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Although the conquest metaphor has limited applicability in the control of infectious diseases, the diversity of warfare situations offers a diversity of metaphors. The matches should not be surprising, because in a very real sense we are in a state of war with many of our microbes. They are invading us. We are killing them. The mistake in the standard war metaphor was in thinking that there was only one successful solution: unconditional surrender. In real warfare as in antimicrobial warfare we have learned, sometimes very painfully, that there are other solutions.Consider the Soviet war in Afghanistan. Although the Soviet Union had overwhelming superiority in fire power, the United States saw that it could tip the balance in favor of the Afghan rebels by providing Stinger missiles, which could knock out the main Soviet threat: attack helicopters. The United States provided this weapon after considering which of the two sides was more dangerous to U.S. interests. There was no opportunity to groom a successor. If there had been, the U.S. government might have called on the CIA to deploy a different strategy. Whether one supports or condemns any such covert action depends on how one weighs the expected geopolitical benefits against the compromises of individual rights and national sovereignty. The quality of the assessment depends on the range of strategies considered.Health policy strategists have a wider range of opportunities because bacteria and viruses do not have rights. They are free to use any strategy regardless of the destruction that is imposed on innocent microbes. Yet in spite of this freedom of action, health strategists have not drawn on the range of tactics the CIA employs. Imagine how much less effective it would have been if the United States had intervened in Afghanistan by battering down both sides. Yet that is just what vaccination programs attempt to do. Instead of making vaccines that favor the mild strains by selectively knocking out the truly dangerous opponents, or by grooming the microbial successor, we have been trying to make vaccines for over two centuries that knock out all the variants of a target microbe, whether the variants are mild or extremely dangerous. When a vaccine does that, we no longer have the mild variants predominating in the wake of the campaign to protect against the harmful variants.If vaccine efforts lapse, as they often do, then the mix of pathogens that was there before the vaccine effort will quickly expand to fill the void. If only mild variants are left, the situation is more stable against reinvasion by harmful variants. The overall kill rate is lower, but it is selective; the outcome is thus more favorable.The second most cost-effective vaccination program in history, the one that controlled diphtheria, inadvertently showed how well this selective strategy can work. The people who made the diphtheria vaccine may have thought of their efforts as an all-out war to eradicate an enemy, but the bacterium that causes diphtheria, Corynebacterium diphtheriae, was not eradicated by the vaccine program. Rather, the vaccine selectively suppressed the dangerous competitor, altering the balance in favor of the benign competitor. This selective intervention virtually banished diphtheria for more than a half century without the need for an all-out eradication campaign. If we understand why this campaign worked so well, we might use it as a model for other vaccine campaigns.The diphtheria bacterium causes most of its damage as a result of a toxin it produces when it is short on resources, particularly iron. The toxin costs the bacterium about 5 percent of its protein budget, but the investment pays back dividends because the toxin kills the cells of the respiratory tract near the bacterium, thereby liberating the nutrients the bacterium needs. The diphtheria vaccine was made by modifying this toxin a little so that it no longer damaged respiratory tract cells but still caused the immune system to generate antibodies that would recognize and sequester the unmodified toxin. If a toxin-producing C. diphtheriae invades a person who has been vaccinated, the toxin is sequestered by antibodies before it can destroy a person’s cells and provide nutrients for the bacterium. The 5 percent cost of toxin is simply a drain on the bacterium’s ability to compete with toxinless bacteria. The overall effect is that the strains that do not produce the toxin win out over the harmful strains. Wherever the strains left in the wake of a diphtheria vaccination program were assessed, the same trend occurred: the toxin-producing strains vanished, replaced by the milder, toxinless strains. That is a good outcome for us because strains that do not produce toxin not only fail to cause diphtheria but also protect us against the harmful strains that do. They therefore act like free live vaccines.These arguments lead to a simple rule for vaccine development. Whenever possible, use virulence antigens: those components of a pathogen that make viable, benign organisms harmful. Doing so will generate an immune response that selectively protects against the harmful organisms. Including antigens against components of the pathogen that do not make it virulent must be avoided. Otherwise the vaccine will remove mild strains that could further suppress the harmful strains.This virulence antigen strategy has been used inadvertently in one other vaccine program, the one against Hemophilus influenzae, which has been an important cause of encephalitis in children. That program was so successful that it left researchers scratching their heads. But extraordinary success is what one should expect from virulence antigen vaccines. The strategy should be applicable to