- It's easy to imagine the possibilities for making genetically
modified people, whether with artificial chromosomes or some other technology.
A double helping of genes that boost memory, intelligence, longevity, or
strength could be on the menu soon. That might seem scary to us. But will
it seem scary to our kids?
-
-
- The Remastered Race
-
- Artificial chromosomes and in vitro screening are giving
new life to the eugenics debate. The question is not whether we want to
engineer embryos but how far it should go.
-
-
- You'll hear the debate on Crossfire or NewsHour or perhaps
The 700 Club. There'll be coverage in your newspaper, probably accompanied
by thundering editorials - ripe with clichÈs like "slippery
slope" and "brave new world." It will sound, in fact, a
lot like last year's dustup over stem cells and cloning. But this summer's
biotech grudge match will be over designer babies.
-
- Two new books are framing the debate. In Our Posthuman
Future, heavyweight social and political theorist Francis Fukuyama warns
of "class war" and the eventual obliteration of what it means
to be human - all as a direct consequence of genetic fiddling. It comes
out April 10. The very next day, Gregory Stock's Redesigning Humans will
hit stores. Stock, director of the UCLA School of Medicine's Program on
Medicine, Technology, and Society, celebrates the promise of genetic engineering:
longer lifespans, better health, smarter kids.
-
- In the ensuing made-for-TV matchups, expect Fukuyama's
followers to toss a hand grenade from history - eugenics. Look for Stock
and his supporters to cry foul and bat the word away as a relic from the
Third Reich.
-
- Do not get caught up in the rhetoric. The fact is, eugenics
is here. Brought to you by high technology and the free market, it looks
nothing like a Nazi newsreel. The question isn't "Should we have eugenics?"
but rather, "How far should we go?"
-
- Technology has pushed the eugenic moment to the point
of conception. Now enhancement is impossible to distinguish from treatment.
-
- This is not an academic question. The technology to create
wholesale alterations in the genome, and to take charge of human evolution,
is already in development.
-
- Take the notion of an artificial chromosome. Chromos,
a Vancouver-based biotech firm, is growing artificial chromosomes inside
cells the way the Japanese grow pearls in oysters. Chromos farms them,
seeding cells with a DNA structure called a centromere. Then its scientists
use a machine called a flow cytometer to separate natural chromosomes from
artificial ones at a rate of up to 2 million an hour.
-
- Just like natural chromosomes, these artificial ones
are made of chromatin, ropes of DNA molecules and proteins. But there's
a difference. Natural chromosomes are like a CD issued by a record company.
They come prerecorded with genes that tell cells what to do. The artificial
chromosomes flowing out of the cytometers at Chromos are blank, ready for
anything from the Melvins to Mozart, meaning that Chromos can burn onto
them whatever genes it wants.
-
- The company says it's not interested in making genetically
modified people; it wants to alter animal cells used in the manufacture
of drugs. New protein-based pharmaceuticals are often made by stewing cells
in big vats. The cells produce the desired drug. Chromos can pack those
cells with more copies of the gene that makes the drug, so the cells will
produce double or triple their natural amount. Or if you're a person with,
say, sickle-cell anemia, artificial chromosomes might be recorded with
correct copies of the malfunctioning gene and placed in blood-making cells.
When the CD is played, your platelets wouldn't be skinny and cockeyed,
but round and fat.
-
- "We could modify cells with our chromosomes and
have them reside in a dish, a liver, or a muscle and express a therapeutic
protein," CEO and president Alistair Duncan says. "That would
be very cool."
-
- Indeed, but as cool as that would be, the impact of these
near-term applications would make barely a ripple compared with what Stock
has in mind: an age of genetically enhanced people. Chromos steers clear
of such talk, but, Stock asks, why stop at modifying cells in a vat? Why
not engineer disease-free life from the get-go?
-
-
- Rob and Suzy Ashley couldn't care less about how artificial
chromosomes may change the future. But they're supremely grateful for the
reproductive technologies available today. When Rob, a NASA engineer, and
Suzy, a former teacher, were first married and settling into life in Florida,
they never suspected that their union could produce a tragic genetic combination.
