The gene that causes sickle cell anemia, for example, also prevents malaria—useful on the plains of Africa, but not on the streets of New York. Most of the genes we believe may predispose us to heart disease were harmless until certain other events occurred—the availability of fats, sweets, and tobacco, the migration to densely populated cities, and the public health measures and medical innovations that enable us to have markedly longer average life spans than we did only a hundred years ago.
This is so because natural selection does not select for health, but only for reproductive success. It has no plan, no intent, no direction; survival, that is, increases fitness only insofar as it increases later reproductive capabilities, and fitness leads to survival only when it has aided reproductive success.
Since the gene for Huntington’s chorea, for example, causes little harm before the age of forty, and so cannot decrease the number of children born to someone who later develops this disease, natural selection does not eliminate the gene. In a similar way, it would seem, since cancer and heart disease commonly occur after the age of reproduction, natural selection has not eliminated those genes that may predispose us to cancer or heart disease.*
From an evolutionary point of view, we age and we die in the ways that we do, then, not because we have done something wrong (eaten too many Mallomars), but because the diseases that, in our time, generally do us in are those that occur after the age of reproduction. What evolution seems to care about—the pathetic fallacy writ large in the example I offer to Rich—is not Rich or Neugie, but simply being able to produce another Rich or Neugie.
Seen from this perspective, we are only, as Richard Dawkins suggests, vessels created by genes for the replication of genes, and thus may be discarded when the genes are through with us.
In addition, as Ewald points out, from an evolutionary perspective it makes no sense that our immune systems would suddenly, early in the twentieth century, begin malfunctioning on their own in a higher and higher proportion of people.
Conversely, after thousands of years of exposure to disease agents such as smallpox and tuberculosis, one would expect natural selection to have produced a population of individuals all of whom were resistant to these diseases. But this has not happened, Ewald explains, because “natural selection obtains its power from the differences in the survival and reproduction of competitors within a species, which in turn determine differences in the passing on of the genetic instructions that individuals house.” That is where one must look if one wishes to understand why infectious diseases are the way they are and what we can do to control them, because that is where the strategies of pathogens are being shaped.
What evolutionary biologists thus recommend to researchers as holding promise for significant progress in the understanding and treatment of disease is, first of all, the investment of greater resources in investigating those selective processes that favor increased or decreased virulence of viral strains.
The race, they submit, is between what Ewald calls “the biological weaponry” our bodily defenses impose on pathogens, and the pathogens’ resistance to them. And, as we know from the increasing resistance to antibiotics, or the decreasing potency of many antiretrovirals—most pathogens evolve much more swiftly, and ingeniously, than we can create medications capable of eliminating, suppressing, or moderating their effects.
Consider, for example, streptococcus. Here is a bacterium that has evolved along with us for millions of years. When we create antibodies that attack strep, these antibodies, which are capable of imitating the codes of our cells, are prone to attack our own tissues too, and while we produce a new generation of Neugies and Riches every twenty years or so, strep evolves and produces a new generation of pathogens every hour or so. Until now, antibiotics have generally proven capable of dealing with these newly evolved variants. But as we know from the alarming rise in the presence and lethal power both of new infectious diseases (AIDS, ebola, legionnaires’ disease) and of reemerging diseases (tuberculosis, malaria, streptococcal pneumonia), this may be only a temporary blessing. By the late 1970s, Laurie Garrett informs us in The Coming Plague, “strep B was the most serious life-threatening disease in neonatal units all over the industrialized world, and 75 percent of all infections in babies under two months of age were fatal, despite aggressive antibiotic treatment.”* And by the year 2000, the New York Times reports, fourteen thousand people were dying each year from drug-resistant infections contracted in hospitals.
