One morning early last winter a small item appeared in my local
newspaper announcing the birth of an extraordinary animal. A
team of researchers at Texas A&M University had succeeded
in cloning a whitetail deer. Never before done. The fawn, known
as Dewey, was developing normally and seemed to be healthy.
He had no mother, just a surrogate who had carried his fetus
to term. He had no father, just a "donor" of all his
chromosomes. He was the genetic duplicate of a certain trophy
buck out of south Texas whose skin cells had been cultured in
a laboratory. One of those cells furnished a nucleus that, transplanted
and rejiggered, became the DNA core of an egg cell, which became
an embryo, which in time became Dewey. So he was wildlife, in
a sense, and in another sense elaborately synthetic. This is
the sort of news, quirky but epochal, that can cause a person
with a mouthful of toast to pause and marvel. What a dumb idea,
I marveled.
North America contains about 20 million deer. The estimate
is a rough one (give or take, say, 5 million), since no one
could ever count them. Some biologists suspect that the number
is higher now than it was five hundred years ago, reflecting
the impacts of European settlement on the American landscape.
Predators eradicated, old forests cut or thinned, more second
growth, more edges and meadows--these changes are happy ones
for deer. By any measure we've got plenty, and they're breeding
like gerbils, poaching lettuce from suburban gardens, overflowing
onto highways to become roadkill. Of the two species, mule deer
and whitetail, the whitetail (Odocoileus virginianus) is more
widely distributed and abundant--more abundant, in fact, than
any other large wild mammal on the continent. Given such circumstances,
it struck me as odd that someone would use postmodern laboratory
wizardry to increase the total. Odder still to increase it,
at some considerable cost, by just one. Cloning is expensive.
Deer, I imagined, in my ignorance, are cheap.
The news item, drawn from wire services, was only a column
filler that didn't offer much detail. It barely alluded to the
central question: Why clone a deer? It mentioned that Dewey
had been born back in May, seven months earlier, his existence
kept quiet pending DNA tests to confirm his identity as an exact
genetic copy. That settled, he could now be presented to the
world. Dr. Mark Westhusin, of the College of Veterinary Medicine
at Texas A&M, spoke for the team that created the fawn,
explaining fondly that Dewey had been "bottle-fed and spoiled
rotten his whole life." The item noted that A&M, evidently
a leading institution in the field, had now cloned five species,
including cattle, goats, pigs, and a cat.
One other claim in this little report (which had the flavor
of a reprocessed press release) went unexamined and unexplained:
"Researchers say the breakthrough could help conserve endangered
deer species." Seeing that, I began planning a trip to
Texas.
The notion that cloning might help conserve endangered species
has been bandied around for years. Very little such bandying,
though, is done by professional conservationists or conservation
biologists. One lion biologist gave me a pointed response to
the idea: "Bunkum." He and many others who study imperiled
species and beleaguered ecosystems view cloning as irrelevant
to their main concerns. Worse, it might be a costly distraction--diverting
money, diverting energy, allowing the public to feel some bogus
reassurance that all mistakes and choices are reversible and
that any lost species can be re-created using biological engineering.
The reality is that when a species becomes endangered its troubles
are generally twofold: not enough habitat and, as the population
drops, not enough diversity left in its shrunken gene pool.
What can cloning contribute toward easing those troubles? As
for habitat, nothing. As for genetic diversity, little or nothing--except
under very particular circumstances. Cloning is copying, and
you don't increase diversity by making copies.
Or do you? This assumption, like the one about cheap deer,
turns out to merit closer scrutiny.
