Stop That Germ!
By LEON JAROFF
It's a jungle out there, teeming with hordes of unseen enemies. Bacteria, viruses, fungi and parasites fill the air. They cluster on every surface, from the restaurant table to the living-room sofa. They abound in lakes and in pools, flourish in the soil and disport themselves among the flora and fauna. This menagerie of microscopic organisms, most of them potentially harmful or even lethal, has a favorite target: the human body. In fact, the tantalizing human prey is a walking repository of just the kind of stuff the tiny predators need to survive, thrive and reproduce.
Humans are under constant siege by these voracious adversaries. Germs of every description strive tirelessly to invade the comfortably warm and bountiful body, entering through the skin or by way of the eyes, nose, ears and mouth. Fortunately for man's survival, most of them fail in their assault. They are repelled by the tough barrier of the skin, overcome by the natural pesticides in sweat, saliva and tears, dissolved by stomach acids or trapped in the sticky mucus of the nose or throat before being expelled by a sneeze or a cough. But the organisms are extraordinarily persistent, and some occasionally breach the outer defenses. After entering the bloodstream and tissues, they multiply at an alarming rate and begin destroying vital body cells.
The invaders soon receive a rude shock, for they encounter one of nature's most incredible and complex creations: the human immune system. Inside the body, a trillion highly specialized cells, regulated by dozens of remarkable proteins and honed by hundreds of millions of years of evolution, launch an unending battle against the alien organisms. It is high-pitched biological warfare, orchestrated with such skill and precision that illness in the average human being is relatively rare.
Early-warning cells constantly monitor the bloodstream and tissues for signs of the enemy. With the gusto of Pac-Man, they gobble up anything that is foreign to the body. They envelop dust particles, pollutants, microorganisms and even the debris of battle: remnants of invaders and infected or damaged body cells. Other early warners direct the production of unique killer cells, each designed to attack and destroy a particular type of intruder. Some of the killers, alerted to body cells that have become cancerous, may annihilate these too.
Endowed with such specialized weapons, the properly functioning immune system is a formidable barrier to disease. Even when an infection is severe enough to overcome the system's initial response and cause illness, the immune cells are usually able to regroup, call up reinforcements and eventually rout the invaders. But when the system is weakened by previous illness or advancing age, for example, the body becomes more vulnerable to cancers and a host of infectious diseases. And should the system overreact or go awry, it can cause troublesome allergies and serious disorders called autoimmune diseases.
As they probe the intricate workings of the immune system, scientists are awestruck. "It is an enormous edifice, like a cathedral," says Nobel Laureate Baruj Benacerraf, president of Boston's Dana-Farber Cancer Institute. The immune system is compared favorably with the most complex organ of them all, the brain. "The immune system has a phenomenal ability for dealing with information, for learning and memory, for creating and storing and using information," explains Immunologist William Paul of the National Institutes of Health (NIH). Declares Dr. Stephen Sherwin, director of clinical research at Genentech: "It's an incredible system. It recognizes molecules that have never been in the body before. It can differentiate between what belongs there and what doesn't."
Knowledge about the inner workings of the immune system has undergone an astonishing explosion in the past five years. Although researchers began to pry loose its secrets in the late 19th century, it was not until after World War II that the pace of discovery began to quicken, boosted by such achievements as the deciphering of the genetic code and recombinant DNA technology. But no early advances can match those of recent years, which have enabled doctors to devise ingenious new treatments for a host of disorders. Says Immunologist John Kappler, of the National Jewish Center for Immunology and Respiratory Medicine in Denver: "The field is progressing so rapidly that the journals are out of date by the time they are published."
Kappler is not exaggerating. In the past few months alone, dozens of new immune discoveries and promising therapies have been reported. Researchers announced in March that by activating certain immune cells, they had increased by 20% the five-year survival rate of patients in the early stages of lung cancer. In the same month, European scientists reported eliminating the need for insulin shots in some diabetic children by administering a drug that suppresses the immune system. Researchers in Colombia have tested a malaria vaccine that, unlike previous efforts, seems to provide protection against the disease. Advances have come so fast, says Dana-Farber's Benacerraf, that "we're now on the threshold of being able to activate the different components of the immune system at will to provide therapies for cancer and even for AIDS."
