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.

BIOSAFETY

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.

BIOTERRORISM

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.

US Forces Changes In India's GM Policy

Suman Sahai

The Government of India had issued a notification on August 23,2007,which came into effect on September 11,2007,withdrawing all existing regulatory oversight over the import of GE foods. Now, GE foods can be imported without having to take any permission from regulatory agencies, as has been the case so far. The new notification exempts importing agencies from even informing the government.

Gene Campaign filed a writ petition in the Supreme Court challenging the notification issued by the government. It appealed to the Court to strike down the notification since it is "unconstitutional, being violative of Articles 14 and 21 of the Constitution"; it had further requested the Court to strike down the new provisions since these give uncanalised power to the government which power is likely to be abused and is therefore

violative of Article 14 of the Constitution.

The Supreme Court heard the matter on November 19 and issued a notice to the Government of India. The Court issued a further notice on Gene Campaign's application that a stay be granted on the notification till the issue is finally decided. This means that the government has been put on alert that the Supreme Court was now watching the deregulation of GM foods.

Until now, in view of the known health risks associated with GE foods, government guidelines required that import of GE foods can only take place with the express permission of the apex regulatory body in India, the GEAC (Genetic Engineering Approval Committee).Further, any handling of GM foods was to be done only after these were labelled as such.

The regulatory oversight that existed prior to the new notification was necessary and appropriate since it had allowed India to monitor the entry of food products produced by a new technology that is known to produce toxic and allergic compounds. It also allowed India to maintain vigil that food products rejected by other countries in Europe, Africa and Middle East are not in fact being dumped on us. The arbitrary withdrawal of the regulatory oversight without any scientific reason and without any consultation with a range of stakeholders that are engaged with GE technology and policies associated with it, is a dangerous development. It will benefit the producers and exporters of GM foods, like the US, and pose health dangers to the Indian population.

The move is all the more inexplicable, at a time when scientific evidence is mounting from laboratory tests in various parts of the world, that GE foods can in fact cause serious damage to health. Confronted with this scientific data, we need to upgrade our food testing systems and make them more stringent and comprehensive, not dismantle them, as the government is doing. It is incomprehensible that instead of strengthening our systems to ensure that foods which have the potential to damage health do not reach the market, the government has decided to withdraw all opportunities to test and regulate such novel and controversial foods.

It is also a matter of considerable concern that unfettered access to unknown foodstuffs is being allowed in the absence of a legal regime for liability and redress. India has still not introduced a law on liability for this sector, even though it is required to do so by the Cartagena Protocol on Biosafety. This means there is no law in the country that can fix responsibility and claim compensation if something should go wrong with the environment or with animal and human health, from the cultivation and consumption of GE crops and foods.

The new notification of the Ministry of Environment and Forests will in effect provide unrestricted entry to untested foods of dubious origins, especially since the imported GM food does not have to be labelled. This denies consumers the right to exercise free choice in the matter of the food they wish to eat. This is in violation of the Consumer Protection Act that grants consumers the right of informed choice.

The government's notification also goes against India's commitment to mandatory labelling of GE foods, a position the Indian delegation has consistently maintained in international negotiations, particularly at the WHO-FAO led Codex Committee on Food Labelling. Both the dilution of India's position on mandatory labelling and the curious deregulation of the GM food sector appear to be the result of increasing American interference in Indian policy. The move to deregulate the GM crops and foods sector appears to be linked to the Indo-US deal on Agriculture. It is truly ironic that the future of the Indo-US nuclear deal, the reason why India gave concessions in the agriculture sector, is uncertain, but the agriculture deal is moving ahead, securing gains for the US GM industry at the cost of public health in India