Unknowingly, both are carriers of Gaucher's disease, and in the roll of
the dice that is reproduction, they passed it to their first child, Jared.
-
- Gaucher's disease is a gene-based disorder in which a
critical enzyme, controlling the disposal of old blood cells, malfunctions.
Some types of Gaucher's can be treated by replacing the enzyme. Jared's
could not. The Ashleys' pediatrician first noticed that something was wrong
at Jared's six-month checkup. The child's eyes did not quite move with
his head. Rob and Suzy had thought that the trait was a cute affectation;
they were shocked to hear that he had roughly one year to live. It would
be a torturous year. Jared suffered daily throat spasms that left him gasping
and coughing, forcing the Ashleys to perform mouth-to-mouth resuscitation
two or three times a day to keep him alive.
-
- Then, in December 1997, just two months after Jared's
diagnosis, Suzy discovered she was pregnant. "'Give me a gun,' that's
how I felt," Suzy says. "It was horrible. I was a nervous wreck.
I cried and cried over Jared's crib. I could only pray for Jared. I did
not have the strength to pray for another baby."
-
- Suzy decided to undergo a common prenatal test called
chorionic villus sampling. Like amniocentesis, CVS can tell a woman whether
the fetus she carries has certain genetic diseases. If the test is positive
for any of them, parents are faced with a difficult decision.
-
- Such a choice has been available for centuries. The history
of eugenics traces at least as far back as the ancient Greco-Roman world,
when deformed or weak newborns were often killed. Prenatal testing allows
a decision to be made as early as 10 weeks after conception. Most women
who test positive for diseases like Down's syndrome opt to abort: up to
86 percent, according to one Boston-area study.
-
- In the end, Suzy and Rob did not have to choose. The
CVS was negative, and Quentin was born healthy. Jared died almost exactly
a year after his diagnosis. The ability of CVS to prevent such tragedies
is why society on the whole approves of prenatal testing, why even people
like the Ashleys - both devout Catholics - are willing to consider abortion.
-
-
- Today, the Ashleys are thinking that they may want another
child and have looked into a new screening technology called PGD - pre-implantation
genetic diagnosis. This is a test that goes beyond CVS and amnio, looking
at embryos before they become fetuses. Here's how it works: A couple undergoes
in vitro fertilization to make an embryo in a dish. When the embryo has
divided into eight cells, one is removed. The DNA in that cell is then
analyzed for known disease-causing genetic mutations. Only embryos that
are disease-free are implanted in the uterus.
-
- The Catholic church condemns PGD on the same right-to-life
grounds as it condemns abortion, but to Suzy Ashley, at least, there is
a big difference between not implanting an eight-cell embryo and aborting
a growing fetus. Technology has pushed the eugenic moment almost to the
point of conception.
-
- To learn about PGD, the Ashleys called on Mark Hughes
at Wayne State University in Detroit, who runs one of the world's top PGD
labs. One of only a handful of PGD experts, he screens for single-gene
disorders like Gaucher's, cystic fibrosis, and Tay-Sachs disease. Another
PGD pioneer, Santiago Munne of New Jersey's Saint Barnabas Center for Reproductive
Medicine, focuses on chromosomal abnormalities like Down's syndrome. And
then there's Yuri Verlinsky, at Chicago's Reproductive Genetics Institute,
whose use of PGD to detect early-onset Alzheimer's disease was featured
in a February issue of the Journal of the American Medical Association.
-
- Munne, Verlinsky, and Hughes - the three tenors of PGD
- account for most of the testing on earth. So far, about 1,000 babies
worldwide have been born healthy after receiving the PGD stamp of approval,
and the numbers are growing exponentially.
-
- "We are responsible for making the world a better
place," says one theologian. "I know of nothing that says God
has deemed DNA sacred."
-
- The increase is driven in part by the ability of PGD
to ferret out many diseases, even disease propensity. Hughes has screened
embryos for BRCA1, one of the so-called breast cancer genes, and for the
cancer-suppressing p53 gene.
