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Building on Darwin's theory

Andrew Feinberg
Epigeneticist Andrew Feinberg of the Johns Hopkins School of Medicine has a big idea that could improve on Darwin's theory of natural selection, the basis of our understanding of evolution. But can he prove it? Photo: Johns Hopkins Medicine

During a tourist's trip to Westminster Abbey three years ago, Andrew Feinberg felt the jolt of an epiphany. While visiting the Abbey graves of Charles Darwin and Isaac Newton, and admiring a plaque memorializing Paul Dirac, one of the fathers of quantum mechanics, Feinberg pondered the random, multifaceted nature of evolution.

As a biologist who works in a burgeoning field called epigenetics—the study of how proteins activate DNA and influence the behavior of our genes—Feinberg marvels at Darwin's ideas on natural selection and the groundbreaking effect his evolutionary theories have had on science. But like many scientists, he wonders whether the story of natural selection ends with Darwin. The evolutionary journey would seem to involve more than purely genetic possibilities, but how? Why?

Could epigenetics itself have an influence on the long, strange trip humanity's genes have been taking it on?

As he pondered these questions, the bolt of inspiration struck, leading Feinberg to power stride off to a nearby London pub, where while ordering a meat pie and a pint of Guinness, he asked a bartender, "Can I have a napkin to write on? I just had this exciting idea about evolution!"

What Feinberg, a professor of molecular biology, biostatistics, genetics, and oncology at the School of Medicine, scribbled down went something like this: Suppose that not all of the principles of natural selection come from the behavior of our DNA. What if there were another method above and beyond our genes that adds a layer of random variability to how we develop—a mechanism that, while based in the genes, offers a range of potentialities beyond what genes alone can? And what if that wider scope makes species more fit for survival as they adapt to changing environments?

"I thought maybe this randomness, this regulated variance, might be more than just some kind of noise or clutter, but something necessary to developing a multi-celled organism," says Feinberg, Med '76, SPH '81. If that variance is necessary in development, and is present in many common diseases, he reasons, "there's a possibility it's a deeper part of what we and other species are."

Feinberg loves to tell this story, but he knows mere narratives are rarely accepted by science. In other words, he must take many painstaking experimental steps to test his theory. Fortunately, he is well practiced in the arts of scientific quibbling and questioning.

Epigenetics (literally: "above the genome") was largely unknown as a field 30 years ago, when Feinberg started to investigate its connections to illness. Back then, he and another Johns Hopkins researcher made a seminal link between certain epigenetic processes and cancer. Nowadays, as director of the Johns Hopkins Center for Epigenetics in the Institute for Basic Biomedical Sciences, Feinberg is attempting to find new ways to measure epigenetic connections and their effects on how species develop, from inception on up. But it's a daunting task; proving that random epigenetic variations ("stochasticity" is the term of art) occur over unimaginably long stretches of time is mind-blowingly difficult. For one thing, samples of chemicals or tissue from organisms dead for thousands of years aren't available. And developing a calculus for computing how an "epigenome" or two may have changed in a species over time is seemingly next to impossible.

Still, even in the face of criticism from other scientists who question whether he can get to the heart of the issue, Feinberg forges ahead, cheerily but soberly looking for clues that could yield new treatments for disease, and for concrete signs of where we've been and how the mechanisms of epigenetics have led our species (and others) to adapt.

Science will continue to learn more about evolution from a variety of viewpoints—as will he. "Epigenetics and genetics are equally important," Feinberg says. "It's the combination that matters. And the points where they come together is likely where we'll find answers."

Adapted from "Evolution, Evolved," Johns Hopkins Magazine

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