March 7, 2015

TOWARD THE END of World War II, the Nazis blocked all food and fuel supplies to the Netherlands, leading to famine. Many babies born during this famine suffered long-term effects, including a higher incidence of a variety of conditions such as heart disease, obesity, glucose intolerance, and obstructed airways. Severe trauma altered the victims’ gene code for life, even if the victim had yet to be born.

But here’s the weird part: The effects didn’t stop with a child or with a generation. Postwar and post-famine, later-born siblings were also affected. Even in periods when food was available and the war over, a genetic memory lingered.

And it appears to linger a long time. In follow‑up studies, the daughters of Dutch mothers who had suffered through WWII’s famine while pregnant in turn had daughters with twice the average rate of schizophrenia. In other words, mothers’ wartime duress was passed on to their daughters, in the form of mental illness, and then on to the granddaughters: a genetic scar, inherited collectively by many individuals across at least two generations. Somehow, genes had been altered even for those who had no direct contact with the famine itself.
Excerpted from Evolving Ourselves by Juan Enriquez and Steve Gullans
Excerpted from
Evolving Ourselves by Juan Enriquez and Steve Gullans

If our gene code can change in real time because of our surrounding environment, and if these changes can be passed on, then a long-discredited biologist, Jean-Baptiste Lamarck, may not have been 100 percent wrong. In the early 19th century, Lamarck was run out of bio-town for daring to suggest that evolution can take place in one generation; he argued that if giraffes stretch their necks to reach the upper branches of trees, their necks will lengthen and this beneficial trait will be passed to their progeny.
In other words, Lamarck was saying that evolution isn’t the very slow and apparently haphazard process Darwin described. And today, of course, the AP Biology review (or any other relevant text) states something like, “We now know that Lamarck’s theory was wrong. This is because acquired changes (changes at a ‘macro’ level in somatic cells) cannot be passed on to germ cells.” Cut and dried, case closed . . . except that the Dutch famine cases seem to contradict this assertion.

The Case of the Voodoo Tomatoes
Until very recently, “transgenerational inheritance” was a concept typically banned from all polite geneticists’ conversations. But then doubts began to creep in when scientists performed experiments and observed the various nifty tricks and speed with which various bacteria adapted to new environments.

The experimenters realized two things: First, there was a very low likelihood that rapid adaptation was taking place due to random, beneficial mutations. Second, given how fast a trait like antibiotic resistance could spread within a species and across many species of microbes, there had to be some real-time evolutionary reset mechanism. So a few brave souls revived the term “epigenetics,” first coined in 1942 by Conrad H. Waddington, a British scientist.
In one experiment, scientists shocked mice every time they smelled almonds. When these mice reproduced, their kids and grandkids were born afraid of the same smell.
Most early epigeneticists were ignored or written off as “voodoo biologists.” What they preached was such a radically different discipline from core genetics that as long as their experiments were confined to bacteria, the outcomes and modes of action could be considered a fluke.
But then came tomatoes, in which scientists observed and quantified transgenerational changes from mother to daughter to granddaughter tomato after exposure to drought, extreme cold, or great heat. The discoveries kept piling on; in 2013, a Cornell team demonstrated that epigenetics, not gene code, was a critical factor when trying to figure out when and why a tomato ripens.

Similar epigenetic effects were discovered in worms, fruit flies, and rodents; a creative and slightly mean-spirited experiment involved letting mice smell sweet almonds and then shocking their feet. Soon mice were terrified of the smell of almonds. When these mice reproduced, the kids were never shocked, but they were still quite afraid of the same smell. So were the grandkids. The brains of all three generations had modified M71 glomeruli, the specific neurons sensitive to that type of smell. We do not yet know how many generations epigenetic tags can survive for, but in rats the effects can last at least four generations. In worms, disrupting epigenetic control mechanisms can have consequences persisting for 70 generations.