-
- Furthermore, PGD can be used to make a baby with certain
sought-after traits. Increasingly, says Hughes, parents are seeking to
match their child's tissue types with that of a sibling embryo, conceived
for this very purpose. Some children suffer from diseases that can be treated
by transfusing umbilical cord blood from a tissue-matched newborn. This
practice gained notoriety in 2000 with the birth of Adam Nash (see "Embryo
Police," Wired 10.02), but Hughes - who consulted with the Nashes
- has been doing it since at least 1995. One of his first cases involved
a little girl named Lisa who suffered from SCIDs, the "boy in the
bubble" immune disorder. Before taking her on, Hughes sought consultations
with ethicists and review boards. Finally, Lisa's impatient father burst
into his office. He was fuming. "Our daughter is dying! Give us a
break. What's the matter with us loving a new member of our family who
can also save the life of our daughter? How could that be bad?" Hughes
knew at that moment he had to help. Now he handles two or three such cases
per week.
-
- While ethicists now generally agree that tissue-matching
within families is an acceptable use of the technology, there's less consensus
on the issue of using PGD to select for sex. Fukuyama opposes gender selection
as dehumanizing. Stock thinks it's a nonissue, arguing that most parents
don't care about the sex of their babies and that those who do are better
off being able to choose the sex they want.
-
- The schism widens further when the discussion turns to
the subject of "enhancement" - the use of technology to actually
improve the genome instead of merely curing a genetic disease. Stock is
in favor, Fukuyama adamantly opposed. This is the crux of the debate: Should
eugenics move beyond where it stands right now? Should we take ever-more
exquisite control over our evolutionary destinies? The problem is that,
while all sides agree enhancement is very close, no one can agree on what
qualifies as an enhancement.
-
-
- Theodore Friedmann works out of a small office next to
his lab at UC San Diego. When it comes to the implications of genetic manipulation,
he has a reputation as one of the most thoughtful scientists in the field:
He holds an ethics chair at UCSD and serves on the government's Recombinant
DNA Advisory Committee; in addition, he works with the World Anti-Doping
Agency, an investigative bureau established by the International Olympic
Committee.
-
- In 1972, Friedmann coauthored a seminal paper in the
journal Science that proposed the then-radical idea of inserting new genes
into people as a way to treat disease. Friedmann was one of the first to
worry that gene therapy could be misused. In that paper, he specifically
cited enhancement - "the improvement of human intelligence or other
traits"- as a danger.
-
- Today, Friedmann worries less: "It's now not clear
to me that there are these taboos against all kinds of enhancement."
In 1972, he says, any kind of enhancement just somehow sounded wrong. But,
Friedmann continues, "I don't believe that any longer. Enhancement
isn't off the table ... eugenics is a very different kettle of fish from
what it was 100 years ago."
-
- Enhancement is inevitable, he argues, because it is impossible
to distinguish it from medicine: "There is no sharp division between
disease and nondisease traits." For example, one of many ongoing gene
therapy trials is aimed at overcoming a mutation that prevents the proper
processing of cholesterol. People with this defect tend to suffer from
heart attacks in their thirties. A question that Friedmann and others have
asked is, what happens if the therapy works so well it reduces a patient's
"bad" cholesterol from beyond 100, which is about normal, to,
say, 65? Is this enhancement? Could somebody who did not have the mutation
but simply wanted to eat rib-eye steaks and still avoid cardiovascular
disease undergo the treatment? Is this enhancement? Or is it preventive
medicine?
-
- Fukuyama doesn't buy this line of reasoning. Government,
he says, makes such distinctions every day. Take Ritalin. It's illegal
when used as a study aid but not when prescribed to treat attention deficit
disorder. "We need a regulatory system to permit therapeutic uses
and go slow on the enhancement ones," he says.
-
- And, he continues, we need regulation, because enhancement
is just plain wrong. Fukuyama believes that it betrays human nature, destroying
something he calls essence or factor X. Start mucking around with our genes,
and we'll lose whatever it is that makes us human. Leon Kass, the chair
of the White House's Council on Bioethics, seconds Fukuyama (who also sits
on the council), calling the argument "the wisdom of repugnance."
Kass' commission, which meets almost every month, is expected to issue
its first official findings this summer. The report will address human
cloning. For now, Kass, Fukuyama, and their allies have the president's
ear.
