Alan Sipress - The Fatal Strain

Flu specialists outside Vietnam did not share her enthusiasm. To outsiders, her unconventional methods looked like reckless endanger ment. Yet to Vietnam, already facing recurring bird flu outbreaks, it was necessity, a clear case of national security. “We cannot wait,” Van told me.

Few pharmaceutical endeavors could save as many lives as the development of a pandemic flu vaccine. Yet the obstacles are many. For years, international research into any kind of flu vaccine languished, in large part because government investment was directed toward AIDS and other diseases considered more pressing. The drug industry had no incentive to put its own money into influenza at a time when anemic public demand even for seasonal flu shots often fell short of existing supply. As a result, the technique for making flu vaccines, an unwieldy process that uses fertilized chicken eggs, remained largely unchanged since the 1950s. Since bird flu began proliferating in Asia, researchers have been chipping away at the challenge. But without significant scientific advances, vaccines against a pandemic strain will only become available long after it has circled the globe because of delays inherent in the technology. An analysis in 2007 found it would take more than half a year after the pandemic strain emerged for the first doses to be delivered. This reflects a timeline that includes about a month for WHO to isolate and distribute the seed strain, a month and a half to ramp up manufacturing, and another four months to produce the vaccine and release it for use. And even after the initial doses debut, most people will still have a long wait because of the world’s modest production capacity.

The H5N1 strain has been particularly nettlesome. The virus has continued to rapidly evolve, spinning off various subtypes that confound efforts to develop a single vaccine in anticipation of an epidemic. The strain has also proven unusually resistant to experimental vaccines. This means higher doses are required to produce immunity, and the higher the dose, the less vaccine there is to go around.

Scientists have been experimenting with new ways to get over these hurdles. One has centered on using cells, rather than chicken eggs, to incubate vaccines. This could cut the production time for a pandemic vaccine in half while increasing available doses. Initial clinical trials of a bird flu vaccine made by Baxter Bioscience using this technology showed promising results, according to a 2008 report.

Another approach has centered on the use of chemicals called adjuvants, which enhance the effectiveness of a given dose by stimulating a person’s immune response. In 2007 the Belgian drug company GlaxoSmithKline reported the results of a study showing that an experimental vaccine against bird flu containing an adjuvant worked at lower doses than even seasonal flu shots. Later that year, WHO announced that these boosters could radically increase the global supply of pandemic vaccines. The agency predicted that by 2010, the world might be able to produce enough to immunize 4.5 billion people per year. But as WHO acknowledged, this would still fall short of what would be required to protect everyone on Earth.

Even with these scientific advances, Vietnam has long suspected it would be at the back of the line if it waited for someone else to come up with a vaccine. Health officials in Hanoi—as well as those in Bangkok, Jakarta, and other Asian capitals—often told me they were sure industrialized countries would look after their own people first. And even if there were enough to go around, who could afford it? The drug industry “can’t provide vaccines to the world free of charge,” stressed Wayne Pisano, chief executive of French vaccine-maker Sanofi Pasteur.

Van had no illusions. “If another country develops this vaccine, the cost will be very, very high,” she explained. “Vietnam is still very poor and could not afford a vaccine with a high cost. We need to provide this essential vaccine through local production at an affordable cost.”

She had been down this road before. In 1997 she had been involved in developing a local vaccine against hepatitis B, which at the time infected at least 15 percent of all Vietnamese. The availability of this low-cost alternative to imported vaccines allowed Vietnam to immunize millions of children against the potentially fatal disease. Five years later, using genetic engineering, Van’s company produced a new generation of vaccines against both hepatitis A and B. She crowed at the time that Vietnam was one of only three countries able to make them. The potential savings were tremendous. At sixty cents per dose, the locally produced hepatitis A vaccine cost less than one-fifteenth the price of those on the international market.

In the 1970s, Van had studied biochemistry in the Soviet Union before returning to get her doctorate in Vietnam. She had done subsequent training in Japan, Russia, and twice at the CDC in Atlanta. For most of her three decades at the institute, hepatitis had been her specialty. But after bird flu erupted in 2003, one of her mentors, a senior Vietnamese virologist who had earlier developed the vaccine that helped eradicate polio in their country, suggested that Van tackle influenza. He told her to hurry. “It was difficult at the beginning, because we did not have the experience,” she recounted, smiling and laughing softly. “But it isn’t really new for me. Any vaccine has similar steps and similar techniques.”

With Japanese assistance, Van’s researchers obtained samples of the flu virus and then engineered a prototype vaccine strain by reverse genetics. The team began growing vaccine in monkey kidney cells, the same method the institute had used in making hepatitis A and polio vaccines. But before clinical trials could begin, WHO asked Vietnam in February 2005 to apply the brakes.

A special WHO delegation, which included officials from agency headquarters in Geneva and the U.S. Department of Health and Human Services in Washington, was sympathetic to Vietnam’s predicament. “No licensed H5N1 vaccine for human use is available from vaccine manufacturers and future availability to Vietnam is doubtful,” the mission wrote.

But the visiting officials objected that Van’s approach was too hazardous. Her team had flouted international guidelines by using monkey kidney cells, which were unapproved for making flu vaccines and might allow the virus to mutate into epidemic form. The use of cancer cells to accelerate the growth of the vaccine strain could introduce another fatal ingredient. Moreover, her lab lacked strong enough safety measures to ensure that the new, genetically engineered strain would not escape. The WHO mission also raised “serious ethical reservations” about the institute’s plan to ask its own scientists to volunteer as guinea pigs. The issue was coercion. “There are concerns that the volunteer ‘spirit’ may not be universally shared and some volunteers may feel uncomfortable and unable to state that for various reasons,” WHO wrote.

Members of the delegation later told me they had received official guarantees from Vietnam that it would abandon the program. But Van had been in those two days of meetings and came away with a different impression. “I believe in our procedures and all the laboratory testing,” she said. “I’m sure our vaccine is safe. So I’m not concerned.”

Clinical trials would go ahead in five months, Van told me. The first phase would involve about twenty volunteers. She would be one of the first. If production stayed on schedule, her company could deliver a half-million doses by the end of the year.

When senior health officials in Geneva and Washington read Van’s comments on the front page of the Washington Post several weeks later, they were taken aback. The United States dispatched the health attaché at its Hanoi embassy to privately confront NIHE’s director and insist that Vietnam make good on its pledge to suspend the program. WHO officials made the same demand in public. Under duress, senior Vietnamese health officials sidetracked the vaccine program, and for a time Van’s drive for national self-sufficiency ran aground on the conflicting anxieties of rich and poor.