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The Dangers of Synthetic Biology

Nobel Prize winner David Baltimore explains why building smallpox from scratch is a key safety concern in synthetic biology.

The emerging field of synthetic biology – the quest to design and build new life forms that can perform useful functions – brings exciting promise and potentially dangerous capabilities. Scientists have the ability to synthesize entire strings of DNA and put together complicated molecular machinery. But that power has raised some troubling questions. Could terrorists recreate viruses such as smallpox? Or engineer a virus even more deadly than avian flu? (see “The Knowledge”).

David Baltimore, winner of the 1975 Nobel Prize in physiology or medicine, and president of the California Institute of Technology. (Courtesy: the California Institute of Technology.)

In the 1970s, scientists faced a similar dilemma. The advent of recombinant DNA technology meant biologists could manipulate DNA as they never could before. Concerned about the potential perils of this new tool, a prominent group of scientists held the now-famous Asilomar Conference in 1975 (formally titled the “International Congress on Recombinant DNA Molecules”) to determine how to proceed safely.

Thirty years later, at the Synthetic Biology 2.0 meeting at the University of California, Berkeley this month, scientists met to discuss not only new developments in the field, but also how the community should deal with the growing safety concerns surrounding synthetic biology.

David Baltimore, a winner of the 1975 Nobel Prize in physiology or medicine, and president of the California Institute of Technology, was one of the organizers of the Asilomar Conference. At the Synthetic Biology conference last week, he reflected on changes in the field over the last 30 years. Baltimore talks here with Technology Review about what scientists have learned since 1975 and the specific dangers we should be most worried about.

Technology Review: What were you were most concerned about 30 years ago?

David Baltimore: The Asilomar Conference was convened in a very different context than we have today. We were marveling at a wholly new world of experimentation – we literally had no experience with moving DNA around. But people were also concerned, and rightly so, about issues of intrinsic safety. They were worried, for example, that we could create organisms that we didn’t know how to control.

At the conference, we decided to focus purely on safety, rather than ethics or biowarfare. We believed, somewhat naively, that there was a treaty that everyone held to prohibiting use of technology to make biological weapons. In retrospect, the U.S.S.R. had a huge clandestine program. We also didn’t have the situation we have today, where terrorist organizations cross boundaries and are not held by treaties. So we clearly have an unfinished agenda from Asilomar on biowarfare.

TR: What issues are you most worried about today?

DB: The real danger today is from organisms that already exist. The idea of synthesizing something worse than that, of taking bits of Ebola and other viruses to create something more deadly, underestimates how hard it is to survive in the natural world.

Adapting to the human lifestyle is very complicated, so I would guess that we would fail if we tried to engineer a dangerous organism. Ebola, for example, is very pathogenic. It infects families and health workers, but it never spreads widely because it is too lethal – it isn’t in the community long enough to spread. Bird flu is not likely to spread widely until it mutates to become less pathogenic.

TR: Among existing organisms, what has the biggest potential for harm?

DB: I think viruses are the major focus of concern. They are relatively simple to make and control and some are quite lethal. Smallpox, for example, is very potent, and we are not protected against it. The smallpox sequence is published, so you could recover it by synthesis if you had the lab facilities to do that. But getting the pieces of DNA to make smallpox is not a backyard experiment. You need a large lab with significant biosafety precautions. I don’t see this as something that would happen clandestinely in the U.S., but a well-funded lab outside of this country could do something quite nefarious.

TR: Is regulation within the scientific community enough to deal with these threats?

DB: I find that the scientific community is sensitive to the need for appropriate control of research and that the scientific community does this better than outside groups. That is the message from Asilomar and the message from the Fink report [issued by the National Research Council in 2003 reviewing regulations of dual-use biological research].

TR: What should the outcome of the Synthetic Biology 2.0 conference be?

DB: I hope the outcome would be sensitizing people to the potential concerns. And if there is a focused question, such as: What is the danger associated with this research? then bringing together groups of biologists is appropriate. It’s important not to keep the discussion solely within the government.

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