The people most bullish on cloning are the cloners themselves,
a correlation that's neither surprising nor insidious. They
don't call themselves "cloners," by the way. Their
résumés speak of expertise in reproductive physiology
and "assisted reproductive technologies," a realm
that stretches from human fertility medicine to livestock improvement,
and includes such tasks as in vitro fertilization (IVF, as it's
known in the trade), artificial insemination (AI, not to be
confused with artificial intelligence), sperm freezing, embryo
freezing, embryo transfer, and nuclear transfer (which refers
to the information-bearing nucleus of a cell, where the chromosomes
reside, not the energy-bearing nucleus of an atom). There's
also a process called ICSI (pronounced "icksy"), meaning
intra-cytoplasmic sperm injection, helpful to elderly gentlemen
whose sperm cells can no longer dart an egg with the old vigor.
The collective acronym for all such assisted reproductive technologies
is ART. To its practitioners, cloning is just another tool in
the ART toolbox.
These ARTists are smart, committed people. Like others who
feel a vocational zeal, they do what they believe in and believe
in what they do. Blessed is the person so situated. But in their
enthusiasm for cloning research, in their need to justify their
time and expenditures to boards of directors, university deans,
or the public, they send their imaginations to the distant horizon
for possible uses and rationales. See what cloning could do
for you, for society, for the planet? Some of the applications
they propose are ingenious and compelling. Some are tenuous
and wacky. Three of the more richly peculiar ones, each fraught
with complexities and provocations, are cloning endangered species,
cloning extinct species, and cloning pets. College Station,
Texas, home of Dewey the duplicate deer, is where I picked up
the sinuous trail that interconnects them.
"So this guy brought these testicles to me," says
Mark Westhusin, as we sit in his office at Texas A&M's Reproductive
Sciences Laboratory on the edge of campus. The testicles in
question, he explains, came from a big whitetail buck killed
on a ranch in south Texas. The fellow had got hold of them from
a friend and, intending to set himself up as a "scientific
breeder," hoped that Westhusin could extract some live
semen for artificial insemination of his does.
Westhusin, an associate professor in his mid-forties, is an
amiable man with a full face and a fashionably spiky haircut.
He has already explained to me about "scientific breeders,"
the term applied to anyone licensed by Texas for the husbandry
of trophy-quality deer. Deer breeding is a serious business
in Texas, where the whitetail industry accounts for $2.2 billion
annually, and where open hunting on public land is almost nonexistent,
because public land itself is almost nonexistent. Most deer
hunts here occur on private ranches behind high fences, allowing
landowners to maintain--and to improve, if they wish--their
deer populations as proprietary assets. Texas contains about
3.5 million whitetails, some far more valuable than others.
An affluent hunter, or maybe just a passionate one, might pay
$20,000 for the privilege of shooting a fine buck. A superlative
buck, a giant-antlered prince of the species, can be worth $100,000
as a full-time professional sire. And the market doesn't stop
at the Texas border. Westhusin has heard of a man who had a
buck--it was up in Pennsylvania or someplace--for which he'd
been offered a quarter million dollars. He didn't take it, because
he was selling $300,000 worth of that buck's semen every year.
Such an animal would be considered, in Westhusin's lingo, "clone
worthy."
Now imagine, Westhusin tells me, that they're collecting semen
from that deer one day, and the deer gets stressed, and it dies.
Damn. So what do you do? Well, one answer is that you take cells
from the dead buck and then clone yourself another animal with
the same exact genotype. While you're at it, you might clone
four or five.
"You're certainly not going to go out and clone any old
deer just for the sake of cloning it," he says. Then again,
when you're practicing--when you're developing your methods
on a trial basis--you won't wait for the Secretariat of whitetails.
The buck from south Texas, the one whose testicles landed in
Westhusin's lab, wasn't superlative but it was good, and the
experiment evolved haphazardly.
Working with his students to extract the semen, Westhusin suggested
also taking a skin sample from the buck's scrotum, on the chance
they might find a use for it. "We'll grow some cells,"
he said, "and maybe, later on, if we have the time and
the money, we'll do a little deer-cloning project." Eventually
the effort produced a few dozen tiny embryos, which were transferred
into surrogate does, resulting in three pregnancies, one of
which yielded a live birth. That was Dewey, born May 23, 2003,
to a surrogate mother known as Sweet Pea. The donor buck remained
nameless.
