Synthetic Biology was not a term I’d ever come across before my boyfriend announced he was taking a job working on it. So, being a curious type, I looked it up. According to syntheticbiology.org (the natural first calling point for lazy googlers) synthetic biology is A) the design and construction of new biological parts, devices, and systems, or B) the re-design of existing, natural biological systems for useful purposes. To translate from jargon, synthetic biologists aim to manipulate existing biological ‘parts’ and put them together in new ways to generate organisms with new functions. This still sounds pretty vague to me, but it’s important to pay attention to synthetic biology. Regardless of how familiar you are
with the field’s concepts, it’s going to become a part of your life in some way in the future. In the first of a two-part blog to try and get to the bottom of the bumf, I’ll look at the rise of synthetic biology, to try and understand the driving forces behind the field.
The exact date at which this field emerged is up for debate, but the first scientific papers to discuss synthetic biology in the kinds of terms used today were published at the turn of the millennium. According to Michael Elowitz and Stanilsas Leibler, who performed some of the earliest experiments in this field, the aim was to ‘present a complementary approach’ to the standard methods used to study biology, which typically try to dissect a biological process in the hope of understanding how it works. Instead, they reasoned, why not try and make an organism perform a chosen function, in order to better understand how this comes about in nature? So they set about making an oscillating circuit in E. coli – a bacteria that, aside from giving you food poisoning, is often used in labs because it’s extremely easy to grow and is not at all bothered about having extra bits of DNA stuck into it. An oscillating circuit (a circuit that turns on and off repeatedly) was chosen because this sort of regulatory loop is seen in nature all the time – for example, an oscillating circuit is used to turn genes on and off to control formation of the vertebrae in our spines one at a time. Elowitz and Leibler took genes that are NOT normally used in oscillating circuits, and inserted them into E. coli cells in such a way that they could turn a gene on and off. When turned on, the gene in question made a protein called green fluorescent protein, which is found in certain species of jellyfish that glow in the dark. The result? A colony of bacteria that, over time, flashed green.
This breakthrough and others like it paved the way for a new kind of science, in which nature can be manipulated to do the bidding of synthetic biologists. By reorganising existing DNA ‘parts’, scientists can introduce almost endless new functions into living organisms. In theory this technology could soon be used to generate yeast that produce new antibiotics, or cheap and environmentally friendly fuel, or maybe even cheaper and tastier beer. It’s unfortunate, really, that with all this potential to do good just over the horizon, the most prominent breakthrough in synthetic biology to date has been something extremely controversial: the generation of life.
In 2010, multi-millionaire entrepreneur Craig Venter announced that his team at the J. Craig Venter Institute had generated a synthetic strain of bacteria called Synthia. With DNA that was entirely synthesised in the lab, Synthia was hailed as ‘artificial life’, and met with the expected ‘the apocalypse is coming’ style controversy. But, was this really a God-like achievement? After all, although Synthia was made in the lab, the bacteria was made using DNA from a naturally occurring organism.
To make Synthia, Venter’s group constructed a replica of the DNA of a bacteria called Mycoplasma mycoides (does that make anyone else think of bedknobs and broomsticks?), chosen because of its relatively small and simple genome. They then put this synthetic DNA into the empty shell of a different bacterial cell, Mycoplasma capricolum, to create a synthetic lifeform. The genetic content of the new strain was identical to that of M. mycoides, apart two sets of differences. Firstly, 19 small differences in the DNA of Synthia were introduced accidentally during the synthesis process, although they had had no effect on the function of the bacteria. Secondly, 4 ‘watermark’ sequences were added. These watermarks are extra stretches of DNA, added to ensure that the synthetic DNA is instantly recognisable, because the single letter symbols for the amino acids made by the watermark spell out words and phrases. These sequences include the names of the scientists involved (well, you would, wouldn’t you), and a quote from none other than Robert Oppenheimer, one of my ‘evil scientists’, which reads “see things not as they are but as they might be’. The result was a bacteria whose genetic makeup was completely artificial – confirmed by checking for the watermarks – but which could grow and divide just like M. mycoides does naturally.
Synthia was generated as a ‘proof of principle’ experiment, to show that production of synthetic organisms is achievable. And as Synthia brought publicity to the field, it also brought funding. The financial opportunities that open up from construction of synthetic bacteria are vast, as in theory synthetic lifeforms could perform myriad functions – from quick and inexpensive generation of new vaccines, to purification of dirty water, all patentable and profitable.
Despite the hype surrounding synthetic biology in the wake of Synthia, until very recently there was little evidence to convince the public that the field would produce anything more than the promise of useful tools. However, April this year saw the announcement that pharmaceutical company Sanofi, along with non-profit biotech organisation PATH, had industrialised a genetically engineered yeast that may help to combat malaria.
Artemisinin is the major active ingredient in modern anti-malarial drugs. Until now, the chemical has been obtained from the sweet wormwood plant, Artemisia annua. However, due to fluctuations in the market and poor survival of the crops in bad years, sources of artemisinin are not always readily available, and prices vary with the market. With the aim of stabilising and bolstering the supply of artemisinin, scientist Jay Keasling set up a fledgling biotechnology company, Amyris, to attempt to engineer microrganisms to produce the chemical. In 2003, he succeeded in introducing a few of the genes involved into our old friend E.coli. A further ten years work, including a partnership with Sanofi and a huge injection of cash from the Bill and Melinda Gates Foundation, resulted in the generation of a yeast strain that could produce the precursor to artemisinin, artemisinic acid. From there, the group developed simple chemical reactions by which the precursor, when extracted from the yeast cells, could be converted into artemisinin.
It is hoped that the production of this semi-synthetic artemisinin (so called because half the process uses synthetic yeast, half chemical reactions) could be the backbone of a reliable worldwide supply, helping to prevent some of the 660 000 deaths that occur due to malaria each year (according to the Worldwide Health Organisation). Keasling has made his method for manufacture of the drug public, with the aim of encouraging other biotech companies to pursue production of anti-malarials. What’s more, Sanofi is committed to selling their supply of artemisinin not for profit, bolstering the supply gained from farmers rather than trying to monopolise the market. Are these guys angels or what?
Thanks to the enormous promise that synthetic biology brings, the field is now booming. Last week saw the 6th international meeting on synthetic biology, imaginatively titled SB6.0, at Imperial College in London, which was attended by over 700 scientists, an impressive number given the length of time this speciality has been around. What’s more, the government is firmly behind the field: they have named synthetic biology of one of their ‘great 8’ – a list of new technologies into which they plan to plough large investments, with the aim of reaping big financial rewards down the line. This week pompous twerp and science minister David Willetts took great pleasure in announcing that the government is giving £60 million investment to the field.
Will the bubble burst? As the publicity around the field grows, so do the murmers of unease from the tabloids and increasingly the general public. In the next installment of this two-part special, I’ll examine the future of the field, and ask whether it’s doomed to suffer the sort of public crucifixion that so badly affected the prospects of GM. Can it weather the oncoming storm? Riding on a wave of success stories, synthetic biology is so far coming up trumps. But can it last?