Harvard Public Health Review
Spring 2005



Dean's Message

"Only Connect ... "

What can we learn from vaccines?

Imagine a hypothetical epidemic in your city or town that looks like this:

September 12: 1 case of flu-like illness

September 18: 6,000 cases

September 23: 12,000 cases (700 deaths)

Within six months, 25 percent of the civilian population is infected and 4 percent die.

Within a year, the virus spreads around the globe and kills between 20 and 40 million people

These data are not hypothetical. They are, in fact, the real data recorded at Ft. Devens, Massachusetts, and globally, resulting from the great influenza pandemic of 1918.

We know that different strains of influenza virus emerge each year -- usually from Asia, usually from the genetic mixing of bird or pig viruses and a human strain that is easily transmitted -- and they spread around the world. In one of the triumphs of modern public health, 87 World Health Organization (WHO) reference laboratories collect the strains as they are transmitted, then pick the three candidates most likely to spread, from which the vaccine companies produce vaccines within months. We know that these vaccines provide a remarkable degree of protection for people who receive them, partly because the new strains are usually related to previous strains to which we already have some immunity. Yet approximately 36,000 people die each year in the U.S. from influenza and pneumonia. WHO now estimates that the total annual global production is 260 million vaccine doses --only enough vaccine for 4 percent of the world’s 6.2 billion people.

Only two companies supplied flu vaccines to the U.S. in 2004. One of them failed to produce a safe product, and we faced a major threat from an acute shortage. Then, everyone wanted to be vaccinated, but distribution was limited to the highest-risk individuals. We are very lucky to have gotten through a mild flu season with borrowed vaccine from abroad, but as availability has increased, ironically demand has almost disappeared, and the U.S. will again have to discard enormous amounts of vaccine. Despite the fact that vaccines represent the most cost-effective intervention known to prevent disease and death, the vaccine system in the U.S. remains seriously broken.

A New Flu Strain is Emerging
In the past year we have seen the emergence of a new set of strains of influenza: avian (bird) flu, or A(H5N1) --to which, like the 1918 strain, most humans around the world have not previously been exposed. A(H5N1) has resulted in the deaths of 150 million chickens in Vietnam, Thailand, Laos, Cambodia, China, and South Korea, either directly or through culling to stop the spread of virus. As of mid-April, A(H5N1) had spread to at least 80 humans and killed 50, and many experts believe that in at least one case the virus appears to have been transmitted directly between humans.

When SARS struck in 2003, the epidemiological work of Marc Lipsitch, Megan Murray, and their collaborators at HSPH, published on the web by Science, revealed that every infectious case on average transmitted the infection to about three more individuals who also became infectious. While there is no information on how readily a variant of A(H5N1) might spread among humans, at HSPH, Christina Mills, Jamie Robins, and Lipsitch have given us the next best thing: They have modeled the deadly 1918 influenza pandemic using extraordinarily good but largely overlooked data like that above from 1918. As an article on their work in this issue of the Review reports (see "Preparing for a Pandemic"), the good news is that the 1918 flu appears to have been no more transmissible than SARS. The bad news is that the time between exposure and illness was much faster for the 1918 virus than for SARS, so we will have far less time to prepare for a major public health threat.

Clearly we must be prepared -- for rapidly producing vaccines for a new bird flu strain that can be transmitted readily between humans, but does not yet exist, for dispersing a drug that is effective in preventing death if given early, and for taking care of enormous numbers of people who would be acutely ill, many of whom may die. Equally clearly, although there is a national plan, we are not prepared.

The Problem with Vaccines
In 1994 I wrote a controversial article in Science arguing that the U.S. was unprepared to deal with infectious threats for which vaccines could be life-savers, and proposed that a national vaccine authority be created to protect the public’s health. In the case of influenza vaccine, even in a good year we produce only enough vaccine to immunize about a fourth of the population and we do a terrible job of getting people at risk to be immunized.

