Daniel Tencer
Sun
OTTAWA — Arturas Petronis and Moshe Szyf know a little something about the fads of science. As pioneers in the budding field of study known as epigenetics, they took their share of abuse for supporting scientific theories that, for many years, were considered heresy by most scientists.
Petronis, head of epigenetics at the University of Toronto’s Centre for Addiction and Mental Health, once applied for a research grant and received the following anonymous, written comment: “This is shit.”
Szyf, a professor of pharmacology at McGill University in Montreal, had a proposed research article of his described as “a misguided attempt at scientific humour.”
“What they do is crush any opinion that doesn’t fit theirs,” Szyf says. “I was told not to work on [epigenetics] if I ever wanted a career.”
FROM HERETICS TO PIONEERS
What a difference a few years makes.
Petronis and Szyf are now both mini-celebrities in the increasingly accepted field of epigenetics, which postulates that there is a “second code” of programming on top of our DNA, a code that — unlike DNA — can change during our lifetime. In the past half decade, epigenetics researchers have theorized that our diet, the chemicals we are exposed to and even our behaviour towards one another can cause changes in the way that our genes are expressed and some of those changes may even be passed on to future generations.
That, in turn, has caused many scientists to rethink almost everything we know about how genetic information is passed on from parent to child. The traditional view of genetics has been almost deterministic: We are born with a code that dictates everything we are, physiologically. Our genes work the same way from the day we are born to the day we die. Our destiny, geneticists said, was written in our DNA. But now, scientists are beginning to think that people aren’t just shells to carry on DNA, but rather the “caretakers” of our genetic code. How we live, epigenetics researchers say, changes the way our genes function, and some of those changes can be passed on to future generations.
This is a seismic shift in our view of heredity, but to understand how we got to epigenetics, first we have to look at genetics.
Remember the Human Genome Project? A decade ago, it was the darling of molecular biologists everywhere.
Once completed, proponents said, it would clue us in to almost everything that happens with humans.
But as genetics-mania swept the world through the 1990s and the Human Genome Project came to fruition, it slowly became clear DNA wouldn’t answer all the questions scientists had believed it would.
Enter epigenetics. The basic science behind it had been theorized for some time. As recently as 30 years ago, researchers proposed that there are chemicals attaching themselves to our DNA and changing the way genes function.
The idea of epigenetics was meant to answer some fundamental questions that genetics could not.
One of those was the problem of identical twins. Even though twins carry the exact same DNA, it has been known for decades that one twin can develop hereditary diseases the other one does not.
This was the problem Petronis set off to explore about eight years ago. He noticed that in about half of the cases of schizophrenia found in twins, only one twin developed the condition, even though schizophrenia is widely considered to be genetic.
“After 50 or 60 years of study, there was no specific explanation of twin discordance,” Petronis says.
“Ninety-nine per cent of geneticists still believe environmental factors play a role, but when you ask for specifics, they can offer nothing.”
TWIN ANOMALIES
By studying sets of twins where one twin had a psychiatric disorder and the other didn’t, Petronis found the psychiatric patients had more in common with each other, epigenetically, than they did with their own twins.
“Any two random people share 99.7 per cent of their DNA, but at the epigenetic level, people are very, very different,” Petronis says.
But the more eyebrow-raising aspect of epigenetics has to do with heredity. Evidence is beginning to mount that the epigenetic code, or at least parts of it, can be passed down from parents to their children.
One of the most prominent backers of this idea is Marcus Pembrey, a geneticist at University College London in the U.K., who studied the unusually detailed historical medical records of the isolated northern Swedish city of Overkalix.
What Pembrey and his colleagues found was astonishing: The grandsons of men who experienced famine during mid-childhood went through puberty earlier and had longer lifespans, while the grandsons of men who were well fed in early childhood had an increased likelihood of diabetes.
For females, the effect was similar but it was tied to the grandmother, rather than the grandfather.
“This is not a ‘trickle-through’ [of genetic material], this is clearly an evolved response,” Pembrey says. He speculates the purpose of such a response “would be to adjust early growth and reproduction to accommodate unpredictable or adverse environments.”
In a contemporary study of two generations, Pembrey found fathers who had started smoking before age 11 had sons who were significantly fatter than average. There was no similar effect on daughters.
For the first time, it seemed there was a scientific basis for that old adage that the sins of the father are visited upon the son.
Yet, the idea that what we are exposed to can be recorded in our genes and passed on to our descendants is still controversial, even within the field of epigenetics itself.
“You ask five people to interpret these findings, you get five different answers,” Petronis says, adding the interpretation of cross-generational data is “very speculative.”
“There could be lots of compounding factors.”
MAPPING A MOVING TARGET
The major problem with epigenetics is that researchers still know so little about it. According to Szyf, we have yet to learn 90 per cent of what there is to know about how these processes work, and figuring it all out will be “much more complicated than reading genes.”
“Epigenetic codes are moving targets. They could change at any time. And the same gene, one gene, could have 700 epigenetic programs. So that complicates things.”
If serious progress is to be made in understanding epigenetics, it will require a thorough map of how the epigenetic code works. In 2003, a consortium of public and private firms in Europe began the first Human Epigenome Project, which aims to have 10 per cent of the human epigenetic structure mapped by this fall.
Just last month, the group released its first major findings, comprehensively mapping the epigenetics of three human chromosomes. The researchers found that about one-fifth of the genes in those chromosomes can have their behaviour changed.
So what can we glean from all this?
We have reason to believe that the food we eat, the chemicals we ingest and even our parents’ behaviour toward us can all change the way our genes function. But what can and should we be doing to protect ourselves — and our descendants — from harm? Few are willing to say just yet. But Pembrey doesn’t beat around the bush.
“Child care has a whole new meaning,” he says.
© The Vancouver Sun 2006