In fact, it is the AIDS epidemic that has spurred much of the recent interest in immunology. The AIDS virus strikes a key component of the immune system, destroys it, and in so doing virtually knocks out the entire system. Nothing illustrates the importance of a healthy immune system more dramatically than the disastrous consequences of its loss. AIDS sufferers become vulnerable to many kinds of invading organisms. Fungal growths corrode the skin and lungs. Normally dormant parasites in the lungs become active, causing Pneumocystis carinii pneumonia. As viruses and bacteria multiply out of control, competing for body cells and destroying them far faster than they can be replaced, victims can be stricken with severe cases of herpes and tuberculosis. What is more, they lose their resistance to some types of cancer, particularly Kaposi's sarcoma.
Tragic as it is, says Dr. Anthony Fauci, the AIDS research coordinator for the National Institutes of Health, the AIDS epidemic has provided important new insights into the immune system. "AIDS is the perfect disease for studying the immune system," he explains. "The virus destroys one of the + major cells of the system. So now nature is doing the experiment. It has just pulled out a major chip, and we're watching everything else go haywire." On the other hand, AIDS Expert Robert Gallo of the National Cancer Institute believes that much of the progress in AIDS research would have been impossible without discoveries about the immune system made shortly before the epidemic bloomed. "If AIDS had come along in the 1970s," he says, "we'd still be looking under rocks for the cause."
Now, however, scientists have a good grasp not only of the broad workings of the immune system but of many of the nitty-gritty details as well. In a typical infection, for example, a flu virus burrows into a cell in the lining of an air passage, takes over the machinery of the cell, and orders it to produce more flu viruses. Quickly engorged, the invaded cell bursts, releasing new viruses to infiltrate other cells and replicate further. Left unchecked, the onslaught would eventually kill enough cells to cause death. But the intruders soon encounter roving scavenger cells called phagocytes, which simply engulf and digest them. These defenders -- monocytes, neutrophils and macrophages -- secrete substances that dilate nearby blood vessels and make them more permeable, enabling even more defenders to get from the bloodstream to the infection site. Other proteins, those belonging to the complement system, aid in this process.
Upon meeting a virus, the macrophage, which moves about, amoeba-like, on long cellular extensions known as pseudopods (false feet), does more than just ingest the intruder. It has another, even more important function. On its surface, like virtually all body cells, the macrophage carries MHC (for major histocompatibility complex) molecules, protein badges that enable other immune cells to recognize the macrophage as friend, or self, and not attack it. After digesting the virus, the macrophage proudly displays strips of protein from the virus in the grooves of some of its MHC molecules. Once a bit of protein -- which is part of the virus's own identity molecule, or antigen -- is nestled in the groove of the macrophage's MHC molecule, it acts as a red flag for the immune system, warning it that a particular type of virus is loose in the body.
"At this point, it's still a race between the immune system and the virus," says Dr. Carl Nathan of Cornell University Medical College. "The virus is trying to replicate before the immune system has a chance to gear up." In order to mobilize the system, the macrophage must find -- or literally bump into -- a helper T cell, the battle manager of the immune system. The catch is that only a tiny fraction of the billions of T cells in the body are capable of attaching to the antigen of this particular flu virus and taking action. To increase its odds of meeting up with an appropriate T cell, the macrophage probably moves from the body tissue into the nearest lymph node, through which helper T cells of all kinds continually pass. Robert Coffman, a scientist at Palo Alto's DNAX Research Institute, likens the site to a busy Manhattan sidewalk. "If you walk the street enough," he says, "pretty soon you'll run into almost everyone who lives in New York City."
When the macrophage finally runs into a compatible helper T cell, it inserts its antigen-bearing MHC molecule into a T-cell receptor shaped to receive it, much as a key would fit into a lock. The macrophage then secretes a protein called interleukin-1, a chemical signal that causes the T cell to begin replicating. Simultaneously, interleukin-1 acts on the body's central thermostat, causing a fever, which may depress viral activity and enhance the immune response.
The rapidly multiplying helper T cells now begin releasing a flood of their own chemical signals, the so-called lymphokines, which include gamma interferon and other types of interleukin. These stimulate the defense system even more, spurring the proliferation of phagocytes, including macrophages, and other immune fighters -- something like a draft call in wartime. The result is the familiar swelling and inflammation of an infection.
