I've been debating whether to respond to James Randerson's recent front page story in The Guardian, "Revealed: the lax laws that could allow assembly of deadly virus DNA ", about mail ordering genes for smallpox. The bottom line is that the story as published is neither well-reported nor a particularly useful contribution to the discussion about emerging biological threats.
Years ago, I was fortunate to take a science writing class from the great science and war correspondent Malcom Browne, who for many years provided exceptional science reporting at The New York Times. Among his suggestions for an ideal (!) newspaper story is that it be no longer than a Haiku. Of course, this makes all articles published in the history of the press less than ideal. (No news there.) Here is my version of the Guardian article:
Humans play with fire!
Newspaper sales are lagging!
Set our hair alight!
Alas, I've ignored most of the stylistic requirements for a Haiku (no mention of a season, or of nature), and the exclamation points are unforgivable. Still, it captures the essence of Mr. Randerson's story.
Although the article does make one, albeit brief, nod to, "Legitimate reasons for researchers to buy lengths of DNA from pathogens, for example in developing treatments or vaccines against them," the majority of the text is simply alarmist and a rehash of arguments that have appeared previously (The New York Times, Wired, Technology Review; the list goes on).
The worst bit, from my perspective, is that Mr. Randerson promulgates the facetious notion that producing a live, infectious 1918 pandemic influenza virus is as easy as ordering out the DNA from a gullible company. I've written about this before, and refer readers to those posts (here, and here). This isn't quibbling on my part. The capabilities of the technology are central to evaluating the immediacy of the threat.
The Guardian article spends many inches (not an Internet concept, those newsprint inches) announcing the need for regulation without even mentioning the potential detrimental effects of limiting access to the technology. Because the threat is not immenent, instituting regulations would certainly only reduce our capacity to learn who is employing the technology and thus reduce our capacity to respond to any threats that do arise. Again, arguments I have made extensively elsewhere (in Wired, at Future Brief, and in Biosecurity and Bioterrorism (via Kurzweilai.net), for example).
The short version of why regulation is bad is this: Because it is not physically possible to control access to the reagents or instrumentation used in DNA synthesis, our only defense in this situation is to keep track of, as best we can, who is doing what. Our sole weapon is information, in other words. The only thing regulation will do is cause people to be more secretive, whether they have a nefarious or an innocuous intent. That is, regulation will restrict our ("we" being the good guys, of course) access to information. Moreover, regulation in the U.K. and/or the U.S. will only limit activity in those countries. You can order synthetic genes from a large number of convenient countries, these days.
In a companion article, "Lax laws, virus DNA and potential for terror", Mr. Randerson introduces his readers to Synthetic Biology:
Edward Hammond, a biological weapons expert with the Sunshine Project, an NGO that campaigns against the development of biological weapons, said: "The most worrisome thing ... is that [the field of synthetic biology] is going to enable people to create potentially very dangerous diseases that don't otherwise exist or to recreate ones that have been wiped off the face of the earth."
Mr. Randerson makes no effort to explain that you don't need synthetic methods to create new, potentially dangerous organisms. (Harder to sell newspapers if you don't stoke the fires, after all.) Breeding and artificial selection can produce pathogens for you, and these tried and true techniques will do a much better job of it. And if you want a nasty bug ready-made, you just need to visit a poultry farm here in the US, where due to all those fantastic "growth hormones" a soil sample will provide you with Cipro-resistant anthrax.
I was perplexed through the entire article why no mention was made of Drew Endy's efforts to synthesize novel viruses for the sake of learning how they work. In other correspondence with Drew, I learned that he had been approached by Mr. Randerson, but was so troubled by the very idea of the article and project that he declined to participate or be interviewed. Here (PDF warning) is a log of their email exchange.
The most remarkable thing about the email is that it demonstrates Mr. Randerson is hell bent on doing exactly what he warns against, namely letting loose in the world a sequence from a deadly pathogen that has been extinct in the wild for quite some time. It doesn't matter that he introduced three small changes rendering the gene supposedly incapable of being used to produce a protein. Those changes would be trivial for any college, and perhaps high school, student to remove (laborious, perhaps, but trivial), thus restoring the functionality of the smallpox gene.
By my reading, Randerson's correspondence with Drew clearly shows The Guardian reporter hasn't thought about the bigger context. He had his teeth into a story and wedged himself into discussing only his own ill-informed conclusions rather than carefully exploring what it will take to keep us safe from emerging threats. He simply didn't do his homework.
I hope The Guardian can do better in the future.
The suggestion that one could join 78mers to form a variola gemone "in a basic lab" is ludicrous. You'd need something like 2500 of the fragments, joined in the correct order with no joining artifacts. The Guardian even admits this, contradicting their own claim, by saying that it's "theoretically possible"; which it may be, but it's out of reach of even the biggest and best labs today or for a long time to come.
But there's an even more ridiculous aspect to their call for regulation. They ordered a 78mer corresponding to the variola genome, they say. Yet variola and vaccinia -- inoffensive vaccinia, used in tens of thousands of labs, that was injected into millions of people -- are 97% identical over 41,000 base pairs. Line up vaccinia and variola, and you'll find hundreds, if not thousands, of 78mer stretches that are identical. Is the Guardian demanding that all vaccinia researchers (who are, perhaps, working on cures for smallpox) stop work? If not, which agency is going to devote hundreds of people to investigating these labs each time they order a vaccinia -related oligo? (Or for that matter, a cowpox oligo, or a rabbit-pox oligo, or a volepox oligo, or something from any of the hundreds of similar poxviruses.)
It's an irresponsible, scare-mongering article.
The blatant pseudo science fear mongering that "scientific" journalists use to publish their stories is just aweful. Will it be possible to take 75 mers and string them into a genome, yes probably. But I agree with Rob's point on the way that a terrorist would make a bad bug. Going into a Texas cow pasture or a chicken coop on the eastern shore of Maryland would be an easier way to get anthrax than buying 2000 oligos and stitching them together. I really like the email correspondence from Drew. I am very glad he bowed out of th article. The sequence that they eventually decide to make the oligo of, when blasted against NCBI, gives Monkey, Cow, Rabbit and Camel Pox virus homologues to about 100% identity, not to mention about a 20bp homology to mouse, human, zebrafish and C elegans genes. Wouldnt want those getting into the wrong hands.
The idea of screening every oligo produced is quite ridiculous. Should long stretches of DNA synthesized by companies be screened, of course. Over 500bp stretches are screened against pathogen databases from companies like Blue Heron and Bio Basic. And every company producing large lengths should know who and where they are sending their products to. The fact that this company the author used for the oligo actually agreed to send it to a residential house shows the lack of scruples of the company more than anything. I would like to see if that would work with IDT or Operon, i would bet not.
I guess the question is which is easier, getting smallpox from a foreign government scientist or trying to synthesize it yoruself from 75mer oligos.
The trouble with this article from The Guardian is that people without a science background write it and people without a science bakground are reading it. Just hope George Bush doesnt get a copy of it, he might close down all DNA synthesis labs to keep biological weapons out of the hands of terrorists. Luckily he doesn't read the newspaper.
Rob, Thanks for writing this! Drew