As Stanford University professor Irving Weissman reflects on his lifelong quest to solve the mysteries of cancer, he bristles at the prospect that his work could be outlawed. A bill sponsored by Senator Sam Brownback (R-Kan.) introduced last spring would make it a crime to place human brain cells in animals. That means Weissman's work -- which involves transplanting human brain-tumor cells into mice -- could conceivably land the 65-year-old scientist behind bars.
Weissman, who directs a stem-cell research institute at Stanford and also co-founded a company called StemCells Inc. (STEM), believes that treatments for brain disorders such as Alzheimer's and amyotrophic lateral sclerosis (Lou Gehrig's disease) could emerge from research like his. Experiments on mice with partially humanized brains could shed light on how brain diseases progress. And such animals could provide testing grounds for embryonic stem cells and other methods of regenerating diseased brains. "Tell me, Mr. Brownback, which of these diseases should we not pursue?" says Weissman as he points to a list on his laptop. "There are people whose window of opportunity is very brief to get these therapies. As far as I'm concerned, he's condemning them."
The bill sponsored by Brownback, who declined to be interviewed for this story, is part of a mounting debate about animals that incorporate human cells. Opponents worry that scientists will be tempted to create a whole zoo full of scary creatures -- evoking H.G. Wells's 1896 tale of murderous half-human beasts, The Island of Dr. Moreau. Others fret that by giving animals human traits, we will somehow alter their moral status -- and that's a sin, according to some religions. At the crux of the debate is a single perplexing question: What does it mean to be human? Says John D. Loike, a bioethicist at Columbia University: "We're entering territory we're just beginning to understand."
Supporters of research on humanized lab animals insist that mere genes -- tiny molecules of nucleic acid -- do not define human beings. It's the capacity to think, reason, and speak that distinguishes our species, they argue. And what gives us that ability is a whole basket of biological processes involving DNA, RNA, proteins, and a symphony of chemical signals. Most important, it's the complex structure of our brain that endows us with uniquely human powers.
In this context the act of swapping a few genes between species is really not much different than breeding a horse with a donkey to create a mule. "There's a bizarre misunderstanding about the nature of life," says Henry T. Greely, a law professor at Stanford who is advising Weissman on the ethics of his mouse experiments. "There aren't 'human genes' and 'goat genes.' There are just genes that have different functions."
Implanting human brain cells into animals, however, could take researchers onto treacherous ground. The resulting critters aren't actually transgenic, as the alterations are not in the genes, and will not be passed down through generations. Nevertheless, there are some frightening potential scenarios. In one, altered creatures might achieve consciousness and self-awareness but be unable to communicate their awakening. To prevent the emergence of animals that would rather be debating Sophocles than running on exercise wheels, bioethicists working with Weissman suggest putting experiments on hold if humanized rodents exhibit any starkly unmouselike brain structure or behavior.
When the lab animal is a close relative to man, ethical concerns are heightened. Last April, the National Academy of Sciences published guidelines advising scientists to avoid implanting human embryonic stem cells into the developing brains of nonhuman primates. Bioethicists at Johns Hopkins University published a paper in the journal Science seconding the recommendation.
Both groups suggest setting up oversight committees to review experiments that involve humanized animals. "Society needs to feel comfortable that moral issues are being handled well," says Ruth R. Faden, executive director of the Phoebe R. Berman Bioethics Institute at Hopkins. "For the science to proceed, for the funding to proceed, we must have the confidence of the public." The National Council of Churches USA advocates setting up a governing body to review transgenic and brain-cell experiments. The organization believes the discussion should include both religious leaders and scientists.
Perhaps such committees are inevitable, but many scientists warn that there will be a cost. Stem-cell research in the U.S. is already constrained because of political controversy. Too many meddling hands could strangle the science, warns Evan Snyder, program director and professor at the Burnham Institute in San Diego, who has injected monkeys with human brain cells as part of his research on pediatric brain diseases: "If we're going to make mistakes, isn't it better to discover them in animals rather than having them pop up in your child?"
By Arlene Weintraub