The fair and the fowl

October 7, 2005

A researcher working on a global health issue at a top institution on a five-year contract should feel secure. But Ruth Harvey, who is investigating avian flu, tells Anna Fazackerley that the pressures of making a name are inescapable

Ruth Harvey, a postdoctoral researcher working on avian influenza at Oxford University, hates chickens. She dreads visits to see her boyfriend's parents when she will have to confront bantam hens and "a very scary rooster" in the garden.

Her phobia is not groundless. On a global level, these seemingly innocuous domestic birds present a terrifying danger. This summer, a deadly bird flu virus known as H5N1 spread from Asia to Siberia. It has killed tens of millions of animals, chief among them chickens. So far only about 120 humans have been infected, but half of these have died.

Scientists fear that the virus will continue to mutate until it gives rise to a novel subtype with human genes that could be transmitted with frightening ease from person to person. Should this occur, experts warn that millions of people could die in a global pandemic reminiscent of the events of 1918-19, when Spanish flu killed more people than the First World War.

This nightmare scenario drives Harvey. "What makes research in this area attractive is that it is such a global health issue. It is by no means a niche area," she says. "If you make an advance, it can truly have an impact on millions of lives. It is not just test tubes. For me, that is important."

As a molecular virologist, Harvey's work is at quite a remove from the disease's front line, but it could prove to be a vital part of a bigger research jigsaw puzzle. She is investigating the difference between the avian flu virus and human viruses on a molecular level. Her group - led by George Brownlee, head of the chemical pathology unit at Oxford - is interested in polymerase, an enzyme carried by the flu virus that is responsible for replicating the virus's RNA.

Other research teams have shown that the enzyme might be important in the adaptation of the avian virus by allowing it to overcome the species barrier and infect human cells. Harvey explains that her group now understands which residues are central to this process, but they do not understand why. A better comprehension of what changes are occurring could allow scientists to quickly detect bird viruses that are potentially dangerous to humans.

She says her project reflects her personal interests more than those of Brownlee, who is more concerned with biochemistry. "That is important. You need something that fires you up," she remarks. "Just doing something your boss wants to do is hard."

Whether or not this project will make her career remains to be seen. "You do not know if you will be successful," she says. "A bit of it is luck - whether you will hit on the right residue. But I am confident that we are on the right track."

Yet she knows that she is working against the clock. She is in a high-profile field, and many other groups are racing to publish similar results. "From a career perspective, I have to be first to publish or it does not count," she says. And, like many researchers, although she would be happy with a paper in a respected specialist publication such as the Journal of Virology , it is the intimidatingly competitive general journal Nature that is her "golden goal".

Happily, though, Harvey's project is financially secure, which is no small achievement at such an early stage in her career. She is funded by a five-year grant from the Medical Research Council, which she admits has made her feel considerably more relaxed about her job choice. "These grants are like gold dust, so I could not believe my luck," she says. "With three-year contracts, it is often in the last six months that you are really getting somewhere. Those extra two years really make a difference."

Beyond that five-year horizon, her future remains uncertain. Brownlee will retire in 2007, when Harvey's contract comes to an end. She is aware that she will have to find a new job and that early-career researchers are expected to demonstrate a willingness to move around and gain experience in different scientific institutions.

Having already worked two and a half years in industry after completing her first degree, Harvey is determined to stay in the university sector. "I think you suit either industry or academia," she says. "Personally, I found industry frustrating, as the whole point of your research is the end product and making a profit. Even though you are helping people by making diagnostics, it does not feel as though that is why you are doing it," she adds.

While she is in academia, she feels free to follow any interesting new leads as long as they do not wander too far from her original funding remit.

But she is anxious about the pressure to try a spell in research in another country. "I have been told it would be good for my career to move to the US. But I do not have any interest in going to work there," she explains with some exasperation. "It may be the best thing for my career, because there are a lot of high-profile teams there, but it is too far away."

Her partner, who is an IT manager, has already had to move to support her career. She works in Oxford, but he has to commute 50 miles to and from work each day. And Harvey is uncomfortably aware that they will have to move again to further her career - and probably more than once.

"Reasonably short contracts are hard because you never know where you will go next. Will it be Scotland? It is hard when you are in a relationship," she says.

In the meantime, while she is passionate about her research and the goal of understanding a deadly new disease, Harvey is determined it will not take over her life completely. "There are a lot of people in the lab on Saturday and Sunday. But I make sure I get weekends off," she says. "I think that's frowned on, but I'm better working that way."

CV: RUTH HARVEY

Age: 32

Education 1999-2003: PhD at Reading University and Public Health Laboratory Service, researching type A influenza H5N1

1991-94: Degree in biological sciences at Plymouth University

Research work

Currently is a post-doctoral research scientist at Oxford University, focusing on the influenza virus with an MRC-funded programme grant

1997-99: research assistant, Reading University. Functional studies of influenza proteins

Focus: Sars

Severe acute respiratory syndrome, or Sars, swept the world in 2003, causing widespread panic and almost 800 deaths.

Two years on, scientists still do not know where the Sars virus came from or, more importantly, where, when and who it could strike next.

Researchers have developed vaccines against many similarly lethal and virulent viruses. But a Sars vaccine is a long way off. Scientists working on the virus need to understand how it interacts with the immune system and why just 800 of the more than 7,000 people infected died.

Xiao-Ning Xu, a senior clinical scientist at the MRC Human Immunology Unit at Oxford University, is working on the Sars virus.

He says: "Under-standing the protective immunity for vaccine development is a high priority. So far, little is known about host immune cells' response to this new virus."

The virus is so contagious that samples cannot be removed from the UN Hospital in Beijing, so Xu spends part of his time working there. "We are examining samples from 137 Chinese patients who survived the epidemic in 2003. So far, we have found a distinct T-cell [immune cell] response common to all these people, which provides us with some direction for further investigation."

The 2003 outbreak is thought to have originated in the Guangdong province of southern China.

Although the Sars virus is highly contagious, the epidemic was eventually contained by isolating patients and by confining inhabitants of the cities affected - including Beijing, which is known for its bustling street life - to their homes.

Xu recalls: "I remember being there at the time. As a doctor, I was allowed out, but the streets were deserted - there was not a soul in sight. It stayed like this for three months."

Scientists have since found a virus almost identical to Sars in the civet cat, a species bred widely in Guangdong and often served up for dinner. But there could easily be other sources.

"We cannot pinpoint the exact origin of Sars, whether in cat, mouse or rat.

It is this element of the unknown that is the worry," Xu says.

Of equal concern is the fact that the genome of Sars is known and available in the public domain. In the wrong hands, it could make an ideal biological weapon, especially in the absence of a vaccine.

Xu warns: "It is currently rated as a category C virus, one grade down from anthrax. This means it is considered highly pathogenic. It is, quite simply, deadly."

Becky McCall

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