The fellow who brought in the testicles remains nameless, too,
at least as the story is told by Mark Westhusin. "People
don't want it to get out that they've got these huge, huge deer
on their ranch. Because then the poaching gets so bad,"
Westhusin says. Down in south Texas, people circle their land
with high fences not just to keep the deer in but to keep the
poachers out.
Dr. Duane C. Kraemer, a senior scientist and professor at the
Texas A&M veterinary college, is also sometimes called Dewey,
though not by visiting journalists or staffers reluctant to
presume. He's a gentle, grandfatherly man with pale eyes and
thinning hair, whose casually dignified style runs to a brown
suit and a white pickup truck. His ART specialty is embryo transfer,
and that's the step he oversaw on the deer-cloning project.
Kraemer was the mentor of Mark Westhusin, who did his doctorate
at A&M and then worked for several years in the private
sector before returning as faculty. The relationship between
academic reproductive physiologists and the live-stock business
tends to be close, even overlapping, because this is a practical
science. There's money in assisting the reproduction of elite
bulls, cows, and horses, and that money helps fund research.
Kraemer himself, raised on a dairy farm in Wisconsin, has been
at A&M for much of the last fifty years, during which time
he took four degrees, including a Ph.D. in reproductive physiology
and a D.V.M., and performed the first commercial embryo transfer
in cattle.
Working on yellow baboons, a more speculative project with
implications for human medicine, he did the first successful
embryo transfer in a primate. He also did the first embryo transfer
in a dog and the first in a cat. Embryo transfer isn't synonymous
with cloning--the embryo being transferred needn't be a clone--but
it's a necessary stage of the overall cloning process. Within
that specialty, and beyond it, Kraemer has been a pioneer. In
the late 1970s, he and colleagues engineered the birth of an
addax, a rare African antelope, using artificial insemination
with sperm that had been frozen. People at the time asked, Why
work with addax? The species, Addax nasomaculatus, didn't seem
endangered. Now it's extinct everywhere except for a few patches
of desert in the southern Sahara. After five decades of quietly
working the boundary zone between veterinary medicine and reproductive
science, Kraemer is one of the patriarchs in the ART field.
Dewey the deer was named in his honor.
For Kraemer, the impetus to work with wildlife came partly
from his students, some of whom asked him to teach them skills
that might be applied to endangered species. Semen freezing
and artificial insemination were proven techniques twenty-five
years ago. Embryo transfer and in vitro fertilization showed
great promise. Cloning--that was a dream. Kraemer had some small
grants to support the student training, but after graduation
his young people faced poor odds of landing a job in wildlife
or zoo work. "We had told them right up front," he
says. "You better have another way of making a living,
and you may have to do this on the side." Mark Westhusin,
for one, took a job doing research for Granada Bio-Sciences,
part of a large cattle company.
Kraemer meanwhile established an effort he called Project Noah's
Ark, aimed at putting students and faculty into the field with
a mobile laboratory. The lab, in a twenty-eight-foot trailer,
was equipped for collecting ova, semen, and tissue samples from
threatened populations of wild animals in remote settings, such
as the desert bighorn sheep in west Texas. The project's three
purposes were to train students, to research techniques, and
to preserve frozen tissue samples for possible cloning. Presently
the trailer contains a surgical cradle capable of holding an
anesthetized bighorn, a portable autoclave (for sterilizing
instruments), a laparoscope with fiber optics (for extracting
ova from ovaries), three 50-amp generators, and an earnest sign:
"Ask not only what Nature can do for you, but also what
you can do for Nature.--D. C. Kraemer." Asking what he
could do for Nature by way of assisted reproductive technologies
didn't bring Kraemer much financial support. The training has
gone forward, but the ark itself is in dry dock.
