The technique used to create the first synthetic polio virus, revealed last week, could be also used to recreate Ebola or the 1918 flu strain that killed up to 40 million people, experts have told New Scientist.
(Photo: J Bieber/Network)
(Photo: J Bieber/Network)
What is even more worrying is that there are easier ways of recreating microbes. You can simply add key genes to a close relative. The key in all cases is knowing the genetic sequence. That raises fundamental questions about the wisdom of publishing the genomes of deadly pathogens on the internet (see New Scientist magazine, 20 July, p 7).
To recreate polio, the team at Stony Brook University in New York bought bits of its sequence from companies that make any piece of DNA to order. At the moment, only short stretches of DNA can be custom-made, so the team had to assemble the genome, which is about 7500 base pairs long, by stitching together sequences of about 70 base pairs. When copies of the genome were made into RNA in a quick lab reaction and put into a vial full of cellular components that mimic a human cell, out came perfectly formed viral particles.
Dramatic as it sounds, this was no scientific tour de force. All the steps are routinely followed in thousands of labs worldwide. That means anyone armed with the knowledge of a virus's sequence, some science training and a few common tools could recreate the virus in a test tube. "What is shocking to people is that, suddenly, it's a reality," says Eckard Wimmer, leader of the team.
The report will not affect the World Health Organization's campaign to eradicate polio, officials said on Friday. "It's not an 'Oh my God' situation," adds Wimmer, who is a member of a WHO committee on the containment of polio samples held around the world. "They know that getting rid of the polio virus in all the freezers in the world will be too hard."
But it does mean that vaccine stocks will have to be maintained when vaccination ceases, he says. That's supposed to happen in 15 years, though this is already looking doubtful.
The real worry is that bioterrorists could use the method to recreate viruses such as Ebola and smallpox. Experts have been quick to point out that this would be much harder than making polio.
Its genome is relatively easy to assemble because it is so small. And the virus's way of hijacking cells' resources is also simple. An RNA copy of the genome is enough to set off the cascade of events leading to the production of viral particles. That is not how most viruses work: with Ebola or smallpox, for instance, replication requires key viral proteins as well as the genome.
Ebola from scratch
But this obstacle has already been overcome. In January, scientists reported they had made Ebola using "reverse genetics". They took the virus's genome plus pieces of DNA coding for the key viral proteins and added them to cells.
Once made, those proteins kick-start the replication process. The team got their genome from the virus itself. But since the Ebola genome is only slightly larger than polio's, there is no reason why it too cannot be assembled from scratch.
Or take the 1918 influenza virus, fragments of which have been recovered from preserved tissue samples. The sequences of three out of eight gene segments have already been published, and two more have been sequenced and will probably be published this year, says Jeffery Taubenberger of the Armed Forces Institute of Pathology in Washington DC.
It will take a couple of years to finish sequencing the remaining three, but after that anyone could use reverse genetics to bring it back, he says.
Recreating smallpox by painstakingly assembling its genome would be more difficult than polio or Ebola because its sequence, at around 185,000 base pairs, is much longer.
But it could be done, says Lev Sandakhchiev, a smallpox expert and head of Russia's Vector biodefence lab in Siberia. "I am sure scientists may do it sometime," he told New Scientist.
So how do you stop this happening? Right now, the companies making DNA molecules such as the ones used to recreate the polio virus do not check what their clients are ordering. "We don't care about that," says a technician at a company that ships DNA to more than 40 countries around the world, including some in the Middle East.
And even if all orders were monitored to make sure nobody is trying to make, say, smallpox, it would not be enough. Instead of trying to assemble a genome, you could simply take a closely related cousin and change the key portions of its sequence to those of smallpox.
Such cousins include camelpox and the easily obtained vaccinia virus. Bacteria resembling anthrax could also made this way. And if you are going to go to all this trouble, why not tweak the virus while you're at it? New Scientist magazine revealed last year (13 January 2001, p 4) that scientists experimenting with mousepox had created a far deadlier strain.
All this means that restricting access to dangerous pathogens and certain kinds of equipment will not stop determined bioterrorists. It does not even matter if a virus has been totally eradicated. All that is needed to bring it back is knowledge of its sequence and, in some cases, of what it needs to make more copies of itself.
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