Catherine Zentile

Synthetic Biology: Making Life from Scratch

From reading the genetic code to writing it

Scientists recently announced that they have synthesised the genome of a bacterium, Mycoplasma genitalium, bringing the world one step closer to the creation of the first artificial organism.

Courtesy of Equinox Graphics

Unravelling the genome has meant that in the last 20 years biologists have moved "from reading the genetic code to writing it" and the result is an emerging area of research called synthetic biology - the precise construction of biological systems from a single gene to an entire genome.

The success of this new technology promises an enormous diversity of applications: friendly pathogens that patrol the body killing cancer cells before you know you have them; custom-built bacteria that pump out biofuels without the environmental impact of current methods, and the ability to tailor-make drugs and other bio-molecules fast, cheaply and efficiently. The pace of progress is staggering, but synthetic biology could also be dangerous - is the world ready for this new technology and will it ever be?

The field just recently took a giant leap forward with the announcement in the journal Science by a 17-strong team of scientists including Nobel prizewinner Hamilton Smith and the genome pioneer Craig Venter, that they had constructed an entirely synthetic chromosome for M. genitalium using pre-assembled “cassettes” of DNA. The cassettes, each made up of four or five genes, were linked together into larger and larger units until the team had two halves of the chromosome, which they then stitched together inside a yeast cell.

But wannabe synthetic engineers should not reach for their pipettes too soon, however, cautions Cambridge University geneticist Dr Gos Micklem, because there's more to success in building artificial life than just the genome. "It's possible to get DNA to replicate in a test tube, it is not yet possible to get the molecular machinery set up so that you can take dead molecules and turn them into a cell that will divide and propagate."

"The crucial question is," Micklem continues, "if you had a bag of all the right ingredients for life: an energy supply, enzymology to drive basic metabolism and a pool of building blocks and apparatus to build DNA, RNA and proteins and then you added DNA, would it come to life? I'm not sure that it would: the packaging of the DNA is important to its operation, both within chromosomes and within cells. Certainly for complex organisms, like humans, it is unlikely that cell division and development can get going without being jump-started by the previous generation."

Venter, however, remains positive. "We consider this the second in our three-step process to create the first synthetic organism. What remains now that we have this complete synthetic chromosome … is to boot this up in a cell."

Science is a Golem: powerful yet potentially dangerous
But what about the ethical implications of this research? The implications of a new technology when it goes beyond the laboratory to affect society at large include health and safety aspects and also economic concerns.

Courtesy of Equinox Graphics

One of the advances in synthetic biology that was used in this study was that the starting point was not the raw DNA nucleotides but "cassettes" ordered from commercial suppliers. This means that, in principle, anyone with a well-equipped laboratory and some genetics know-how could do likewise: bioterrorism or a bioweapons arms race could follow, with devastating consequences. As Cambridge University philosopher Dr Richard Jennings puts it, "science is a Golem: powerful yet potentially dangerous."

Indeed some fear that if the technology is a success it could have a negative impact in developing countries where naturally occurring commodities may be devalued if synthetic production competes. "Say a synbio-organism that could produce natural rubber was created," Jennings explains, "countries that produce rubber from natural crops can lose part of their market. So the economic advantages of new technologies could contribute to a greater divide between rich and poor. You can end up widening the poverty gap – which is a concern for all new technologies, for example the digital divide in computing."

But Derek Burke, a member of the BBSRC's Bioscience for Society Strategy Panel, points out that these concerns shouldn’t prevent us from investigating new technologies. "All new technologies supplant previous technologies: wood was replaced by coal, coal by oil, oil by nuclear power. The risks attached to new technologies don’t demand that we abandon them. Instead, we learn how to the harness them in such a way that the adverse effects, whether on people, on the environment or on societal systems, can be controlled.

Molecular Biology Refresher The nucleus of almost every cell in the body contains chromosomes, which are made up of continuous pieces of DNA. DNA is a molecule made of two strands, one the chemical mirror image of the other, which fit together as a double helix. This structure means that the DNA molecule is extremely compact and can store a lot of information: an average human cell is approximately a tenth of a millimetre long but has about 2m of DNA in its nucleus! The two strands are made up of nucleotides: adenine (A), thymine (T), cytosine (C) and guanine (G). Between the strands, adenine always bonds to thymine (A:T) and cytosine always bonds to guanine (C:G): this is the complementary base pairing that holds the two strands together. Many genes code for proteins which are formed in two steps: first an RNA copy of a gene is made in a process known as transcription and then the resulting RNA transcript is read or translated’ into the protein sequence that it encodes. Not all the DNA molecule is used for coding proteins (only about 3%, in fact, for humans) but when the time comes the coding part (the gene) unwinds itself and the two strands separate, ready to be transcribed into messenger RNA (mRNA). The mRNA then takes the coded message outside of the cell nucleus into the cytoplasm where it is translated: transfer RNA (tRNA) molecules bring the appropriate protein building blocks (amino-acids) to the growing protein chain. Image courtesy of Equinox Graphics

We want to make sure that new technologies are used for the benefit of mankind, rather than just a subset of mankind.
Intellectual property for synthetic biology can be applied to methods, techniques and technologies as well as specified sequences of DNA. The J. Craig Venter Institute in the US has applied for broad patents covering the creation of any synthetic genome. It has also applied for rights to a gene sequence representing the "minimal requirements for life". In other words it would be a sequence that contained only the genes necessary for survival and reproduction. If the first players in a new scientific field patent some of the basic techniques involved, especially if that field is undergoing rapid development, then nobody else can use those techniques to further the science. Richard Jennings argues that this could stifle progress and limit competition, "We want to make sure that new technologies are used for the benefit of mankind, rather than just a subset of mankind."

But what about the ethical implications of not pursuing this technology? One of the possible applications is in biofuels. In South East Asia, palm oil forests have replaced acres of both tropical rainforest and fields where crops were grown (contributing to the world food shortage). We know that the impact of global warming would be devastating, so can we really afford to turn our backs on an avenue that could help mitigate its consequences? We have been able to control the safety issues arising from radioactivity, nuclear power stations and genetic engineering. Government, industry and consumer awareness of the ethical sourcing of commodities is at an all time high. On top of that there is growing feeling among scientists that the public should be engaged in debates about the applications of science. Maybe we can say that although the world is in bad enough shape to need the benefits of synthetic biology, perhaps it’s in good enough shape to deal with the risks associated with it.

- March 2008

About the Author

Catherine Zentile is a member of the Quantum Matter research group in the Cavendish Laboratory at Cambridge University.