Open Heart (39 page)

I ask what high blood pressure (where the genetic factor is also modest, the concordance rate for identical twins being only 30 percent) does to the arteries that makes it a risk factor.

“You ask the right questions,” Rich says. “But again, though theories abound—perhaps it weakens the walls of the arteries, or it induces dysfunctions in the endothelium, which is the innermost layer of blood vessels and is critical in determining the contractile state of the underlying smooth muscle, or it may reduce the activity of nitric oxide, which has anti-atherosclerotic effects—the real answer is that we don't know.

“What we
do
know is that high blood pressure is
statistically
associated with higher rates of heart disease and heart attacks, though
labile
hypertension—the condition you evidenced—so-called white coat syndrome, where your pressure goes up when you're in the doctor's office and see the white lab coat in front of you—is not anything like the risk factor other, more repeatable and predictable patterns are.

“And all of this is why I keep saying that you are living evidence, my friend, of a much larger point.”

Which is? I ask.

“That we simply don't know what causes atherosclerosis. But remember—these statistical correlations
do
have great importance from a preventive point of view, because a lot of information shows that people with severe elevations of cholesterol who lower them with diet, drugs, or exercise have lower rates of atherosclerosis. People who take aspirin have fewer coronary events, and if you stop smoking, treat your high blood pressure, your obesity, et cetera, your risk will go down—statistically—and this is important. But it is by no means conclusive.

“Because the average temperature in Palos Verdes on August
21
is sixty-eight degrees, doesn't mean that it will be sixty-eight degrees today. Because it might be sixty-eight degrees in Northampton today doesn't mean that every flower that blooms here can bloom there. Because, let's say, we discover that most cardiologists who own fancy cars also play tennis well doesn't mean that being a cardiologist and owning a fancy car will make you a good tennis player. As I said to you when you were at Yale, when ‘n' equals one—when it comes to each individual instance: to the patient we are treating—associations and statistics break down.”

Arthur and I have talked about this—yes, an airplane is statistically the safest way to travel, he says, unless you happen to get on the wrong plane—and I quote him to Rich now, Arthur saying that it used to be “Neugie died of a heart attack,” but now it's “Neugie died of a heart attack because he ate too many Mallomars…or too many eggs, or because he didn't exercise enough.”

Rich laughs, and says that what is true for heart disease—that we don't really know why somebody with few if any risk factors dies, and somebody with a multitude of risk factors lives to a ripe old age—is also true for cancer.

“Heart disease and cancer—in our time, these are the two biggies,” he says.

The reading I've been doing in evolutionary medicine, or what is sometimes called Darwinian medicine, has, with regard to these two killers, been instructive, I say. What those who work in this discipline, most notably, Paul W. Ewald, with whom I've talked about this (he teaches at Amherst College across town from the University
of Massachusetts), believe is that medical research and practice could be significantly enhanced if questions of adaptation and historical causation were routinely taken into account along with questions of more proximate physical and chemical causation.

Evolutionary biologists ask intriguing questions: for example, If evolution by natural selection can shape mechanisms as sophisticated as the eye, heart, and brain, why hasn't it shaped ways to prevent nearsightedness, heart attacks, and Alzheimer's disease?
^*
If our immune system can recognize and attack millions of foreign, harmful pathogens and proteins, why do we still get sick?

Since we know that smoking and excessive exposure to the sun are implicated in causing lung and skin cancer, why hasn't natural selection eliminated the genes (if genes they are) that make us crave cigarettes and sunshine? And why can't our bodies repair clogged arteries, sun-damaged skin, and brain lesions the way they repair bruises and skin abrasions, and nerve and muscle damage?

When placing present infirmities within evolutionary contexts—taking a long historical view—researchers such as Ewald begin with a fundamental observation: that the bodies and immune systems we now possess have come into being over the course of millions of years, most of which—perhaps 90 percent of the years since we became recognizable as the species we are today—we spent as hunter-gatherers living in small groups on the plains of Africa. Natural selection, therefore, has not in many instances had the time, or the biological wherewithal, to enable us to accommodate to more recent conditions of environment and history.

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.