Animal cloning began, back in 1951, with frogs. Robert Briggs
and Thomas J. King were embryologists, based at a cancer-research
institute in Philadelphia, with a medical interest in understanding
how genes are turned on and off during embryo development. Briggs,
the senior man, figured that a cloning experiment might bring
some insight. What he envisioned was transferring the nucleus
of a frog cell, taken from an embryo, into an enucleated frog
egg--that is, one from which the original nucleus had been scooped
out like the pit from an olive. King, hired for his technical
skills, would do the micromanipulation, using delicate scissors
and tiny glass needles and pipettes. The transferred nucleus
would contain a complete set of chromosomes, carrying all the
nuclear DNA required for guiding the development of an individual
frog. If things went as hoped, the reconfigured egg would divide
into two new cells, divide again, and continue dividing through
the full course of embryonic growth to yield a living tadpole.
From 197 nuclear-transfer attempts, Briggs and King got 35 promising
embryos, of which 27 survived to the tadpole stage. Although
the success rate was low, barely one in eight, their experiment
represented a huge triumph. They had proved the principle that
an animal could be cloned from a single cell.
Two questions followed. First, could it be done with mammals?
Second, could it be done not just from an embryo cell, as DNA
donor, but from a mature cell snipped off an adult? The second
question is weighty because cloning from embryo cells is, except
under special conditions, cloning blind. If you don't know the
adult character of an individual animal--is it healthy, is it
beautiful, is it swift, is it meaty, does it have a huge rack
of antlers?--why take pains to duplicate it?
For decades, both questions remained in doubt. Nobody succeeded
in producing a documented, credible instance of mammal cloning.
One researcher claimed to have cloned mice, but his work fell
under suspicion, and it could never be verified or repeated.
In 1984 two developmental biologists went so far as to state,
in the journal Science, that their own unsuccessful efforts
with mice, as well as other evidence, "suggest that the
cloning of mammals by simple nuclear transfer is biologically
impossible."
Well, no, it wasn't--as proved, that very year, by a brilliant
Danish veterinarian named Steen Willadsen. Unlike the developmental
biologists who experimented with. frogs or laboratory mice,
but like Kraemer and Westhusin, Willadsen focused on farm animals.
Working for the British Agricultural Research Council at a laboratory
in Cambridge, he achieved the first verified cloning of a mammal.
He did it--a dozen years before the famously cloned bovid, Dolly--with
sheep. He took his donor cells from early sheep embryos, which
had not yet begun to differentiate into the variously specialized
cells (known as somatic cells) that would eventually form body
parts. Such undifferentiated cells, it seemed, were crucial.
Transferring one nucleus at a time to one enucleated ovum, fusing
each pair by means of a gentle electric shock, following that
with a few other crafty moves, Willadsen got enough viable embryos
to generate three pregnancies, one of which yielded a living
lamb. The following year, afloat on his reputation as a cloner,
he left Cambridge for Texas, hired away by the same cattle company,
Granada, that soon afterward would also hire Mark Westhusin.
"And so," Duane Kraemer says, "Dr. Willadsen
then came and taught us how to do cloning."
But Willadsen couldn't teach them to clone an animal from a
skin sample sliced off a buck's scrotum, because he hadn't solved
the special problems of cloning from somatic cells. Between
early embryo cells (which all look alike) and somatic cells
(specialized as skin, bone, muscle, nerve, or any sort of internal
organ) lurks a deep mystery: the mystery of development and
differentiation from a single endowment of DNA. Each cell in
a given animal carries a complete copy of the same chromosomal
DNA, the same genetic instructions; yet cells respond differently
during development, fulfilling different portions of the overall
construction plan, assuming different shapes and roles within
the body. How does that happen? Why? What tells this cell to
become skin, that cell to become bone, another to become liver
tissue? What signals them to implement part of the genetic instructions
they carry, and to ignore all the rest? Big questions. Cloning
researchers, if they were ever to produce an animal cloned from
an adult, didn't necessarily need to answer those questions,
but they needed to circumvent them. They needed to erase somehow
the differentiation of the donor DNA, and to conjure it into
operating as though its role within a living creature had just
begun anew.
