A case of DIY viruses

Just how easy is it to make a deadly virus? This disturbing question has been on the minds of many scientists recently, thanks to a pair of controversial experiments in which the H5N1 bird flu virus was transformed into mutant forms that spread among mammals.

After months of intense worldwide debate, scientists recommended recently in favour of publishing the results. There is no word on when those papers – withheld since last fall by the journals Nature and Science – will appear. But when they do, will it be possible for others to recreate the mutant virus? And if so, who might they be and how would they do it?

Scientists are sharply divided on those questions, as they are on the whole complex of issues surrounding the mutated virus known as mutH5N1. Over the past decade, more amateur biologists have started experimenting. The website, DIYbio.org, now has over 2,000 members.

Creating viruses

The simplest and oldest way of making viruses, is to get them do all the work. In the 19th century, doctors produced smallpox vaccines by inoculating cows with cowpox viruses. The viruses replicated in the cows and produced scabs, which were then applied to patients, protecting them from the closely related smallpox virus.

By the turn of the century, scientists had discovered how to isolate a number of other viruses from animals and transfer them to new hosts. By mid-century, scientists were rearing viruses in colonies of cells. (Viruses have to infect host cells to reproduce; they cannot replicate on their own.)

More recently, scientists discovered how to make new viruses, or at least new variations on old ones. The biotechnology revolution of the 1970s enabled them to move genes from one virus to another. Flu vaccines can be made this way. Scientists can move some genes from a dangerous flu strain to a harmless virus that grows quickly in chicken eggs. They inject the engineered viruses into the eggs to let them multiply, and then kill the viruses to prepare injectable vaccines.

Scientists have also learned how to tweak individual virus genes. They remove a portion of the gene and then use enzymes to mutate specific sites. Using other enzymes, they paste the altered portion back into the virus’ genes. In the serial passage method, scientists infect an animal with viruses. The descendants of those viruses mutate inside the animal, and some mutations allow certain viruses to multiply faster than others. Scientists then take a sample of the viruses and infect another animal.

Viruses can change in important ways during this process. If it is done in the presence of antiviral drugs, scientists can observe how viruses evolve resistance. And viruses can become weak, making them useful as vaccines. At the bio-security meeting in Washington, Ron Fouchier, who led the Dutch team that created one of the mutant H5N1 viruses, described part of the experiment.

The scientists used well-established methods: First they introduced a few mutations into the H5N1 flu genes that they thought might help the bird flu infect mammals. They administered the viruses to the throats of ferrets, waited for the animals to get sick and then transferred viruses to other ferrets.

After several rounds, they ended up with a strain that could spread on its own from one ferret to another in the air. If trained virologists could see the full details of the paper, there would be several ways they could make mutH5N1 for themselves. The most sophisticated way would be to make the viruses from scratch.

They could take the publicly available genome sequence of H5N1 and rewrite it to include the new mutations, and then simply copy the new sequence into an email. “It’s outsourced to companies that do this for a living,” said Steffen Mueller, a virologist at Stony Brook University on Long Island, who regularly synthesizes flu viruses to design new vaccines.

A DNA-synthesis company would then send back harmless segments of the flu’s genes, pasted into the bacteria’s DNA. Scientists could cut out the viral segments from the bacteria, paste them together and inject the reconstructed virus genes into cells. If everything went right, the cells would start making mutH5N1 viruses.

Trained virologists could use a simpler method. Knowing the mutations acquired by mutH5N1, they could simply alter ordinary H5N1 viruses at the same sites in its genes to match it.

Not a costly affair

Some of the equipment that scientists use to work on viruses has grown so inexpensive that it is no longer limited to university labs. Devices for duplicating pieces of DNA sell for a few hundred dollars.

Todd Kuiken, a senior research associate at the Woodrow Wilson Centre in Washington who specialises in the movement, points out that typical DIY projects are relatively simple, like inserting a gene into bacteria to make them glow. Producing viruses involves much more expensive equipment to do things like rearing host cells.

“If you are a farmer somewhere in China, you could do it,” said Mueller, the virologist at Stony Brook. All that would be necessary is to bring some sick chickens in contact with ferrets or other mammals. “Without knowing what you’re doing, you could do it anyway.”
Of course, someone trying to make a new flu this way might well end up its first victim.

Some experts say that regardless of how a lethal virus might arise, the important thing is to be able to defeat it when it appears, so that we can avoid a global catastrophe like the 1918 flu pandemic, which killed 50 million people. A vaccine could be the answer, according to Ron Atlas, a University of Louisville microbiologist and expert on bio-terrorism.