Creation (20 page)

The current actions and motivations of Take the Flour Back, and the policies of Friends of the Earth and ETC, are not significantly different from those expressed forty years ago at the birth of genetic engineering. But the field has exploded. The question, then, is whether the original opponents were prescient in their opposition, or if their rhetoric is as irrelevant as it is unchanged, when the science has progressed. We'll now look at some of the major claims and scenarios.

Biological Weapons

The specific case of weaponizing engineered life-forms is one of the key arguments put forward in opposition to both genetic engineering and synthetic biology. Our advancing skills in DNA technology have kept the fear of bioterrorism very much alive, as well. Weaponizing life is not a new phenomenon. The use of living things (other than humans) to create havoc has a rich but utterly ignoble tradition that predates our conquest of DNA by millennia. Hannibal used his attack elephants in Roman antiquity. A Mongolian chieftain invading India in the fourteenth century dispatched camels ablaze to charge scimitar-wielding elephants. Even in the modern era, rats, cats, pigeons, and dogs have all been used as either bomb-detecting or bomb-bearing devices. In the Second World War, the Russians had some arguable success training dogs to run under German panzers while carrying explosives triggered by a knock to the tanks' underbelly.

The potential threat of living weapons is no less bizarre nowadays, but far more potent, and, as with all aspects of genetic engineering, the key difference is the introduction of precision control of the language of life. Much like most biology, bioterrorism has been reduced in size from the use of animals to the microcosm of genetics.

The universality of genetic code is something that viruses have exploited throughout life's history, as they can insert their own DNA into an unwitting genome to usurp that host cell's own biological mechanics. We live in a world that has always been plagued by disease. Death by infectious agents far outnumbers death at the hands of another human, and our mastery of genetic manipulation has presented the possibility of terrorism with these tools. In 2006, reporters from the
Guardian
attempted to make a point by acquiring parts of the smallpox genome. This is a disease that has been eradicated from Earth.
²
Its genome sequence is freely available online, as all publicly funded genome sequences are, and the intention was to question how easy it would be to build a maleficent creation. By ordering a few sections of the genome of
Variola major,
the virus that causes smallpox, it was suggested that a whole genome could be stitched together from smaller pieces. The short, seventy-five–base sections were manufactured by an unremarkable UK gene-synthesis company and sent to a residential address in North London, unchecked for their weapon potential. As responsible investigative journalists, they introduced deliberate errors, and the sequences ordered encoded part of the virus that was itself not toxic. Nevertheless, the story ran with startling revelations:

DNA sequences from some of the most deadly pathogens known to man can be bought over the internet, the
Guardian
has discovered. In an investigation which shows the ease with which terrorist organizations could obtain the basic ingredients of biological weapons, this newspaper obtained a short sequence of smallpox DNA.

Shocking though this might sound, it was a ham-fisted stunt at best. Its only real triumph was to show that some DNA synthesis companies were not particularly vigilant in taking orders from members of the public. Also, their claim to have acted responsibly by building errors into the code was lip service. Once you'd gotten hold of the sequence, correcting the errors would be a trivial matter for any competent genetics graduate student.

Yet the overall premise was shaky. Using this technique of stitching together 75-letter fragments to make up a 186,000-letter genome is a tall order, akin to reassembling a shredded document twice the size of this book. “Theoretically possible,” the article asserts, but in reality paralyzingly arduous. In 2002, a New York–based team did successfully assemble a working polio virus from mail-order synthesized segments of DNA. However, that genome is only 7,500 bases long and still took a team of molecular biology experts two years. These are not directly scalable problems. Recall that Venter's Synthia in 2010, with its 582,000-letter genome, took twenty people ten years at an estimated cost of $40 million. There is a wide range of actuality when discussing the theoretically possible.