That's what Ian Wilmut, Keith Campbell, and their colleagues
in Scotland managed in 1996, using some further touches of biochemical
trickery. The result was Dolly, her existence revealed in Nature
the following year. Dolly's donor cell came from the udder of
a six-year-old Finn-Dorset ewe. Her birth was significant, because
it meant that cloners could now shop before they bought.
Lou Hawthorne, a cagey businessman with a trim beard, a weakness
for droll language, and a soft heart for animals, tells me how
the notion of dog cloning arrived at Texas A&M. Hawthorne
is the CEO of a California-based company called Genetic Savings
& Clone, which offers the services of "gene banking
and cloning of exceptional pets." Another man, Hawthorne's
chief financial backer, who prefers to avoid media attention,
set the enterprise in motion with a personal whim. "It
was just one morning, he was reading the paper," says Hawthorne.
"Dolly had been cloned. There was an article about it,
and he said: 'I think I'd like to clone Missy. I can afford
it.'"
The "he" refers to John Sperling, founder of the
Apollo Group, a $2 billion empire that encompasses, among other
things, the University of Phoenix, a lucrative enterprise in
higher education for working adults. Missy was ten years old
at the time of Sperling's brainstorm, a dog of unknown lineage
but winning charms, adopted from a pound. Asked by Sperling
to make inquiries, Lou Hawthorne solicited proposals from a
dozen laboratories; the best came from Texas A&M.
Westhusin remembers telling Hawthorne that they could give
it a try but that trying might cost a million dollars a year,
take five years, and still be uncertain of success. Okay, said
Hawthorne. John Sperling, as he'd declared, could afford it.
So the R&D effort toward producing a duplicate Missy--or
maybe a multiplicity of copies--began at College Station in
1998. Hawthorne, a word man among scientists, named it the Missyplicity
Project.
At the start, it was a joint venture between Texas A&M
and an earlier company led by Hawthorne, the Bio-Arts and Research
Corporation. Missy contributed a patch of skin cells, which
were multiplied by culturing in vitro and then frozen for future
use. Westhusin's team gathered a pool of female dogs to serve
as egg donors. The eggs, harvested surgically from the oviducts
whenever a dog showed signs of ovulation, were emptied of their
nuclei using micromanipulation tools (tiny pipettes guided by
low-gear control arms within the field of a binocular scope)
and then refitted with Missy's DNA by nuclear transfer. These
refitted cells were nurtured in the laboratory until some of
them showed good embryonic development. Promising embryos were
then implanted surgically in ready (that is, estrous) surrogate
mothers. Among the factors that make dog cloning difficult is
that female canines come into estrus irregularly. Unless you're
keeping a riotous kennel, you may not have a bitch in heat when
you need her. Westhusin and his Missyplicity partners struggled
against that limitation and others for almost five years.
Missy herself died in 2002, still unitary, un-cloned. But of
course it isn't too late. Her genome is on ice.
Meanwhile, two interesting new entities were born in College
Station. One was a cloned cat, the world's first, a little domestic
shorthair kitten given the name CC, standing for "copycat."
The other was Hawthorne's present company, Genetic Savings &
Clone, a for-profit enterprise devoted to the gene-banking of
pets (in the form of frozen cells) toward the possibility of
their eventual cloning. CC, created with nuclear DNA from a
calico donor named Rainbow, was delivered by cesarean section
just before Christmas of 2001. GSC came into being in response
to popular demand.
