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Stanford Report, January 12, 2000

Ethicists ask scientists to ponder research consequences

BY MITCH LESLIE

Scientists have a habit of springing unsettling discoveries on an unprepared public, which must then struggle with social, legal and ethical repercussions. But two years ago when molecular biologists began research that could ultimately enable scientists to create new forms of life, they broke form and sought guidance from a panel of ethicists led by Mildred Cho, PhD, of the Stanford Center for Biomedical Ethics.

While finding no grounds to suggest prohibiting the research, the ethicists nonetheless recommended a pause for contemplation and public deliberation because the work raises so many sticky questions -- even possibly leading to a new definition of life. And the researchers -- from The Institute for Genomic Research (TIGR) and Celera Genomics, both based in Rockville, Md., and the University of North Carolina -- have agreed to halt their work pending the outcome of further discussions.

At first glance, it's hard to see what all the fuss is about. The scientists -- led by gene sequencing virtuoso Craig Venter, now at Celera Genomics -- merely wanted to determine the smallest number of genes necessary to keep an organism alive, the so-called minimal genome. At the level of pure research, identifying this set of genes could help answer questions about the origin of life, the evolution of bacteria and the control of bacterial metabolism.

However, success would also bring far-reaching practical and ethical consequences. For one thing, scientists might eventually use the knowledge to design and assemble new organisms from scratch -- in other words, to create life. Custom-built microbes that slurp up toxic waste or pump out drugs or other useful chemicals would be a boon. But by applying the same technology, someone with an interest in mayhem could synthesize a ferocious biological weapon.

Recognizing these and other vexing possibilities, the genome scientists called for ethical help. "This was initiated by the scientists, which is unusual," said Cho, who is a senior research scholar at the Center for Biomedical Ethics. An unrestricted grant from the TIGR Foundation allowed the creation of a panel that included Cho and colleagues from the University of Pennsylvania and Waco University.

Fresh in everyone's memory was the brouhaha that erupted three years ago after Scottish scientists unveiled Dolly the sheep, the first mammal cloned from an adult cell. As reporters speculated about who would be the first person cloned, politicians rushed before the cameras to condemn human cloning and to demand a ban, which was quickly enacted in the U.S. and many other countries.

Ethicists were just as surprised as everyone else by Dolly. "Attention to the direction in which cloning research was headed before Dolly's creation would have better served society than the overreaction that followed," Cho and colleagues wrote in the December 10 issue of Science.

Instead of scrambling to catch up, this time the ethicists were involved from the start and had an opportunity to explore the ramifications of minimal genome research before any scientific results were divulged, Cho pointed out. As the genome scientists worked to identify the genetic requirements for life, the ethicists deliberated and debated. The two groups made no attempt to influence each other's work and ended up publishing simultaneously.

By knocking out, one at a time, every gene in the simplest known bacterium, the researchers pared down the list of essential genes to around 300. Though formidable technical obstacles prevent scientists from putting together designer organisms today, this list of genes could be the first step in that direction.

For their part, the ethicists concluded that even if the research progressed to the point where scientists could design new organisms, there was no religious or ethical reason for automatically banning the work. However, Cho cautioned that the panel only considered Western religious traditions in making their decision. They hope to incorporate non-Western beliefs in future studies, she said.

The research raises other questions that society should face before work progresses further, the panel concluded. For example, now that we know the minimum requirements for life, should we redefine life as the presence of a particular set of genes? That would have important ramifications, the ethicists wrote, because any definition of life is bound to get entangled in the longstanding debate over abortion, as well as in newer disputes over the use of embryonic stem cells and genetically engineered organisms. And if we adopt a gene-based definition of human life, will we then have to grant human status to hybrid organisms containing human DNA?

A pure reductionist approach like this is cause for concern in other ways, the panel stated. For one, though reductionism is a powerful way of understanding nature, it is scientifically incomplete and sometimes leads to erroneous conclusions. Moreover, a reductionist approach to defining life is bound to raise the hackles of scientists and non-scientists who are dismayed by a "Genes-R-Us" attitude. "There is serious danger that the identification and synthesis of minimal genomes will be presented by scientists, depicted by the press or perceived by the public as proving that life is reducible to or nothing more than DNA," the group wrote.

The ethicists hope they have started a wide-ranging discussion. "One of the things we are trying to do is to involve disciplines outside science and ethics, such as social science and religion," Cho said. She is also keen to get input from the biotech industry, which could reap huge rewards from this technology, and from the public. Stanford and other institutions could play a role at this stage as the "junction" between academic experts and the public, perhaps through town hall-style meetings, Cho said.

Cho said the ethicists are far from finished and plan further discussions to refine and expand their conclusions. There are many issues left to ponder, she said, such as the adequacy of current laws and the views of a broader range of religions. SR