Short abstract
The scientist who helped to confirm the identity of the SARS virus is now asking countries to stockpile antiviral drugs in case of an influenza pandemic
Professor Albert Osterhaus is known in the Netherlands as the "virus hunter." He hit the headlines in April when the Dutch newspapers proclaimed that the virus responsible for severe acute respiratory syndrome (SARS) had finally been unmasked in the Netherlands, after a press conference convened by the World Health Organization announced the results of Osterhaus's experiments with macaque monkeys.
Previously a coronavirus had been identified by teams in Hong Kong, Canada, the United States, and Germany as a possible cause of the new syndrome, and now Osterhaus's work has confirmed the identification. He published his results in Nature on 15 May ( 2003;423: 240)12748632.
His involvement in tracking the cause of SARS had begun in March, when Klaus Stöhr, a virologist with the World Health Organization, had approached his laboratory and had asked him and his team to join the collaborative research effort, which eventually involved 13 laboratories across the world.
Osterhaus's laboratory was ideally suited to the challenge, because of its track record and Osterhaus's own special interests. His doctoral dissertation was in feline coronavirus, and his team at the Erasmus Medical Centre, Rotterdam, had identified the human metapneumovirus in 2001 and the avian flu virus strain H5N1. Osterhaus also has a special interest in viruses that cross the species barrier, which seemed to be the case with SARS.
By mid-March a new coronavirus had been identified as a likely cause of SARS, but it was not the only contender. Some of the collaborating scientists thought that they should also be investigating the human metapneumovirus.
"There was no full agreement in the group," said Osterhaus. "Somebody had to do the animal experiments. We set out to do it fast. We do monkey models for other virus infections. We made the space and the animals available." Once the virus samples arrived from Hong Kong the experiment and laboratory analysis took only two weeks.
The Osterhaus group carried out experiments on three groups of monkeys. The first group was infected with the coronavirus, the second with the human metapneumovirus, and the third with both. The results showed that the pneumonia resulting from infection with the coronavirus in the first group was histologically indistinguishable from human SARS.
In acting so fast, however, Osterhaus had cut some corners and thereby incurred criticism from some quarters. Despite the urgency of the situation—in one week in March the number of suspected new cases of SARS had tripled to more than 450—Osterhaus applied to his university's animal ethics committee, only to be told that it would probably take at least a week to respond.
Osterhaus decided he had to cut through the red tape. An afternoon of phone calls in which he describes himself as being "pushy" and "sticking his neck out" got him written permission from the senior civil servant at the Ministry of Health.
"I was given permission, but the person who gave it to me was probably not entitled to do so under Dutch law. I have no regrets and I would do it again... If I had been told no I would have persuaded them to say yes. I would not have taken no for an answer."
Figure 1.
Professor Albert Osterhaus said he "stuck his neck out" for permission to do the animal experiments
Credit: ANP/PA
Today he takes pains to stress that "generally" he is in favour of "good regulations," especially in experiments with monkeys, but "in an emergency, when people are dying, you need to control the outbreak, to move fast."
His action led to a reprimand in the Dutch parliament but also to a clarification of the Dutch regulations so that scientists can be granted urgent approval within 48 hours. It may also have resulted in Osterhaus's regrettable return to smoking.
The significance of his success can never be known, but once the cause of SARS had been confirmed the rest of the "intervention strategy" could fall into place. "Now we could focus all our attention on the coronavirus. Before that we had also been looking at another virus, and that was counterproductive."
Today, he admits that no one can predict whether SARS will return. His and other laboratories are "gearing up" in a race to develop faster and more specific diagnostic tools and to understand the pathogenesis of the disease. The problem so far has been that the polymerase chain reaction analysis does not identify the virus in the first couple of days of symptoms appearing. This would mean that if SARS emerged in the middle of a winter flu epidemic it would be hard to distinguish cases of SARS from severe flu cases. However, work is well advanced to identify 80% of cases in the first days of symptoms appearing.
But Osterhaus, who was made a Knight of the Order of the Dutch Lion last week in recognition of his virology work, does not see the re-emergence of SARS as the most serious health problem facing the world today. He is extremely worried about the emergence of new viruses and the possibility of an influenza pandemic—similar to those that killed millions of people on several occasions in the 20th century.
He said that during the outbreak of avian flu in the Netherlands in March all the "predisposing factors" were right for such a disaster. The H7 avian flu virus had crossed the species barrier to humans at the same time as a normal human H3 flu virus was prevalent, leading to the possibility that if someone was infected with both viruses they could exchange genetic material and a new virus would emerge.
As chairman of the European Scientific Working Group on Influenza and director of the Dutch National Influenza Centre, Osterhaus has advice for health departments across the world: "At this stage there is no country in the world that is sufficiently prepared if we get a new pandemic outbreak of flu. My suggestion to policy makers is: why don't you stockpile antivirals? There is a lot of data available to show they reduce the severity of the disease and save lives."