First of all, hiv is a retrovirus, a type of virus that rarely infects humans. This crafty bug—protein-and-sugar molecules embedded in a fatty coat around a bundle of genetic material—invades a cell and copies its genetic material, rna, turning it into dna and then inserting it into the good nuclei of the hosts own cells. The viral dna becomes part of the person. Today antiretroviral drugs interrupt that process—they prevent the viral rna from becoming dna, or keep it from integrating into the cellular genome, or stop the cell from making new virus. But take the antiretrovirals away, and the virus starts churning out again. Maybe even more importantly, hiv attacks cells that would otherwise mediate a response to a pathogen—among them, cd4 T-cells. CD4 is a protein on the outside of certain cells critical to the human immune response; its also the protein that hiv latches onto and uses to break into those cells. A hybrid sugar-protein on the outside of the virus called gp120 hooks onto cd4 like a key, opening the door for other hiv proteins and allowing the virus to fuse with the cell and inject its genes. Not only does the virus make a lot of copies of itself very, very quickly, its many different strains also mutate.
He just kind of did. Polio has been almost eliminated on Earth, and smallpox no longer exists in the wild. The past half-century has been miraculous—something like 50 vaccines exist for humans, and hundreds for nonhuman animals we live with. The process for making almost all those drugs, essentially, involved subjecting a pathogen to every tool a laboratory can bring to bear—how to grow it in culture, how to kill or attenuate it, what chemicals to administer alongside it, how many doses to give and. Ideally in the end you hit on a combination that confers immunity. Its a process that a tech entrepreneur like sam Dorman would identify pretty closely with product development. But heres the catch: Classical vaccinology might not essay work on hiv. Theres no documented case of someone who got infected, truly infected, and then cleared the virus, fauci says. The same person can even get infected with two different strains.
Jump ahead to the mid-1950s, when 16,000 people, mostly children, got paralytic polio every year in the. Working from the idea that a vaccine didnt actually have to infect someone with a disease to jump-start immunity, jonas Salk learned to kill poliovirus with formaldehyde and administer. This whole killed virus vaccine worked, though people like albert Sabin thought the formaldehyde would lead to a shorter period of immunity. Roosevelt enjoying after-luncheon conversation with polio patients of the warm Springs foundation in Warm Springs, georgia. Bettmann/Getty Images, this is classical, empirical vaccinology, 20th century style. The road wasnt always straight. Shots in the dark lays out, salk tested his vaccine on children—with few if any of the permissions and safeguards a researcher would need today, like fda approvals or signoffs from Institutional review boards.
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But hes also the first to write point out: no one else knows, either. Name just about any terrifying infectious disease, and no matter how Grand guignol its symptoms, some people who get it also get better—thats true for smallpox, polio, even Ebola. In a broad range of viral diseases, says Anthony fauci, director of the national Institute of Allergy and Infectious Diseases, the overwhelming majority of people survive, and when they do they completely eradicate the virus. And not only that, but theyre immune for the rest of their lives. That recovery hints that a vaccine is possible for those diseases—and many others. Its a matter of creating a trigger that will speed up some processes that already happen in nature.
In the late 1700s, people knew that getting cowpox made you less likely to get smallpox, which in those days in Europe killed up to 400,000 people a year. Cowpox was a virus that their immune systems could fight off, and the cellular recording of that fight—the creation of a defense protocol in the immune system—would often ward off smallpox, too. This led the scientist. Edward Jenner to try intentionally infecting a boy with cowpox as a prospective treatment. When the boy was subsequently found to be immune from smallpox, jenners method took off, and the death toll from smallpox plummeted. The latin name for cowpox is vaccinia, after the latin for cow, so jenner named his process vaccination.
But an equally diligent effort should be made to extract what we can from methods that have already been invented. That is what he has been saying for three decades. To the mainstream scientific community, dormans quest is quixotic at best, tilting at windmills made of glycoproteins and rna. But Dorman, now a spry 80, hasnt given. Hes convinced that if the rest of the scientific community had joined him decades ago, millions of lives would have been saved. They still could.
