Craig Venter
Craig Venter at Fortune Brainstorm Health | by Stuart Isett | CC BY-NC-ND 2.0 | via Flickr

Remember the exhilarating day when the completion of sequencing the human genome was announced by no other than the President of the U.S.? It was indeed a watershed event, culminating years of hard labor in many university and government laboratories in the U.S. and Europe. But this consortium, which for several years was the only player in the field, found itself competing with a brash young entrant: Dr. Craig Venter and his group working at Celera, a private company which he had founded. Craig invented a new method of sequencing the “letters” of the genomic code which was vastly more efficient and faster than the plodding methodology employed by the consortium. A fierce race to the finish line developed, but in the end, both labs announced the results on the same day, in a joint press conference. This was a glorious moment for science and humankind. After that, the consortium by and large disbanded, although individual members continued doing important genomic sequencing work. What did Venter do with himself?

He founded the J. Venter Institute, as well as a biotech company to commercialize discovering made at the Venter Institute, and proceeded to start a project of breathtaking audacity and limitless possibilities.

 

Synthetic biology

Once the genomic sequences of human and other species became known, it became possible, at least in theory, to mimic Mother Nature and synthesize in the lab any gene of a known sequence of nucleic acid bases (the “letters” whose sequence makes up the instructions for synthesis of a specific protein). Now consider the possibilities. Synthesizing one gene is exciting enough, but what about synthesizing a whole genome and thereby creating a new synthetic organism? It is easy to visualize synthetic robot-bacteria that are basically machines that would follow instruction coded into their synthetic genome.

However, formidable hurdles had to be overcome.

  • Genes are typically hundreds of thousands of bases long. There was no capability to synthesize anything approaching this length.
  • Once a gene was synthesized, it was necessary to stitch it to other genes in order to create a complete genome with its complete set of instructions.
  • Another hurdle: It would be necessary to insert the whole genome into a bacterial “shell”, to protect it from destruction by enzymes.
  • This artificial bacterium would need to contain the “minimum genome” to sustain life, in addition to the genes that were programmed to perform the “robot’s” tasks. For instance, if we wanted to create a synthetic bacterial species that would perform the synthesis of ethanol, we would have to provide it with the genes that code for ethanol synthesis, plus the genes that would allow it to function and possibly even divide, namely genes that control energy metabolism.

 

Incredible progress

  • Round 1: In August of last year, Venter’s group published a paper titled, “Genome Transplantation in Bacteria: Changing One Species to Another,” which described their success in transplanting the whole genome of a small bacterium, Mycoplasma mycoides, into another bacterium, Mycoplama capricolum, thus changing one species to another. Sounds like science fiction. And why stop with bacteria? Can you see one day transplanting a synthetic human genome into a mouse? The medical possibilities and the ethical dilemmas are mind-boggling!
  • Round 2: On January 24, 2008, the online edition of Science magazine published the second installment in Venter’s epic journey toward a completely synthetic life. The paper titled, “Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome” is a tour de force. The bacterial genome that was synthesized consisted of 582,970 base pairs, the chemical units of the genetic code represented by the letters A, C, G and T. The longest stretch of synthetic DNA reported in a scientific paper was about 32,000 bases long, though some companies say they have made ones with about 50,000. As Venter pointed out, this is a 20-fold increase in length over what had been accomplished by others. Why is it important to have long stretches of DNA? One reason is that the longer the protein, the more complex its structure and the more complex functions it can perform. Some chemical reactions in the body are so complex that one protein cannot perform it; several proteins form a complex, each protein in the complex performing only one step of the reaction.
  • Round 3: The last step in the process of creating “life by design”, as Dr. Venter called it, is to insert a completely synthetic chromosome into a bacterium, and have this genetic material take over completely the functioning of the host. I would be surprised if this is not accomplished in six months. This will be a technical knock-out.

 

The possibilities

In my posting of October 3, 2007, I speculated on some of the immediate applications of such robot-bacteria. Here they are again:

Synthetic bacteria whose whole mission in life is to convert coal and oil into ethanol at a rate faster than we could extract the hydrocarbons from the ground. And much cleaner and enormously cheaper, to boot.

  • Synthetic bacteria that will consume any pollutant or toxic material we manage to create
  • Synthetic bacteria that will consume prodigious amounts of carbon dioxide from the atmosphere, and convert it into ethanol—a twofer.
  • Synthetic bacteria that will course our blood vessels and convert LDL into HDL particles, and consume triglycerides while they are at it.
  • Synthetic bacteria that will be able to sense glucose levels in the blood and release the appropriate amount of synthetic insulin in response.

These are not pipe dream ideas; there are several start-up biotech companies already working hard to make them a reality. Venter’s biotech company, among others, are already racing to create bacteria that synthesize ethanol.

We are witnessing here a true paradigm shift in the way we live: in the economy, energy policy, medicine, all aspects of human activity. Isn’t that amazing?

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.