Artificial Life Forms

By modifying a simple microbe, scientists hope to create a new form of single cell life.

     A group led by J. Craig Venter, a principle investigator (P.I.) on the Human Genome Project at Celera Genomics, has received a $3 million Department of Energy grant to make a new type of bacterium using DNA manufactured in the lab.

     The goal, Venter said, 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.

     The Department of Energy grant was given to the Institute for Biological Energy Alternatives, IBEA, a subsidiary of the Institute for Genomic research, a new company Venter founded in July 2002. The organization now has 10 scientists, including Nobel laureate Hamilton O. Smith, an expert in genomic sciences (he determined how restriction endonucleases work) who is know to have great skill in handling DNA in the laboratory.

     Venter said the plan is to extend work he and others started in 1995. Researchers sequenced the genes of a bacterium called Mycoplasma genitalium.

     M. genitalium is a gram-positive parasitic bacterium, whose primary infection site may be the human urogenital tract. It probably causes non-gonococcal urethritis. It adheres to host cells by means of adhesin proteins. Mycoplasmas are the smallest known organisms capable of growth and reproduction outside living host cells. Like all mycoplasmas, M. genitalium lacks a cell wall, has a very small genome (M. genitalium in particular has the smallest genome of known cellular organisms capable of independent replication)> It has a few genome anomalies including a low G+C content (32%)and a UGA codon (normally a stop codon), which in this organism encodes for the amino acid tryptophan.

     Therefore M. genitalium is 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 needs of M. genitalium to between 265 and 350 genes.

     The research group at IBEA will use standard molecular techniques to synthesize a man made DNA for insertion into M. genitalium. They will then radiation to kill the native chromosome in a normal bacterium and replace it with lab-made DNA genes.  The cell will retain some parts, such as enzymes, but all of its genetic structure will be synthetic.

     One genomic goal will be to learn on a molecular level the minimum genes a cell needs to thrive and reproduce and how to artificially make those and other genes.

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

Science will ultimately achieve what Venter's group is attempting, but there must be careful oversight. Many bioethicists are saying... ''we have to be very careful about controlling the purposes of this research.''

November 22, 2002.