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Similar But Different
By Ray Greek, MD on National Anti-Vivisection Society
Why animals cannot be used to predict human response
Last week we learned that the cow genome has been sequenced and a particular worm is actually two different species of worms. The genome of the cow is about the same size as the human genome. It is around 22,000 genes and resembles the human genome more than do the genomes of mice or rats. But it is also very different; hence humans are different from cows. Likewise, one worm has, due to DNA analysis, now been discovered to be two separate species whose genomes differ (based on limited analysis) by 17 percent. Similar but different.
Similar but different has been a recurrent theme is my analysis of why animals cannot be used to predict human response. We know that monozygotic twins (formerly called identical twins) are not actually identical when it comes to genetic makeup. Neither are men identical to women. Genetic differences also occur among different ethnicities, explaining, in part, why some people are predisposed to certain diseases or more severe forms of the same disease. These differences translate into different predispositions to diseases and different responses to drugs.
As more genomes are sequenced and more is learned about the similarities and differences among species, we will see time and again that very small differences on the genetic level invalidate the long held belief that different species can predict human response to drugs and diseases. Even if humans shared all the same genes with an animal species, there would still be room for very different responses due to: (1) differences with respect to mutations in the same gene; (2) differences with respect to proteins and protein activity; (3) differences with respect to gene regulation; (4) differences in gene expression; (5) differences in protein-protein interactions; (6) differences in genetic networks; (7) differences with respect to organismal organization (humans and rats may be intact systems, but may be differently intact); (8) differences in environmental exposures.
The points listed below are from the April 2009 issue of Scientific American:
Chimpanzees are the closest living relatives of humans and share nearly 99 percent of our DNA.
Efforts to identify those regions of the human genome that have changed the most since chimps and humans diverged from a common ancestor have helped pinpoint the DNA sequences that make us human.
The findings have also provided vital insights into how chimps and humans can differ so profoundly, despite having nearly identical DNA blueprints. (Emphasis added.)
The above is very misleading and I would even say it is simply wrong. The small differences in DNA sequence do not make us human and chimpanzees nonhuman. As my 3rd paragraph above explains, the differences between us and them can only be accounted for when all 8 items in paragraph 3 are considered.
The above announcements are interesting in light of a third announcement from the National Institutes of Health. A Memorandum of Cooperation regarding alternatives to using animals in toxicity testing was posted on the Internet expressing agreement among international agencies to reduce the number of animals. The Memorandum was long on rhetoric but short on specifics. It did not address, or even mention the fact that animal models of toxicity lack predictive value for humans.
The simplistic and misleading essays, of which the Scientific American essay and the NIH Memorandum are but two examples why many Americans believe the similarities between species outweigh the differences and hence why animals can be used as predictive models in biomedical research. Erroneous beliefs have consequences. Reducing the number of animals used in tests that do not work in the first place makes sense only in the government and in groups that have a financial interest in animal tests continuing.
Cows are outwardly pretty different from humans yet their genomes appear more similar to ours than the most commonly used animal in research, the mouse. Genetic similarity does not mean one species can predict response for another. Even different humans cannot do that. So when you hear about different genomes being sequenced and how similar they are to ours, remember that we can be very similar but still are very different in terms of disease and drug response. Also, when you hear the government is working hard to help animals, consider the source.
Also visit Americans for Medical Advancement (AFMA).
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