Creation (21 page)

In a sense, these two studies were the first and most obvious experiments on a flu threat. Evolution is tenacious, and life-forms strive for immortality. In terms of understanding how that will unfold, we are always playing catch-up. We cannot predict every possible natural threat but we should do what we can to arm ourselves against the ones we can anticipate. Any knowledge in this arms race is better than none. That, to my mind, is good science, and good policy. It is using the precautionary principle in an aggressive way. It was unclear until these two flu studies whether it was even possible for these strains to jump the species barrier. They also provide clear genetic flags for public health sentries to look out for in emerging flu strains. By figuring out how to upgrade a flu into one that can cause a pandemic, we arm ourselves against the very real possibility of it happening naturally.

Agenda Politics

Another line of attack is that genetically modified food might be bad for us to eat. In biology we look for mechanisms that explain observations, and it's not easy to imagine what mechanism would result in an adverse effect on our health after eating a modified food. Nevertheless, if it were an observable phenomenon, it would warrant explanation. Opponents of genetic modification often cite the idea that GM foods might be bad for us, even though it has been thoroughly refuted in many independent reports. With many modified foods having been approved a long time ago, there is also more evidence than a scientist could wish for in demonstrating that they are safe to eat. According to one estimate, two trillion meals containing genetically modified food have been consumed in 2009 and 2010. The U.S. Department of Agriculture calculated that GM revenues in 2010 were $76 billion, with the products being part of the human food chain.

Despite this, the arguments continue. In September 2012, a small study published in a minor journal hit the headlines and stirred the GM debate yet again. A French team of scientists, led by a molecular biologist named Gilles-Eric Séralini, fed a type of genetically modified maize to rats over their whole lifetimes and observed any effects on their health. The modified feed had been developed by biotech company Monsanto to resist a widely used herbicide. It has been widely approved as food for humans and animals around the world, and previous studies have shown no adverse health effects with this particular modified maize (called NK603, previously Roundup). Indeed, in 2012, a systematic review of multiple long-term studies, which is considered to be the gold standard in these types of trials, also concluded that there were no adverse health effects for a diet of GM food. In Séralini's study and the surrounding press, they claimed some of these previous studies were qualitatively different from theirs. Their paper graphically showed that the rats used were profoundly affected by their GM diet, suffering grotesque tumors and dying significantly before the control rats.

Immediately, though, the study began to unravel. The authors and the paper were bluntly criticized for the quality of the work, and also for the way it was reported. With a swiftness enabled by the Internet, scientists began condemning the data, saying that the experimental design, the statistical analysis, and the presentation of the data were all substandard. Some expressed surprise that such a paper was published at all. Specifically, critics noted that Séralini had used rats that were already prone to developing tumors, as well as inadequate numbers of control rats compared to experimental ones.

It soon emerged that the release of the results was part of an orchestrated PR campaign that included a book by Séralini, who has a track record of anti-biotech activism, and a television documentary. The paper itself was not freely distributed to the press before publication, which is extremely unusual and makes science reporters highly suspicious: most science journalists will seek comment from other scientists, albeit under embargo. With Séralini's paper, a signed agreement was required for those who were offered access to the paper, which came with another highly unusual stern warning: “A refund of the cost of the study of several million euros would be considered damages if the premature disclosure questioned the release of the study.”

An organization called the Sustainable Food Trust (SFT) had spearheaded a campaign to spread the work as far and as wide as possible, including a dedicated web page resource, wanting to promote what it calls “Good Science.” The SFT encouraged supporters to pass on prefabricated messages of support on the influential social media site Twitter. Almost all of the mainstream press had covered the paper, although interestingly, some of the coverage, such as by the BBC, had included some of the immediate profound criticisms from scientists. A few days later, the European Food Safety Authority (EFSA) issued a statement: “The design, reporting and analysis of the study, as outlined in the paper, are inadequate,” adding in the press release that the paper is “of insufficient scientific quality to be considered as valid for risk assessment.”