Researchers first began studying the inflammatory process in atherosclerosis in the 1820s, first proposed infectious causation of atherosclerosis in the 1870s, and found evidence that chlamydia was implicated in arterial disease in the 1940s. Evolutionary biologists now contend that atherosclerosis is most probably an inflammatory disease of infectious origin, and the arguments and evidence they present in support of this view are persuasive. Until very recently, they maintain, it was mostly in order to develop a consensus that other medical researchers and cardiologists shied away from statements of causation in favor of a much less informative concept, that of risk factors—high cholesterol, high blood pressure, smoking, obesity, lack of exercise, genetics, et cetera.
None of the risk factors for atherosclerosis, though, appears to be a primary risk factor—for each risk factor, that is, many of us are found who do not have it, yet still have atherosclerosis.* In fact, as we have known for some time, and as Ewald reminds us, if you add up all the known noninfectious risk factors, they still explain only about half the risk of acquiring atherosclerosis, a finding corroborated by Dr. Joseph B. Muhlestein, director of research at the cardiac catherization laboratory, and a professor of medicine at the University of Utah Medical School. “Although much is known about the pathologic process whereby atherosclerotic plaque develops,” Dr. Muhlestein writes, “in many cases, the underlying cause remains unclear. Certain risk factors associated with the development of atherosclerosis are well defined, including diabetes mellitus, hypertension, hyperlipidemia, tobacco abuse, and a positive family history. These risk factors, however, combine to account for only about 50% of the observed incidence of atherosclerosis. Additionally, these risk factors generally are only associations, and the exact mechanism by which they may contribute to the development of atherosclerosis is not known.”
Moreover, as Lewis Thomas observed more than thirty years ago, and as Ewald argues now, most major achievements in medicine have resulted from principles of primary causation: this holds for large theoretical discoveries such as the germ theory of disease, as well as for practical interventions such as surgery, antimicrobial drugs, vaccines, and improved nutrition and hygiene.*
Rich agrees. The efficacy—and genius—of vaccines is due not so much to the medications themselves, but more to our ability to make use of what we know about the human immune system. As to risk factors for atherosclerosis, Rich compares each new risk factor put forth as the key risk factor to the old flavor-of-the month posted at our local ice cream parlors; and with regard to each such risk factor heralded as “the ultimate bad guy,” he likes to tell the story of the cop who comes upon a drunk crawling around on his hands and knees under a lamppost. The cop asks him what he’s doing, and the drunk says he’s looking for his wallet. “Where did you lose it?” the cop asks. “Oh, I lost it inside the bar,” the drunk says. “Then why are you looking for it under the lamppost?” the cop asks. “Because,” the drunk replies, “the light’s better here.”
Still, Rich says, the prevailing theory among cardiologists these days does corroborate Ewald’s hypothesis. In fact, he goes on, he and his team at the University of California at Irvine contributed to the discussion of the possible inflammatory origins of atherosclerosis with work they did in the mid-nineties.
“The entire process of atheroma formation is complex and difficult to pin down because, among other things, lots of elements seem to play a role,” he says.* “But what I have believed for years, as you know, is that it is not the atheroma itself�
�the fatty deposits in the walls of the arteries—that kills people, but the rupture of the atheroma, and if we could identify what causes the rupture, and find ways to prevent it, we would make a huge impact on the prevention of heart attacks.
“We have a lot of indirect and experimental evidence to explain the process that leads to coronary disease, and from coronary disease to heart attacks,” Rich explains, “and it all seems to indicate that something happens to the inner layer—the endothelium—of the coronary blood vessel. An abnormality develops, which in turn allows cells carrying the bad cholesterol—the LDL—to seep through and get caught up in the artery’s wall. When that process matures, cholesterol deposits leak out of the cells and, essentially, form masses, and these masses protrude back into the opening of the artery—the lumen—causing a partial obstruction.
