Synthetic life has been created, scream the headlines, and well, it is no hoax, at least not entirely.The man at the center of it all, Craig Venter, is no stranger to those in the field of biotech, having been associated earlier with mapping the human gene.Such a breathtaking announcement is not just of academic interest to us at Oilgae, because Venter has reportedly mentioned that the first real-world use to which he plans to try his synthetic life creation technique will be in – hold your breath – algae fuels.Exxon Mobil entered into a partnership with Craig Venter’s Synthetic Genomics (SGI) in mid 2009 in order to explore applying SGI expertise in genetic engineering to create algae that can produce biofuels on a large scale, in an economically sustainable manner.While ExxonMobil brings in the engineering expertise and tons of money, SGI brings in the genetic engineering knowledge. Exxon Mobil had committed to invest over $600 million in this effort to make sustainable algae fuels a reality.Now you can well understand why all of us here at algae have been burning our midnight oil last one week over Craig Venter’s work. Well, we have been following Craig Venter since the time Exxon Mobil invested in his company, but his recent achievement added an extra level of importance to his work for all of us at Oilgae.I hence thought that I’d dedicate this issue of the newsletter to providing inputs and perspectives on Craig Venter’s work and how it could influence algae fuel research.The following are the sections in this detailed article:Background of Craig Venter and his recently breakthrough.Critical challenges in algae fuelsHow genetic engineering could help overcome these challengesCraig Venter – Background and Recent BreakthroughJohn Craig Venter is an American biologist and entrepreneur, most well-known until recently for his role in being the (joint) first to sequence the human genome. Two weeks back, he became equally famous for booting up the first living cell with a synthetic genome.Venter has been a founder of companies/organizations such as Celera Genomics, The Institute for Genomic Research, the J. Craig Venter Institute and Synthetic Genomics. He was listed on Time magazine's 2007 and 2008 Time 100 list of the most influential people in the world.His work on human genomeCraig Venter isn't exactly your idea of a normal human being. Far from it. While working on the project to map the human genome, Craig Venter believed that the maverick approach of shotgun sequencing (rather than a classical long-winded approach) was the fastest and most effective way to get useful human genome data. The method was controversial since some geneticists felt it would not be accurate enough for a genome as complicated as the human.With funding from the private sector, Venter founded Celera Genomics, whose goal was to sequence the entire human genome and release it into the public domain for non-commercial use in much less time and for much less cost than the public human genome project. DNA from five demographically different individuals was used by Celera to generate the sequence of the human genome, one of them being Venter himself!In 2000, Venter and Francis Collins of the National Institutes of Health and U.S. Public Genome Project jointly made the announcement of the mapping of the human genome. Despite some claims that shotgun sequencing was in some ways less accurate than the clone-by-clone method chosen by the Human Genome Project, the technique became widely accepted by the scientific community and is still used today.After the human genome project, Venter founded - and is the president of - the J. Craig Venter Institute, which conducts research in synthetic biology. In June 2005, he co-founded Synthetic Genomics, a firm dedicated to using modified microorganisms to produce clean fuels and biochemicals.The first synthetic life formIn May 2010, a team of scientists led by Venter became the first to successfully create what was described as "synthetic life".Craig Venter and his team had succeeded in building the genome of a bacterium from scratch and had incorporated it into a cell to make what they called the world's "first synthetic life form."How exactly did they do this?In a decade-long work, Venter and his researchers first mapped the genome of a simple bacteria, Mycoplasma mycoides. A genome is the 'brain' and control center of a cell, and contains sequences of DNA which carry all the genetic information needed for the cell — and by extension, the organism — to function. Genomes, like all other living matter, are made of chemical compounds.Once the genome was mapped, Venter’s team manufactured the M. mycoides' genome in the lab, using chemicals. This synthetic genome was identical to the 'original' except for certain harmless 'signatures' the team put in to identify it as synthetic. The synthetic genome was then inserted into another type of bacteria after the bacteria's own genome had been taken out.Voila! As soon as the synthetic genome was inserted into the genomeless cell, it started making new proteins encoded in its DNA and converted it into a new synthetic species. That is, the cell was able to understand the synthetic genome and started "working with it". According to Craig Venter, the cell has replicated over a billion times, and the only DNA that the cell has now is the synthetic one that Venter’s team made. Exciting stuff!(For trivia buffs, the new organism has been nicknamed Synthia, and the Mycoplasma mycoides bacterium causes mastitis in goats.)Is this really an example of synthetic life? Not everyone agrees. For instance there are some who - in my opinion, correctly - point out that Craig Venter did not create a live cell, he only created an artificial part of the cell which integrated itself nicely with the existing cell. And then there are others who say that the synthetic cell achievement does not fully demystify life's underlying code, the genome. They claim that the researchers built much of the bacterium's genome without fully understanding the function of many of the million-plus base pairs involved. About half of the genes, in fact, are still "a complete black box," said Richard Roberts of New England Biolabs, Inc., in a commentary after Venter's talk. (Source: http://bit.ly/ahSN4Z). In order words, some of these experts feel that it is a fairly dumb reconstruction of an existing design, with no clue of what the components of the design mean.They might have a point after all. In an earlier instance, when the team had got just one piece out of the millions of pieces wrong, the genome simply did not work. And well, this also does not mean that the team has the ability to create a genome that is original. In fact, some experts feel that the technical expertise and understanding required to create an entire, original cell might take a long, long time – long after you and I are dead and gone.Leaving aside these technical points, a more pertinent question for us at Oilgae is: Whether or not this event qualifies as a “synthetic life creating event”, what consequences does it hold for the future of algae fuels? If scientists do not fully understand what component of genome does what but only have a “black box” understanding, isn’t their capability restricted to simply making copies of existing genomes without being able to create absolutely original ones? If that is indeed so, and all they do is to “synthetically” produce a genome that already exists in some other algal strain, isn’t it easy to simply “extract” the genome from that desired strain than painstakingly create it in the lab? Put another way, is this experiment by Venter only of academic interest or does it make a practical difference?I had a lengthy discussion on this with my biotech team-mates, and they assured me that this event can make a practical difference.A bit of reading helped me to identify the following advantages that synthetic genes have over their natural counterparts:They are obtained more quickly and less expensively than conventionally cloned genesThey are simple to modify in order to facilitate downstream manipulationsAny sequence you wish is possible.
(COURTESY: OILGAE)
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