But the PR offensive had done its work. Many press outlets published the story uncritically. The French weekly newsmagazine
Le Nouvel Observateur
shouted out on its cover,
“Oui, les OGM sont des poisons!”
(“Yes, GMOs are poisonous!”). The French prime minister declared that France would defend banning these genetically modified crops across Europe (though he had the good grace to specifically add the caveat of needing to validate the results). Bearing in mind the distinctly unusual way the paper was published, the results are not invalid until other studies show them to be. That is not to say that they are correct; given the strong criticism of the methodology itself, it seems fair to say that at the very least, Séralini's study demands the most rigorous replication of the results, releasing the original data for independent analysis, and shoring up the methodology to establish beyond doubt its validity.
³

Within minutes of publication, many were forensically investigating not just the paper, but the way it was published. To get traction for an idea is the aim of such a PR exercise, and in this case they partially succeeded, in the face of the rapid scrutiny of critics. Some have suggested this case study marks a turning point in the conflict over GM, as the condemnation was so quick and so severe that some of the mainstream press included it. Just like rumors, once scientific ideas like this are out in the open, they are very difficult to correct, regardless of poor methodology, or knowing the agenda of the perpetrators, or anything else.

There are many volumes of publications on GM; in these pages I am mentioning the tiniest handful from the very recent past. This is not to cherry-pick the data to fit a particular stance, a crime of agenda that I denounce, but to illustrate how research into GM is subject to manipulation and is thrust into the limelight because it evokes passionate and polarized responses. Public and political opinion can, and has been, skewed by the way these types of campaigns are reported; the deliberate polarization of public debates detracts from nuanced, informed, and necessary analysis of the application of biotechnology.

Malaria

To focus on the possibility of harm from GM foods or bioterrorism is to fixate on a threat, whether looming or currently implausible. As an industry instead poised to provide opportunities, the nascent field of synthetic biology has so far yielded few genuine success stories. In this book I have expressed enthusiasm for its potential, but in this chapter and elsewhere I have looked at some of the harder realities of applying groundbreaking science into society, which is explicit in synthetic biology's mandate. There have been innumerable examples of the scientific successes of genetic engineering in its broadest sense, not least in terms of understanding the basics of biology and the underlying causes of thousands of diseases. The work I once did in the lab helped identify a form of blindness in children, and this would not have been possible without the genetic modification of mice.

Synthetic biology has yet to deliver on that scale. However, it is set to start, and just like any discipline that involves extremely complex and constantly changing science, it is subject to the scrutiny of not just people and politics, but also market forces and economics. The story of the synthetic biology company Amyris and their stalled attempt to turn synthetic biodiesel to market is described on pages 156–59. Probably the single biggest success story of synthetic biology, however, along with the quagmire of real markets, comes from exactly the same team, labs, and genetic circuit board.

Throughout human history, malaria has been a constant lethal presence. Some estimates put the number of people who have perished at the hands of plasmodium, the malaria parasite ferried by mosquitoes, in the tens of billions, depending on how you define human species. Currently, a quarter of a billion people become infected every year, and the highest estimates are that more than a million will die, mostly young children. Apart from the staggering human cost, the WHO estimates that the cost of malaria to gross domestic product for sub-Saharan Africa since the 1960s has reached $100 billion dollars. The impetus to reduce the burden of malaria is profound.

Since the seventeenth century, quinine, extracted from South American cinchona trees, was the preferred treatment, though it came with a suite of unpleasant side effects. A chemical cousin called chloroquine usurped quinine as the standard antimalarial drug following the Second World War. However, as with all life-forms, the parasite wants to continue to live, and it does so by evolving. Mass treatment with chloroquine resulted in the 1950s in the emergence of plasmodium strains that were resistant to chloroquine, and spread across the world in a bid to ensure their own survival in the face of man-made extinction.