This isnt a matter of science—at least, its not a matter of only science. Its a matter of scientific culture—of a framework for making decisions about a research agenda. The aids memorial quilt is shown for the first time on the mall in Washington dc, 1987. Lee snider/Getty Images, aids memorial quilt on the national Mall lawn; 20,000 quilts are displayed, 1992. Jeffrey markowitz/Getty Images, that doesnt mean Dorman is right and theyre wrong. Hell be the first to say that he doesnt know.
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It can work—and indeed often has—without a researcher knowing much, if anything, about the essay underlying immunology. Because of how hiv works—how the virus infects a cell, what kinds of cells it infects, how it mutates and reproduces—and because of how vaccines get tested and developed, most scientists working on hiv immunology dont think that such a classical approach can work. Instead, they aim to break apart and rearrange the specific pieces of the virus, like the sugars and proteins embedded in its shell, and deliver those alongside enhancing agents. These approaches, arising from recombinant dna and protein technologies, are by their very nature more hypothesis-driven. This is the approach that garners almost all research funding from government agencies and pharmaceutical companies. Dorman, then president of Advanced Genetics Research Institute, 1985. Courtesy of Sam Dorman. And yet, in the 35 years since scientists isolated the virus that causes aids, 35 million people have died of the disease worldwide while waiting for a vaccine. Its a nice thing to argue that we will one day understand the biology well enough to do rational design of a vaccine, dorman says.
Since then, new therapies like antiretroviral drugs have made hiv infection into something its possible to live with rather than die from—at least, in the developed world. The search sales for a vaccine continues, a decadal, tidal ebb and flow of optimism followed by failure. Burt Dorman with his son Sam at age 12, 1988. Courtesy of Sam Dorman, dorman, too, is still. But hes pushing an approach to developing a vaccine that he argues the entire scientific edifice has largely abandoned. Dorman advocates a path that you might broadly term classical. Its almost trial-and-error, a methodology that goes back to smallpox and rabies. Like early vaccinologists—Jenner, pasteur, salk—dorman is a tinkerer who figures out how to grow, kill, and administer viruses in a way that sparks an immune response.
meeting at his office; his son Sam remembers one at their house in Berkeley. My image as a kid was of my dad feeling duty-bound, that there were people suffering and in danger, and they could do something, sam says. Dorman decided to try. Today his name peeks through some of the stories of the early days of the epidemic and the hunt for a vaccine against the virus. He photobombs, metaphorically, books about the early years of the effort like jon Cohens. Shots in the dark and Patricia thomas, big Shot (both published in 2001).
Still, by 1987 the first vaccine trial was underway, the world health Organization had launched a global fight against the contagion, the playwright Larry Kramer had started the activist group act up, and the first antiretroviral drug, azt, was available. Even so, science was still woefully short of understanding writing the plague or coming up with a vaccine that could prevent. By the end of the decade, more than 100,000 people were infected in the United States. Absent treatment, the mortality rate for these patients, then as now, was effectively 100 percent. Dorman knew vaccines; he started talking to other people in the vaccinology world about being part of the fight. Don Francis, a longtime disease hunter then with the centers for Disease control and one of the main characters in the book. And the band Played On, got in touch—Dorman had tackled feline leukemia, and its caused by the same type of virus that triggers aids.3 Why not try to tackle hiv? Dorman, 80, has been pushing to do classical vaccine research on hiv since the 1980s.
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In the late 1980s, burt Dorman was ready to get out of the vaccination game. A biophysical chemist, hed spent years running a successful company making animal vaccines—a dozen of them, against diseases like feline leukemia and vesicular stomatitis. Now Dorman was starting a new company in a new field, aiming at disease diagnostics. And then the aids epidemic hit. The first resume hint that a new disease was killing people had come in 1981, in a publication called the. Morbidity and Mortality weekly report. What followed were years, decades even, of tragedy and homophobia-tainted ignorance.