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The synthesis of creation

First organism controlled by an artificial genome proves that DNA really is the chemical recipe of life

JCVISynthetic strain of the Mycoplasma mycoides bacterium: artificial life JCVI

When on the 20th of last month the American scientist Craig Venter announced the creation of the first strain of viable cells of a living being controlled by a genome entirely synthesized in a laboratory, he did not economize words to describe the achievement. He reminded everyone that never before in the history of the world had a creature been presented to mankind with no ancestors. No parents. The message was clear: the Mycoplasma mycoides – this being the name given to the variety of this bacterium whose DNA was produced by chemists at Blue Heron, a biotech firm – was the offspring of a new era, of synthetic biology. “It is the first species on Earth to self-replicate whose father is a computer,” stated the bold researcher-entrepreneur, who became famous a year ago when he headed a private project for the sequencing of the human genome capable of rivaling (and of speeding up) the work conducted by the public consortium.

The allusion to the machine as the bacterium’s father is no accident. After all, the information required to make a genome, in the form of a huge sequence of chemical bases (A, C, T and G) was stored in computers. In the case of the natural variety of the M. mycoides bacterium, it is a sequence comprised of 1.08 million pairs of bases (with about one thousand genes) , found in its single chromosome. It was with this chemical recipe that a synthetic copy of the natural DNA of this bacterium was made in a laboratory, following a number of specifications of the team from the J. Craig Venter Institute (JCVI), founded by Venter. The genome was not synthesized as a single large sequence of DNA, but rather in more than one thousand small pieces. The set of fragments was inserted into a yeast, where they were brought together and resumed the form of a chromosome. Finally, the scientists removed the synthetic genome from the yeast and transplanted it into the cells of another bacterium, Mycoplasma capricolum. The artificial chromosome managed to take over control of the receptor cells, which then started to produce all the typical M. mycoides proteins. Two days after the transplant, the cells stopped containing the original M. capricolum DNA (either because it was destroyed or diluted in the replication process) and held only one type of genetic material, the M. mycoides synthetic chromosome. In this entire operation, only 14 relatively unimportant M. mycoides genes were lost or annulled. “This is both a philosophical and a technical advance,” said Venter, summing up, from his point of view, the implications of this undertaking.

The climax of an effort that took US$40 million and almost 15 years of research plus a JCVI team of 24 researchers, including Ham Smith, the 1978 Nobel Prize laureate for Medicine, the emergence of a strain of bacteria with a synthetic genome was praised by scientists worldwide. Some preferred to rank the work, electronically published in the journal Science, as a major technological feat, a change in the scale of man’s capacity to modify the DNA of organisms, but not as a scientific revolution. Other researchers, even though they acknowledge the technical nature of the undertaking, stressed that the work is indeed relevant for science. The views of three scientists on this matter is published in articles especially written for the current Pesquisa Fapesp issue.

044-051_DNAsintetico_172The biologist Fernando Reinach does not deny the scientific merits of Venter’s experiment. According to him, the work irrefutably proves a concept, namely, that there is nothing special about living matter and that it too is subject to the laws of chemistry and physics. Just with DNA information, one can recreate a genome and, therefore, a form of life. “Everybody already knew this in theory, but someone still needed to demonstrate, in practice, this broadly accepted theory,” states Reinach. “After the publication of the human genome, Venter’s work is the most important to appear. There is no reason to try and make its importance relative,” says José Fernando Perez, CEO of Recepta Biopharma and FAPESP’s scientific director from 1993 to 2005. “It crowns a major effort to achieve scientific understanding of DNA.  Major scientific advances don’t result from great ideas, but from technological achievements.” Reinach also stressed a second important point, also of a scientific nature, which emerges from the analysis of the Science article. To date, life has been seen as a continuum. All beings descended from other similar organisms that had lived in the past. “Venter’s work shows that life can be interrupted and re-started,” states Reinach, alluding to the fact that the bacterium has no biological ancestors, but that it is the fruit of a sequence of chemical letters stored in a computer.

The geneticist Mayana Zatz, who coordinates the Human Genome Studies Center at the University of São Paulo (USP), compared the repercussion of Venter’s work to a similar event that took place 14 years ago. “This feat reminded me of Ian Wilmut’s cloning of the sheep Dolly, in 1996. The two spurred a media revolution,” writes Mayana in an article published on page 47.

Most of the financing of JCVI research studies comes from Synthetic Genomics Inc (SGI), an enterprise established by Venter and which has filed 13 patent requests regarding the methods used in synthetic biology work. Venter says that the M. mycoides experiment will enable one to design microorganisms that are useful for man and that can, for instance, produce vaccines and biofuel. Exxon, the oil company, has already committed an investment of US$600 million in SGI for the development of algae that manage to produce ethanol.

According to the geneticist Lygia da Veiga Pereira, from USP, Venter has a lot of work ahead to fully engage in the exercise of synthetic biology. “The main challenge will be to design a totally new genome and to choose which genes will be used for an organism to perform a given task,” says Lygia. Even though the US scientist’s efforts may take a while to generate palpable fruit, the mere presence in the research environment of a person such as Venter, who is polemic and provocative, is undoubtedly seen as healthy by some of his peers. “To understand Venter, I think about the human being as a child, a child left in a very large room called the world. This child fiddles with everything; sometimes  gets burnt when it sticks its finger into a socket, but other times it ends up discovering how to climb a chair to get to the delicious food stored up high,” writes João Meidanis, from the State University of Campinas (Unicamp), in his article on page 48.

Scientific article
GIBSON, D. G. et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science. Published online on May 20, 2010.