Vaccination against smallpox hasn’t been necessary for decades (Image: Lynn Pelham//Time Life Pictures/Getty Images)

The US government has taken delivery of the first drug said to cure smallpox. It was developed under a government plan to buy biodefence drugs that would otherwise stall in development for lack of a market. The country plans to buy enough to treat two million people, for $410 million.

On the face of it, that looks like a good plan. Yet as New Scientist reported this week, thousands of people are dying from antibiotic-resistant bacteria, for want of just such funding for new antibiotics. No one has died of smallpox since the disease was declared eradicated in 1980. So what’s going on?

Developing a drug is expensive. It won’t happen without either a lucrative market or public funding. After the US anthrax attacks of 2001, the country massively boosted public funding for biodefence.


In 2001, “smallpox virus as a biological weapon posed the most serious threat”, says D.A. Henderson of the University of Pittsburgh, Pennsylvania, who helped lead smallpox eradication. The fate of tonnes of weaponised smallpox that was stockpiled by the Soviet Union was unknown. And as vaccination had stopped, many people were not immune to the fast-spreading and deadly virus that kills a third of its victims.

There was little smallpox vaccine left, and companies could not make more, because with the disease gone, no one would want to buy a drug to combat it. So the US government gave a total of more than a billion dollars to various companies for them to make a stockpile of 220 million doses of new vaccine.

The government also gave Siga Technologies in Corvallis, Oregon, $110 million to develop an antiviral drug to treat smallpox. The company has now sold two million courses of the drug, called Arestvyr, to the government, and hopes to sell another 12 million.

Containment

Developing a drug to treat smallpox alongside a vaccine made sense initially, says Henderson.

“Let’s say someone releases the virus in an airport and you have 50,000 sick,” says Eric Rose, Siga’s CEO. Vaccination can stop smallpox if it is given soon after infection. The plan would be to limit spread of the virus by vaccinating people who contact the first victims after they develop the “pox” rash and become contagious.

But authorities won’t know there has been a smallpox attack until those rashes appear – so for the first victims, vaccination will arrive too late. Arestvyr would save some of those people, says Rose, as well as slowing their spreading of the virus.

Moreover, it can be given at the same time as the vaccine, even though the vaccine is made of a live virus related to smallpox, called Vaccinia. The drug stops every virus in the smallpox family, including Vaccinia, from escaping the cells they infect. Even though this means the immune system is less likely to come into contact with the virus, somehow it doesn’t stop Vaccinia from giving the recipient immunity to smallpox.

This means that people given both drugs will be protected from the virus during the few days that the vaccine takes to kicks in.

Healthy people at risk may refuse vaccination, as it can cause its own, sometimes devastating infections and heart damage. However, if unvaccinated people succumb to smallpox, they are unlikely to reject the new antiviral treatment, which should help stop spread of the virus.

Value for money?

Arestvyr could have uses, says Henderson, “but at $200 per treatment versus $3 for vaccination, I don’t believe we gain that much”.

During eradication, he says, “even in areas where few people were immunised, vaccination of the patient’s family and perhaps 30 nearby families” was enough to banish smallpox. Moreover, Arestvyr has never been tested against smallpox in people, he says, and tests in monkeys were not done in the later stages of the disease when symptoms develop and when people would be treated.

He thinks the money it would cost for more Arestvyr could be better spent.

Yet the cost is modest for a new, patented antiviral drug, says Rose, and is precisely why the funding programme, called Project BioShield, was set up – and renewed, for $2.8 billion, this month.

It isn’t all for hypothetical bioterror threats. The Center for Biosecurity at the University of Pittsburgh Medical Center in Pennsylvania reports that 83 per cent of the $71.83 billion the US has spent on biodefence since 2001 has gone on broader infectious disease research, public health and disaster response. But perhaps we need another Project BioShield – for threats, like antibiotic-resistant bacteria, that are already here.