Anti-synthetic biology activists ETC produced a report on synthetic biology in 2007 that refers to the
Guardian
's stunt, which managed to enhance the theoretical possibility of further danger: “A commercial outfit could theoretically crank out the entire DNA for a synthetic version of
Variola major
in less than two weeks, for about the price of a high-end sports car.” This might well be theoretically possible, but only if its meaning is stretched a long way beyond the practically feasible. As synthetic biology expert Rob Carlson says at the beginning of this chapter, “It is easier to fixate on the threat than embrace the opportunity.”

It is important to acknowledge that there is a potential threat, and that synthetic biology and genetic engineering are dual-use technologies. Defunct diseases
can
now be reconstructed in the lab, and ones that we haven't conquered yet can be engineered to be more dangerous. We are capable of eradicating diseases such as smallpox, now consigned to history thanks to vaccination. Polio is likely to be next, and in time, diseases that kill us today will only be of historical interest to our children. Though it is unequivocal that science and medicine have transformed humanity's survival, it is equally apparent that millions die each year from incurable diseases. Yet how realistic is the possibility of genetic engineering's being the tool that malefactors use to bring the terror?
The
Guardian
's smallpox story ran six years ago, and as we have seen, the technology in question is evolving at a breathtaking rate. In 2012, the game changed yet again.

Killer Flu

Influenza comes primarily from birds. The virus annexes a host cell's workings to enact its own genetic program and make its own proteins. In flu viruses, two of these proteins sit on their surface as they drift from victim to victim: hemagglutinin (H), which hooks onto a target cell to gain entry, and neuraminidase (N), which newly made virus particles use to get out again. Variations in this pair of break-in and bust-out proteins give different flu strains their names, such H5N4. For the most part, H5N4 flu remains a bird disease. That's not to say it doesn't cause symptoms, just that humans won't make new viruses, so we can't spread it. But it is constantly evolving and finding new ways to spread. Once in a while, a strain will make the evolutionary leap to become a human disease, with both symptoms and the ability to transmit from person to person, with sometimes apocalyptic results. In 1918, the flu pandemic, caused by an H1N1 strain, infected billions and caused the deaths of fifty million people.

In 1997, patients in Hong Kong started dying from a new strain that hadn't been found in humans before: H5N1. This was a version that abounded in Chinese open-air chicken markets, to the extent that it was considered endemic. The very real worry was that, as it was a new strain, humans wouldn't have adapted any immunity to it. Flu's accelerated evolution can happen when two different strains infect the same cell, where they can trade genes. Therefore, if H5N1 swapped genes with a strain that struck humans and was transmissible from person to person, we would be looking at the beginning of disaster.

Knowing full well that highly infectious chimera strains are a theoretical possibility, teams of flu researchers set about fulfilling Feynman's maxim “What I cannot create, I do not understand.” Scientists in the Netherlands and North America set about preempting nature by attempting to assemble the new combinations exactly as they might evolve to brandish pandemic-causing qualities. Yoshihiro Kawaoka from the University of Wisconsin–Madison and Ron Fouchier from Erasmus Medical Center in Rotterdam each designed flu viruses that would infect mammals, in this case ferrets. Kawaoka's design shuffled two decks of viral genes to put together one that not only would break into cells in a ferret's nasal passages, but could replicate and infect other ferrets via airborne droplets. Fouchier's design was similar but had just five genetic alterations, all seen in other natural strains, which enabled the virus to clamp onto ferret cells and infect. These also were passed on to other ferrets via a sneeze. Neither strain was lethal, though Fouchier's creation caused death when delivered in concentration via an inhaler. Given the importance of this work, these two studies were sent to the two most important scientific journals in the world: Kawaoka's to
Nature,
and Fouchier's to
Science
. What followed was a tortuous tale of negotiating a delicate path through frontier territory.

