On May 20, the day that Science published a study describing the first synthetic bacterial genome, President Barack Obama asked his advisory panel on bioethics to focus on synthetic biology as its first assignment. The commission will provide, within 6 months, recommendations on how to maximize the benefits of this emerging field while minimizing the risks and respecting ethical concerns. The commission held its first public meeting July 8–9. More information, transcripts, and the agenda are available online.
Synthetic Biology and Cancer: Exploring the Possibilities
Ten years ago, researchers created the first devices (here and here) widely viewed as launching the field of synthetic biology. In the decade since, advances in genomics and the chemical synthesis of DNA, among other fields, have created new tools for investigating and understanding the behavior of biological systems. Some researchers now believe that the time is right to harness these tools in new efforts against cancer and other diseases.
To explore how these tools might be used, NCI and the National Institute of General Medical Sciences convened a workshop in April called “Synthetic Biology and Biomedicine: Progress, Outlook, and Challenges.” The meeting brought leaders in the field to Bethesda, MD, to discuss everything from state-of-the-art technologies and their potential applications in cancer research to ethical questions raised by new discoveries. (See the sidebar below.)
“The goal was to see where the field of synthetic biology is, in terms of cutting-edge research, and to learn from experts about what the current hurdles are, especially hurdles involved in translating basic synthetic biology research into cancer research,” said Dr. Jerry Li, a program director in NCI’s Division of Cancer Biology (DCB).
Dr. Drew Endy of the Department of Bioengineering at Stanford University and Dr. Aristides Patrinos, president of Synthetic Genomics, Inc., chaired the workshop. (The workshop agenda is available online.)
While there are many definitions of synthetic biology, one of the central ideas is the belief that to truly understand how something works, one has to build it. In this sense, synthetic biology refers to the design and creation of the components of biological systems that are not found in the natural world, as well as to the redesign and fabrication of existing biological systems.
“Synthetic biology brings together knowledge learned from a number of fields—biology, engineering, physics, chemistry—and uses this information to try to redesign and engineer biological components,” said Dr. Daniel Gallahan, deputy director of DCB. For cancer research, these approaches could both reveal new insights into the disease and potentially lead to new treatments, he added.
“Coming of Age”
The Department of Energy and the National Science Foundation have funded research using synthetic biology approaches to address environmental and energy issues, but NCI does not yet have a program in synthetic biology. Dr. Dinah Singer, the director of DCB, told meeting participants that NCI was interested in integrating synthetic biology approaches into its research programs. DCB’s mission, along with supporting and coordinating research projects in cancer biology, is to facilitate the emergence of new ideas, concepts, and technologies.
“In our efforts to understand and treat cancer, NCI wants to be prepared to exploit any advance in technology that emerges from this field,” said Dr. Gallahan. “The technology has reached a point where we can not only begin to understand cancer in new ways,” he continued, “but we may also be able to intervene in the disease at different levels.”
In a recent article titled “Synthetic Biology: Applications Come of Age,” Dr. James Collins, a professor of biomedical engineering at Boston University, and Dr. Ahmad Khalil, a postdoctoral fellow in his laboratory, wrote that engineered biomolecular networks are starting to move into “the application stage,” including for cancer.
Although more work is needed “to elucidate the biological design principles, this foray into practical applications signals an exciting coming-of-age time for the field,” the authors continued. They cited as examples synthetically engineered viruses and organisms that are able to sense cues in the local environment as the basis for therapeutic activity.
At the workshop, Dr. Chris Anderson of the University of California, Berkeley, described his group’s efforts to engineer bacterial cells that selectively target and then invade cancer cells. The engineered bacteria are designed to release toxic enzymes to kill the host cells once they have entered the cells. While this work is not yet ready for testing in humans, it demonstrates what might be possible with synthetic biology approaches.
In another example, Drs. Ron Weiss at the Massachusetts Institute of Technology and Christina Smolke of Stanford University have been independently designing molecular switches that could be used to construct new signaling networks inside a cell. They have used these new devices experimentally to detect and react to abnormal cellular signaling events that may be associated with the development of cancer.
Although the work is still in preliminary stages, “One could envision that these approaches, if developed further, could be used in the early detection and treatment of cancer,” said Dr. Li.
Also at the workshop, Dr. Daniel Gibson of the J. Craig Venter Institute described his group’s efforts to synthesize the genome of a bacterium and transplant it into the cell of a closely related species. The results of this work were published a month later in Science. Transplanting the synthetic genome into the new host cell had essentially “rebooted” the cell, causing it to behave like bacteria with the same genome, the researchers said.
“By changing the chromosome in the cell, it completely changes the cell from one form to another,” said Dr. J. Craig Venter, the study’s senior author. Both Drs. Gibson and Venter emphasized that their experiments sometimes did not go as planned, leading them to revise their approaches based on the new information they uncovered.
This idea of “learning as you go” was a theme of the workshop, as others shared similar stories from their own projects. Even so, many participants expressed optimism about the future of the field.
“It’s a very exciting time,” said Dr. Li. “More people are becoming interested in learning how to apply their knowledge and skills in synthetic biology to biomedicine. This field is ready to take off.”
—Edward R. Winstead