Why Genes Aren't Destiny

[Guest guest]

Unfortunetly, I am unable to access this with my screen reader technology as

the links list doesn't seem to want to materialize. It sounds interesting.

Carson Wood.

Westbrook, ME USA.

[Mod: Extracts:

In the 1980s, Dr. Lars Olov Bygren, a preventive-health specialist who is now at

the prestigious Karolinska Institute in Stockholm, began to wonder what

long-term effects the feast and famine years might have had on children growing

up in Norrbotten in the 19th century — and not just on them but on their kids

and grandkids as well. So he drew a random sample of 99 individuals born in the

Overkalix parish of Norrbotten in 1905 and used historical records to trace

their parents and grandparents back to birth. By analyzing meticulous

agricultural records, Bygren and two colleagues determined how much food had

been available to the parents and grandparents when they were young.

Around the time he started collecting the data, Bygren had become fascinated

with research showing that conditions in the womb could affect your health not

only when you were a fetus but well into adulthood. In 1986, for example, the

Lancet published the first of two groundbreaking papers showing that if a

pregnant woman ate poorly, her child would be at significantly higher than

average risk for cardiovascular disease as an adult. Bygren wondered whether

that effect could start even before pregnancy: Could parents' experiences early

in their lives somehow change the traits they passed to their offspring? (See

the top 10 medical breakthroughs of 2009.)

It was a heretical idea. After all, we have had a long-standing deal with

biology: whatever choices we make during our lives might ruin our short-term

memory or make us fat or hasten death, but they won't change our genes — our

actual DNA. Which meant that when we had kids of our own, the genetic slate

would be wiped clean.

What's more, any such effects of nurture (environment) on a species' nature

(genes) were not supposed to happen so quickly. Darwin, whose On the

Origin of Species celebrated its 150th anniversary in November, taught us that

evolutionary changes take place over many generations and through millions of

years of natural selection. But Bygren and other scientists have now amassed

historical evidence suggesting that powerful environmental conditions (near

death from starvation, for instance) can somehow leave an imprint on the genetic

material in eggs and sperm. These genetic imprints can short-circuit evolution

and pass along new traits in a single generation. (See TIME's photo-essay

celebrating Darwin.)

For instance, Bygren's research showed that in Overkalix, boys who enjoyed those

rare overabundant winters — kids who went from normal eating to gluttony in a

single season — produced sons and grandsons who lived shorter lives. Far

shorter: in the first paper Bygren wrote about Norrbotten, which was published

in 2001 in the Dutch journal Acta Biotheoretica, he showed that the grandsons of

Overkalix boys who had overeaten died an average of six years earlier than the

grandsons of those who had endured a poor harvest. Once Bygren and his team

controlled for certain socioeconomic variations, the difference in longevity

jumped to an astonishing 32 years. Later papers using different Norrbotten

cohorts also found significant drops in life span and discovered that they

applied along the female line as well, meaning that the daughters and

granddaughters of girls who had gone from normal to gluttonous diets also lived

shorter lives. To put it simply, the data suggested that a single winter of

overeating as a youngster could initiate a biological chain of events that would

lead one's grandchildren to die decades earlier than their peers did. How could

this be possible?

Meet the Epigenome

The answer lies beyond both nature and nurture. Bygren's data — along with those

of many other scientists working separately over the past 20 years — have given

birth to a new science called epigenetics. At its most basic, epigenetics is the

study of changes in gene activity that do not involve alterations to the genetic

code but still get passed down to at least one successive generation. These

patterns of gene expression are governed by the cellular material — the

epigenome — that sits on top of the genome, just outside it (hence the prefix

epi-, which means above). It is these epigenetic " marks " that tell your genes to

switch on or off, to speak loudly or whisper. It is through epigenetic marks

that environmental factors like diet, stress and prenatal nutrition can make an

imprint on genes that is passed from one generation to the next.

Epigenetics brings both good news and bad. Bad news first: there's evidence that

lifestyle choices like smoking and eating too much can change the epigenetic

marks atop your DNA in ways that cause the genes for obesity to express

themselves too strongly and the genes for longevity to express themselves too

weakly. We all know that you can truncate your own life if you smoke or overeat,

but it's becoming clear that those same bad behaviors can also predispose your

kids — before they are even conceived — to disease and early death.

