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Authors: Randolph M. Nesse

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M
UTAGENS AND
T
ERATOGENS

M
utagens are chemicals that cause mutations, which may cause cancer or damage genes and thus lead to health problems for many generations. Teratogens are chemicals that interfere with normal tissue development and cause birth defects. Mutagens and teratogens are not sharply separate from each other or from toxins with short-range effects. Ionizing radiation and mutagens such as formaldehyde and nitrosamines can all cause distress immediately or cancer or birth defects years later.

While it is important to learn which poisons harm everyone, people vary in their susceptibility to many substances, such that one man’s meat may be another’s poison. We will deal with special aspects of individual variability in the chapter on allergy. Vulnerability varies by age and sex. It seems particularly unlikely that detoxification capability is the same in both adults and the very young, especially during embryonic and fetal development. There are abundant theoretical reasons, as well as data from many experimental studies, that show that actively metabolizing tissues are more vulnerable to toxins than dormant ones, cells that divide rapidly more than quiescent ones, and cells that differentiate into specialized types more than those that merely reproduce more of the same.

All these perspectives suggest that embryonic and fetal tissues may be harmed by lower concentrations of toxins than adult tissues are. We regard
Figure 6-1
as a likely picture of vulnerability through human prenatal development. Vulnerability rises rapidly from the level characteristic of a quiescent egg in an ovary to a peak in the critical stages of organ formation and tissue differentiation, then slowly declines to closer to the adult level of tolerance at full term.

We will return to this graph in a moment, but first let’s look at a classic mystery of traditional medicine. So-called morning sickness is often the first reliable sign of pregnancy, especially for women who recognize it from prior experience. This nausea and its associated lethargy and food aversions are so common as to be considered a normal part of pregnancy, although they are quite variable in intensity. For some women they mean many weeks of misery, while others aren’t bothered much. We may even think of morning sickness as one of the symptoms of pregnancy, as if pregnancy were a disease. The current clinical approach seems to be: pregnancy sickness makes
women distressed, so let’s find a way to alleviate the symptoms and make them feel better. Unfortunately, making people feel better does not always improve their health or secure other long-term interests. As pointed out in
Chapters 1
and
2
, natural selection has no mandate to make people happy, and our long-range interests are often well served by aversive experiences. Before we block the expression of a symptom, we should first try to understand its origin and possible functions.

F
IGURE
6-1. Toxin vulnerability at different prenatal ages.

Fortunately, a biologist thoroughly committed to the adaptationist program has recently wondered at the mystery of morning sickness and devised an explanation. Margie Profet, an independent scholar and biologist in Seattle, argues that a condition as common and spontaneous as pregnancy sickness is unlikely to be pathological. Note on the graph how fetal vulnerability corresponds almost exactly to the course of pregnancy sickness. This concordance provided Profet with a crucial clue. Nausea and food aversions during pregnancy evolved, she argues, to impose dietary restrictions on the mother and thereby minimize fetal exposure to toxins. The fetus is a minor nutritional burden on the mother in the early weeks of pregnancy, and a healthy, well-nourished woman can often afford to eat less. The food she is inclined to eat is usually bland and without the strong odors and flavors provided by toxic compounds. She avoids not only spicy plant toxins but also those produced by fungal and
bacterial decomposition. A lamb chop that smells fine to a man may smell putrid and repulsive to his pregnant wife.

Profet amassed diverse evidence in support of her theory. One example is the correlation between toxin concentrations and the tastes and odors that cause revulsion. Another is the observation that women who have no pregnancy nausea are more likely to miscarry or to bear children with birth defects. Much more evidence needs to be gathered on the evolutionary and related medical questions. We think it unlikely, for instance, that the phenomenon is uniquely human. Is it found in mammals in general, especially herbivores? Do newly pregnant rabbits eat less and choose their food more carefully than either before pregnancy or later on? Studies of wild animals would be the best way to answer these evolutionary questions. The medically more important research can be carried out on laboratory animals. An essential premise to be tested is that some toxins of trivial importance for normal adults have seriously deleterious effects on fetal development. We also need to know the common environmental toxins that are most likely to harm a fetus. We also need to look for associations between diet during pregnancy and the more frequent kinds of birth defects, as well as at individual variations in detoxification enzymes.

Some practical applications of this theory are illustrated by the history of the antinausea medication Bendectin. Pregnant women, understandably, often ask their physicians to do something about their nausea. Recognizing the dangers of drug administration during pregnancy, physicians were generally cautious, but the drug Bendectin was thought to be safe and was widely prescribed. After the thalidomide tragedy, there were many studies on the possible harmful effects of Bendectin, and the equivocal evidence has even been the topic of Supreme Court deliberations. Unfortunately, none of the studies has ever considered the possible functions of morning sickness. Perhaps anything that suppresses morning sickness may cause birth defects indirectly by encouraging harmful dietary choices.

If Profet’s theory is correct, it means that pregnant women should be extremely wary of all drugs, both therapeutic and recreational. Fetal alcohol syndrome is perhaps the biggest current problem, affecting thousands of babies every year. Cigarettes can also cause problems, and coffee, spices, and strong-tasting foods may well best be avoided. Certainly, it would be wise to avoid taking any medications if possible. Studies can determine which medications cause
major birth defects, but because others may have more subtle effects, it is better to be safe than sorry.