The U.S. National Science Advisory Board for Biosecurity (NSABB) has oversight on exactly these types of scenario. NSABB is a collection of scientists, lawyers, and policymakers who advise on dual-use research in biology. Although it has no power to compel, in December 2011, NSABB recommended that the two papers should be published but redacted to “not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm.” This initial judgment prompted some serious and necessary hand-wringing by all parties involved. When controversial science is reported, the debates mostly tend to be between researchers and nonscientists. But this time around, unusually, there was intemperate disagreement between scientists on whether to publish in full, redacted, or not at all. As had happened at Asilomar, this confrontation prompted a dialogue open to the public. Also emulating the actions of Paul Berg in 1975, Fouchier and Kawaoka both called for a sixty-day voluntary moratorium on flu research in order to work out the right thing to do. The World Health Organization (WHO) stepped in, and after much gnashing of teeth the NSABB changed its mind, recommending full publication of the Kawaoka paper and a clarifying edit of Fouchier's. By this time,
Nature
had reached the same decision independently.

These studies show the very real possibilities of new and dangerous flu viruses emerging in the real world. They also show that to weaponize a flu virus would be a feat of genetic engineering, not something that anyone could do with any degree of ease; those studies took major investment and tens of thousands of highly skilled working hours. For a potential terrorist, this would not be the only disadvantage: a transmissible mutant mammalian flu virus could not be targeted at any one group of people, so any attempt to murder a specific population would be impossible.

Nor do viruses respect geography or nationalities. One theory behind the global spread of the devastating 1918 flu was that it began at a poultry farm in Kansas that supplied a local military base with chickens, and that the soldiers then took it with them as they were sent off to fight the first global war. These days, with world travel and a virus emerging in a dense conurbation such as Hong Kong, the potential for reaching humans all over the world is even greater. There is a threat from accidental release of transmissible viruses from a lab as well as malevolent intent. Even if you were hell-bent on creating a synthetic indiscriminate killer virus, rather than the millions it would take to make, the very well-proven process of artificial selection would be much more efficient. You could evolve the virus from chickens in a farm with dubious hygiene. Poor poultry-farming practices are far more likely breeding grounds for killer flus.

The utility of flu as a weapon is also questionable. If mass murder is your goal, then flying a passenger plane into a skyscraper is considerably easier. But the whole point of synthetic biology is to reduce the entry level for artisan genetic engineering, and the open culture of the BioBricks project has meant that gene manipulation, impossible a decade ago, is now school science. Does this make the entry level for bioterrorism lower? Currently, there are no bricks in the library that could be directly associated with a biological weapon. Yet it is possible to build a nail bomb out of components that are individually innocuous enough and can be bought from a standard hardware store. Indeed, one can make all kinds of explosives using simple household items, if one were so inclined. ETC's 2007 report on synthetic biology describes it as “genetic engineering on steroids,” which ultimately will mean “cheaper and widely accessible tools to build bioweapons, virulent pathogens and artificial organisms that could pose grave threats to people and the planet.” Maybe there is a flicker of truth in that sentiment, in that any progress in synthetic biology will allow the development of new technology with dual-use potential. Currently, though, and indeed for the foreseeable future, the reality of a genetically engineered weapon relies on the most generous use of the words
theoretically possible
.

This tale of the killer-flu experiments also raises a very fundamental question about the nature of science. One of the key principles in scientific research is the freedom to research any subject and for the results to be published. Perhaps with the advent of such potent dual-use technologies, this era is drawing to a close. But to censor scientific information about potential agents of terror is to ignore two problems. The first is that by studying how pathogens work, we understand better how to deal with them. This might be in the face of a terrorist threat, or simply to help treat patients, especially when virulence harbors epidemic potential. This study of pathogens needs to happen in an open, unrestricted way, as the richest, most productive, and most creative science comes when information is unfettered by barriers and shared freely. In doing just that we equip ourselves to tackle exactly the same threat should it come at all. Knowledge of how new virulent or even weaponized life-forms work will ready us for both natural and created threats. On publication of the Kawaoka paper, an editorial in
Nature
ruled that “A paper that omits key results or methods disables subsequent research and peer review.” The final point is also a practical one. Keeping the information under wraps is simply not enforceable.
Nature
was aware that there were many versions of the paper circulating outside the official channels of the publication process, which has become increasingly common in the Internet era. The editorial went on to say that it could not “imagine any mechanism or criterion by which to sensibly judge who should or should not be allowed to see the work.”