Why We Get Sick (14 page)

Plants’ escalations of the arms race are numerous and varied. Some plants make little defensive toxin until they are mechanically
damaged, after which toxin rapidly accumulates in or near the injured part. Damage to a tomato or potato leaf induces production of toxins (proteinase inhibitors) not only at the site of the wound but throughout the plant. A plant has no nervous system, but it does have electrical signaling and a hormone system that can keep all its parts informed about what takes place in a small region. Some aspen trees have even more impressive communication. When a leaf is damaged, a volatile compound (methyl jasmonate) evaporating from the wound can turn on the proteinase response in nearby leaves, even those on other trees. The usual result of such defenses is that insects are discouraged after feeding even briefly. Some particularly adept insects, however, begin their meal by cutting the main supply vein to a leaf so the plant cannot deliver more toxins. And so the arms race goes on.

T
he best defenses are, of course, the sorts of avoidance and expulsion already discussed in relation to infectious diseases. We avoid eating moldy bread or rotten meat, which smell and taste bad, because we react with an adaptive disgust to the toxins produced by fungi and bacteria. We rapidly expel toxic substances by spitting or vomiting or diarrhea. We quickly learn to avoid whatever gives us nausea or diarrhea.

Many swallowed toxins can be denatured by stomach acid and digestive enzymes. The stomach lining is covered with a mucous layer that protects it from ingested toxins and stomach acid. If some cells become contaminated, the effect is temporary since stomach and intestinal cells, like those of the skin, are shed regularly. If toxins are absorbed by the stomach or intestine, they are taken by the portal vein directly to the liver, our most important detoxification organ. There, enzymes alter some toxic molecules to render them harmless and bind others to molecules excreted in the bile back into the intestine. Toxin molecules in sufficiently low concentration will be quickly taken up by receptors on cells in the liver and rapidly processed by the liver’s detoxification enzymes.

For instance, our protection against cyanide depends on an enzyme called rhodanase, which adds a sulfur atom to cyanide to form a chemical
called thiocyanate. Although thiocyanate is far less toxic than cyanide, it still prevents the normal uptake of iodine into thyroid tissue and thus can cause the overworked thyroid gland to enlarge—a condition called goiter. Plants from the genus
Brassica
(including broccoli, Brussels sprouts, cauliflower, and cabbage) get their strong taste from allylisothiocyanate. The ability to taste a related compound, phenylthiocarbamate (PTC) varies greatly, as is well known by generations of students who have tasted a bit of PTC-impregnated filter paper as part of an experiment to demonstrate genetic variation. While some people can’t taste PTC, those with a different gene experience it as bitter. They may have an advantage in avoiding natural compounds that cause goiter. About 70 percent of individuals in most populations can taste PTC, but in the Andes, where such compounds are especially likely in the diet, 93 percent of the native people can taste it.

Oxalate is another common plant defense. Found in especially high concentrations in rhubarb leaves, it binds metals, especially calcium. The majority of kidney stones are composed of calcium oxalate, and doctors have for years recommended that such patients keep their diets low in calcium. However, a study of 45,619 men, published in 1992, showed a higher risk of kidney stones for those who had
low
calcium intakes. How is this possible? Dietary calcium binds oxalate in the gut so that it cannot be absorbed. If dietary levels of calcium are too low, some oxalate is left free to enter the body. If, as researchers S. B. Eaton and D. A. Nelson have argued, the amount of calcium in the average diet is now less than half of what it was in the Stone Age, our current susceptibility to kidney stones may result from this abnormal aspect of our modern environment, which makes us especially vulnerable to oxalate.

There are dozens of other classes of toxins, each with its own way of interfering with bodily function. Plants in the foxglove and milkweed family make glycosides (e.g., digitalis), which interfere with the transmission of electrical impulses needed for maintaining normal heart rhythm. Lectins cause blood cells to clump and block capillaries. Many plants make substances that interfere with the nervous system—opioids in poppies, caffeine in coffee beans, cocaine in the coca leaf. Are such medically useful substances really toxins? The dose of caffeine contained in a few coffee beans may give us a pleasant buzz, but imagine the effect of the same dose on a mouse! Potatoes contain diazepam (Valium), but in amounts too small even to cause relaxation in humans. Other plants have toxins that cause cancer or
genetic damage, sun sensitivity, liver damage—you name it. The plant-herbivore arms race has created weapons and defenses of enormous power and diversity.

