Scientists hope to make life from chromosomes

WASHINGTON -- By modifying a simple microbe, scientists hope to create a new form of single-cell life that could lead to new and cleaner energy and perhaps play a role in biological warfare. But there are safety and ethical concerns in this new world of biology, experts say.

A group led by J. Craig Venter, director of a private program that mapped the human genome, has received a $3 million Department of Energy grant to make a new type of bacterium using DNA manufactured in the lab from basic chemicals.

The goal, said Venter, is to build a bacterium that is capable of making hydrogen that could be used for fuel, or to develop a microbe that could absorb and store carbon dioxide, thus removing a surplus of that greenhouse gas from the atmosphere.

Along the way, said Venter, scientists will learn on a molecular level the minimum genes a cell needs to thrive and reproduce and how to artificially make those and other genes.

"This is true basic science," said Venter. "Even though we've found all those genes in the human genome, we can't understand the most basic simple cell yet. That is what is driving this."

Some experts worry that by learning how to artificially create the basic genes essential to life, even in a fragile, obscure microbe, scientists may open a new door to biological hazards and, perhaps, put a new weapon into the hands of terrorists.

"We have to be very careful about controlling the purposes of this research," said Kathy Kinlaw, an executive in the Center for Ethics at Emory University. She said that science will ultimately achieve what Venter is attempting, but that there must be careful oversight to prevent the technology from being misused.

The DOE grant was given to the Institute for Biological Energy Alternatives, a company founded by Venter. The organization now has 10 scientists, including Nobel laureate Dr. Hamilton O. Smith, an expert on genetic science and famed for his skill in handling DNA in the laboratory. Eventually, IBEA will grow to a scientific staff of about 25.

Extending work

Venter said the plan is to extend work that he and others started in 1995 at the Institute of Genomic Research. Researchers there sequenced the genes of a bacterium called Mycoplasma genitalium, one of the simplest microbes known with only one chromosome and 517 genes. By contrast, humans have about 30,000 genes and 23 pairs of chromosomes in each cell.

Once the normal gene complement of M. genitalium was identified, the researchers began systematically removing genes to determine how many were essential for life. In 1999, they published a paper that narrowed the minimum needs of M. genitalium to 265 to 350 genes.

Under the new grant, Venter said the researchers will use basic chemicals to snythesize the DNA in M. genitalium's single chromosome. They will then use radiation to kill the chromosome in a normal bacterium and replace it with the lab-made DNA.

Venter said the cell will retain some of its functioning parts, such as enzymes and RNA, but that all of its genetic structure will be synthetic.

"The description of this being a modification rather than making new life is probably correct," said Venter. "There is a philosophical question of how many genes can you change in an organism" before it becomes a new life form.

Dr. Clyde Hutchison of the University of North Carolina, a microbiologist who was part of Venter's team at TIGR, said M. genitalium is a good microbe to use because it is so simple and poses no safety concerns.

"It is very fragile and really can't live outside the laboratory," said Hutchison. He said the microbe normally lives in the genital tract of humans, but causes few health problems.

The microbe lacks the tough cellular wall of most bacteria and is a total parasite, depending on its host to make even the most basic amino acids, he said.

In theory, a new understanding about the basic workings of a cell could help develop new bioweapons, said Venter, but the plans call for withholding some key information his group discovers.

"We will be cautious about how and where we disclose new techniques," he said. "We don't want a group of crazies to deliberately make something that is harmful."

Venter was the head of Celeria Genomics, a private group that sequenced the human genome at the same time as an international, government-supported project. The two groups published their findings in separate journals and were jointly honored in a 2000 White House ceremony.