“Sometimes nothing happens—even severe blockages cause at most only three out of every ten heart attacks—and sometimes the obstruction reaches a point where it interferes with the amount of blood flowing through the passageway of the artery. And when the heart is under stress because the oxygen it needs exceeds the ability of the blocked coronary artery to supply it—you’re exerting yourself more than usual: swimming, walking fast, playing tennis—this imbalance causes the symptoms of angina pectoris. But the most dangerous thing that can occur is for the atheroma to rupture into the blood vessel itself, causing a clot to form.
“This is the same kind of clot you get when your skin is cut—it’s nature’s way of healing us—and when these atheroma rupture, their surfaces are very sticky, and platelets bind to them. But the clot closes off the artery and the coronary artery becomes occluded. Suddenly, an area of heart muscle is starved of oxygen, and if this is not relieved quickly enough, that area of the heart dies—in other words, a heart attack occurs. If the area is large enough, you don’t survive it.”
Rich talks about the experiment he and his research team performed, in collaboration with the local coroner’s office and pathology researchers, in which they studied the hearts and arteries of people who had died in automobile accidents, and compared them with the hearts and arteries of people who had died of heart attacks.
“What we found,” he says, “was that the people who died of heart attacks had huge collections of macrophages—white blood cells—in their atheroma. More importantly, these macrophages secreted substances with the fancy term of matrix metalloproteinases, which are enzymes that digest proteins.
“What these enyzmes were doing was digesting away tissue that contained the fatty deposits, thus weakening the walls of the arteries, and making them susceptible to rupture. And we found something else that was fascinating—and totally unexpected. When we looked at other arteries in the patients whose atheroma had ruptured—at the arteries that had not ruptured—we found the same collection of lesions containing macrophages and metalloproteinases.
“Yet this was not the case in those people with atheroma where no rupture had occurred. This strongly suggests that the process is systemic—in other words, that the inflammatory process is not taking place only in the one susceptible atheroma.
“Add to this recent studies that have shown that people with elevated levels of C-reactive protein—which are nonspecific markers of inflammation circulating in the blood—are much more susceptible to heart attacks, and that high levels of C-reactive protein, even in the absence of high cholesterol, are fairly reliable indicators of heart disease and of potential heart attacks, and you can see why infectious and inflammatory disease explanations make sense.* In addition, it now seems that aspirin and the statins, which we thought were effective against coronary heart disease because they reduced clotting and/or lowered cholesterol, may owe a large part of their effectiveness to the fact that they reduce inflammation.
“All of which suggests that there is some kind of total body inflammatory process involved in triggering heart attacks, and that this process is triggered for reasons no one understands.”
My researches confirm much of what Rich tells me. Ewald’s hypotheses about the infectious causes of heart disease, along with evidence that he and other evolutionary biologists present—that there are significant associations between atherosclerosis and both Chlamydia pneumoniae and gingivitis (Porphyromonas gingivalis); that treatment of bypass patients with antibiotics improves their recovery; and that an inflammatory hypothesis makes sense since it does not specify whether the atherosclerotic damage is caused directly by the infectious organism or indirectly through the organism’s stimulation of an inflammatory response—these arguments are reiterated, reinforced, and expanded upon in an abundance of medical journal articles.
Here, for example, is the simple declarative sentence with which Dr. Russell Ross begins a January 1999 article in the New England Journal of Medicine: “Atherosclerosis is an inflammatory disease.”*
After taking us through a substantial body of evidence to support this proposition, Ross concludes that “atherosclerosis is clearly an inflammatory disease, and does not result simply from the accumulation of lipids.
“If we can selectively modify the harmful components of inflammation in the arteries and leave the protective aspects intact,” he adds, “we may create new avenues for the diagnosis and management of disease in the 50 percent of patients with cardiovascular disease who do not have hypercholesterolemia.”