-
- But there are other voices struggling to be heard. A
small but growing faction argues that enhancement is the most human of
all instincts. Ted Peters, a theologian at the Pacific Lutheran Theological
Seminary, thinks it is our job. He calls human beings "created cocreators."
God made us, he reasons, but the rest is up to us. "We humans are
responsible for making the world a better place, and technology is one
means whereby we can do it. ... My approach is a free-market eugenics."
-
- Both Friedmann and Peters see potential dangers, but
Peters rejects appeals to the divine plan, saying, "I know of no theological
reason why anyone would say that God has deemed DNA sacred."
-
- Stock, an enhancement radical, argues that we have been
tinkering with our own evolution for a long time now. "Every intervention
we make that allows a person with diabetes to have a larger family, or
to have a family at all instead of dying young, has a big impact,"
he says. Enhancement technology is no different, except that it would work
better and faster. So why not get under the hood of the genome, Stock argues,
and fix it - even soup it up - and not just for every new generation, but
for all time?
-
- Chromosomes can be wired with on-off switches that permit
parents, or the engineered children themselves, to activate the genes they
carry.
-
- Stock is proposing a type of genetic engineering in which
the changes we make to our DNA are passed on to our kids, and our kids'
kids, and so on down the line. But such meddling is so morally fraught
that, before any gene therapy trial is approved, the federal government
demands assurances that such changes will not occur. The medical consensus
is dead set against creating heritable genetic alterations. Genetic experiments
affecting somatic (body) cells are OK, but those that affect sperm or eggs
- germ cells - are not. Yet here Stock is, advocating germline engineering.
-
- He has been cheerleading for the practice for about five
years and has always been a lonely voice. Not only are there practical
considerations, such as how to conduct a safety test of a technology that
might not play out for generations, there is the ethical question: Should
we be making medical choices for people who have not yet even been conceived?
-
- To Stock, germline engineering is no more morally confounding
than PGD. "We are making choices about the genetic constitutions of
our children right now," he says, "and we are doing it in more
and more sophisticated ways. Soon these will include actual genetic manipulations."
-
-
- Recently, Stock has gotten a lot less lonely. A number
of scientists are now willing to talk openly about the idea of gene therapy
on embryos or fetuses. As they see it, therapy on embryos could be more
effective than postnatal therapy. Gene therapy at that early, embryonic
stage would almost certainly create germline changes.
-
- Perhaps the most promising germline engineering technology
is Chromos' artificial chromosomes. Not only can they carry huge genetic
payloads, they can be wired with on-off switches to permit parents, or
even the genetically engineered children themselves, to activate the genes
they carry, thus solving the moral dilemma of imposing parental will on
the unborn.
-
- Such on-off switches already exist and are routinely
deployed in lab animals like rabbits and monkeys. Of course, introducing
an extra chromosome could prove dicey. After all, a spare chromosome in
humans causes Down's syndrome, though scientists theorize that it's the
genes on the extra chromosome that actually produce the defects. Chromos
bred a mouse, Lucy, with an artificial chromosome. She passed it to her
pups and they, like Lucy, were normal.
-
- It's easy to imagine the possibilities for making genetically
modified people, whether with artificial chromosomes or some other technology.
A double helping of genes that boost memory, intelligence, longevity, or
strength could be on the menu soon. That might seem scary to us. But will
it seem scary to our kids?
-
- Could it be that in 20 years artificial chromosomes become
the tool that turns us into Ted Peters' "cocreators"? That's
what Stock thinks. For him, there's no slippery slope. Instead, he says,
we've been on a "slippery sidewalk" for thousands of years, not
uncontrollably sliding toward a genetic dystopia but doing what we've always
done, whether it's called eugenics or some less-loaded term. "The
whole argument against enhancement denies the reality. It's what we want.
We want to be healthier. We want to be stronger. We want to be smarter.
We want to live longer. It's obvious."
-
- Contributing editor Brian Alexander (alexander@pacbell.net)
wrote about the US national standards agency in Wired 9.06.
-
- Copyright © 1993-2002 The CondÈ Nast Publications
Inc. All rights reserved. Copyright © 1994-2002 Wired Digital, Inc.
All rights reserved. http://www.wired.com/wired/archive/10.05/eugenics.html
|
