University Times

An overflow crowd jammed the Alumni Hall 7th floor auditorium to hear genomics guru J. Craig Venter, founder and president of the J. Craig Venter Institute and CEO of Synthetic Genomics, deliver the Dickson Prize in Medicine Lecture at the Science 2011 symposium.

J. Craig Venter, founder and president of the J. Craig Venter Institute and CEO of Synthetic Genomics, delivered the Dickson Prize in Medicine lecture to an overflow crowd in the Alumni Hall auditorium.

In his Oct. 6 lecture, “From Reading to Writing the Genetic Code,” Venter outlined the pursuit of understanding of questions about existence, starting with questions of what life is, how extensive it is and whether it could be pared down to basic components to be better understood.

Now that the genome has been sequenced — in 2007 Venter’s was the first complete human diploid genome to be published — new questions have emerged.

Can life be digitized? “That’s what we do now when we read the genetic code,” he said.

“Can we regenerate life out of that digital world?” In other words, “After digitizing life, can we start with the computer and go the other way?” Venter said.

Last year, Venter’s team reported it had created the first self-sustaining organism with a synthetic genome. “The cell that we made is the first cell to have a computer as its parent,” Venter said. “I would argue that this might be the ultimate interface between the computational world and biology.

“Could we even go back and forth between the two? I think it’s an area right now where we’re limited only by our imaginations — and perhaps research money — to go in some very exciting new directions.”

Prior work

The field of synthetic genomics sprang from questions about what exactly would constitute a minimal organism, Venter said, offering a brief history.

How many genes are essential? How few genes are required in order to have a cellular operating system? “We decided the only way to answer that is to try to design and construct a minimal genome,” he said. “Would chemistry even allow us to try and make these complex DNA molecules … and even if we could, could we actually boot up that piece of DNA?”

Starting with the first virus to have been sequenced — phi X 174 —Venter’s team synthesized its 500 base pairs of DNA, then inserted it into E.coli. “The E.coli recognized the synthetic DNA molecule … and started making proteins that self-assembled and formed the virus, which then killed the E. coli cells. We call this a case where the software is building its own hardware. … The DNA is the software; we put the software into the cell and the cell builds whatever that software tells it to,” he explained.

Knowing that they’d succeeded in making small, viral-size pieces of DNA, his team moved to larger genomes, developing a way to stitch those pieces together to construct a larger, bacterial chromosome.

They have continued to work on DNA synthesis assembly techniques, he said, adding that a new method, isothermal in vitro recombination, is revolutionizing the field. “It allows us to automate everything, going right from that digital world to recreate the analog without much in the way of human intervention.”

Interspecies presto-chango

A 2007 study “is one of the most important ones, at least on a philosophical basis and also scientifically, that we’ve ever done,” he said. “Simply stated, we changed the DNA in the cell and by doing that completely converted one species into another.”

Using two related types of mycoides bacteria, his team inserted the DNA of one into another, creating a cell that had “two completely different sets of genetic instructions,” he said. The inserted DNA began to be read immediately and produced proteins that recognized the host cell’s DNA as foreign and destroyed it.

“Now we have the cell of one species with the genetic instructions of another,” he said. “Just by changing the cell’s DNA, it completely converted one species into another,” he said.

“Our view on this is life is a DNA software system. You change the software, you change the species. This becomes an important concept for understanding basic biology as well as how we proceeded with the synthetic cell,” he said.

Newer synthesis techniques prompted the group to make a synthetic mycoides genome in yeast cells, “watermarking” the genome to distinguish the synthetic DNA from naturally occurring DNA.

The team published the work in 2010. “Separating our understanding of what’s synthetic life from naturally occurring life, I think, is going to be very important or it’s going to be impossible to do evolutionary research,” he cautioned.

Putting synthesis to work

Why do these things? He noted that the world’s population is expected to surpass 7 billion later this month and that projections estimate another billion humans will be added to the population every 12 years.

“If we can’t provide sufficient food, clean water, medicine, energy, for 7 billion people, how are we going to do it for 9 or 10 [billion] in a very short period of time?” he asked. “We’re trying to see how we can use these new tools to solve problems.”

Implications for medicine and energy

Genetic sequencing of meningitis bacteria has led to the development of more effective vaccines that are expected to be on the market in Europe next year, he said.  Similar techniques are being tested in producing components for flu vaccines with a goal of cutting the amount of time it takes to prepare a vaccine from months to a matter of days. “If the FDA accepts it, I think this is a paradigm for rapidly developing vaccines using these synthetic approaches,” he said.

In the realm of agriculture, the potential for engineering cells such as microalgae could produce exponentially larger sources of oil. Corn can produce 18 gallons per acre per year, while oil palm can produce 635 gallons per acre per year, he said. In contrast, microalgae could create 10,000-20,000 gallons per acre. These are huge changes for the petrochemical industry as well as for agriculture, he said.

“We’re actually trying to design new cells that use carbon dioxide as their carbon source, sunlight as their energy source, to take metabolic products in a variety of directions,” he said. “Exxon Mobil put up $600 million to help us do this and create a biocrude out of CO2 that can go into their refineries and make gasoline and diesel and jet fuel.” His group is testing tens of thousands of strains and new ways to grow them in a greenhouse facility. “Ultimately it’s going to come down to biology,” he said, noting that the best naturally occurring strains only produce about 2,000 gallons per year. “Without dramatic changes in biology, it won’t be achievable. We’re actually trying to make a completely synthetic eukaryotic algae cell so we can control about 100 different parameters that are important in the photosynthetic development.”

—Kimberly K. Barlow

Editor’s note: A link to Venter’s lecture is posted at www.science2011.pitt.edu/speaker1.htm.