What happens if we overload our bodies with so many toxin molecules that all the processing sites in the liver are occupied? Unlike the orderly queues of shoppers in the supermarket, these molecules do not just wait their turn to be processed. The excess toxins circulate through the body, doing damage wherever they can. While our bodies cannot instantly make additional detoxification enzymes, many toxins stimulate increased enzyme production in preparation for the next challenge. When medications induce these enzymes, this may hasten the destruction of other medications in the body, thus necessitating dose adjustments. Timothy Johns’s book notes the interesting possibility that inadequate exposure to everyday toxins may leave our enzyme systems unprepared to handle a normal toxic load when one occurs. Perhaps with toxins, as with sun exposure, our bodies can adapt to chronic threats but not to occasional ones.

Grazers and browsers limit their consumption of certain plants to avoid overloading any one kind of detoxification machinery. This dietary diversification also helps to provide adequate supplies of vitamins and other trace nutrients. Left to our own devices in a natural environment, we do the same. If your favorite vegetable is broccoli and you were given an unlimited supply of it and nothing else, you would not eat as much as you would if given both broccoli and cucumbers. Many weight-loss diets are based on the principle that we eat less if given only a few foods than we would if we had access to a well-stocked cafeteria. We minimize the damage caused by dietary toxins by this instinctive diversification, as well as with our own special array of detoxification enzymes. These enzymes are not as potent or diverse as those of a goat or a deer, but they are more formidable than those of a dog or cat. We would be seriously poisoned if we ate a deer’s diet of leaves and acorns, just as a dog or cat would quickly sicken on what we might regard as a wholesome salad.

We can also, more than any other species, protect ourselves from being poisoned by learning about how to avoid it. Only we can read about the dangerous plants in our gardens and woodlands, and we are the species whose diets are most shaped by social learning. A food our mothers fed us can usually be accepted as safe and nourishing. What our friends eat without apparent harm is at least worth a try. What they avoid we would be wise to treat cautiously.

More broadly, there is great wisdom in our innate tendency to follow the seemingly arbitrary dictates of culture. The rituals of many societies require that corn be processed with alkali before it is eaten. Can’t you just imagine prehistoric Olmec teenagers ridiculing their elders for going to all the bother? But those teenagers who ate only unprocessed corn would have developed the skin and neurological abnormalities characteristic of pellagra. Neither rebels nor elders could have known that boiling corn with alkali balances the amino acid composition and frees the vitamin niacin, which prevents pellagra, but the cultural practice accomplished what was needed, despite the lack of scientific understanding.

Or consider the prehistoric residents of California, whose main sustenance came from acorns. The abundant tannins in acorns are astringent and combine strongly with proteins, properties that make them especially useful as leather-tanning agents. As noted above, they are highly toxic as they come from the tree. Whether the tannins evolved to protect the acorn against large animals or against insects and fungi is uncertain, but dietary concentrations of over 8 percent are fatal to rats. The tannin concentrations in acorns can reach 9 percent, and this explains why we cannot eat acorns raw. The Porno Indians of California mixed unprocessed acorn meal with a certain kind of red clay to make bread. The clay bound enough of the tannin to make the bread palatable. Other groups boiled the acorns to extract the tannin. Our enzyme systems can apparently cope with low concentrations of tannin, and many of us like its taste in tea and red wine. Small amounts of tannin may even be helpful by stimulating production of the digestive enzyme trypsin.