The good news: scientists are learning to manipulate epigenetic marks in the

lab, which means they are developing drugs that treat illness simply by

silencing bad genes and jump-starting good ones. In 2004 the Food and Drug

Administration (FDA) approved an epigenetic drug for the first time. Azacitidine

is used to treat patients with myelodysplastic syndromes (usually abbreviated, a

bit oddly, to MDS), a group of rare and deadly blood malignancies. The drug uses

epigenetic marks to dial down genes in blood precursor cells that have become

overexpressed. According to Celgene Corp. — the Summit, N.J., company that makes

azacitidine — people given a diagnosis of serious MDS live a median of two years

on azacitidine; those taking conventional blood medications live just 15 months.

(See 25 people who mattered in 2009.)

Since 2004, the FDA has approved three other epigenetic drugs that are thought

to work at least in part by stimulating tumor-suppressor genes that disease has

silenced. The great hope for ongoing epigenetic research is that with the flick

of a biochemical switch, we could tell genes that play a role in many diseases —

including cancer, schizophrenia, autism, Alzheimer's, diabetes and many others —

to lie dormant. We could, at long last, have a trump card to play against

Darwin.

The funny thing is, scientists have known about epigenetic marks since at least

the 1970s. But until the late '90s, epigenetic phenomena were regarded as a

sideshow to the main event, DNA. To be sure, epigenetic marks were always

understood to be important: after all, a cell in your brain and a cell in your

kidney contain the exact same DNA, and scientists have long known that nascent

cells can differentiate only when crucial epigenetic processes turn on or turn

off the right genes in utero.

More recently, however, researchers have begun to realize that epigenetics could

also help explain certain scientific mysteries that traditional genetics never

could: for instance, why one member of a pair of identical twins can develop

bipolar disorder or asthma even though the other is fine. Or why autism strikes

boys four times as often as girls. Or why extreme changes in diet over a short

period in Norrbotten could lead to extreme changes in longevity. In these cases,

the genes may be the same, but their patterns of expression have clearly been

tweaked. (See the best pictures of 2009.)

Biologists offer this analogy as an explanation: if the genome is the hardware,

then the epigenome is the software. " I can load Windows, if I want, on my Mac, "

says ph Ecker, a Salk Institute biologist and leading epigenetic scientist.

" You're going to have the same chip in there, the same genome, but different

software. And the outcome is a different cell type. "

How to Make a Better Mouse

As momentous as epigenetics sounds, the chemistry of at least one of its

mechanisms is fairly simple. Darwin taught us that it takes many generations for

a genome to evolve, but researchers have found that it takes only the addition

of a methyl group to change an epigenome. A methyl group is a basic unit in

organic chemistry: one carbon atom attached to three hydrogen atoms. When a

methyl group attaches to a specific spot on a gene — a process called DNA

methylation — it can change the gene's expression, turning it off or on,

dampening it or making it louder. (See more about DNA.)

The importance of DNA methylation in altering the physical characteristics of an

organism was proposed in the 1970s, yet it wasn't until 2003 that anyone

experimented with DNA methylation quite as dramatically as Duke University

oncologist Randy Jirtle and one of his postdoctoral students, Waterland,

did. That year, they conducted an elegant experiment on mice with a uniquely

regulated agouti gene — a gene that gives mice yellow coats and a propensity for

obesity and diabetes when expressed continuously. Jirtle's team fed one group of

pregnant agouti mice a diet rich in B vitamins (folic acid and vitamin B12).

Another group of genetically identical pregnant agouti mice got no such prenatal

nutrition.

The B vitamins acted as methyl donors: they caused methyl groups to attach more

frequently to the agouti gene in utero, thereby altering its expression. And so

without altering the genomic structure of mouse DNA — simply by furnishing B

vitamins — Jirtle and Waterland got agouti mothers to produce healthy brown pups

that were of normal weight and not prone to diabetes.

Can epigenetic changes be permanent? Possibly, but it's important to remember

that epigenetics isn't evolution. It doesn't change DNA. Epigenetic changes

represent a biological response to an environmental stressor. That response can

be inherited through many generations via epigenetic marks, but if you remove

the environmental pressure, the epigenetic marks will eventually fade, and the

DNA code will — over time — begin to revert to its original programming. That's

the current thinking, anyway: that only natural selection causes permanent

genetic change. (See " The Year in Health 2009. " )

And yet even if epigenetic inheritance doesn't last forever, it can be hugely

powerful. In February 2009, the Journal of Neuroscience published a paper

showing that even memory — a wildly complex biological and psychological process

— can be improved from one generation to the next via epigenetics. The paper

described an experiment with mice led by Larry , a Tufts University

biochemist. 's team exposed mice with genetic memory problems to an

environment rich with toys, exercise and extra attention. These mice showed

significant improvement in long-term potentiation (LTP), a form of neural

transmission that is key to memory formation. Surprisingly, their offspring also

showed LTP improvement, even when the offspring got no extra attention.

