Infectious diseases are diverse. They are diverse in transmission modes, diverse in their use of host tissues, and diverse in the harm they cause. Medicine understands the acute infectious diseases fairly well because the chains of infectious transmission range from being very conspicuous to pretty conspicuous. A few, such as smallpox and malaria, cause terrible problems for people. But the vast majority rarely kill, and most are so mild that the fitness costs they impose on humans would not be sufficiently high to implicate infection.

No one grasps yet the distribution of virulence among chronic infectious diseases because the health sciences are now still in the midst—or perhaps at the beginning—of discovering the scope of infectious causation of chronic diseases. The germ theory has been widely accepted since about 1880. During the first century of this period, almost all the recognized chronic infectious diseases had a distinct acute phase. Diseases like tuberculosis had chronic phases that were easy to link to infectious causes because the development of chronic disease involved a slow and observable transition from the acute phase to the chronic. The chronic phases of diseases like syphilis were a bit more difficult to recognize as being caused by infection, because of gaps

between the acute and chronic phases and because the different phases had fundamentally different symptoms. The acute phase was characterized by lesions on the genitalia, the first chronic phase by a generalized rash, and the late chronic phases by such a variety of disease states, including heart disease, insanity, and paralysis, that syphilis became known as the great imitator. A chronic disease such as shingles was still more difficult to link to its infectious cause because it surfaced after a long disease-free period had elapsed after the acute phase, which we call chicken pox; moreover, shingles does not occur in everyone who has had chicken

pox—some people die before it would have occurred, and the immune systems of other people have apparently so thoroughly controlled the virus that it cannot resurge in the form of shingles.

During the first three decades of the germ theory, from about 1880 to 1910, the scope of acute infectious diseases was quickly resolved, and hypotheses for infectious causation of chronic diseases were advanced. Chronic diseases that were the most easily linked to their acute

beginnings were broadly accepted during this period as different manifestations of specific infectious processes.

During the first half of the twentieth century, medical researchers confirmed that infections caused various chronic diseases that appeared as delayed consequences of acute diseases with entirely different symptoms. In 1909 the Hungarian pediatrician J. von Bokay provided evidence that convinced many of his colleagues that the hypothesis he first published in 1892 was true: shingles is a delayed manifestation of chicken pox. After about a half century of observation, experimentation, and debate about rheumatic fever, it was finally accepted during the 1940s as a delayed, often chronic manifestation of previous infection with Streptococcus pyogenes, the primary agent of strep throat.

By the middle of the twentieth century medical science was poised to move into an even more cryptic realm of the spectrum of infectious disease—those chronic diseases that were caused by infections that did not generate obvious acute phases. Then medical science dropped the ball. A few people noticed it, and kicked it around a bit, but for the most part it was left alone. This period strikingly parallels the three decades before the first flowering of the germ theory in the nineteenth century, when Jacob Henle’s call for investigating infectious causation of acute diseases was similarly dismissed without any evidence to justify the dismissal. It is not entirely clear why medicine dropped the ball between 1950 and 1980. In the 1940s the hypothesis for the infectious causation of peptic ulcers, cardiovascular disease, and cancer was still being considered. In some cases people were even being cured with antibiotics. A combination of developments in science and medicine were misinterpreted and misapplied as leaders failed to guard against the biases of human thought.

Ironically, one of the reasons for this slowdown was the same reason for the tremendous success in identifying infectious causation during the preceding three quarters of a century: the adherence to Koch’s postulates. In a presentation to the Tenth International Medical Congress held in Berlin in 1880, Robert Koch set out powerful guidelines for identifying infectious causation. These guidelines, which have come to be known as Koch’s postulates, were simple rules for maintaining a high standard of evidence in an area of research that was burgeoning at the end of the nineteenth century. Koch advised researchers to (i) demonstrate the putative pathogen in each patient with the disease, (ii) recover and grow the pathogen in pure culture, (iii) produce the disease in humans or laboratory animals with the cultured microbe, and (iv) recover the pathogen microbe from the diseased animals. The historical record shows that when these guidelines were met, the diseases invariably turned out to be caused by infection. This success then led many experts to insist that infectious causation be accepted only when these guidelines had been met—and that is where the logical error crept in. The goal of the experts was laudable; they were trying to ensure that medical research would be rigorous. But they presumed that if a batch of evidence is sufficient for the acceptance of the validity of an argument in one situation, then other kinds of evidence are insufficient for the acceptance of the validity of the argument in other cases. Koch did not make this error; he cautioned that researchers should not use these guidelines as the only basis for ascribing infectious causation. Unfortunately, it is easier to follow guidelines than to think critically on a case-by-case basis, and the experts of the

mid-twentieth century set in stone Koch’s postulates as the standard for ascribing infectious causation. The consequence was that even when important evidence of infectious causation was available, it tended to be dismissed if Koch’s postulates were not satisfied. This dismissal had major consequences for understanding the scope of infectious causation because for some infectious diseases Koch’s postulates can be virtually impossible to fulfill.

