Dangerous Smallpox Ordered Through The Mail 7/5/2006 6:01:11 PM
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Lax laws that allow assembly of deadly virus DNA
Urgent calls for regulation after Britain’s “Guardian” buys part of smallpox genome through mail order
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. The deadly virus has existed only in laboratories since being eradicated from the world's population 30 years ago. The DNA sample ordered had three small modifications to render it harmless before it was sent by post to a residential address in London. The company has since conceded that it was not aware it was sending out a sequence of modified smallpox DNA.
The DNA sequence of smallpox, as well as other potentially dangerous pathogens such as poliovirus and 1918 flu are freely available in online public databases. So to build a virus from scratch, a terrorist would simply order consecutive lengths of DNA along the sequence and glue them together in the correct order. This is beyond the skills and equipment of the kitchen chemist, but could be achieved by a well-funded terrorist with access to a basic lab and PhD-level personnel. One study estimated that because most people on the planet have no resistance to the extinct virus, an initial release which infected just 10 people would spread to 2.2 million people in 180 days.
There are legitimate reasons for researchers to buy lengths of DNA from pathogens, for example in developing treatments or vaccines against them. However, because this industry is so new and unregulated, companies are selling custom-made DNA without making thorough checks on the identities of the people who are placing the orders or what the sequences are. Of the four main companies operating in the UK, none currently screens all their DNA orders. There are 39 companies operating in North America and not all screen their orders.
The potential to manufacture viruses from scratch first came to light in 2002 when US researchers pieced together the genome of the polio virus using short sequences of DNA around 70 letters long. And last year, another team recreated the 1918 flu virus, a devastating and now extinct strain that killed an estimated 50 million people, more people than the first world war. Building smallpox using the same technique as scientists used to make polio and 1918 influenza would be technically difficult because the virus is larger - the smallpox genome is 185,000 letters long, the influenza genome is 13,500 letters and polio is 7,741 letters. But as techniques improve there is no theoretical reason why it could not be done.
Craig Venter, the US entrepreneur famous for sequencing the human genome, announced in 2003 that his team had constructed the virus phage PhiX174 in two weeks. This has a genome 5,386 letters long. He is currently working on making a bacterium Mycoplasma genitalium from scratch, which has a genome around twice as large as smallpox.
The Guardian placed an order online with VH Bio Ltd, a company in Gateshead, Tyne and Wear, that supplies equipment and chemicals used in standard molecular biology labs. They used an invented company name along with just a mobile telephone number and free email address.
VH Bio Ltd rang to check whether the address provided was a residential address. The journalist told VH Bio Ltd that our company was in the process of moving offices and so wanted to make sure the order arrived. The package, which contained a 78-letter sequence of DNA, which is part of one of the smallpox virus's coat protein genes, was delivered by the Royal Mail to a flat in north London. The A5-sized Jiffy bag contained a small plastic phial with a tiny blob of white gel at the bottom - the DNA. The order cost £33.08, plus an additional £7 for postage. Alan Volkers, chairman of VH Bio Ltd said the company had no idea that the sequence they produced was a modified sequence of smallpox DNA. He added that many of its regular customers carry out research, which requires supplies of DNA sequences from pathogenic organisms, and his company does not normally screen DNA orders less than 100 letters long. After discovering that it had supplied a small sequence of smallpox DNA, the company carried out checks on two European databases and a 30-minute check using scanning software, but none of them raised any alert. Dr Volkers added that the company processes several hundred short-sequence orders per day and added: "It would be impossible to run them all through [standard scanning software] and operate successfully."
Before beginning the investigation, the Guardian obtained advice from four independent scientists, including an international expert on pox viruses, the family to which smallpox belongs. They said the order would be safe to produce, transport and receive. Without modifications to the sequence, it could potentially fall foul of the Anti-terrorism, Crime and Security Act 2001. This lists so-called Schedule 5 pathogens and toxins which are illegal to keep or use without first notifying the authorities. Also covered by the act is DNA "associated with the pathogenicity" of the organisms on the same list.
In order to avoid our sequence coming under the act the DNA sequence we ordered had three changes built into it to create so-called "stop codons". These are effectively full stops in the genetic code which mean that if the sequence were ever put together with others to make a smallpox gene the protein production machinery would stop at that point. So the sequence could never form part of a functional gene.
In making and receiving the order neither the Guardian, nor VH Bio Ltd, have broken the law, but the most widely used software (called Blackwatch) for screening DNA orders for potential bio-terror agents picked out our sequence as suspicious in a scan run by Craic Computing. This is because it looks for sequences of DNA letters close to sequences from dangerous organisms.
Everyone waits for a law to “fix” the problem. Why not use common sense? When you are dealing with dangerous pathogens, there should be red flags everywhere.