Other than avoiding toxins, what should a pregnant woman do about her nausea? The easy and obvious answer is “Respect it. Your reactions to food are probably adaptive for your baby. Do not succumb to the urgings of others to eat what you are inclined to avoid. Better to offend the host at the party than to risk imposing a long-term impairment on your child.” But what about your own suffering? It would be easy enough for two male authors to say, “Accept your nausea; it contributes to your long-term desire for a healthy family.” We realize that this is not a satisfactory recommendation. Relief of unpleasant symptoms is desirable as long as side effects are acceptable. We would hope that obstetricians someday will be able to provide their patients with a list of all the substances they ought to avoid. Armed with this knowledge, women could safely use a medication to prevent nausea if it is possible to find one that is effective and to have confidence that it is safe.

People in many cultures, especially pregnant women, eat certain kinds of clay. Although this clay has often been regarded as a mineral supplement, it can relieve gastrointestinal distress and for this reason is used in some modern antidiarrheal medications. Certain kinds of clay, as mentioned in the discussion about acorns, tightly bind soluble organic molecules, including many toxins. In other words, they may relieve symptoms in the best possible way—by removing the harmful cause. Unfortunately, we doubt that it is possible to patent clay. Our present system of drug marketing makes it unlikely that any company would invest the millions needed to test such a product and bring it to market if it could not control an exclusive patent. Regulatory agencies protect us, but they also constrain us.

As fetuses grow older, they become children who tend to hate vegetables. They especially dislike strong-flavored vegetables such as onions and broccoli, the very ones that contain high levels of plant toxins. The developmental course of these dislikes offers a clue to their explanation. Even finicky children often begin to experiment with new foods just as they mature into teenagers and their growth nears completion. The evolutionary explanation for this sensitivity may be the benefits, during the Stone Age, of avoiding the most toxic plants during childhood. Modern-day children and adults would both benefit from eating more of our modern low-toxin vegetables, but there may be a good evolutionary explanation for why children steadfastly resist eating their vegetables.

7
G
ENES AND
D
ISEASE:
D
EFECTS
, Q
UIRKS
,
AND
C
OMPROMISES

T
he medical school lecture hall was surprisingly full for a Monday at eight
A.M.
The lecture dealt with nearsightedness. As the room darkened, the overhead spotlights glinted off the eyeglasses worn by nearly half the students. “So that’s why so many showed up,” murmured the professor.

“The facts are clear,” he summarized an hour later. “Myopia is caused by excessive growth of the eye. When it gets too long from lens to retina, the focal point remains above the surface of the retina, so that the image is blurred. Refractive lenses, in the form of glasses or contact lenses, can refocus the image a bit further back so we can see clearly, overcoming nature’s inexactitude.”

Some hands began to wave. “But what causes the eye to grow too long?” asked one student.

“Genes,” he said. “It’s as simple as that. Some of us were just unlucky enough to get bad genes. If your identical twin is nearsighted, you will almost certainly be also. If your sibling is nearsighted, the likelihood is high, but not as high. Pulling all the figures together, myopia seems to be a genetic disease with a heritability of over eighty percent.”

“But how could such genes survive before glasses were invented?” asked another student. “Without my glasses, I wouldn’t last a day on the African plains.” The class laughed uneasily.

“Well, the genes might be recent mutations,” said the professor. “Or perhaps Stone Age myopic people worked in camp sewing and weaving. In any case, the facts make it clear that myopia is a genetic disorder.”

“But how could that be?” the student persisted. “The force of selection against it would be enormous. If such a severe defect can persist, then why aren’t our bodies riddled with defects?”

“In fact, our bodies don’t work very well,” the professor said pointedly. “As you have been learning, we are bundles of genetic flaws. The body is a fragile, jury-rigged device. Our job as physicians is to fix Mother Nature’s oversights.”

The medical students grumbled a bit more among themselves but did not persist further.

W
HAT
G
ENES
D
O

T
he instructions for making a human body are contained in molecules of DNA, twisted into our twenty-three pairs of chromosomes. We are still learning the details, wonderful almost beyond belief, of how DNA stores and uses information to build a body. Each DNA molecule is like a ladder, with sides made up of alternating units of phosphate and a sugar called deoxyribose. The information is in the rungs, which are composed of pairs of four molecular components with names abbreviated A, C, G, and T. It is hard to comprehend the amount of information in the genetic code. The DNA in a single cell contains a sequence of twelve billion of the A-C-G-T symbols, the amount of information in a small library. If the DNA in a single human cell were untwisted and the molecules put end to end, it would stretch about two meters. If this were multiplied by the ten trillion cells in the body, it would stretch twenty billion kilometers, about the distance to the planet Pluto!

About 95 percent of human DNA is never translated into proteins. The rest can be divided into somewhere in the neighborhood of one hundred thousand functional subunits called genes. Each gene codes for a single protein. How this DNA chain of As, Cs, Gs, and Ts is translated into a protein is the realm of molecular biology, the fast-growing field that may make more changes in our lives than even the discovery of electricity. There are lonely voices crying for attention
to the ethical and political implications of these changes, but the message has not yet gotten through to the general public. Soon it will. Already we have drugs made by DNA cloning. Food plants containing bacterial genes are in production. Pioneering experiments are now relieving previously hopeless diseases by inserting replacement genes into human cells. A less welcome possibility is that an insurance company might, as part of a routine blood test, read samples of DNA and thus learn a client’s risks for a variety of diseases. Screening for some genetic disorders in the early stages of pregnancy is already routine, giving a mother of an abnormal fetus the option of terminating the pregnancy.

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