research, many positive results surfaced in animal models, but not a single antitumor drug emerged for humans. As a consequence, the NCI now uses human cancer cells for cytotoxic screening.
Abate-Shen in Clin Cancer Res 2006:
Although the spontaneous occurrence of carcinoma in mice is rare, mice have become an attractive model for studying human cancer because of the ease of manipulating their genome. Although the earliest mouse models were derived from viral insertions, nowadays, when we refer to mouse models of cancer, we are typically referring to mice that have been genetically modified to express oncogenes or to delete tumor suppressor genes, either of which can lead to cancer phenotypes. Generally speaking, these genetically modified mouse models enable the investigation of cancer phenotypes in the context of the tumor microenvironment and an intact immune system. These are critical distinctions from the widely used xenograft models in which tumor cells or tissues are typically grown in immunodeficient mice, which, as argued by Olive and Tuveson (1), Fomchenko and Holland (2), and Carver and Pandolfi (3), limit their "predictive use" for drug development . . . (Abate-Shen 2006) (Emphasis added.)
It appears that, despite the assurances from vivisection activists, the media and researchers that use animals have not changed at all. Imagine that!
Abate-Shen, C. 2006. A new generation of mouse models of cancer for translational research. Clin Cancer Res 12 (18):5274-6.
Gura, T. 1997. Cancer Models: Systems for identifying new drugs are often faulty. Science 278 (5340):1041-2.
Hau, Jann. 2003. Animal Models. In Handbook of Laboratory Animal Science. Second Edition. Animal Models, edited by J. Hau and G. K. van Hoosier Jr: CRC Press.
Holmes, Bob. 2007. Monkey genome springs surprise for human origins. New Scientist.
van Zutphen, L. F. 2000. Is there a need for animal models of human genetic disorders in the post-genome era? Comp Med 50 (1):10-1.