At the same time, other helper T cells in the lymph nodes move to couple with yet another kind of immune fighter, the B cells. Releasing still more chemicals, the helper T cells stimulate the B cells to reproduce. These proliferating B cells then mature into plasma cells, which DNAX's Coffman calls "dedicated antibody factories," that begin to mass-produce antibodies. Antibodies are proteins capable of recognizing and binding specifically to the flu virus that triggered the alarm. Circulating in the blood to seek out their quarry, they begin attaching themselves to the viruses, signaling the macrophages and other immune scavengers to move in for the kill.
Meanwhile, gamma interferon released by the T cells has not only slowed viral replication but also whipped the macrophages into a feeding fury. Their cell membranes become ruffled, their feet more numerous and their appetites ferocious. "They don't necessarily eat faster," notes Dr. Richard Johnston Jr. of the University of Pennsylvania School of Medicine, "but they kill better."
The flu viruses, however, are not finished yet. Those still multiplying inside the body's cells are momentarily safe from scavengers and antibodies, but the free lunch is over quickly. While the B cells are being activated, other helper T cells have been creating an army of killer T cells. These killers recognize the flu-ridden cells because, like macrophages, infected cells display a bit of viral antigen on their outer membranes. Says Coffman: "For many viral infections, the most important response is the killer T cell. Viruses live inside cells, so it's essential to kill not only the viruses themselves but those cells that are infected with the virus."
The killer T cells are relentless. Docking with infected cells, they shoot lethal proteins at the cell membrane. Holes form where the protein molecules hit, and the cell, dying, leaks out its insides. To ensure that the cell and its viral occupants are destroyed, the killer T cells then deliver the coup de grace by transmitting a signal that causes the cell to chew up DNA from both itself and the virus. Explains Dr. Irving Weissman of Stanford: "This is an overlapping, dual system of killing that ensures that the seed of viral production will be eliminated from the body."
When victory over the virus is achieved, the wildly accelerating responses of the immune system slow, then shut down. Scientists believe that still other immune specialists, known as suppressor T cells, call off the battle. As the carnage wanes, the B cells and T cells perform a last, vastly important task: they form memory cells that circulate in the bloodstream and lymph system for many years, primed to spring into action should the same strain of flu virus ever attack again. In addition, the body is protected by specialized antibodies, strategically deployed in mucus, saliva and tears, that immediately recognize any return of this particular virus.
While a healthy immune system may take as long as three weeks to complete the job against a specific flu virus, its next response to the same viral strain reaches full force immediately, and the invaders are overcome before they can do any significant damage. In other words, the body has become immune -- but only to that specific virus. "You probably wouldn't even know you'd been reinfected," says Carl Nathan. "The immune system has a short track and a long track, and it all depends on whether it's a first encounter or you've seen it before."
How did this astonishing biochemical system develop? The first stages in its evolution are a mystery. But scientists have deduced from the study of primitive species that rudimentary mechanisms against infection existed in various forms of life more than a billion years ago. The first inkling of such progenitors came in 1883, when Russian Zoologist Elie Metchnikoff stuck a rose thorn into the larva of a starfish and a short time later observed that the thorn had been completely surrounded by cells. The cells were phagocytes. "These little guys go back in evolution a very long way," says Carol Reinisch of the Tufts School of Veterinary Medicine. "They have the ability to distinguish between self and nonself, which is the crucial distinction."
Over the eons, these primitive defenders developed increasingly sophisticated weapons to fight off microorganisms, which could mutate far more rapidly and thus evolve faster than higher forms of life. But it was probably not until about 600 million years ago, about the time vertebrates began to emerge, that the modern immune system, with its T cells and B cells, began to take shape. Once in place, these two cell types must have quickly evened the odds, since they have the remarkable ability of producing, respectively, a staggering variety of killer T cells and antibodies capable of attacking any invader.
How these immune cells produce such diversity was elucidated during the mid- 1970s by Immunologist Susumu Tonegawa, now at M.I.T., who in 1987 was awarded the Nobel Prize for his achievement. Tonegawa proved that the B-cell genes that dictate the production of antibodies occur in distinct segments. These pieces, like cards in the hands of a Las Vegas dealer, are constantly and speedily shuffled into different combinations. Coupled with mutations that occur as B cells divide into plasma cells, such genes, in theory at least, could account for as many as 10 million antibody variations. Other scientists have shown that T cells have a similar mechanism. Thus within the slowly evolving human being, the immune system is undergoing a rapid internal evolution of its own. And a good thing too. "If all we had to meet the microorganisms was true evolution," says NIH's William Paul, "we'd long ago have disappeared from the face of the earth."
