Life is launched and propelled by two groups of big, complex molecules: nucleic acids that are assembled into genes and the proteins those genes define. All life uses this bootstrap code to lift itself up from the stillness of inanimate matter.
Like software, this wetware can be erased, corrupted, infected, hijacked, and edited, letter by letter, word by word. Parts of our immune system subtly reconfigure their own code on the fly, in random ways; so do cancer cells. The power in this code resides in molecules that, with the technologies we now have in hand, are as easy to read, copy, and manipulate as silicon chips, or soon will be.
By assembling reams of fragmentary data to map out genomes, then dredging medical and genealogical databases to expose links between genes and disease, powerful computers are helping discover which molecules drugs should target. Drug designers then use that information to unleash two astonishingly brilliant and powerful tools for designing magic-bullet molecules to modulate the chosen targets. One enlists digital code to mimic life: Computers play a large role in designing drugs precisely matched to designated targets. Alternatively, molecular magic bullets are being created using the carbon-based biological code in laboratory animals. Either way, the vital core of medicine is now on the same plummeting-cost trajectory as microchips and software.
But the Food and Drug Administration rules that govern the rollout of these 21st-century drugs were designed for the far less powerful 20th-century tools of pharmacology. The regulations were cobbled together at a time when nobody could read the molecular-scale code that controls so much of health and disease. Drugs were designed mainly by hunches and guesswork, and very few worked well. The safe and effective use of medicine depended on gathering purely statistical information about how drugs affect high-level clinical symptoms.
The old system assumed broad areas of biochemical uniformity among patients where we now know there is none. It conflated differences between people and outcomes, steering medicine relentlessly toward generic drugs for generic patients. And by focusing on clinical symptoms and effects, which often take a long time to surface, it was often very slow. The approach we need going forward must be able to deal systematically with complex biochemical diversity that often lurks underneath a single set of clinical symptoms. And it must do so efficiently enough to take full advantage of modern pharmacology's power to develop a vast array of precisely targeted drugs.
As it happens, important elements of such a system were developed in the 1990s after Washington was suddenly smacked in the face by the horrifying biochemical reality of a retrovirus called the Human Immunodeficiency Virus, or HIV. Biochemists immediately began developing treatments using tools that would have, in the National Academy of Sciences' phrase, a "revolutionary effect on modern drug design." Meanwhile, the Food and Drug Administration (FDA) concocted a bunch of clever ways to dodge its own rules, thereby unleashing the full fury of our biochemists against this quiet, slow-to-kill virus. In doing so, the government hinted at a regulatory framework for unleashing the far greater power of today's molecular medicine against the flaws in human chemistry that sicken and kill us.
The AIDS Revolution
With HIV, nature cooked up an all-purpose anti-vaccine, so tiny and gentle that it spread unnoticed for decades, so innocuous that it never quite got around to killing you. It left that messy job to the bacteria, protozoa, and viruses that take advantage of disabled immune systems to feast on brains, lungs, blood, livers, hearts, bone marrow, guts, skin, and eyes.
On June 5, 1981, the U.S. Centers for Disease Control reported five cases, two of them fatal, of a rare form of fungal pneumonia that had struck "previously healthy young men" living in Los Angeles. A second report, issued a month later, noted additional clusters of Kaposi's sarcoma-a rare, aggressive form of skin cancer caused by a herpes virus. "The fact that these patients were all homosexuals suggests an association between some aspect of homosexual life-style or disease acquired through sexual contact and Pneumocystis pneumonia in this population," the first report declared.
These "previously healthy" patients had in fact been mortally ill for years. Isolating the underlying cause took another three years, by which time the stealth epidemic had been creeping its way across America for almost two decades. HIV has been found in the remains of a resident of Kinshasa, Congo, who died in 1959. By 1985, when Rock Hudson's death gave the virus a dose of Hollywood publicity, 12,000 Americans were already either dead or dying. By 1992 AIDS was the leading killer of young American men.
HIV isn't like cholera, smallpox, or any of the other one-size-fits-all infectious scourges of the past. Contagious properties aside, HIV is more like cancer: It briefly causes some flu-like symptoms soon after it enters the body, then typically hides unnoticed for five to 10 years. The disease discriminates fiercely-based on ancestry, sexual lifestyle, needle-sharing habits, or disability (it killed many hemophiliacs), and against babies born of the wrong mother. It typifies the diseases of the future: slow, subtle, complex, and rooted in lifestyles and genes.
"One in five-listen to me, hard to believe-one in five heterosexuals could be dead of AIDS in the next three years," Oprah Winfrey declared in February 1987. Oprah was wrong. HIV was and remains tightly linked to lifestyles shared by several comparatively small, discrete groups of Americans. The virus doesn't spread fast and indiscriminately; that's the old strategy for staying out ahead of the human immune system. It specializes instead in adapting itself to cooperative hosts and outrunning their immune systems.
HIV isn't so much a virus as a system for spawning new viruses. It replicates fast-so fast that, although the immune system fights back, it can't keep up. Each new particle formed has, on average, one mutation in its 10,000 units of nucleic acid code. "As death approaches," the geneticist Steve Jones writes in his 1999 book Darwin's Ghost, "a patient may be the home of creatures-descendants of those that infected him-as different as are humans and apes."
This process allows HIV to adapt quickly to the lifestyles of different communities. On its trek out of Africa, it found shelter in polygamous communities whose naming and coming-of-age traditions often involve the sharing of mother's milk and blood. It then split into two strains, HIV-2, which predominates among African heterosexuals, and HIV-1, which favors homosexuals. New subsidiary clusters-HIV-1A, 1B, and so forth- continue to emerge.
The predominant form of the virus found in Thailand soon after its arrival in the early 1990s was "something of a specialist at travel by the anal route," Jones writes. A decade later, "in its new nation of sex tourists," that strain had given way to a variant that "prefers conventional sex." In varying degrees, all sexually transmitted germs do much the same. "Every continent, with its own sexual habits, has its own exquisitely adjusted set of viruses."