Naturally failing immune systems and naturally overactive immune systems have been blamed as noninfectious causes of chronic disease. But does it make sense that evolution would have generated such a complex system of checks and balances if these complexities were only to generate the system’s downfall? Imagine making an extravagant security guard system that self-destructs without provocation. We would not expect people to select the ineffective complex system over a more effective simple system. If an extravagant immunological security system self-destructed, then natural selection similarly would favor the simpler system. The more extravagant system wouldn’t be reproduced. We can expect that natural selection will not favor added complexity to immunological security systems when the increased complexity destroys the body without provocation. The immune system may, however, be driven to self-destructive tendencies through the ever-changing strategies of the burglars it is attempting to deter. Streptococcus pyogenes, for example, may damage the heart because one of the germ’s proteins has evolved camouflage that makes it look so much like a protein on the human heart that the immune response against the bacteria attacks the heart. In the absence of such provocation, though, the immune system is the quintessence of efficiency and flexibility.*22\225\2*
Vaccines are simply a tweak that shifts the immune system response from the longer delay to the shorter delay. The tweaking of the immune system with vaccines has so strongly aided the immune system in this conflict that it has eradicated one scourge—smallpox—and virtually eradicated several others, such as polio, measles, and diphtheria, from large regions of the planet. We take pride in our vaccines, but really the vaccines are the simplest part of the defense. A vaccine is a mug shot of a criminal sent to a police station before the criminal is encountered. Sending the mug shot can be terribly important because it allows the police force to recognize and respond quickly to the real criminal. Merely sending the mug shot, though, is far less complex and difficult than tracking down, apprehending, and incarcerating the criminal.
Put bluntly, medicine’s successes at vaccination and antibiotic treatment are trivial accomplishments relative to natural selection’s success at generating the immune system. Recognizing this fact has important repercussions for the long-term control of infectious diseases. We will probably obtain much better disease control by figuring out how to further tweak the immune system and capitalize on its vastly superior abilities than by relying on some human invention such as new antimicrobials (antibiotics, antivirals, or antiprotozoal agents).
Antimicrobials are useful, but the problems they are good at solving differ from the problems vaccines are good at solving. Antimicrobials are not particularly suited to controlling or eradicating disease at the population level. Rather they are good at helping a patient who needs to control an infection now. Vaccines are effective at protecting individuals from becoming infected, at controlling the spread of disease through populations, and sometimes at eradicating a disease from a population. The blurring of this distinction between the roles of antimicrobials and vaccines has hampered the control of disease and exacerbated the dilemma of antibiotic resistance.
I am confident that we have only begun to capitalize on the immune system, though I doubt that we will soon be able to administer safely and effectively the chemical messengers used by the immune system to turn a particular response up or down. Some scientists hope that a more effective immune response could be generated by increasing or decreasing some of these chemical messengers, like turning the volume control on a radio up or down. I expect that the immune system is much too weblike to do that. Radios were engineered to be controlled by a listener. They therefore have controls for particular properties, such as volume, treble, and bass, controls that are well suited for adjustment by the fingers of the listener. The immune system, like the brain, was engineered by natural selection to be a self-controlling unit. It therefore does not have controls that allow an outside user to turn one attribute at a time up or down. If we increased a chemical messenger to try to improve immune function, we would probably cause many unforeseen effects as the immediate response affected other parts of the immunological web.
We can use the brain analogy to get a sense of what can be done with the immune system. If we start stimulating a neuron here and a neuron there, we are unlikely to improve the brain’s ability to function. Attempts to actually change the circuitry have ranged along the spectrum from very crude to moderately crude solutions; they may solve one problem but introduce others. One need only mention the gruesome failures of prefrontal lobotomy and electroshock therapy. A hands-on approach to the brain works best when some neuronal damage causes a shortage of a specific chemical, the effects of which can then be partially ameliorated by supplementing the shortage with the same chemical or a similar one. The use of L-dopa for Parkinson’s disease is this kind of solution; the L-dopa compensates for the shortage of the chemical transmitter dopamine. But even in this case the solution is generally only partially effective. We are headed for the same kinds of disappointments if we try to treat the immune system like a radio that can have its components adjusted, replaced, or removed.
We can effectively improve the brain’s functioning, however, by making use of the brain’s own already wired abilities to improve—we call it learning, or training. Vaccines similarly make use of the immune system’s already wired abilities to control microbes. Vaccines teach and train by providing information to the immune system, information that we humans know sooner than the immune system knows, information about what pathogens are out there ready to invade before they invade. That kind of tweaking has worked marvelously in the past, and it will undoubtedly do so in the near future. Vaccines teach the immune system, but good teachers know they cannot just present the information and leave it to the students to sort it out. Some students will be able to grasp an idea because of their background and inherent abilities, and others will not. A given student will grasp some ideas very well and other ideas poorly. The information that goes out will influence what is absorbed. If a teacher sends it out at too high an intensity, the student can be overwhelmed, and the entire subject can become frustrating and destroy the student’s interest, no matter how inherently interesting and manageable the subject. Medicine needs to figure out how to better teach the immune system, rather than trying to adjust and reconstruct it.
The immune system is an information-processing system that is analogous to the brain, but with different input and a different function. The brain deals with information from the outside world that comes in through sight, hearing, smell, taste, and touch and integrates it in the form of ideas and concepts; the brain’s goal is to interact more adeptly with relatively large organisms, those that we recognize as predators, competitors, and food sources. The immune system takes in information about small invading organisms, integrates it, and mobilizes it with the goal of interacting more adeptly with the microscopic environment. The goal tends to be more restricted, being largely the microscopic analog of avoiding predators and ectoparasites. But the task is more diffuse, more akin to controlling entire police forces or entire military operations than to altering the behavior of one person or one predator.
We rarely think of the immune system as an analog of the brain—as another decision-making system in our bodies—probably because the immune system does not generate sensations. We are therefore oblivious to its information processing and decision making. But it is there, and it integrates information and actions in very complex ways in each of us at every moment. We need not let our senses fool us into overestimating the importance and complexity of one system relative to another just because the one generates sensations and the other does not.
What options for tweaking are there besides vaccines? The brain function of my students can be overloaded with input. Immunological processing can be overloaded by pathogens if the dosage is too high, the harmfulness of the pathogen too great, or the route of entry too direct. One key to a truly preventive medicine will be to intervene in ways that keep the threat of pathogens well within the ability of the immune system to deal with them. We can keep the immune system from being overwhelmed, for example, by adjusting things so that pathogens
entering the body have a combination of low dosage and low inherent harmfulness, but this is a formidable task.
The good news, which will be developed in the remaining chapters of this article, is that evolutionary principles offer new directions that will probably allow .disease prevention programs to make better use of our immune systems by better controlling the evolution of their microbial adversaries. In short, there are ways to make vaccines, use antimicrobials, and improve hygiene so that control of pathogens by the immune system is much more manageable. Often these new methods capitalize on the immune system’s ability to mediate competition. If we intervene in ways that expose the immune system to milder organisms that are circulating in the population before they see the more harmful competitors, we can get the immune system to be better prepared for the more dangerous organisms, very much as if it had been vaccinated against the harmful strains.