Survival of the Sickest: Chapter 7 Summary & Analysis

As of 2007, one-third of American children (25 million kids) are overweight or obese. In the last 30 years, the percentage of obese 2- to 5-year-olds has doubled, and the percentage of obese 6- to 11-year-olds has tripled. This is partially due to the rising popularity of fast food, television, and video games—but it may not tell the whole story. There is emerging evidence that the dietary habits of women in the early stages of pregnancy may impact the metabolism of their children.

This is not to suggest that children inherit the weight problem of their parents. Rather, research in the new field of epigenetics suggests that  certain chemical compounds can suppress the expression of specific genes—these compounds act like a “genetic light switch.” Epigenetics is concerned with uncovering how children can inherit new traits despite their DNA remaining the same.

The first big breakthrough in epigenetics came in 2003, in a study at Duke University. Researchers bred mice with the agouti gene, which is characterized by obesity and a yellow coat. For generations, the mice were bred normally and had the same genetic information. Then, researchers separated pregnant agouti mice into two groups. In the control group, they gave the mice a regular diet, and their babies were also fat and yellow. In the experimental group, they fed the mice a variety of vitamin supplements. Their babies, by contrast, were thin and had a dark coat—but their genes had not changed.

These groundbreaking results proved that one or more of the compounds in the vitamins “turned off” the agouti gene without changing the genes themselves—a process called methylation. One of the leaders of the study explained that maternal nutrition has long been considered important, but that this study illustrates exactly how maternal nutrition can impact how genes are expressed in the mother’s offspring. Epigenetics erased the idea that genetics are set in stone. This wasn’t completely surprising, as identical twins (who have the same DNA) are often very similar but don’t always get the same diseases, nor do they have the same fingerprints.

Researchers have also noted the ability of certain species to adapt to conditions based on the mother’s experiences during pregnancy. For instance, depending on the time of year a mother vole will give birth, baby voles are born with a thick or thin coat. The offspring of the freshwater flea Daphnia will have a larger helmet and spines if the mother is in an environment crowded with predators. One species of lizard is born with either a large body and long tail or a small body and short tail, depending on whether the mother smelled a lizard-eating snake while pregnant.

These epigenetic adaptations are also present in humans and may be partially responsible for the increase in childhood obesity. A British medical professor named David Barker proposed that when mothers eat junk foods, which are low in nutrients, the embryo may receive signals that it will be born into a harsh, food-scarce environment. This can cause them to develop “thrifty” metabolisms that are more efficient at hoarding energy. Ten thousand years ago, this helped a baby survive, but in today’s age, a child with a slower metabolism that is surrounded by calorie-rich, nutritionally-poor food will become overweight.

There is new intriguing evidence that fathers and grandmothers can pass epigenetic information onto their offspring as well. Men who smoked before puberty had sons who were significantly fatter by the time they were nine. The toxins from smoking indicated a difficult environment, resulting in an epigenetic change in their sperm. The same issue was not found in daughters, suggesting that these epigenetic markers are passed on the Y chromosome. In the case of grandmothers, when a human female is born, she already has the complete set of eggs she will have for life. Thus, our mother’s eggs developed in the womb of our grandmother and may have been affected by epigenetic signals in our grandmother’s environment as well.

The researchers who studied the agouti mice believed that early nutrition can affect all genes, including the germ line. Therefore, traits that a parent or grandparent acquires can be inherited by future generations, which follows the theory attributed to Lamarck. Some researchers in epigenetics even call themselves “neo-Lamarckians.”

Epigenetic changes can occur throughout life as well. Researchers studied baby rats that were given to different sets of mothers: one group that was standoffish, and one group that was nurturing. They found that babies who were given to the nurturing group grew up to be confident and relaxed, but babies that were ignored by their mothers grew to be nervous and stressed. This was not only due to “nurture” (i.e., the mothers’ behavior), however. Babies that were groomed by their mothers showed a decrease in methyl markers around the genes involved in brain development because the mothers’ attention triggered methyl markers that would have otherwise impeded the babies’ developing brains. In this case, parental care changed how the babies’ genes were expressed. Researchers believe it’s likely that the same could happen in humans.

Methylation is not inherently good or bad—it depends on the gene being turned on or off. In some cases, methylation can suppress important genes, like in the story of identical twin girls, Elizabeth and Eleanor. The two were treated identically until their early twenties, when they moved apart. In 2000, Eleanor was diagnosed with breast cancer, while Elizabeth had the disease. After studying their genes, researchers showed how their methylation patterns diverged when they moved apart, leading only Eleanor to develop cancer.

There is more evidence to support the idea that methylation is tied to cancer: there is a significant connection between breast cancer recurrence and the amount of methylation of a gene called PITX2. This information allows doctors to tailor patients’ treatments based on their genes. Methylation of certain cancer-suppressing genes can also be an early warning sign, allowing doctors to measure one’s risk.

Epigenetics is still an emerging field, and there is much about it that researchers still don’t understand yet—including which genes are turned off by which methyl donors. It is important not to try to alter our genes with certain methyl donors, because we don’t know what other genes may be affected by them. The first drug that tried to deliberately affect methylation patterns was called azacytidine, and it inhibited the methylation patterns of certain genes to try to prevent MDS—a collection of blood disorders. But six months after the drug was approved, the drugs were turning off as many genes as they were turning on.

Moalem gives another example, illustrating how little we understand of epigenetics. In the months after 9/11, there was a dramatic spike in late-term miscarriages in California—but only in male fetuses. Moalem explains that we can only speculate as to why this might have happened. Males are more demanding on the mother’s body during pregnancy and less likely to survive if malnourished. Perhaps, he writes, we have evolved a kind of system that is triggered in times of crisis: lots of females and a few strong males give a population better chance for survival than the other way around. There is also evidence that in times after conflict, more men are born, and that women who predicted that they would live into old age were more likely to have male babies.

The first big epigenetic breakthroughs were published as the Human Genome Project was completed, which mapped out the 3 billion nucleotide pairs that make up our DNA. But epigenetics proves that this road map is only a starting point, because epigenetics tells us “which roads are open and which roads are closed.” Thus, the Human Epigenome Project identified the chemical changes and relationships that determine how DNA will function, as well as uncovering how environment can impact human health.