Human diets expanded after fire was domesticated. Because heat detoxifies many of the most potent plant poisons, cooking makes it possible for us to eat foods that would otherwise poison us. The cyanogenetic glycosides in arum leaves and roots are destroyed by heat, so that arum could be cooked and eaten by early Europeans. Unfortunately, some toxins are stable at high temperatures, while other new toxins are actually produced by cooking. That tasty char on barbecued chicken contains enough toxic nitrosamines for several authorities to recommend restricting our intake of grilled meat to prevent stomach cancer. Have we been cooking meat long enough to have developed specific defenses against the char toxins? Cooking may have been invented hundreds of thousands of years ago, and it
must have started with barbecues on open fires. It would be interesting to know if we are more resistant to heat-produced toxins than our closest primate relatives are.

Since the invention of agriculture we have been selectively breeding plants to overcome their evolved defenses. Berry bushes were bred for reduced spininess and the berries for reduced toxin concentrations. The history of potato domestication, as described in Johns’s book, is especially instructive. Most wild species of potato are highly toxic, as you might expect, given that they are an otherwise unprotected, concentrated source of nourishment. Potatoes are from the same plant family as deadly nightshade and contain harmful amounts of the highly toxic chemicals solanidine and tomatidine. Up to 15 percent of their protein is designed to block enzymes that digest proteins. Still, a few wild species can be eaten in limited quantity, and edibility can be increased by freezing, leaching out the toxins, and cooking. We enjoy thoroughly edible potatoes today thanks mainly to many centuries of selective breeding by native farmers in the Andes.

Concerns about pesticides have recently spurred programs to breed plants that are naturally resistant to insects. This protection is provided, of course, by increased levels of natural toxins. A new variety of disease-resistant potato was recently introduced that did not need pesticide protection, but it had to be withdrawn from the market when it was found to make people ill. Sure enough, the symptoms were caused by the same natural toxins the Andean farmers had spent centuries breeding out. An evolutionary view suggests that new breeds of disease-resistant plants should be treated as cautiously as artificial pesticides are.

O
ne reason to stress the prevalence of toxins in our natural environment, and our evolutionary adaptation to them, is to provide a perspective on the medical significance of novel toxins. Novel toxins are a special problem not because artificial pesticides such as DDT are intrinsically more harmful than natural ones but because some of them are extremely different chemically from those with which we are adapted
to cope. We have no enzymatic machinery designed to deal with PCBs or organic mercury complexes. Our livers are ready and waiting for many plant toxins, but they don’t know what to do with some novel substances. Furthermore, we have no natural inclination to avoid some novel toxins. Evolution equipped us with the ability to smell or taste common natural toxins and the motivation to avoid such smells and tastes. In psychological jargon, the natural toxins tend to be aversive stimuli. But we have no such machinery to protect us from many artificial toxins, like DDT, that are odorless and tasteless. The same is true of potentially mutagenic or carcinogenic radioisotopes. Sugar synthesized from radioactive hydrogen or carbon tastes as sweet as that made with ordinary stable isotopes, but we have no way of detecting its dangers.

It is not always easy to tell what the effects of a novel environmental factor may be. For instance, the debate about the possible dangers of mercury in dental fillings has gone back and forth, but Anne Summers and her colleagues at the University of Georgia have recently found that mercury fillings increase the number of gut bacteria that are resistant to common antibiotics, apparently because the mercury acts as a selective factor for bacterial genes that protect against mercury and some of these same genes confer resistance to antibiotics. The clinical significance of this finding is uncertain, but it nicely illustrates the unexpected means by which novel toxins can affect our health.

Since we can no longer, in our modern chemical environment, rely on our natural reactions to tell us which substances are harmful and which are not, we often rely on public agencies to assess the dangers and take measures to protect us from them. It is important to avoid unrealistic expectations of such agencies. Tests on rats are of limited reliability as models for human capabilities, and there are many political difficulties that can frustrate public action on environmental hazards. Scientifically illiterate legislatures can pass laws saying that no amount of any chemical that causes cancer can be allowed in food, even though many such chemicals are already present naturally in many foods. Conversely, political pressures can lead to inadequate controls on known toxins, from nicotine to dioxins. There is no such thing as a diet without toxins. The diets of all our ancestors, like those of today, were compromises between costs and benefits. This is one of the less welcome conclusions that arise from an evolutionary view of medicine.