“From a clinical standpoint, chronic inflammation, as evidenced by elevated levels of C-reactive protein, has been shown to be directly associated with the development as well as progression of coronary artery disease,” Dr. Joseph Muhlestein writes in an article published a year later, in January 2000.*
After reviewing research from a sizable number of studies linking various infectious diseases to coronary artery disease, Muhlestein concludes that “the infectious agents with the most evidence to support a causative role in atherosclerosis” include Chlamydia pneumoniae, cytomegalovirus (a member of the herpesvirus genus), Helicobacter pylori (implicated in causing peptic ulcer disease), and several bacterial agents (including Porphyromonas gingivalis) associated with periodontal disease.
Although we may, thanks to the research that lends these propositions their plausibility, be getting closer to understanding the underlying cause or causes of atherosclerosis, what we do not know, Rich maintains, is still infinitely greater than what we do know.
He remains highly skeptical of anyone who claims to know, definitively, what can either cause or cure coronary heart disease, and outraged by the ways those claiming such knowledge go directly to the consumer with sales pitches for their products, as in the extensive campaigns to sell us cholesterol-lowering medications.
“I mean, why don’t they just put the stuff in the well water and be done with it?” he asks at one point, and here again, everything I read lends credence to his skepticism.
Is Zocor really going to help me “live a longer healthier life”? Has Pravachol really been “proven to help prevent heart attacks in people with high cholesterol or heart disease”? Should I, like Dan Reeves, make taking Zocor “an important part of my game plan”—and will it not only lower my cholesterol by 29 to 45 percent, but enable me to “stay beautiful on the inside”?
In an article in Science (March 30, 2001), Gary Taubes, a three-time winner of the Science-in-Society Award from the National Association of Science Writers, reassesses much of what we know about the relation of a diet high in fat to cholesterol and heart disease, and demonstrates that “by the 1970s, each individual step of this chain from fat to cholesterol to heart disease had been demonstrated beyond reasonable doubt, but the veracity of the chain as a whole had never been proven” (italics in original).
Nor has it been proven since. In 1991, a study funded by the U.S. Surgeon General’s Office determined that cutting fat consumption in the United States would delay forty-two thousand deaths each year. The key word, however, as Taubes points out, is delay.
“To be precise,” he explains, “a woman who might otherwis
e die at 65 could expect to live two extra weeks after a lifetime of avoiding saturated fat.* If she lived to be 90, she could expect 10 additional weeks.”
The proposition that reducing fat consumption, whether by diet or drugs, prevents heart disease and leads to longer, healthier lives is, at best, inconclusive, and at worst, as many medical experts maintain, the result of an enormous, often greed-inspired hoax. Rich talks frequently (and is writing about) what he considers unethical collusion between doctors, hospitals, and pharmaceutical firms.* (Corroborating what he has witnessed firsthand, an article in the January 2, 2002, issue of the Journal of the American Medical Association reports that nearly nine out of ten medical experts who write guidelines for treating conditions such as heart disease, depression, and diabetes have financial ties to the pharmaceutical industry, and that these ties are rarely if ever disclosed; moreover, approximately six out of every ten medical experts have financial ties to companies whose medications they either considered or recommended in the guidelines they wrote.)
Although more than 80 percent of the money spent on the promotion of prescription drugs is still directed to health-care professionals, annual spending on direct-to-consumer advertising for prescription drugs tripled between 1996 and 2000, when it went from 791 million dollars (9 percent of annual spending), to just under 2.5 billion dollars (16 percent).*
Taubes reviews not only the research concerning the relation of dietary fat to heart disease, but the history of the ways in which the general public, encouraged by drug companies, politicians, and the media, has come to accept as axiomatic what has never been proven.
Despite the existence of many trials that “showed no evidence that men who ate less fat lived longer or had fewer heart attacks,” Taubes cites Time magazine, for example, declaring, in its headline to a feature story (on the magazine’s cover, below a plate of bacon and eggs arranged so as to resemble a doleful face, “CHOLESTEROL: AND NOW THE BAD NEWS”)—“Sorry, It’s True. Cholesterol Really Is a Killer.”*
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