SUSAN DENTZER: Pamela Mandela is a physician in Kenya, who's seen firsthand the devastation of AIDS. She herself is not infected with Human Immunodeficiency Virus, or HIV, the virus that causes AIDS. But she still wanted to be among the first humans to be injected with a trial vaccine now undergoing initial safety tests.
PAMELA MANDELA: I'm doing it for myself, for Kenyans, and for the world in general. We want to fight AIDS.
SUSAN DENTZER: Thomas Pablo is a salesman for telecommunications networks. He'll spend a week this summer biking across Montana to raise money for AIDS vaccine research. Pablo tested negative for the virus after a former girlfriend developed AIDS. He says the experience propelled him to push in his own way for a vaccine.
THOMAS PABLO: Right now we can either decide to do something about it and try to help out, or we can sit around and watch all the millions of people that have AIDS die, and that's just not acceptable to me.
SUSAN DENTZER: Not acceptable, but some experts worry that it is, tragically, inevitable. Although there are promising approaches on the horizon, only one proposed AIDS vaccine is far enough along the research pipeline that it's being tested for effectiveness in large groups of people. That means there's virtually no prospect that any AIDS vaccine will be in widespread use within the next five years. Dr. Seth Berkley is an AIDS vaccine activist.
DR. SETH BERKLEY, International AIDS Vaccine Initiative: When the world looks back 50 years from now or 100 years from now and looks at this century, the question is going to be, not only why did we not respond faster to that emergency with the tools we have today, but also why were we not thinking about the future? Why were we not investing immediately and very heavily on creating the tools necessary to stop the epidemic? And to me, that is one of the great failures the world is going to see.
SUSAN DENTZER: It's been 20 years since the U.S. Centers for Disease Control first reported on the condition subsequently dubbed AIDS, Acquired Immune Deficiency Syndrome. Victims were undergoing a crippling of the immune system that left them vulnerable to other infections, ranging from pneumonia to rare cancers. In those early years, a diagnosis of full-blown AIDS was a virtual sentence to die a wasting death within weeks. By 1984, the cause had been found: HIV.
DR. SETH BERKLEY: When we figured out in 1984 that this was a virus, everybody said we have to make a vaccine.
SUSAN DENTZER: After all, it was only through vaccines that earlier viral enemies of humankind had been tamed or eliminated: measles, hepatitis, polio, smallpox. What's more, HIV was transmitted largely through sexual contact, and scientists knew that efforts to change human behavior would only go so far. Philip Russell worked on vaccines for AIDS and other viruses during a long career with the U.S. Army.
DR. PHILLIP RUSSELL, Sabin Vaccine Institute: Promoting of safe sex and other ways of behavior modification are doing a tremendous amount of good, but they're not going to stop the epidemic. The only way we're going to stop this epidemic is with an effective vaccine.
SUSAN DENTZER: Dr. Robert Gallo was among those who did the first work on understanding HIV.
DR. ROBERT GALLO, Institute of Human Virology: I thought there would be a rather intense crash program and that we should be able to get there in some... I didn't know when, I could only guess, some years, but not too many years.
SUSAN DENTZER: In fact, based on the advice of Gallo and other scientists, some predicted that success in making a vaccine was just around the corner. Margaret Heckler was Health and Human Services Secretary under President Ronald Reagan.
MARGARET HECKLER: (1984) We hope to have such a vaccine ready for testing in approximately two years.
SUSAN DENTZER: The reasons that prediction proved false constitute a complicated tale about economics, politics, and the evolving science of AIDS. (Chanting) Berkley says that the notion of devoting billions of dollars to preventing AIDS quickly lost out to demands for treating those already afflicted.
DR. SETH BERKLEY: The constituency who cared about this disease were those who were HIV infected, and rightfully so. They demanded treatment, and they pushed very hard. Science said, "we don't know how to make drugs for viruses." They said, "We don't care. Put money, put effort."
SUSAN DENTZER: The government and private companies responded. They poured billions of dollars into research that eventually produced breakthrough anti-viral drugs that did extend patients' lives. But a big disparity had cropped up between the money spent on treatment versus the funds devoted to preventive measures, like a vaccine.
