AAAS Lecture: Synthetic Life Research Shows Progress—And Raises Questions

Scientists are becoming increasingly adept at using synthetic building blocks to design and construct living systems, an effort with great promise for the engineering of microbes to make drugs or other valuable products.

But the emerging discipline of synthetic biology also has some experts worried about the accidental or deliberate creation of harmful organisms.

Even undergraduates are learning to use the tools of synthetic biology and the cost of assembling stretches of DNA, base pair by base pair, has been coming down rapidly.

The cost, now about $1 per base pair, dropped 50 per cent during the past two years and is expected to drop to even more within three years, according to Pamela Silver, a professor in the Department of Systems Biology at the Harvard Medical School.

Bacteria range in size from about 300,000 base pairs to about five million. At current costs, Silver said, the genetic sequence for a small bacterium could be assembled for less than $1 million.

That remains quite pricey for the standard lab, Silver said. There also are practical issues. “We still can’t make long sequences of DNA,” she said. “But people are working on this. This is an active research field.”

Silver discussed the status of synthetic biology in a 10 November lecture at AAAS. The lecture was sponsored by the association’s Dialogue on Science, Ethics and Religion program.

In synthetic biology, researchers no longer need rely only on nature as a source of gene segments for manipulation. They can chemically synthesize stretches of genetic material to make custom-ordered proteins. They are developing a kit of standardized parts, or “biobricks,” much as engineers use resistors, capacitors and transistors to build electronic circuits.

The Massachusetts Institute of Technology, a hotbed of synthetic biology, has a Registry of Standard Biological Parts that records and indexes available parts, such as discrete regions of DNA that code for specific proteins. The Registry also offers assembly services to construct new parts. Commercially, more than two dozen companies worldwide that are doing DNA synthesis, according to Silver.

Synthetic biology made headlines in 2002 when Eckard Wimmer of the State University of New York at Stony Brook and his colleagues announced they had been able to assemble a synthetic version of the polio virus from mail-order materials. The feat drew criticism, but Wimmer said his team had done the work to show the feasibility of assembling potentially dangerous microorganisms essentially from scratch. "This approach has been talked about, but people didn't take it seriously," he told a reporter at the time the paper was published. "Now people have to take it seriously. Progress in biomedical research has its benefits and it has its down side. There is a danger inherent to progress in sciences. This is a new reality, a new consideration."

Researchers would like to be able to design and assemble benign biological structures with predictable behavior and functions. Jay Keasling and his colleagues at Lawrence Berkeley National Laboratory in California have been using synthetic biology to engineer a bacterial strain that can rapidly produce the precursor to artemisinin, a plant-derived drug that is highly effective against malaria. The work is promising enough to have drawn a $42.6 million grant from the Bill and Melinda Gates Foundation.

For the future, there is talk of crafting microbes that can efficiently produce hydrogen for energy use or convert the energy from sunlight into other chemical forms. There is also talk of biological computers and design of cells that can “count.”

Why would you want to build a cell that can count? Silver asked. “Well, you can count the number of times the cell has divided,” she said. “You can isolate cells of a specific age. This would simplify the ability to search for drugs that might affect cell aging.”

Silver’s lab is developing a simple cell-cycle counter using cells from yeast as a model system. The cells are engineered with synthetic elements that fluoresce, or “light up,” and disappear at certain stages of cell division and aging.

While synthetic biology is still a young field, Silver said it has proved to be very engaging for students. Teams from 13 colleges participated this summer in the second intercollegiate Genetically Engineering Machines competition, dubbed “iGEM.” A team from Harvard created a biological “wire” that was able to transmit a signal from one point to another. A team from the University of Texas designed a biofilm with bacteria engineered to fluoresce in response to a light-encoded image. The first picture on their small lawn of bacteria was the words “Hello World.” A paper describing the students’ bio-camera has been accepted for publication, Silver said. “This is a remarkable piece of work,” she said.

The enthusiasm for synthetic biology must be tempered with questions about potential misuse, said Lisa N. Geller, an attorney with the law firm WilmerHale. Geller, who has a Ph.D in biology, spoke as respondent to Silver’s lecture.

Geller said that synthetic biology is moving beyond the realm of basic science to the potential for real-world applications. “Just think of it more as a technology than a science,” she suggested. She urged the practitioners to discuss their work openly and bring in the public and outside specialists, such as ecologists, to talk about concerns such as the unintended consequences of releasing newly engineering organisms into the environment. She also said it made sense for practitioners of synthetic biology to adhere to something like an engineering code of ethics.

Silver said the ethical concerns are receiving attention by scientists in the field and are discussed at gatherings such as iGEM. “We’ve got undergraduates and graduate students talking about this,” Silver said. She said some have suggested that scientists take responsibility for their work by leaving an identifiable “mark” on the synthetic biological parts they design. That would allow users to trace the origin of any parts that inadvertently produce mischief.

Earl Lane

15 November 2005