All this explains why the scientific community is so nervously excited about

epigenetics. In his forthcoming book The Genius in All of Us: Why Everything

You've Been Told About Genetics, Talent and IQ Is Wrong, science writer

Shenk says epigenetics is helping usher in a " new paradigm " that " reveals how

bankrupt the phrase 'nature versus nurture' really is. " He calls epigenetics

" perhaps the most important discovery in the science of heredity since the

gene. " (See the top 10 nonfiction books of 2009.)

Geneticists are quietly acknowledging that we may have too easily dismissed an

early naturalist who anticipated modern epigenetics — and whom Darwinists have

long disparaged. Jean-Baptiste Lamarck (1744-1829) argued that evolution could

occur within a generation or two. He posited that animals acquired certain

traits during their lifetimes because of their environment and choices. The most

famous Lamarckian example: giraffes acquired their long necks because their

recent ancestors had stretched to reach high, nutrient-rich leaves.

Exploring Epigenetic Potential

How can we harness the power of epigenetics for good? In 2008 the National

Institutes of Health (NIH) announced it would pour $190 million into a multilab,

nationwide initiative to understand " how and when epigenetic processes control

genes. " Dr. Elias Zerhouni, who directed the NIH when it awarded the grant, said

at the time — in a phrase slightly too dry for its import — that epigenetics had

become " a central issue in biology. " (See TIME's health and medicine covers.)

This past October, the NIH grant started to pay off. Scientists working jointly

at a fledgling, largely Internet-based effort called the San Diego Epigenome

Center announced with colleagues from the Salk Institute — the massive La Jolla,

Calif., think tank founded by the man who discovered the polio vaccine — that

they had produced " the first detailed map of the human epigenome. "

The claim was a bit grandiose. In fact, the scientists had mapped only a certain

portion of the epigenomes of two cell types (an embryonic stem cell and another

basic cell called a fibroblast). There are at least 210 cell types in the human

body — and possibly far more, according to Ecker, the Salk biologist, who worked

on the epigenome maps. Each of the 210 cell types is likely to have a different

epigenome. That's why Ecker calls the $190 million grant from NIH " peanuts "

compared with the probable end cost of figuring out what all the epigenetic

marks are and how they work in concert.

Remember the Human Genome Project? Completed in March 2000, the project found

that the human genome contains something like 25,000 genes; it took $3 billion

to map them all. The human epigenome contains an as yet unknowable number of

patterns of epigenetic marks, a number so big that Ecker won't even speculate on

it. The number is certainly in the millions. A full epigenome map will require

major advances in computing power. When completed, the Human Epigenome Project

(already under way in Europe) will make the Human Genome Project look like

homework that 15th century kids did with an abacus.

But the potential is staggering. For decades, we have stumbled around massive

Darwinian roadblocks. DNA, we thought, was an ironclad code that we and our

children and their children had to live by. Now we can imagine a world in which

we can tinker with DNA, bend it to our will. It will take geneticists and

ethicists many years to work out all the implications, but be assured: the age

of epigenetics has arrived.]

Why Genes Aren't Destiny

Colleagues,

In the current issue of Time magazine, there's a fascinating cover story on

epigenetics entitled " Why Genes Aren't Destiny " :

http://www.time.com/time/health/article/0,8599,1951968,00.html

The take-away message is that the choices we make and stressors we

experience can influence our genetic expression as well as those of our

children. While the body of research is relatively young, certain

nutritional factors have been shown to have powerful effects. Going forward

it will be interesting to see what is revealed about exercise and other

environmental factors.

At one point the article quotes science author Shenk: the epigenetics

paradigm " reveals how bankrupt the phrase 'nature versus nurture' really

is. " It seems that we should be thinking in terms of nature via nurture.

Regards,

Plisk

Excelsior Sports •Shelton CT

www.excelsiorsports.com

Prepare To Be A Champion!

[Guest guest]

I'm catching up on a backlog of magazines and found this article from January.

Thought it was interesting.

http://www.soulmedicineinstitute.org/TimeMag.pdf