all vaccines, yet it has not been considered as part of the strategy for making any vaccine, largely because vaccine developers tend not to look at their task from an evolutionary point of view.The virulence antigen strategy requires that vaccine experts shift away from eradication as a goal. This shift is dictated for some diseases by the ability of vaccines to prohibit disease but not infections. When children are vaccinated against pertussis (whooping cough), for example, the disease is generally prevented but the organism is still present and transmissible. Prospects for eradication by such vaccines are obviously very dim, no matter how pervasive the vaccination program. We can expect to be living with the agents. If we have to live with the organism anyhow, we should make it a benign organism that supplements vaccination efforts rather than a mix of largely harmful organisms. Pertussis vaccination is a perfect candidate for a virulence antigen strategy, not just for this reason but also because virulence antigens are already identified and can generate a protective effect that is comparable to the best vaccines available. The pertussis vaccines that are currently being used have other antigens, particularly one called filamentous hemagglutinin, which trigger immune responses that suppress benign strains as strongly as harmful strains.*62\225\2*

Even with all my training, the women in my life have taught me much I needed to know about health and health care. A few years ago, my older daughter wrote her senior research project on women’s medical issues, focusing on how the entire medical system is not geared toward humans of the female persuasion. Of course, I was pleased and proud she was showing an interest in medicine, but I teased her at first about being up on her soapbox. It’s not like I took a course on how not to treat women, I told her, and except for whatever handful of male chauvinist doctors were out there (unfortunate, but unavoidable), I felt sure women received medical care on a par with men. But as she researched, and I thought about the stories my patients brought to me, and we talked, she showed me she was right.Around this same time, as my wife was going into perimenopause, she had her first bone density measurement. She came home to report that the radiologist just said that everything was fine. But when a copy of the report arrived in the mail, I saw that it actually showed significant bone loss. At her routine visit to the gynecologist, the doctor didn’t comment on the bone scan (which she had received a copy of), but did suggest calcium, exercise, and hormone replacement therapy (HRT), which, aside from the calcium, my wife declined. And so, with just one approach mentioned—and major components rejected—with no “Plan B,” no plan for follow-up, no discussion of protective eating strategies or types of exercise or alternatives to standard HRT my wife might find more appealing, these doctors were satisfied to let the whole matter go, without even explaining the potential for serious trouble ahead! Once it hit this close to home, I finally realized the extent of the problem my daughter had pointed out to me. And nowhere was it more extreme than when it came to osteoporosis.Until recently, bone fragility has been more or less shrugged off as an inevitable part of aging—and basically a woman’s lot. Though this is a totally preventable disease, the incidence of osteoporosis has been increasing because it hasn’t been properly addressed. As some new drugs were approved that provided a real treatment for low bone density for the first time, and I began to get visits from sales reps bearing information on the extent of osteoporosis among women, it became clear just how ignored this health issue had been. Most insurance companies wouldn’t even pay for screening tests, and I saw too many of my patients do without the scans that could have given them crucial information for preserving their health and lifestyle, simply because they couldn’t afford them. My practice was aging right along with Boomer me, and the topic was coming up more and more often. In talking with my patients with a sharper focus on bone health, I also realized how little information on the topic was available for women. Most patients, even those who could rattle off fat grams and recommended heart rates for aerobic exercise, knew precious little about how to correctly protect their bones—or even of the necessity of doing so. So began my crusade. If the ideal doctor-patient relationship is a true partnership, I saw I was going to have to educate myself and my patients if we were going to be able to promote the strongest possible bones.*10\228\2*

While CT scanning has revolutionized our ability to see the brain, magnetic resonance imaging (MRI), which is even newer, has increased our ability to see the brain even more clearly. Unlike CT scanning, MRI does not employ x-rays but rather uses a huge magnet to create an image which is then analyzed by computer in a fashion similar to the CT. It produces pictures of even greater detail. The principal disadvantages of the MRI are that, with current equipment, a scan takes about forty-five minutes, during which the child must lie perfectly still in the tunnel-like machine and thus may require sedation, and also that the test is more expensive than CT. However, when detail of the brain is important, or when subtle changes must be seen, the MRI is indicated. It produces far better pictures of the brain and of most abnormalities than the CT scan does.If your physician wants your child to have an EEG or a CT or MRI scan, you should feel free to ask him why he wants the test and what he hopes to learn from it. These questions are even more appropriate if he wants to repeat the test.*90\208\8*