DR. SETH BERKLEY: You were talking about, in the actual drug development area, $2 billion to $3 billion a year in the overall research area, and maybe as much as $4 billion a year. But in vaccines until, let's say, five years ago, we were talking about maybe $100 million globally, and on vaccines for the developing world, a few million dollars a year, almost nothing.
SUSAN DENTZER: Small groups of scientists did continue to conduct AIDS vaccine research in government, universities, and private industry. Yet they discovered early on that the scientific obstacles to fighting HIV were even more formidable than the political and economic ones. For one thing, HIV is a member of a family of viruses, known as retroviruses. A scientific team led by Dr. Gallo discovered that their peculiar method of entering and infecting human cells and then reproducing themselves gave them a permanent lease on the human body.
DR. ROBERT GALLO: All retroviruses, therefore HIV included, it's a retrovirus, put their genes into ours. So that if I get infected now and it targets cells in my blood, the viral genes will become part of my chromosomal DNA. And that means that cell is infected forever, and when the cell divides into two daughter cells, the viral genes are transmitted with the cell genes. It'll be reproduced with the DNA as the DNA is reproduced as the cell divides. That means, likely, the individual is infected forever.
SUSAN DENTZER: That wasn't the only scientific obstacle posed by HIV.
PEGGY JOHNSTON: One of the critical challenges in AIDS vaccine development is that this isn't just one virus. This is really families of viruses.
SUSAN DENTZER: Peggy Johnston oversees AIDS vaccine research at the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health. She says there are two separate, highly divergent classes of HIV: HIV-1, the principle variant in Europe and North America, and HIV-2, found mainly in Asia and East Africa. But the variation doesn't stop there.
PEGGY JOHNSTON, National Institutes of Health: There are at least ten different subtypes of HIV that circulate around the world, and all the viruses within that subtype, within that family can differ from each other by about 30 percent to 35 percent in their genetic sequence.
SUSAN DENTZER: On top of that, the virus is also a genetic moving target, evolving constantly, even once it infects a given individual. And HIV has another major feature that sets it apart from other viruses. Take a measles virus. When it enters a human body, it may target a variety of different body cells before being battled back by disease-fighting cells of the immune system. So a measles vaccine is designed to wake up these immune system cells to recognize the measles virus early, then clear the virus from the body before it can cause disease. Contrast that with HIV. When it enters the body, it first seeks out and infects one of the immune system's key soldiers: white blood cells, called T-4 lymphocytes. These are among the same cells needed to battle back HIV, but they can't do that if too many become infected and killed first. They're also the cells that an HIV vaccine has to gear up for action against the virus before HIV can copy its DNA into the body's other cells.
PEGGY JOHNSTON: So there's a race that's underway. What's going to happen first? Can the immune response control the virus before it gets too far along and gets disseminated and destroys the same cells that are needed to mount that immune response?
SUSAN DENTZER: Many of these scientific obstacles proved daunting, and for years little progress was made to overcome them. In a speech in 1997, then-President Bill Clinton set 2007 as a new target date for a vaccine.
BILL CLINTON: (1997) With the strides of recent years, it is no longer a question of whether we can develop an AIDS vaccine, it is simply a question of when.
SUSAN DENTZER: The government redoubled its own efforts, among other things, creating a new vaccine research center at the National Institutes of Health. Meanwhile, private research efforts moved forward at small biotechnology companies and at pharmaceutical giant Merck & Company. And Berkley and others established the international AIDS vaccine initiative, or IAVI.
DR. SETH BERKLEY: We believe that the world ought to take up to 25 vaccine approaches and move them forward simultaneously, and then narrow them down and pick the best six or eight, and those are the ones then that should move forward into widespread clinical testing to see what works.
SUSAN DENTZER: IAVI has formed research partnerships with universities and private industries. One of the first fruits is that vaccine safety trial now underway in the United Kingdom and Kenya. But it's far from clear whether this approach will succeed, as is true for any of roughly a dozen other proposed vaccines now in various stages of animal or human trials. That means it could be five to seven years before a vaccine is widely available. And by that time, an estimated fifty to one hundred million more people are likely to be infected.