Synthetic biology is a promising field of research that aims, in part, to engineer organisms to produce medicines and biofuels. Its allure lies in using biological building blocks and pathways, already exquisitely designed by nature, to produce essential materials for human use (instead of trying to re-invent everything ourselves from scratch). This technology is currently being used to produce the anti-malarial drug artemisinin from bacteria in large-scale amounts, which would significantly lower the cost.
Tinkering with existing life forms, and even creating new ones to suit our purposes, brings up serious ethical questions regarding evolution, the nature of life, and our responsibilities in designing it. These questions have recently been receiving a lot more attention, in the wake of the announcement on May 20th in Science Express by Craig Venter, Hamilton Smith and colleagues that they had created a bacterium with a chemically synthesized genome. It’s being billed as the creation of a synthetic life-form, which is arousing quite a bit of interest.
Congress is holding hearings, and the President has ordered a six-month review of the field because of its potential to produce biofuel. The Economist likened Venter’s creation to our own real-life version of Mary Shelley’s famous monster. The controversy surrounding this research even already has its own parody, courtesy of the Richard Dawkins Foundation. Arthur Caplan, a professor of bioethics at the University of Pennsylvania, calls it “the end of vitalism” because no supernatural vital force had to be used to breathe life into the bacterium. We can now construct life ourselves from biological nuts and bolts.
But there is one detail which tends to get lost in all the hype: the researchers did not dream up, design and make an original genome from scratch. What they did was, in a powerful display of how far our DNA sequencing and synthesis technology has advanced, synthesize a known genome of a certain bacterium and insert it into an existing cell of a different bacterium whose own DNA had been removed. First, they sequenced the 1 million-base genome of M. mycoides, a fast-growing bacterium with a relatively small genome. Then they purchased over a thousand 1080-base sequences covering the genome of M. mycoides and assembled them in stages in yeast. Finally, they transplanted the completed synthetic genome into a DNA-free version of M. capricolum. The colony started growing, but now it was making proteins usually found in M. mycoides.
This success was not unexpected, and builds on smaller achievements that Venter has been publishing over the past 10 years. For example, in 2007, his team showed that they could take the natural chromosomes from one microbe and put them into another. While this work is a necessary step towards the larger goals of synthetic biology, it comes as no surprise to many scientists.
So why all the attention? First, Venter has a long history as a successful scientific entrepreneur, and as anyone who has seen him speak can attest, he excels at promoting his work. This research was also very expensive, requiring 20 people working for 10 years at an estimated cost of $40 million. And because of the ethical questions surrounding the field, any new announcement can be provocative. After all, if humans start engineering life forms instead of letting evolution do its job, who knows what kind of monsters we might create?
For the moment, anyway, this kind of work remains sufficiently technically and financially challenging that it is unlikely to be used to make designer armies in a basement. It’s worth noting, too, that even though the genome was created synthetically, because of how it was assembled, the team was unable to keep complete control over the sequence. After it was completed, they found some additional insertions and eight point mutations.
Thus, engineering new life forms or metabolic pathways remains tricky. One future goal of some scientists in the field is to simplify the problem by figuring out the minimal genome required for an organism to function, and then adding the desired metabolic pathways on to it. This would have the added benefit of giving us insight into the origin of life and into our own complex signaling pathways. All of these advancements depend on improvements in our ability to write genetic code and on the price of DNA synthesis continuing to fall (it seems to be obliging, following the so-called Carlson curve).
However this announcement is ultimately viewed, let’s hope that a consequence of all the attention will be more public involvement in the ongoing ethical discussion around creating new life forms.
Gibson, D., Glass, J., Lartigue, C., Noskov, V., Chuang, R., Algire, M., Benders, G., Montague, M., Ma, L., Moodie, M., Merryman, C., Vashee, S., Krishnakumar, R., Assad-Garcia, N., Andrews-Pfannkoch, C., Denisova, E., Young, L., Qi, Z., Segall-Shapiro, T., Calvey, C., Parmar, P., Hutchison, C., Smith, H., & Venter, J. (2010). Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome Science, 329 (5987), 52-56 DOI: 10.1126/science.1190719
Further reading:
BSR coverage of synthetic biology from Issue 8
