Will Your Lifestyle Hurt Your Grandchildren?

Scientists find visible evidence some scars can be passed on.

ByCOLUMN by LEE DYE
September 28, 2014, 9:49 AM
PHOTO: A multi-generation family smiles for a portrait in this undated file photo.
A multi-generation family smiles for a portrait in this undated file photo.
Getty Images

— -- Laura Gaydos couldn't believe her own eyes. Excited but unsure, she pulled other people into the lab on the campus of the University of California, Santa Cruz, to see if they could see what she thought she had just seen.

They could.

What they saw was the first visual confirmation of one of the most fundamental tenets of a new field that is revolutionizing the world of biology. The powerful microscope revealed clear evidence that scars from environmental stresses can be passed on from one generation to the next and probably to many generations that follow.

It didn't change the DNA, but it changed how the DNA was regulated, and that was a big step forward in the field of epigenetics.

In the past couple of decades researchers in labs around the world have compiled epigenetic evidence that the so-called blueprint for life -- the rigid collection of genes and chromosomes and cells that are supposed to define us -- isn't as rigid as we had thought.

Epigenetics is sort of like software running the DNA hardware, determining which genes are expressed and which are repressed, or simply turned on or off.

DNA is still quite clearly the 500-pound gorilla in the room, but there's a new player that has some control over the beast. It is expected to open new avenues for medical treatment, including the prevention of cancer, and it could explain some scientific mysteries that have baffled experts for generations.

The microscope showed that what scientists call an epigenetic mark, an environmental memory of famine, abuse, exposure to toxic substances, or even less than nutritious meals, can be passed from one cell to new cells formed during DNA replication in the critical early stage of building an embryo.

Some scientists have argued that the scar would be so diluted as it spread into thousands of cells that it would have no effect on whatever the embryo eventually became, whether it was a worm or a human.But the Santa Cruz researchers watched the show through five cell divisions, and the mark never dimmed.

"What's so compelling is the evidence is very visual." Susan Strome, coauthor with Gaydos of a study published in the journal Science, said in a telephone interview.

"It's really a dramatic display of this passage" from one generation to the next, she said.

Strome's lab was able to pull it off because the lab is equipped to manipulate both the sperm and the egg as they combine to start the embryonic process. They could add an enzyme, for example, to see how that effected the transmission of the mark.

"We could control what we allowed dad to contribute, and we could control what we allowed mom to contribute," added Strome, professor of molecular, cell and development biology at UC Santa Cruz. "That was really the key."

For this experiment, dad and mom were roundworms, C. elegans, a tiny workhorse in labs around the world. For obvious reasons they couldn't do the same experiment with humans. But do the findings apply to more complex organisms, like us?

"I think the answer is definitely yes," she said. "We all have similar genetic material, humans, mice, fruit flies, all the multicellular organisms I know of. I think all of these organisms will show something similar to what we documented."

A scientist at the National Cancer Institute has described the research as "quite remarkable."

Scientists are studying a broad range of issues from diabetes to mental health for links to epigenetics.

Boston University school of Medicine researchers think it may supply an "on and off" switch for some types of cancer.

Cornell University scientists have suggested that a woman who consumes too much of the nutrient choline during pregnancy may trigger an epigenetic switch that will make her baby more vulnerable to stress.

Probably the most famous study grew out of what is called the Dutch Hunger Winter, when more than 20,000 persons starved to death because of a German blockade during 1944. Most of the deaths were in the heavily populated western Netherlands, where medical records were carefully maintained.

In recent years, scientists looking back on that era made an astonishing discovery. If a mother was malnourished during the last months of her pregnancy, the baby was much more likely to be very small, and remain smaller throughout life.

That could have been explained by damage to the developing fetus, but epidemiologists followed the people of that region for decades, including the small babies, and found a real surprise. When those small babies grew up and had babies of their own, the infants were much more likely to be very small too, so the impact of the food shortages has lasted into the second generation.

And here's another twist. Mothers who were malnourished early in their pregnancy had children with higher obesity rates. And that, too, followed through with the grandchildren.

That has led many experts to conclude that memory of the food shortages lingered on for at least two generations, apparently turning up the volume for some genes, and down for others.

This was a dramatic trauma for thousands of persons, and that's probably why the effect shows up so clearly. Several scientists presented evidence in the Journal of Epidemiology two years ago showing that lifestyle changes, including nutrition, are not likely to produce a noticeable epigenetic effect on an individual level. But it might show up at the population level.

That's why the tragedy in Holland is so convincing. Even though not every pregnant woman suffered the same consequences, the numbers on a population level are huge.

On an individual level it's harder to say. But scientists have warned for years that a mother who drinks alcohol while carrying her baby, for instance, is taking a great chance with her unborn child. Maybe it's not as hard to switch genes on and off as we had thought.

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