Nobel laureate probes minimums needed for cellular life

Hamilton O. Smith, M.D.

Hamilton O. Smith, M.D.

Figuring out the minimum set of genes needed to sustain life is a key mission of Nobel Laureate Hamilton Smith. He and a team of researchers at the J. Craig Venter Institute are working to find out that information and use it to construct the first synthetic cell in history.

“We’re trying to learn what it takes to be a living cell,” said Smith, who gave a lecture recently to a standing-room-only crowd at University of Florida’s Cancer and Genetics Research Complex.

If he pulls off the feat of figuring out what minimal set of genes are essential for cellular life, his work is bound to be in Chapter 1 of biology textbooks.

Not only that, it would enable the creation of new kinds of cells that can produce new products, such as biofuels or pharmaceuticals.

“A cell can often accomplish very complicated syntheses that would be very difficult in the lab,” Smith said.

So far, Smith’s team has chemically synthesized the entire genome of Mycoplasma genitalium, a bacterium which has the smallest known genome.

In addition, they have also done a DNA “transplant,” extracting the naked DNA from another bacterium called M. Micoides, and inserting it into a “recipient” cell of another called M. Capricolum.

They “created” their first cell by stringing together bits of genetic material to make gene-size pieces, then combining those into subsections of a chromosome, then assembling those subsections into a new genome. Finally, the synthetic genome is inserted into a recipient cell.

The researchers have to take great pains to make sure that gene sequences are correct, because a single error in one DNA building block could be fatal.

Smith says his team is close to successfully duplicating the transplant experiment, but using genetic material from M. genitalium, as they originally set out to do.

“He’s always on the cutting edge of what is going on in biology,” said Dr. Ken Berns, director of the UF Genetics Institute, who hosted Smith at University of Florida.

Smith won the Nobel Prize in Medicine 1978 for discovering so-called “restriction enzymes” which can target and cut DNA at specific sites, and for his work in developing recombinant technology, in which DNA sequences from varying sources are joined.

So in a way, Smith’s quest to create a synthetic cell has taken him back to his roots in research.

Smith — who attended P.K. Yonge Developmental Research School in the 1930s when his father was on the faculty at University of Florida — likens the inner workings of cells to computer technology:

“The genome of a cell is the operating system, and the cytoplasm is the hardware,” he said. “We’re not smart enough yet to make the hardware, so we borrow that from a living cell.”