) Long before scientists even began to unravel the mysteries of this remarkable system, the ancients were aware of immunity. They knew from experience that anyone who survived certain diseases would not be likely to get them again. As early as the 11th century, Chinese doctors were manipulating the immune system. By blowing pulverized scabs from a smallpox victim into their patients' nostrils, they could often induce a mild case of the disease that prevented a more severe onslaught. In the 1700s, people rubbed their skin with dried scabs to protect themselves against the disease.
These primitive practices were introduced to England and the American colonies. In 1721 and 1722, during a smallpox epidemic, a Boston doctor named Zabdiel Boylston scratched the skin of his six-year-old son and 285 other people and rubbed pus from smallpox scabs into the wounds. All but six of his patients survived.
A much safer approach to immunology was made in 1796, when Edward Jenner decided it was more than coincidence that milkmaids stricken with a mild form of the cattle disease called cowpox were rarely victims of smallpox. He inoculated James Phipps, 8, with cowpox, then exposed him to smallpox six weeks later. The boy never came down with the disease, confirming that the immunization had worked. More than a century and a half passed before scientists knew the reason: the antigens on the cowpox virus are so similar to those on the smallpox virus that they can prime the immune system to repel a smallpox infection.
In 1880 Louis Pasteur, a French microbiologist, concocted a vaccine against chicken cholera after discovering that weakened cholera organisms, while incapable of making chickens sick, would immunize them against the malady. Pasteur, who is credited with founding the science of immunology, went on to create a human rabies vaccine from the brains of rabies-infected sheep and rabbits.
Building on Pasteur's work, 20th century scientists have learned to mass- produce bacteria and viruses, then weaken or kill them and use them as the major ingredient in vaccines for such varied diseases as typhus, yellow fever, influenza, polio, measles and rubella. Unfortunately, the vaccines occasionally cause the disease they are designed to ward off. (Reason: the "killed" viruses sometimes survive, while the weakened versions often fail to cause an immune response.) In general, however, the vaccines have been quite effective; in recent years the National Academy of Sciences has reported only a handful of polio and diphtheria cases and only a few deaths caused by whooping cough and rubella. Maurice Hillemen, director of Pennsylvania's Merck Institute for Therapeutic Research, characterizes the early vaccine era as the "stumbling-along period."
These days the explosive growth of both molecular biology and immunology has enabled vaccine makers to take a safer and more effective approach to their work. Instead of using dead or attenuated bacteria or viruses, they remove from the bug's surface the marker protein, or antigen, that provokes the immune response. Employing gene-splicing techniques, they mass-produce the antigen, or a portion of it, and use it as the prime ingredient of the vaccine.
Researchers are also creating vaccines that consist largely of antigens synthesized from chemicals on the laboratory shelf. When these vaccines prove ineffective, scientists can now usually determine why. Says M.I.T. Molecular Biologist Malcolm Gefter: "Today, when a vaccine doesn't elicit a protective response, it is possible to detect what is or is not working -- the B cells, the T cells, the lymphokines, whatever." Scientists can then "fix" the vaccine. For example, the 1985 vaccine against Hemophilus influenzae Type B, which causes bacterial meningitis, was only partially effective; although it protected older children, it did not work for babies under two years, who are most at risk. The antigen used to make the original vaccine has been re- engineered to make it more potent, and the new vaccine is being tested in infants.
Despite such advanced techniques, it seems tougher than ever to create new vaccines. Some viruses, bacteria and parasites are so complex and well evolved in their defenses against an immune reaction that no vaccine strategy has yet been entirely effective. Flu viruses, for example, mutate rapidly, continually changing their antigens in the process. As a result, an immune system strengthened by a flu shot against last year's predominant strain of flu will probably not be helped by it this year. The common cold virus is also troublesome, because it comes in at least 100 identifiable varieties. The parasite that causes malaria poses still other problems: it penetrates cells so quickly that it is hidden from antibodies. To complicate matters, it goes through three stages of life, displaying different antigens in each stage. Because none of the malaria vaccines yet developed can cope with these diverse strategies, the affliction is still rampant in the tropics.