*19\225\2*

Now that we are done with this casual review of your brain 1 % in action, stand back and think (your brain again). If activities as trivial as a day-in, day-out morning routine or watching the news on television are so demanding of brain resources, can you imagine the brain machinery behind the complex professional activities of a physician or an engineer, the intellectual rigor of a mathematician or a chess player, or the creative surge of a violinist or a dancer? Cognitive neuroscience is only beginning to address these issues, but it is no longer possible to think or talk about the mind without the brain, or about the brain without the mind.

As a typical reader of this book, you are not a brain scientist, but you are a brain user, a consumer of brainpower, so to speak. And the odds are that you have not been particularly inquisitive about the inner workings of your brain. This is a curious phenomenon, and it concerns all of the human body, not just the brain. Ironically, most of us generally do not care about our body, as long as it leaves us alone, does not ache, hurt, itch, or malfunction, and allows us to feel good. If Johnny contracts hepatitis A from bad oysters, he does not go to the doctor because his liver enzymes are elevated and viral titers are up; he goes because he feels lousy and tired, and because his face and eyeballs have turned yellow—not a highly valued trait on the dating circuit.

Even though Johnny does not particularly care to know about the inner workings of his body, he accepts the general premise that how he feels depends on, among other things, the condition of his liver, which has to be dealt with in order for Johnny to feel good again and regain a desirable complexion. But when it comes to the mind-brain relationship, the closeness of this link does not seem to have trickled into the public awareness yet. The general public is only beginning to appreciate the fact that any assault on the brain will affect your mind.

But is the inverse true? Can we improve the quality of the mind by improving the function of the brain? If the answer to this question is “yes,” then Johnny should start learning how to take care of his brain, just as, in the last few decades, he has embraced the notions of healthy physical living (raw oysters notwithstanding). In this book, I will argue that what happens to one’s brain as one ages depends to a great extent on what one does with it at a younger age. I will also argue that it may be possible to improve one’s mind by improving one’s brain even at an advanced age. I will discuss how this happens in everyday life and what can be done to accomplish it better in a more structured manner.

First, though, we need to understand the natural processes in the brain throughout the life span. “Seasons of the mind” or seasons of the brain is, of course, a metaphor, but not too farfetched a metaphor. The brain and the mind go through stages in the course of a lifetime. Like the seasons of the year, the seasons of the mind are not separated by clear-cut absolute boundaries, but morph gradually and seamlessly into one another. So any attempt to link these boundaries to precise chronology is a matter of convention rather than of real biological discontinuities. Just as the change between seasons may vary from year to year (early summer one year, late spring another year), so too the exact timing of transition from one “season of the mind” to the next varies somewhat from person to person. To complicate matters even further, not all aspects of the mind and the brain move through the stages in perfect synchrony. This means that how exactly you set the boundaries between the stages depends to a large degree on your choice of the criteria. Unlike the four seasons of the year, it is common to speak about three seasons of the brain: development, maturity, and aging.

*5\302\2*

Q fever is an acute illness often accompanied by pneumonia which results from infection with a form of Rickettsia. The first human cases of the disease were observed in Australia in 1933. Since they originated in Queensland, the infection was named “Q fever.” Now a similar organism has been isolated from ticks captured in Montana and cases have been found in other areas of the United States.

Human beings are highly susceptible to Q fever; from 25 to 40 per cent of those exposed may be attacked by the disease. The condition was found much more often in Australia among people exposed to cattle. Before 1946 the disease was rare in the United States but has now been found particularly in epidemics in stockyards such as the one in Amarillo, Texas, in Chicago, and among dairymen in Los Angeles county. Workers in research institutes have frequently been infected.

From twelve to twenty-six days after exposure, the disease comes on with symptoms like those seen in other Rickettsial diseases. The two striking features that make Q fever different from other infections with Rickettsia is the absence of any characteristic rash and the almost invariable presence of pneumonia. However, pulmonary symptoms are often mild or absent. About one-half the patients have aches in the chest. X-ray of the chest shows that the lungs have been infected in at least 90 per cent of the cases.

Q fever may be confused with primary virus pneumonia, with tuberculosis, with psittacosis or infected bird fever, and must also be distinguished from ordinary influenza, sinusitis, undulant fever, dengue, and other Rickettsial infections.

Here again aureomycin, chloromycetin, and terramycin have been found useful in treatment. Relapses are rare. Most of the patients recover. Thus far only some eight or ten deaths have occurred among perhaps 1,000 cases that have been reported in medical writings.

*14/318/5*