Tuesday, December 11, 2007

What Will Synthetic Biology Deliver?

Suman Sahai

The behaviour of bioengineered systems remains unpredictable, a function of the fact that genetic circuits that have been created artificially tend to mutate rapidly and frequently and often become non-functional.Synthetic microorganisms should undoubtedly be treated as dangerous till proven to be otherwise.

In 2005 , scientists at the US Center for Disease Control and Prevention succeeded in synthesising the virus responsible for the Spanish Influenza , the pandemic which killed almost 100 million people between 1918 and 1919.

“Learning from gene therapy, we should imagine the worst case scenarios and protect against them” George Church, Nature, 2005

Synthetic biology is one of the new biologies. Not really a biology in the classical sense, synthetic biology is a mixture of engineering , biology , chemistry and physics which together aims to reconstruct life at the genetic level.

The era of synthetic biology has been described as an era in which significantly new gene

arrangements can be constructed and evaluated for a diverse range of applications. Craig Venter, the scientist who raced ahead of the multigovernment Human Genome Project in 2000 to crack the human genome first, is also in the forefront of the most recent breakthrough in synthetic biology. Venter’s group created a new organism, which they have termed Mycoplasma laboratorium. Starting with the bacterium Mycoplasma genitalium, the Venter group stripped the bacterium of most of its original DNA and built up a new genome using pieces of DNA synthesised in the lab. The Mycoplasma with the

largely artificial genome synthesised in the lab, has been named Mycoplasma laboratorium.

Most of the work on synthetic biology is happening in the US, with scientists at the Craig Venter Institute in Maryland taking the lead. There are other research groups also working in Europe, Japan , Israel and to some extent in India, where the National Center for Biological Science (NCBS) seems to be in the forefront. Synthetic biology is likely to expand as a discipline as more labs take up this research, specially those where genetic engineering is already established.

Although similar in many ways, there is a fundamental difference between the two disciplines. Whereas genetic engineering deals with shifting individual (natural) genes from one species to another, synthetic biology seeks to assemble new genes from bits of DNA that can be synthesised in the lab, and now increasingly, even just bought from companies selling custom made bits of DNA, called oligonuleotides.

Actually, assembling commercially available oligonucleotides to create artificial semi life forms started even before Venter’s newest achievement. In 2002, a virologist Eckard Wimmer and his research team at the University of New York, announced that they had succeeded in assembling a live, infectious polio virus from oligonucleotides bought from a commercial supplier and using as a blueprint, a map of the viral genome that they downloaded from the internet.

Going a step further, scientists at the US Center for Disease Control and Prevention managed, in a similar way, to synthesise the virus responsible for the Spanish Influenza , the pandemic which killed almost 100 million people just after World War I. Those concerned with bioterrorism, have something to worry about!

The promises of synthetic biology are many but so are its many potential risks. Synthetic biology is projected to go far ahead of genetic engineering and perform many functions

which are almost unimaginable today. Artificially constructed systems made through synthetic biology, in effect, organisms that have been constructed like Venter’s new bacterium, but far more precisely, are being projected to produce cheap drugs for malaria as also other medically useful chemicals.

Other applications are the production of industrial chemicals, cellulosic ethanol for use as a biofuel and microorganisms equipped with artificial biochemical pathways aimed to attack specific pollutants and detoxify the environment. Along with the promise of bioremediation, synthetic biology also offers more far-fetched promises like making bacterial films that can distinguish light and shade such that visual patterns can be recorded, almost like photographs. This property could have value in diagnostic tools in medicine, for detecting mineral deposits and for mapping the earth’s surface from close up.

Despite its promise and the fact that synthetic biology has grown extremely rapidly as a discipline, there are quite a few fundamental bottlenecks that still remain unresolved. One major problem is that the behaviour of bioengineered systems remains unpredictable, a function of the fact that genetic circuits that have been created artificially tend to mutate rapidly and frequently and often become non-functional. This has echoes in the phenomenon of gene silencing, encountered after genetic engineering. Silencing happens

when certain genes get switched off and stop functioning.

Drew Endy, of MIT in the US, one of the leaders in the field, has spoken often that synthetic biology will not deliver unless scientists can accurately predict how a new genetic circuit will behave once it is put into a living cell. This is the same problem as obtains in genetic engineering.

Scientists cannot predict the exact performance of a new gene once it is introduced into a living plant or animal. This explains why we see most of the problems arising, with the new genetically modified plants producing allergens and toxins. Until scientists are in a position to understand and reliably predict the molecular processes in a cell before and after intervention, the engineering of biological systems either through genetic engineering or through synthetic biology will remain ad hoc and undependable, ultimately even dangerous. It is to be hoped that the proponents of synthetic biology do not adopt the reckless path chosen by the powers that have pushed genetically engineered products prematurely onto the market , often disregarding the caution that was sounded

on safety.

With respect to potential risks, even though genetic engineering and synthetic biology are different, there is a fundamental similarity, leading to a similar approximation of risks in

both instances. In both cases, the nature and magnitude of the risk is defined by two key properties that demarcate these fields as different from those where classical risk is encountered, for instance, with hazardous waste.

One of these properties is the fact that new organisms generated either by synthetic biology or by genetic engineering are self replicating and capable of evolution. The other is that the outcome of both processes is ultimately unpredictable and so many of the risks

associated with synthetic biology (and genetic engineering) remain indefinable and unpredictable at present. The potential risks associated with synthetic biology are essentially those related to biosafety and to biosecurity.


The risk of unintended release is as real for products made from synthetic biology as for genetic engineering but they could have graver consequences. Synthetic genomes that are entirely artificial have no genetic pedigree, so to speak. They come from nowhere recognizable and hence their properties cannot be predicted. What’s more, they could have emergent properties that could result from complex interactions between the constituent genes. The risks associated with the ‘escape’ of such organisms into natural ecosystems would be difficult to assess, nor would it be possible to foresee the kinds of damage this would unleash. The precautionary approach would dictate that synthetic microorganisms should be treated as dangerous till proven to be otherwise.


Scientists have found it very easy to put together DNA pieces bought from commercial suppliers and reconstitute the polio virus and the Spanish flu virus. There is reason to be concerned in these times of terrorism, that bioterrorists can add more deadly weapons to their arsenal in the form of virulent new organisms, particularly of a kind not known to humans and against which humans would have no immunological defence. Sophisticated scientific laboratories exist in many places which feed terror and it is not unthinkable that

such laboratories could produce novel microorganisms and infectious agents using the sophisticated tools of the new biologies. The threat of bioterrorism certainly increases with the development of technologies like synthetic biology. Introducing and implementing regulatory control is a challenge that governments will have to think about but a realistic appraisal would indicate that this is almost certainly impossible to enforce. The scenario of dangerous microorganisms in the ‘wrong’ hands is all too real and in my view, out of the possibility of control. Scientists must do serious introspection to see whether this research should continue.

No comments:

Post a Comment