Born to Be Wild?

Some mice are born to be bad mothers. It’s in their genes.

Most mice are maternally inclined, licking and grooming their pups and arching their backs to encourage nursing. But not BALB/c mice, an albino strain that’s frequently used in cancer and immunology tests. Famously aggressive, these mice have a genetic mutation that makes them as likely to step on or even bite their young as groom them.

Enter Francis Champagne and her colleagues, who found a remarkable and lasting change in mothering behavior among a particular group of BALB/c mice, based more on nurture than nature.

Mice usually raise their young alone. But when these researchers encouraged a kind of group parenting involving both healthy mothers and some mice with the BALB/c mutation, something strange happened. The BALB/c mice seemed to observe and learn nurturing mothering techniques from their roommates.

That’s impressive. But not as impressive as what Champagne discovered when the BALB/c pups were allowed to grow up under the improved care of their own mothers. Eventually this generation was mated and permitted to parent their own young alone. Despite their genetics, these second-generation mouse mothers licked their young, groomed them, and displayed arched-back nursing. And so did their pups once they grew up.

In other words, Champagne and her research team determined that a caring upbringing beat the BALB/c genetics in a way that lasted for generations.

While there could certainly be psychological or sociological explanations for some of the improvements in these mothering techniques, the team’s findings drift into a new area of research called transgenerational epigenetic inheritance.

Every cell in a mouse has the same set of genetic instructions written in its DNA. The instructions are interpreted and used differently in each cell type. Every cell has to make choices regarding which genes are used and which are not. Epigenetics involves chemical changes that tell the cells how—or whether—to use the genes, without actually changing the DNA sequence itself.

The epigenetic interpretation of the genome is usually reset between generations—after all, the next generation will need access to all of its genes in order to make all its various cells, from neurons to heart muscles. But it is becoming increasingly clear that in some instances, parents give to their offspring not just a set of DNA, but epigenetic instructions as to how the DNA should be read. Through epigenetics, parents can pass on not just the basic genetic information, but suggestions for its wise use.

The BALB/c mice showed changes in epigenetic marks on genes that code for important stress hormone receptors in the brain. The experience of being raised well had led to an epigenetic change that seemed to counteract potentially damaging genes. And the beneficial epigenetic marks were passed on to the next generation.

Reprogramming Our Bodies

This powerful combination of nature and nurture causes epigenetic changes in humans as well. Indeed a terrible, but well-documented, example of epigenetic inheritance comes from the Dutch Hunger Winter.

In the winter and spring of 1945, the citizens of the western Netherlands suffered a tragic famine. Unusually cold weather, the devastation of four years of war, and a German blockade combined to reduce food provisions to less than a third of what they had been. More than 20,000 people were killed by widespread starvation; the survivors struggled with life-long health complications.

Researchers later examined the famine’s effect on those who experienced it from within the womb. Mothers who were in the final trimester of pregnancy when the famine began were likely to give birth to underweight babies. Those who were finishing their first trimester of pregnancy as the famine ended gave birth to babies of average size.

As the children who experienced the famine in their first months of development became adults, they had lower rates of obesity than their peers who were born just months earlier or later. Somehow, experiencing famine as a fetus had reprogrammed how they processed food.

And this disruption extended across generations. These survivors passed down a change in the epigenetic marks that suppress a gene involved in fetal growth, IGF-2. Grandchildren of the women who became pregnant at the end of the Dutch Hunger Winter were more likely to have a number of health issues, from obesity to schizophrenia.

How we live, what we eat, and which chemicals we are exposed to may make permanent changes to our epigenetics—and affect generations to come. We’ve known for a long time that obesity and diabetes run in families. The assumption was that these tendencies were from either nature or nurture: that is, either the family genes themselves predisposed family-members to these conditions or their shared lifestyles explained their shared disease. Epigenetics, however, suggests there may be more at work. Rat studies show that female rats whose fathers were fed a high-fat diet respond to sugar as though they are already pre-diabetic—even though they have the same diet, exercise, and genetics as their brothers. The diet choices made by a couple long before they have children may start to write how their kids—or even their grandchildren—will interact with food for their whole lives.

The full implications of transgenerational epigenetic inheritance are not yet understood. We’ve discovered, for example, that adults who were physically abused as children have an epigenetic difference in stress hormone receptors in the brain. Are these changes inheritable? Would their children be affected biologically by the abuse their parents suffered? And if a child is rescued from an abusive home, can the nurturing parenting they receive in adoptive care lead to positive epigenetic changes that will last for generations?

At this point we do not know. Nor do we know where current research will lead. Consider those mothering mice. Champagne and her fellow researchers were able to erase the effects on parenting attributed to epigenetic changes by injecting a drug called trichostatin A into mice’s brains. “It was crazy to think that injecting it straight into the brain would work,” Moshe Szyf, one of the researchers, told Discover. “But it did. It was like rebooting a computer.” Now drug companies are trying to find epigenetic treatments for depression and a litany of other difficult conditions. As Discover asked: “If a pill could free the genes within your brain of the epigenetic detritus left by all the wars, the rapes, the abandonments and cheated childhoods of your ancestors, would you take it?” Would it make us less resilient? Would it risk undoing the gifts of grace amid generations of conflict? Or would we see it as a new gift of God in his work of making all things new and freeing us from generational curses?

Clay Carlson is associate professor of biology at Trinity Christian College in Palos Heights, Illinois.

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