Suppose parents-to-be could guarantee their children will grow up
to be unusually healthy. Or extra smart. Or maybe just a little better
looking than mom and dad.
Sound pretty good?
Now, suppose that guarantee requires a level of planning that goes
way beyond the usual prenatal care. Suppose it requires some fiddling
with the future kids' DNA, adding a few genes here and there to slow
down aging or rev up the brain circuitry or lock in resistance to
viruses.
Still sound good?
Even if your answer is a definite no, some scientists believe many
parents will find this a very attractive option. For now, the choice
is science fiction-- but just barely so.
The time is coming, many scientists say, when parents will pick
their children's genes.
From the menu of possibilities, parents might select genes to make
their babies resist common diseases and infections, things like cancer,
AIDS, heart attacks and Alzheimer's disease. Maybe they would like
their children to have fabulous memories or winning personalities
or a talent for playing the piano.
A couple of extra inches of height and a thick head of hair could
be nice, too.
To hear these scientists talk, all of this and much more will be
possible in the not-so-distant future. "There's nothing beyond
tinkering," says Lee Silver, a Princeton biologist.
Not this year or next, probably, and maybe not in the next 10 or
even 20 years. But these scientists predict the amazing breakthroughs
in genetically engineering lab mice and farm critters will eventually
be applied to the animals at the top of the food chain.
"It's not a question of 'if' but 'when' and 'how' this will
occur," says Gregory Stock, head of the Program on Medicine,
Technology and Society at UCLA's School of Medicine.
Stock and Silver are visionaries in their field, men who enjoy painting
the big picture of an over-the-horizon science called human germline
engineering. Germline refers to the sperm and egg. These scientists
are talking about changing the genetic makeup of a person-to-be at
the moment of conception.
Something like this: Insert block of new genes into a freshly fertilized
egg. The one cell becomes two, then four, then eight. Each new version
carries the extra information. In nine months, a baby is born. Every
cell in his or her body contains the extra genes.
The child grows up. Marries. Passes the extra genes on to the next
generation of babies. And they on to theirs. And so on. Or maybe not.
The unsettling prospect of handing these genetic fixes down the generations
is just one of the many controversies of this obviously hot-button
field.
"The reason people are fascinated by this whole area is that
it will challenge our fundamental thinking about who we are and what
it means to be human," says Stock. "We are talking about
remaking human biology."
But what part of biology to remake first? Typically the answer is
to reduce our tendency to get sick.
While personal habits and medical care play an obvious role in health,
inheriting good genes gives some folks a powerful edge. Scientists
already know some of the combinations of genes that help people resist
some big-ticket illnesses. So one goal of human germline engineering
could be to help the genetically less fortunate share these built-in
health advantages.
For instance, the risk of heart disease depends in part on the levels
of HDL, the good cholesterol. More is clearly better. In the human
body, a gene called ap0-A1 makes a major piece of HDL. The same is
true in mice, whose biology, scientists love to point out, is not
so different from ours.
"It's possible in mice to dial in virtually any HDL level you
want by introducing more copies of this gene," says Dr. R. Sanders
Williams, a cardiologist at the University of Texas Southwestern Medical
Center.
So why not add some extra apO-A1 genes to one-cell persons-to-be
and reduce their chance of dying from humanity's leading killer?
Perhaps resistance to the AIDS virus would also appeal to gene-shopping
parents. Scientists can imagine a way to do that. Those who are born
with two defective copies of a gene called CCR5 can escape HIV infection
despite thousands or risky sexual encounters. The reason: CCR5 makes
a protein that the AIDS virus locks onto when it invades white blood
cells. So, no CCR5 protein on the surface of a cell--no infection.
Of course, there is no reason to stop with disease protection, the
visionaries say. Many genetic "enhancements," as they are
called, can also be imagined.
One obvious enhancement is extra brain power. At Princeton, scientists
have already created mice--nicknamed "Doogie" after TV's
physician prodigy --that are rodent geniuses. They learn faster, remember
longer and adapt to changes better than any ordinary mouse.
What makes these mice unique is an extra copy of a gene that produces
a brain chemical called NR2B. This stuff boosts the cellular switches
that help the brain store associations. (When you remember the name
that goes with a face, that's an association.) While a human brain
is more complex than a mouse's, the basic machinery of learning may
be pretty much the same in both.
Even selecting a child's personality in advance might be possible.
Experts believe that half of people's personality traits are hard-wired
by their genes. Of course, lots of genes combine to create any individual's
melange of quirks and temperament. So building a child with, say,
David Letterman wit, Mother Theresa compassion and Warren Buffett
business sense may not be real easy at first.
