Scientists on the verge of 'building' artificial life

Scientists on the verge of 'building' artificial life

By MAGGIE FOX

ANAHEIM, Calif. (January 23, 1999 9:23 p.m. EST http://www.nandotimes.com) - Scientists trying to map all the genes in creatures ranging from bacteria to humans think they are on the verge of figuring out how to build an artificial life form from genes.

Just as Mary Shelley's doctor Frankenstein used bits of corpses to make a monster, doctor J. Craig Venter hopes to salvage DNA from dead bacteria to construct his artificial bug.

"Shelley would have loved this," Venter laughed when asked about the comparison.

Their guinea pig is a tiny bacterium called Mycoplasma genitalium. It lives in the human genital tract and lungs, causing no known disease, but has the distinction of having fewer genes than any other organism mapped so far.

While humans have about 80,000 genes, this bug gets along fine with just 470.

That makes it a good model for figuring out precisely which genes are essential for life, and which ones code for extra value such as having blue eyes or the ability to resist heat.

"We are attempting to understand what the definition of life is," Venter, of Rockville, Md.-based Celera Genomics Corporation, told a news conference. "We are trying to understand what the minimum set of genes is."

Not only is Mycoplasma genitalium small and easy to study, but it has a close relative -- Mycoplasma pneumoniae. And while M. genitalium has 470 genes, M. pneumoniae has the same 470 genes, plus 200 extra ones.

"So we decided these genes were not essential to life," Venter, who will explain the project to the annual meeting of the American Association for the Advancement of Science, said.

Venter's team started working backward -- cutting out some genes to see if the organism would still function. They did this using transposons, which are genes that act specifically to cut up other genes.

One by one, they cut out mycoplasma genes to see which ones the organism could live without.

This was harder than it sounds. Organisms have backup systems. "If you knock out one gene, you don't know if there is some other gene there that is serving the purpose," Venter said.

"How many genes can call in sick before you no longer have a living cell?"

Nonetheless, they got M. genitalium down to about 300 essential genes.

This could form the basis for trying to put together an artificial M. genitalium, Venter reckons. Perhaps it could be built base pair by base pair from the nucleotides that make up DNA, which in turn makes up the genes.

DNA is made up of nucleotides, which join together in pairs, called base pairs, in ladder-like strands twisted into a double helix.

The nucleotides might come from a "whole bucket of M. genitalium", Venter said. The cells could be burst open and the raw genetic material taken out to construct the new bacterium.

Even if they could make a new life, Venter's team still might not understand just what they did, because life is much more complex than they thought. It had been hoped that after a few organisms had been sequenced, many genes would arise that every living creature has in common.

After all, everything has many of the same basic functions -- processing food, respiring, building cell membranes to keep themselves together.

But it turns out that different creatures use different genes for these same functions.

"Fifty percent of the genes in every genome is new to science and we don't know what they do," Venter said.

The same is true even of Mycoplasma's 300 basic genes. "One hundred of these we, as scientists, have no clue as to what they do. It's very humbling," Venter said.

But there are types of genes that are essential to all life. Venter says three types have been found so far.

They govern extremely basic cell processes involving the transport of potassium, calcium and phosphorus.

Before he goes any further, Venter said he wants advice from experts on ethics and religion. "We are asking whether it is ethical to synthetically make life," Venter told reporters.

"We think this discussion is totally worthwhile ... because it gets down to the definition of what life is," he said.

Venter left the nonprofit Institute for Genomic Research last year to join Norwalk, Connecticut-based Perkin Elmer Corp. and form Celera. They are using privately developed technology to sequence, or map, all the human genes.