Science Triumphs, Market Fails

Rotavirus is a ubiquitous, equal-opportunity pathogen that infects rich children and poor, the hygienically correct and the unspeakably filthy alike. The vast majority of the 130 million children born each year in the world feel its gastrointestinal bite.

The good news is that the Food and Drug Administration recently licensed Wyeth-Ayerst Laboratories to market an oral vaccine against rotavirus in the United States, where the disease results in about 50,000 hospitalizations and perhaps 40 deaths a year. The bad news is that the vaccine may not be available for many years in the developing world, where the severe diarrhea and dehydration that accompany infection claim somewhere between 600,000 and 800,000 young lives a year.

When I asked Roy Widdus, scientific director of the Geneva-based Children’s Vaccine Initiative, how Wyeth-Ayerst’s initial price of $38 a dose-or a little more than $100 for a full course of treatment-would play in the developing world, he paused, no doubt wondering if he were being interviewed by an idiot. “It’s a nonstarter,” said Widdus with a grim laugh.

Make no mistake, this column isn’t an exercise in company-bashing. Wyeth-Ayerst officials, in addition to providing free vaccine for field trials, have on numerous occasions stated their intent to make this vaccine widely available as soon as possible, and a number of interested parties-including the Children’s Vaccine Initiative, the World Health Organization, UNICEF, the Centers for Disease Control and Prevention, the World Bank and the Rockefeller Foundation-are struggling to help them do it. But they are all up against market forces every bit as ruthless, dispassionate and opportunistic as the virus itself.

Almost since 1973, when the first rotavirus was discovered in Australia, a team of researchers at the National Institute of Allergy and Infectious Diseases led by Albert Z. Kapikian has toiled to concoct a vaccine. Kapikian’s group ultimately developed what he calls a “modified Jennerian vaccine.” Just as Englishman Edward Jenner created a vaccine against smallpox in the 18th century by inoculating humans with the related but milder cowpox (or vaccinia) virus, Kapikian’s team realized that infection with a milder rotavirus common to rhesus monkeys induces immunity in humans to one of the prevalent strains of rotavirus. Since there are four principal strains of the virus in the world today, Kapikian’s team cleverly engineered the monkey viruses to display the surface of the four major human strains.

We already know the vaccine works in a low-income setting. It provided 88 percent protection against diarrhea and 75 percent protection against dehydration, the most severe and life-threatening symptoms of rotavirus, in a study of more than 2,000 Venezuelan children. But the profitable markets lie in the United States and Europe. Wyeth-Ayerst has applied for a license in Europe, but not yet in Venezuela, even though a company spokesman referred to the trial there as “pivotal.”

All isn’t necessarily lost for the children of the poor countries, though, since everyone assumes something called “tiered pricing” will come into play. Once the manufacturer increases production efficiencies, reduces production costs and begins to see some revenues, the argument goes, it can begin to offer the vaccine at a much discounted price. Widdus cites two examples. In 1986, a recombinant hepatitis B vaccine became available in the United States at more than $30 a dose; it took 12 years for “any significant drop in price,” according to Widdus. The initial price for Haemophilus influenzae type b vaccine, introduced around 1990, was more than $20; it took eight years for the dose to drop to around $1 or $2. “With rotavirus,” Widdus says, “we hope that we’ll see some significant price tiering within five years.”

To be sure, compelling scientific questions remain about widespread use of the vaccine. There is a question of whether higher doses may be necessary in situations of poor hygiene and minimal infrastructure in the developing world. And field tests are already under way to see whether the preparation works in India and Bangladesh. “The further you get from the industrial world setting,” Widdus says, “the likelier it is that you’ll encounter strains that are not part of the vaccine.”

There is no easy solution-but there is also no reason to feel comfortable with the status quo. The market forces currently in place impose the cruelest sort of medical triage on the global population-indeed, upon the most helpless portion of that population, in this case infants and children. No one expects Wyeth-Ayerst to underwrite accelerated testing and distribution; shareholders wouldn’t stand for it, and the company is already looking over its shoulder at several competing vaccines in development. The NIH invested considerable resources developing the vaccine, but has no mechanism for providing bridge funding that might initiate field tests sooner in developing countries. WHO, UNICEF and AID all are committed to expediting the process, but no agency is rushing to write a check that might ultimately add up to $50 million.

So while the free market runs its course, the lives of perhaps 2 million children may be lost over five years. At some point we have to look closely at the moral ramifications of economic imperatives: To have an effective medicine and withhold its use does indeed, in the Hippocratic idiom, do harm.