Still, scientists are laying the foundation. In mice, at least,
they have already tracked down genes that influence many habits, including
aggressiveness, overeating and mothering instincts.
As fascinating as mouse personalities may be to scientists, soon
there should be much more information about the genetic underpinnings
of such things in larger, less furry creatures. The federal Human
Genome Project is deciphering the 100,000 or so genes spelled out
by the 3 billion letters of the human DNA library.
Actually, there is no single genetic blueprint, because genes come
in many variations. Otherwise everyone would look exactly alike. In
time, scientists will try to see how the assorted flavors of genes
separate the smart from the slow, the handsome from the homely.
For instance, how do the genes of a sharp and fit 95-year-old differ
from the rest? What is genetically different about people endowed
with unusual strength, muscle tone or endurance? What's special about
concert bassoonists, about silver-tongued litigators, about people
who drop out of college and found gazillion dollar software companies?
Eventually, the thinking goes, scientists will figure out which
genes bestow prized talents and characteristics. These, too, could
go on the menu of genetic possibilities browsed by parents who are
designing their babies.
But this idea brings up just one of a very long list of technical
obstacles. Everyone reading this article already owns two copies of
every standard-issue gene. In most cases, just dropping in another
really good one is unlikely to do much. So engineers will have to
figure out some way to reliably shut down the existing so-so genes
so the supergenes can take over.
The field's visionaries toss off sweep-of-the-hand solutions for
this and many other problems and predict the science fiction will
become science within a generation.
"I think it could occur 10 years from whenever we decide it
should," says John Campbell, a UCLA neurobiologist. "It
depends a lot on motivation. It won't be limited by science."
Human germline engineering will require refining the gene transfer
methods that have been worked out in animals. The basic tools are
already in place, Campbell and others say, the result of the revolution
in genetic technology over the past 20 years.
In 1980, Yale scientists created the first transgenic mouse, an
animal with a gene from the herpes virus in every cell. Now all manner
of genes are added or deleted or changed at the start of life in the
lab. Mice carry whale genes; goats with people genes make useful human
proteins in their milk. While this sort of thing has grown routine,
it has never exactly become easy.
Even in the best of hands, only a small percentage of attempts to
create genetically manipulated animals actually succeeds. Huntington
F. Willard, chairman of genetics at Case Western Reserve University,
says human germline engineering will never be accepted until the process
is foolproof.
"By foolproof I mean with very high efficiency and very low
error rate," he says. "When we go in to fix a gene, we will
fix it. There is no chance of doing harm."
The thing that sets the animal experiments apart from anything possible
in people, says Dr. Theodore Friedmann, is "the whoops factor,"
the luxury of discarding one's mistakes.
Friedmann, a pediatrician at the University of California, San Diego,
cochairs a committee looking into human germline engineering for the
American Association for the Advancement of Science. He doubts the
technology will leap ahead with anything like the ease predicted by
the visionaries.
"The technical issues are not minor details," he says.
"They are major problems."
In experimental animals, the simplest way of adding genes is to
microscopically inject DNA into a one-cell embryo. While it gets the
job done, this approach has big drawbacks, including its unpredictability.
The genes land randomly along the cell's chromosomes. In the wrong
place, they work poorly or not at all, or they fall disastrously into
the middle of some essential gene, crippling it.
Another method is a kind of cut-and-paste approach to swap ordinary
genes for upgraded ones. Scientists add DNA to a plate of embryonic
cells. When all goes well, the new genetic material lines itself up
beside the similar-looking stretch of DNA it needs to replace, then
makes the switch.
However, the idea of actually changing a human's inborn genes gives
many scientists the willies. They would rather talk about adding extra
genes and leaving the original set alone.
One way to do this is to build an artificial chromosome, something
already tested in animals. The chromosome would have no genes of its
own. Instead, it would carry plug-in sets of genes intended to address
a particular health item or characteristic. In time, parents might
be able to pick from hundreds of different gene sets.
Of course, one shortcoming of all this is that conception would
have to take place in an in vitro fertilization lab, not the old-fashioned
way. Another is that the extra chromosome, along with the 23 standard
pairs, would presumably be passed on to the next generation during
sexual reproduction.
The visionaries see many reasons to avoid this. The most obvious:
The genes on someone's artificial chromosome will be embarrassingly
outmoded by the time its owner grows to adulthood and is ready to
have children. Better to booby-trap the artificial chromosome to self-destruct
if it turns up in sperm and eggs, they say.
That way, the next generation will start afresh with the latest
gene technology.
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