Careful oversight is required to ensure that chimeras and transgenic animals continue to serve as powerful biomedical research tools.
Posted 21 September 2011, by Martin Bobrow, The Scientist, the-scientist.com
Research involving the integration of human DNA, cells, or tissues into animals has been undertaken since the 1960s. Transgenic animals (with one or more human genes in their makeup) and chimeras (with some human cells or tissues amongst their own animal tissues) are now important biomedical research approaches. They are used in studies where it is morally or practically impossible to conduct the experiments in humans, and where alternative approaches, such as computer simulations or cell cultures, are not adequately representative of the system being studied. Such approaches are used to determine the function of human genes by expressing the relevant DNA segment in an animal and observing its effect, or to test, develop, and produce therapies for disease, among other applications.
Chimeric mice, for example, are used to study human liver diseases such as hepatitis, and to test antiviral drugs. The mice are made by introducing human hepatocytes into the animals’ livers, which can be comprised of up to 95 percent human cells and so are a more accurate model of human liver function than a normal mouse liver. Similarly, mice with “humanised” immune systems are being used to make antibody treatments for human cancer.
Non-rodent species are also used. Transgenic goats carrying a human gene, for example, are used to produce a human protein now licensed for use during surgery in patients whose blood otherwise fails to clot correctly. Although these animals have some specific human chemicals and cellular functions, they usually do not outwardly resemble humans in any way—the mice still look like ordinary mice; and the goats, to the naked eye, are goats. Many thousands of such “animals containing human material” have been created without major regulatory or ethical concern.
Despite this history, research using such animals has received very little public recognition—or even discussion. Instead, film-makers and novelists have found it an easy subject to dramatise and distort, and have portrayed scientists undertaking seemingly bizarre enterprises to create part-human, part-animal beings. (Some even go so far as to endow apes with enough human capabilities to take over the planet.)
To encourage a more informed debate, the UK’s Academy of Medical Sciences recently organized an expert working group study, which I chaired. Our aim was to consider the research use of animals containing human material from scientific, ethical, social, and safety perspectives, and to make recommendations for the future regulation of this research. We addressed difficult questions (such as the extent to which human cells might be substituted into rodent or primate brains, to study therapies for conditions such as stroke) and considered where the line should be drawn to best fulfil ethical, social, and scientific interests, and how effective regulation might be achieved.
An important aspect of our work was to understand which areas of this research might evoke public concern in the United Kingdom, over and above any concerns some people might have generally about the use of animals in medical research. Our public dialogue, involving participants from across the country, and other evidence highlighted three areas that warranted particularly careful consideration: the substitution of an animal’s brain cells with human cells to a degree which might lead to human-like cognitive capacity in the animal; research involving human–derived reproductive cells in an animal, especially where there is a possibility of fertilisation; and the creation of animals that resemble humans in important aspects of their outward appearance or behavior.
We recommended that these areas of research should be subject to careful oversight by a national expert advisory body. Scientific techniques are advancing rapidly, and will undoubtedly bring new means of developing animals which are, in specific aspects, ever more similar to our species. This will increasingly help us to learn more about human and animal biology, as well as to develop new diagnostics and treatments. We also concluded that a small number of experiments should not for now be undertaken, at least until there is greater understanding of their likely outcomes. Potentially controversial science proceeds best in an open environment, and to make the most of this research, we need to avoid the public distrust that can result from surprise at unexpected scientific developments. An informed and supportive public voice can also act as a mediator to counter the influence wielded by vocal minorities opposed to all animal research.
Our recommendations were intended primarily for the UK research system, but science is an international endeavour, and we hope that our report will encourage other countries to consider these issues, and catalyse the development of international standards and guidelines. We hope that by beginning this debate openly now, future decisions about research using animals containing human material can be made by experts who are fully informed both by scientific possibility and by public opinion. Both must be grounded in scientific fact, not science fiction.
For more information or to downloads the report visit http://www.acmedsci.ac.uk/p47prid77.html.
Professor Martin Bobrow is an Emeritus professor of medical genetics at the University of Cambridge and chair of the Academy of Medical Sciences Working group on “Animals containing human material.”
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