Why? There are many reasons. Vaccines account for only a small percentage of the profits of the pharmaceutical and vaccine industries, and a higher percentage of the liabilities. The costs of research represent only a small percentage of the total cost of vaccines. The major costs are for clinical trials, and for capital investments in new plants and infrastructures required to produce safe, reproducible, and effective vaccines. And for new vaccines, almost all of the investments must be made up front, before their safety and efficacy are fully known and before the markets for them become clear. Finally, we are terribly ineffective at getting vaccines out to very young children or to senior citizens at greatest risk, or to most adults. Our current experience with flu vaccines only reinforces my view that we need a national vaccine authority to oversee the availability and quality of vaccines, to see to it that investments are made in prevention, and to create publicly assured markets to supplement private markets, if necessary, to protect the public’s health.

The sad economic fact about vaccines is that markets generally work. It is not obvious what the market incentives might be for companies to produce vaccines against a human transmissible strain of bird flu that does not yet exist, or against anthrax or smallpox or 80 select agents that could be used for biological terrorism, or diseases of the developing world like malaria, tuberculosis, typhoid fever, or dysentery. Obviously, when an epidemic or pandemic occurs, there will be a terrific market -- but no vaccines.

How Vaccines Can Lead the Way to Health Care Reform
Happily, there is one vaccine problem we have solved, although it remains one of the best kept secrets in Washington. In 1984 there were 14 vaccine companies in the U.S.; in 1994 there were just four. Low profits, high risks for success, and huge liability settlements for vaccine-related injuries, which tragically occur in a very small fraction of children and which cannot be predicted, put most vaccine producers out of business. Then in 1986 an extraordinarily enlightened piece of legislation was passed: Title XXI of the Public Health Service Act (P.L. 99-660). This statute quietly codifies some visionary innovations in health care, most notably "no-fault" health insurance for vaccine-related injuries.

The law established a National Vaccine Injury Compensation Program to enable families of children injured by vaccines to receive compensation for lifetime medical expenses, lost earnings, and pain and suffering. Compensation can be obtained by filing a valid claim with special Masters of the Court, without the need for expensive and protracted litigation. The program is financed by a trust fund created by an excise tax on every dose of vaccine. The program has worked extraordinarily well for both the families and the companies that produce mandated childhood vaccines. In order "to achieve optimal prevention of human infectious diseases through immunization and to achieve optimal prevention against adverse reactions to vaccines," one provision called on the secretary of the Department of Health and Human Services (DHHS) to establish a National Vaccine Program and a National Vaccine Advisory Committee formed with representation from industry, academe, government, and civil society to advise DHHS and Congress. Alas, it has essentially no authority or real responsibility to make a difference. We need to do better.

What can we learn from the National Vaccine Injury Compensation Program?
Let’s consider just one case.

Medical injuries represent a major health problem in this country. Studies from HSPH over the past 15 years by Lucian Leape and his colleagues have revealed that perhaps 45,000-98,000 unnecessary deaths occur each year in hospitals. The studies also indicated that the vast majority of medical errors are not the result of incompetent doctors, but reflect flaws in the system, compellingly summarized in an Institute of Medicine report appropriately titled, "To Err is Human." The idea of creating "no-fault" insurance for medical errors and injury based on the successful working of the National Vaccine Injury Compensation Program is an appealing one, and a very exciting area of policy research at HSPH being developed by Michelle Mello and David Studdert in our new Program in Law and Public Health. If it could be generalized beyond even vaccines and medical errors, it could strengthen prevention systems, improve quality, reduce unnecessary defensive procedures, reduce costs, and provide humane compensation for all victims of medical injuries.

Vaccines hold many lessons for us. They demonstrate the importance of investing in prevention, of protecting the public’s health against infectious threats, and of responding in a humane and non-litigious way to adverse events associated with interventions that safeguard the lives of millions. With exquisite brevity, E.M. Forster epitomized our challenge in two words, "Only connect … ." For us this means not only to create knowledge and evaluate evidence, but to connect that knowledge to policy makers and the public to enable effective and equitable solutions to our major health problems.

Barry R. Bloom
Dean of the School
Joan L. and Julius H. Jacobson II
Professor of Public Health


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