This implies that an environmental stimulus (for example, famine, stress, toxins, affection) can be transmitted via the nervous, endocrine, or immune systems to the DNA in each cell, which in turn sets switches that express hereditary code to silence or activate in a particular situation. Under siege by some invaders? Flip a few switches to cope. Fall harvest plentiful? Flip a few switches to store fat, procreate, and ramp up metabolism. A plague in the neighborhood? Flip a few switches to enhance resistance.
Your DNA genome has “on/off” chemical switches that collectively are known as your epigenome. So your epigenome is unique and changes every time a switch is flipped. Because your epigenome’s switches are considered reversible when they are passed from parent to child, many scientists view this to be “soft evolution,” i.e., not guaranteed to be as enduring as when a mutation arises in the core DNA genome.

The epigenome can be passed on, sometimes reversed, sometimes reinforced. Unlike in classic Mendelian genetics, it is hard to predict and quantify, so you can just imagine how this variation in experimental outcomes has driven many careful, traditional scientists who believed the DNA code was the be‑all and end-all of heredity completely crazy. They would try to eliminate all the variables, use genetically identical rats, and sometimes get completely different results. So it is no surprise that for decades epigenetics was ignored or pooh-poohed by funders, senior biologists, and science magazines. There was no reliable way to trace the precipitating event and no way to easily predict which individuals would be affected in future generations.

So how do our epigenomes become informed about life around us, particularly the epigenome of a fetus or a yet‑to‑be‑conceived child? Most of the science points to our neural, endocrine, and immune systems. Our brains, glands, and immune cells sense the outside world and secrete hormones, growth factors, neurotransmitters, and other biological signaling molecules to tell every organ in the body that it needs to adapt to a changing world.
Soft evolution is like an annotated book. Those who read different annotations of the same book may end up with very different learning.
As we experience stress, love, aging, fear, pleasure, infection, pain, exercise, or hunger, various hormones adjust various physical responses within our bodies. Hormones surge through our blood; changes in cortisol, testosterone, estrogen, interleukin, leptin, insulin, oxytocin, thyroid hormone, growth hormone, and adrenaline make us behave and develop in different ways. And they signal to our epigenomes, “Time to flip some switches!”
Genes get shut off or turned on as the world around us changes.

The Book of Life
Soft evolution is analogous to an annotated book. The basic text and argument of the book remain the same. But if the text is gradually surrounded by margin notes and comments, then those who read different annotations of the exact same book may end up with very different learning, depending on who annotated the particular copy they borrowed, how they treated the original text, how the reader decided to interpret the interplay between the original printed text and the annotations, and whether some of the annotations were erased or modified by other readers.

There are multiple ways to add in rapid, inherited epigenetic adaptations without any change in the core DNA code. One basic and common mechanism is DNA methylation: Enzymes in our cells attach a methyl group (CH3) to a cytosine (C) located next to a guanine (G) in our DNA, forming a methylated island. This tells the gene that follows next, “Shhh, do not express yourself.”

One of the key reasons for human diversity is that about 70 percent, or roughly 14,000, of our genes have these “on/off” switches plus random mutations among them, so there are countless combinations of ways that these switches are flipped in the human population.

Sperm and eggs get a nearly fresh start: An estimated 90 percent of the switches are erased before conception occurs, which means most epigenetic memories are lost. But there is still a lot of recent data moving from generation to generation. (Those who described sperm as simple bags of DNA with a tail could never explain why sperm had so many receptors for so many hormones not directly related to reproduction, including leptin, one of the obesity genes, as well as 19 growth factors, cytokines, and neurotransmitters.)

Epigenetic switches can be flipped on and off in sperm, eggs, or embryos, so your kids and grandkids can share your environmental experiences and knowledge, and be better prepared for the environment they will soon be entering. For instance, if you were a male smoker, and your brother was not, 28 epigenetic signals in your sperm would be different from his. Sperm are listening.

At conception, your grandchildren listen to distant tales, and sometimes pass them on.

Reprinted from Evolving Ourselves by Juan Enriquez and Steve Gullans with permission of Current, an imprint of Penguin Publishing Group, a division of Penguin Random House LLC. Copyright (c) Juan Enriquez and Steven Gullans, 2015.


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