The current drug of choice in malarial areas is a small molecule called artemisinin. It is extracted from sweet wormwood, an Asian camphorous shrub, which is grown all around the world and has been used in folk medicine for centuries. As a treatment for malaria, artemisinin is fast and effective. The WHO specifically prohibits its use on its own, for fear of unintentionally nurturing and selecting strains of plasmodium that are naturally resistant. Instead, the organization recommends that artemisinin be the key player in combined therapies.

Getting enough artemisinin is a pricey and finicky business. It has to be farmed quickly and in very specific ways. From an economic point of view, the very fact that it is cultivated means that the fields of wormwood are competing with crops for food or feedstock.

Drugs are created in chemistry labs. You start with basic chemical ingredients, which can be bought from chemical companies or harvested from the living world. The production of drugs is like forensically accurate cooking, as each ingredient is mixed in to systematically add or subtract bits of molecules until you have the drug desired. Artemisinin is not a large molecule, but unfortunately it's also not easy—or more important, cheap—to synthesize using straightforward chemistry. Early in the process of working on synthetic circuits to create biosynthesized diesel, Stanford University researcher Jay Keasling was alerted by a student to the fact that one of the steps in their chemical pathway was also a key link in the chain that could produce synthetic artemisinin. While he tried to build a genetic circuit that would create diesel, his team also pursued another that would construct artemisinin. They published the first successful circuit for artemisinin synthesis in yeast in 2006, having switched from bacteria in 2003. It's built from twelve genes taken from three different organisms.

In both cases upscaling to industrial production was inherent in Keasling's aims, again marking the intent not merely to create, but to directly apply scientific research to real-world scenarios. It's a strange thing to see in a scientific paper, but from the start reducing the cost of production was clearly set out as a mission: “Industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices.” This exemplifies the problem-solving, engineering sensibility built into synthetic biology. It denotes the application as the goal, not merely to produce a functional drug, but also to do it inexpensively.

Keasling's rationale for this apparent altruism stems from the market forces that had confused artemisinin farming in the preceding years. At the end of the twentieth century, there was a great paucity of wormwood farming, so the market drove the price of artemisinin up. Then, spotting a gap in the market, thousands of African and Asian farmers started growing wormwood. The price dropped. Yet even with the drug being artificially maintained by government clinics at $1 a dose, more than half of patients would buy more expensive versions out of convenience from market stalls not acknowledging the government intervention. Unreliable supply, fluctuations in prices, and variable yields drove the prices back up, and this pattern looked set to continue.

Keasling set up Amyris to develop artemisinin production, along with its diesel sibling (which has tanked, at least temporarily). Following that, the Bill and Melinda Gates Foundation, the charity set up by the Microsoft billionaire and his wife, chipped in with $46 million to the charity Institute for OneWorld Health, which worked with Amyris to realize industrial-scale production. Amyris has run this project on a not-for-profit basis and joined up with organizations such as the Global Fund to reduce the cost and distribute as much artemisinin (as part of a combination therapy) as possible, as cheaply as possible. That means driving the cost down to less than fifty cents per treatment. Amyris granted the pharmaceutical giant Sanofi-Aventis a royalty-free license to produce vats of synthetic artemisinin, which are expected to hit the shelves within the next two years.

Implementation of a cocktail of antimalarial drugs is the WHO's strategy for combating malaria. This way, resistance doesn't evolve against artemisinin and declaw its therapeutic power, as it has for its ancestors. Yet companies disregard the WHO's strategy. Because the constituents of combined therapies can be sold individually, there is profit to be made in ignoring this organization's advice. In 2009, the WHO felt compelled to issue a briefing that warned companies to stop marketing artemisinin as a single therapy. According to the WHO report, the motivation of these companies is strictly financial. Andrea Bosman, part of the WHO's Global Malaria Programme, told
Nature
: “It's terrible. Who says there is no profit to be made in malaria? When you see the number of companies operating in Africa, and the diversity of products, you'd just be amazed.”