Such challenges to the vaccine makers, however, pale in comparison with that presented by the AIDS virus. Says M.I.T.'s Gefter: "We're looking at a strong, well-evolved, well-designed organism that is doing whatever it can to protect itself." The AIDS virus mutates twice as fast as the flu bug. It can lie dormant in body cells, where antibodies cannot attack it, without revealing its telltale antigen (a dead giveaway to killer cells). New findings indicate that the virus also uses immunological decoys that provoke impotent immune responses. Worst of all, the AIDS virus is unique in that it can mount a speedy and lethal attack on helper T cells, which cripples the immune system before it can counterattack. This means that to prevent an AIDS infection from taking hold, a vaccine must stimulate the immune system to incapacitate the AIDS virus immediately after exposure, before it can penetrate the helper T cells.
Scientists are scrutinizing the AIDS virus for any sections of its outer coat that remain unchanged during its rapid mutations. With antigens from these sections, they hope to produce a vaccine that will remain effective despite many mutations. A group led by Dr. Daniel Zagury at the Pierre and Marie Curie University in Paris has created one such vaccine, which he claims produces a weak immune reaction. Zagury and several volunteers went so far as to inoculate themselves with the vaccine last year. Even so, many researchers, Merck's Hilleman among them, believe the prospects for an AIDS vaccine are dismal. Others disagree. "We've known about the tricks of this virus for only a year or so," says Gefter. "With a better understanding of its strategems and with the genetic-engineering tools we have, we can design sophisticated vaccines tailor-made to the life cycle of the AIDS virus."
Even without provocation by the AIDS virus or other infectious organisms, the immune system can sometimes go awry. Often, entirely on its own, it can overrespond, fail to respond or turn against the body it is designed to protect with the same lethal fury it directs against invaders and cancerous cells. Some 80 immune-system deficiencies have been identified so far. About one in 400 people has at least one immune-system component missing or malfunctioning, usually for genetic reasons. In one in 10,000 people, the deficiency leads to serious disorders. Perhaps the most tragic example is severe combined immunodeficiency disease, a rare condition in which both B cells and T cells are lacking. The most famous SCID victim, a Texas boy named David, lived for twelve years in a germ-free bubble while doctors searched in vain for a cure for his disease. He died in 1984, four months after receiving a bone-marrow transplant that doctors hoped would supply his missing immune cells.
As hay fever and other allergy sufferers will testify, the immune system can sometimes react to pollen, animal dander, molds and drugs that are normally harmless. In allergy victims, however, the immune system goes into high gear at the appearance of these substances, or allergens. It begins producing antibodies called immunoglobulin E, which attach themselves to mast cells located in the tissues of the skin, in the linings of the respiratory and intestinal tracts, and around the blood vessels. The mast cells promptly begin to release a number of chemical signals, including histamine, a substance that dilates blood vessels and makes it easier for cells to pass through the capillary walls. These changes, meant to expedite the arrival of immune cells, cause the inflammation and swelling associated with allergic reactions.
Allergy sufferers are now treated with antihistamines, which temporarily block the immune response, as well as steroid nasal sprays and inhalers, which reduce inflammation. But more effective help may be on the way. Scientists have synthesized bits of protein molecules that prevent immunoglobulin E antibodies from setting off an allergic reaction.
One of the more devastating errors of the immune system involves its failure to distinguish between self and nonself, resulting in so-called autoimmune diseases, which can be crippling and sometimes fatal. Dozens of disorders that once mystified doctors are now thought to be autoimmune. Among them: Type 1 diabetes, myasthenia gravis, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. In these and other autoimmune diseases, the immune system mounts a selective and ferocious assault against parts of the body, destroying cells or cell components that it mistakenly identifies as alien.
Type 1 diabetes, for example, which afflicts 1.5 million Americans and is brought on by an insufficient supply of insulin, was for years believed to be caused by a virus. Researchers have now shown that it probably results from a defective immune system. For reasons that are not yet clear, immune cells invade the pancreas and destroy the beta cells, which produce insulin. When this happens, the body cannot convert sugar into the energy that cells need to function. The cells starve, and the unconverted sugar builds up in the bloodstream, damaging the fragile lining of blood vessels. Complications associated with Type 1 diabetes include heart and kidney disease, poor circulation, eye problems and stroke.
