Human Genome Pioneer Talks Personalized Medicine at UCSF Mission Bay

J. Craig Venter, PhD, the first man to have his own DNA decoded in exhaustive detail, addressed the topic of personalized medicine as keynote speaker for the celebration of the opening of the Helen Diller Family Cancer Research Building on the UCSF Mission Bay Campus on Tuesday. Watch the keynote speech. Although few others have similarly had their complete genomes decoded, Venter, during a brief talk titled “From Reading to Writing the Genetic Code,” cited a need to decode 10,000 or more human genomes to take full advantage of the information within them. This goal will become more attainable as the cost of completely decoding a single human genome drops to less than $2,000, or even less than $1,000, in the next 18 months to two years, Venter predicted. Advances in computational science will be key to understanding what these decoded genomes can reveal about human physiology, individual differences and personalized medicine. “That’s how it’s really going to start to impact research that goes on here and around the globe,” he said. Venter has a reputation for provocative speech, but generally appeared low-key in sharing his thoughts about personalized medicine with many UCSF supporters, faculty, staff and news media assembled in the grand foyer of the new cancer research building for the event. Venter later joined UCSF Chancellor-elect Susan Desmond-Hellmann, MD, MPH, Frank McCormick, director of UCSF’s Helen Diller Family Comprehensive Cancer Center, and Brook Byers, a venture capital investor and entrepreneur, in a panel discussion about the future of cancer research.

Supporting Basic Science

In his talk, Venter emphasized the importance of basic science research in generating unanticipated discoveries that then lead to breakthroughs applicable to solving human problems. He honored the role of private philanthropy in advancing fundamental research discoveries. Venter is perhaps most famous – or infamous – for bucking the scientific establishment that launched the federally funded Human Genome Project two decades ago. Venter developed an innovative way of assembling the countless fragments of decoded genetic code that scientists were generating, enabling him to organize a team with private funding to successfully compete with the multi-billion-dollar government program. With DNA from three women and two men – African American, Hispanic, Chinese and Caucasian – he set out to challenge the establishment. The two groups eventually pooled their strengths and cooperated to a certain degree, and Venter, along with Francis Collins, head of the Human Genome Project, simultaneously announced a “working draft” of the complete human genome in 2000, a mosaic of DNA from various donors, heralded by President Bill Clinton at a White House briefing. But in 2002, as biotech ventures began focusing more on drug development rather than gene discovery, Venter stepped down as president of Celera, the privately funded company he helped found to conduct the historic decoding. In 2003, Collins announced the complete decoding of the genome, and the end of the first phase of the Human Genome Project, 50 years after James Watson and Francis Crick first described the structure of DNA. Venter went on to establish the J. Craig Venter Institute, which he still leads. Besides being home to researchers pursuing the development of synthetic life forms to meet global energy and environmental needs, the institute includes a Genomic Medicine Group. The institute and collaborators from UC San Diego announced the decoding of Venter’s genome in 2007. In a first, the researchers decoded DNA from the chromosomes inherited from both the mother and father, instead of just looking at only one of the copies from each chromosome pair. The decoding of Venter’s DNA shed additional light on human genetic variability, leading some scientists to conclude that there is more genetic variability among humans than had previously been thought. That genetic variability – the source of myriad biological differences, subtle and not-so-subtle – also is at the core of most efforts to tailor drug treatments to individual patients. “We thought we differed in one letter out of every 1,000 letters in the genetic code,” Venter said during his talk. “It turns out, we differ from each other by from one to 3 percent – We’re ten to 30 times more variant than anybody thought.” “People in medicine are trained in averages,” Venter noted, reviewing average clinical responses to weigh treatment decisions, for instance. “Averages don’t mean anything,” Venter said. “You’re genetic code is going to be a totally unique combination…. It’s not surprising that not all drugs work on everybody.” Depending on one’s genetic code, drugs – or even one’s daily java jolt – may be protective or harmful, Venter explained. Last year, Venter announced that his research team had used a genome to achieve the de novo synthesis of a bacterium. He now aims to have bacteria make and deliver cancer drugs. “One of things we discovered is that DNA is the software of life…. By changing and swapping the genetic code we can change one species into another….What does this have to with cancer? We can now design on the computer bacterial cells for different functions….We’re working to see if we can design new bacteria cells….to release specific chemicals that the cells makes based on what we engineer them to do.” Venter acknowledged donors in the audience, at the same time tweaking the federal scientific bureaucracy. “Out government is great at funding ideas once we sort of know the answer,” he said. “We’re not so good at funding new ideas in this country. Most of the breakthroughs that actually take place, take place either from scientists using money that they got for something else and switching it to do the research they really wanted to do, or from people like you who give money and provide the freedom to do the research.”