‘Humanizing’ Animals Drives Brain Research

by Guy McKhann, M.D.

July 1, 2007

In his article “Animal Farm,” William Saletan discusses research that “humanizes” animals—that is, introduces human traits into laboratory animals. This is an interesting topic because it crosses several areas of public concern: the use of animals in biomedical research, introduction of human genes into animals, and the ethical issues of “humanizing” the brains of experimental animals, particularly higher primates such as chimpanzees or great apes.

Regarding the use of animals for research, there is a spectrum of opinion. Some feel that animals should not be used, period. Some are selective in their restrictions: uncomfortable about the use of higher primates or dogs or cats, neutral about rodents such as rats or mice, and not concerned about fruit flies or worms. Others would not restrict species, but do insist on humane care and scientific justification for the studies. Most scientists are in that latter camp for most biomedical research.

The introduction of human genetic material into animals does change things a bit, particularly when it comes to the issue of humanizing the brain. I was recently a member of a group of neuroscientists, stem cell biologists, philosophers and ethicists who reviewed the specific issue of grafting human neurons into nonhuman primate brain (“Moral Issues of Human-Non-Human Primate Neural Grafting,” Science, July 15, 2005).

The major restriction proposed was on experiments in which human nerve cells or the cells that give rise to them might be introduced early in the development of the nonhuman primate brain, and potentially result in a majority of the recipient’s cells being of human origin. No such research is in progress, but it is essential that these issues be openly discussed and debated.

Three other recent articles are examples of how the introduction of genetic material into an experimental animal, in these instances rodents, has led to new approaches to human brain disease:

Richard Friedman (“On the Horizon, Personalized Depression Drugs”) describes how introducing a particular human gene into the mouse may result in a valuable tool for screening the effects of antidepressant drugs. As Friedman points out, this new field of pharmacogenomics (the genetics of the response to drugs) is the wave of the future, and it will often depend on humanized animal models.

• Jocelyn Kaiser (“A Gene Fix for Parkinson’s?”) reports on the first gene therapy trial for Parkinson’s disease in humans. Investigators at Weill Medical College of Cornell University introduced a gene that increased the level of inhibitory neurotransmitters in a specific part of the brain, the subthalamic nucleus, with the intent of slowing the neuronal activity of that part of the brain. The positive results in the small number of patients in this initial trial are encouraging. It is worth noting that the decision to go ahead with these human trials was based on the successful results five years ago, where the same researchers used similar strategies in a rat model of Parkinson’s disease.  

• Carey Goldberg (“Fragile X Study Raises Hopes for Autism”) reports on researchers’ combining two mutant mice, one engineered to have Fragile X syndrome (a common cause of mental retardation and autism) and the other engineered to have a decrease in an enzyme involved in the structure of nerve cells. The resulting mice had fewer Fragile X-type mouse features; they were closer to both structural and behavioral normality. These studies suggest that a similar approach might be tried in people with Fragile X syndrome.

It is hard to argue against these contributions to understanding and treating human disease. But what about studies done in primates? The polio vaccine would not have been developed without all the preliminary work performed in monkeys. Ongoing attempts for an AIDS vaccine are following a similar path.

We have mouse models for Alzheimer’s disease, which are valuable for testing possible therapies. A primate model would be even better. Attempts to develop such a model are well under way.

The issues involved in genetic studies using animals are here to stay. It is up to us in science to make clear why such studies are necessary. We must explain the question we are asking or the problem we are trying to solve, how the transition phase using animals is necessary, and what are the long-term benefits. Lastly, we need reporters such as William Saletan to help get our message across.