However incomplete, the emerging understanding of the immune system's role in Type 1 diabetes has led to an experimental treatment. In Canada and Europe, researchers have weaned diabetics from their insulin shots after giving them cyclosporine, a drug used in organ transplants to suppress the immune system. Doses of cyclosporine, which works by dampening T-cell attacks on the beta cells, have provided dramatic results: many patients have been able to discontinue their insulin shots for up to a year. Still, by undermining the entire immune system, cyclosporine leaves the diabetic more vulnerable to other diseases. And when given in high doses, it can have serious side effects, including kidney damage.
In an attempt to find a more selective treatment for Type 1 diabetes, researchers are trying to figure out exactly why the immune system attacks the beta cells. Last October a Stanford University team discovered errant forms of a gene that controls the development and growth of the culprit T cells. The team's conjecture: in Type 1 diabetics, this gene produces a protein badge that differs slightly from the norm in structure, causing the immune system to attack the beta cells. Eventually, the group hopes to find a way to neutralize the harmful effects of the molecule and thus eliminate the need for immune suppressants like cyclosporine.
Another autoimmune disease, myasthenia gravis, a neuromuscular disorder that afflicts 15,000 Americans, is caused by antibodies that attack vital links in the nervous system, and leads to gradual loss of muscular control. Initial studies suggest that small doses of cyclosporine may be effective in blunting the symptoms of the disease. Some researchers, however, are searching for a more selective remedy that involves mass-producing antibodies that are specific to one antigen. These so-called monoclonal antibodies are designed to immobilize only those B cells that produce the antibodies responsible for the disease.
Some of the most promising new therapies arising from recent research involve the chemical signals, or lymphokines, that regulate the immune system. These extraordinary proteins have a bewildering array of names and functions. There are, for instance, three types of interferon -- alpha, beta and gamma. Alpha alone comes in more than a dozen varieties. Interleukins are similarly prolific. "We are already up to interleukin-7 and interleukin-8," says Immunologist Lloyd Old, of the Memorial Sloan-Kettering Cancer Center in Manhattan, "and one can expect that we will go on from there." Scientists have so far discovered at least five different colony-stimulating factors, which cause cells in the bone marrow to mature and differentiate into red and white blood cells. Each of the players seems to have a vital, if sometimes overlapping, role.
Using bioengineering techniques, medical researchers have begun to mass- produce these substances and use them, sometimes in combined "cocktails," to boost the immune system against specific diseases. In clinical trials at Boston's New England Deaconess Hospital, Dr. Jerome Groopman has found that granulocyte-macrophage colony-stimulating factor reverses bone-marrow failure and boosts white-cell counts in AIDS patients. Gamma interferon seems to remedy the defective functioning of monocytes and macrophages in a wide variety of diseases. Alpha interferon has been particularly effective against two types of leukemia and non-Hodgkin's lymphoma, a cancer of the lymph system. Says Dr. Jordan Gutterman, of Houston's M.D. Anderson Hospital and Tumor Institute: "There are ten different tumors in which potentially important anti-tumor activity by interferon has been demonstrated."
Interleukin-2 has shown promising results in treating advanced skin and kidney cancers. In fact, says Gutterman, there appears to be "tremendous synergy" between alpha interferon and IL-2 in attacking cancer cells. While IL-2 works to make the killer cells more potent, he explains, they "have to recognize something unique on the surface of the cancer cell in order to kill it." That something is an antigen, and interferon seems to make it more "visible" to the killer cells.
Scientists are proceeding cautiously with the new therapies. "In any substance that is immunologically active," observes Genentech's Sherwin, "you run the risk of tilting the balance in an unfavorable way. We don't know all of the answers yet."
That may be an understatement. Immunologist Leroy Hood of the California Institute of Technology is certain that the lymphokines discovered so far are "just the tip of the iceberg" and that more subcategories of T cells will be found. He emphasizes that scientists do not yet fully understand, among other things, how B and T cells differentiate, and how the immune system's genes are turned on and off at different times. "In the truest sense," he says, "immunology is just in its youth." Still, says Sherwin, "there's an enormous amount we know now that we didn't know five years ago, and five years from now we'll know even more." Immunology may indeed still be in its youth, but it is growing up fast.
With reporting by J. Madeleine Nash/Chicago, Dick Thompson/Washington and Suzanne Wymelenberg/Boston