Scientists Report DNA Transplant

Scientists said yesterday they had transplanted a microbe's entire, tangled mass of DNA into a closely related organism, a delicate operation that cleanly transformed the recipient from one species into the other.

After the operations, the "patients" -- single-celled organisms resembling bacteria -- dutifully obeyed their new genomes and by every measure exhibited the biological personas of the donors.

"This is equivalent to changing a Macintosh computer into a PC by inserting a new piece of [PC] software," said study leader J. Craig Venter, chief executive of Synthetic Genomics, a Rockville company racing to be the first to create fully synthetic, replicating cells.

The success confirms that chromosomes can survive transplantation intact and literally rewrite the identity and occupation of the cells they move into. That is a crucial finding for scientists who hope to make novel life forms by packing synthetic chromosomes into hollow, laboratory-grown cells.

Venter's goal is to create hand-crafted chromosomes with genes that will instruct cells to secrete biofuels that are cheaper and cleaner than oil or coal. But until now, he said, it has not been clear if chromosomes could spur the machinery of life into action after landing in the innards of an unfamiliar cell.

"This proves we can boot up a cell with another chromosome," Venter said.

The total identity makeover, described in yesterday's online edition of the journal Science, is a modern version of work done in the 1940s, when Rockefeller University scientists moved DNA from one strain of a bacterial species to another, causing a change that was passed to its offspring. That work is enshrined in history books as the first proof that DNA is the chemical carrier of genetic information.

Similarly, scientists at Harvard University earlier this month reported they had performed "whole genome" transplants from mouse cells into fertilized mouse eggs, a move that reprogrammed those eggs to behave differently.

But the new work is the first in which the entire genetic load from one species has been transferred to another species "naked" -- without the cumbersome protein coatings that usually envelop DNA and can get in scientists' way.

Moreover, the size of the transplanted genome, about 1 million genetic letters, or "bases," is large. That offers hope that complicated genetic programs requiring lots of DNA code will be transplantable.

The largest artificial chromosomes made so far are about half a million bases long, but bigger ones are expected soon. Most genetic engineering done today involves the splicing of just a single gene -- perhaps a few thousand bases -- into a cell's own DNA.

Venter said the first transplant of a synthetic chromosome into a cell could happen within a few months. He emphasized that his team has had its plans approved by ethics boards, in part because of the potential to create agents of bioterrorism.

The organisms he is working with do not cause disease, he said, and could be modified so they cannot survive outside the laboratory.

The DNA transplants involve chemical washes that gently clean the donor DNA, and other washes that make the recipient's outer membrane porous, so the new DNA can enter.

It usually fails. But in about one of every 150,000 tries, the new DNA moves in, turns on, and, for reasons that remain unclear, the old DNA disappears.

Barbara Jasny, a senior editor at Science, called the work "a landmark in biological engineering."

Kevin Eggan, of the Harvard Stem Cell Institute, offered a more tempered assessment. He said the very simple cells Venter chose to work with, called mycoplasmas, are not representative of the kinds of cells most biologists believe will be useful in synthetic biology.

And, he said, although Venter's team has had some success, "They don't really understand how it works" -- a criticism that Venter acknowledged as true.

George Church, a Harvard professor of genetics and founder of a competing synthetic biology company, Codon Devices of Cambridge, Mass., said he was impressed by the mega-base size of the transplant. But he said a lot needs to be learned about why most transplants do not work and how the recipient's DNA is shut down.

"There are a lot of missing dot-dot-dots," he said.
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