Alerted to the Missyplicity Project by press reports, dog and
cat owners had begun contacting the A&M lab. Some were grieving
over recently deceased pets; some were concerned in advance
over old animals or sick ones. "We're supposed to be focusing
on research here," Westhusin recalls thinking, "and
we don't have time to take fifteen phone calls a day and talk
to these people about their pets." The callers tended to
be emotional, poorly informed, and hopeful. "I buried him
three days ago. Do you think there's any chance if I go dig
him up that you could get cells off him?" Um, I doubt-it,
Westhusin would say. "Well, the temperature up here is
cold. It's Minnesota ..." Westhusin laughs pityingly and
so do I. "You want to be nice," he says, "so
you sometimes will spend thirty minutes talking on the phone."
With the founding of Genetic Savings & Clone, all that grief
counseling could be outsourced. Dr. Charles R. Long, another
reproductive physiologist and an old friend of Westhusin's,
was hired to get the company launched. As general manager, he
recruited technical staff and established a research lab to
work in partnership with the A&M people. Occasionally he
found himself playing psychologist to prospective customers,
as Westhusin had done. "The people, the overly emotional
ones, many times I would quite frankly try to convince them
not to make this decision," Long says. Why? Because they
were doing it for the wrong reason. "They were doing it
to try to get their special animal back, and you can't get your
special animal back. There's no such thing as resurrection.
At least not in pets." What you get is just a genetic copy,
a new animal with the old DNA, "and it's really important
for people to understand that." Chuck Long is a bright,
unpretentious man with a small neat mustache, the neck of a
linebacker, and huge hands. He once loved a golden retriever
named Tex, but he wouldn't have cloned the animal. A loving
relationship is about discovery. He'd rather discover a new
friend than try to relive life with Tex Two.
Where do people get their misguided ideas about cloning? I
ask.
"Hollywood," says Long.
Half ignoring his answer, I press: Do they get them from scientists
who oversell the technique or from the media?
"From Hollywood, I think," he repeats. "You
know, crazy movies like Arnold Schwarzenegger's The 6th Day."
"Was he a clone in that?"
"Yeah, they cloned him."
"I haven't seen that one."
"You've got to see The 6th Day. It really stinks."
After a couple of years at Genetic Savings & Clone, Chuck
Long parted ways with Lou Hawthorne, and he now works more comfortably
for a Texas company, Global Genetics and Biologicals, involved
in the production and international export of elite livestock.
GSC itself has severed its partnership with Texas A&M and
relocated its headquarters to Sausalito, California, with offices
overlooking a kayak beach.
Genetic Savings & Clone isn't the only company that sells
a gene-banking service for pets; you also might turn to Lazaron
BioTechnologies or PerPETuate, Inc. But GSC alone offers the
full deal: delivery of clonal duplicates in the near future.
The initial cost of putting your pet's genes into the gene bank
is $895. Annual storage runs $100. Dogs, with their unique physiological
complications (such as opacity of the eggs, making them harder
to enucleate), are still problematic. But commercial cat cloning
got under way in 2004, with five clients committed, and if all
goes well, their cats will be delivered very soon. "In
pet cloning," says Hawthorne, "people have an animal
that they perceive is extraordinary. In some cases, it's just
a perception." In other cases, the extraordinariness is
more objective. "You can have an extraordinary mutt,"
he says. "You can have an animal that has extraordinary
intelligence. Extraordinary good looks." Insofar as those
traits are genetic, they can be reproduced by cloning, maybe.
The delivery price of a healthy young feline, custom created
from DNA of proven appeal, guaranteed to resemble closely your
old feline, is $50,000. If you think this might meet your emotional
expectations, act now.
On the other hand, $50,000 buys a Clot of pretty good cats.
Cloning endangered species is a different matter. For starters,
who pays? Why does anyone finance this technical approach, seemingly
so marginal, rather than putting the money toward basic necessities
such as habitat protection? And how can cloning possibly freshen
a gene pool that's been reduced to a stagnant puddle? I carry
these questions to Dr. Betsy Dresser, director of the Audubon
Center for Research of Endangered Species, near New Orleans.
ACRES is part of the Audubon Nature Institute, a non-profit
group of museums, parks, and other facilities (with no connection
to the National Audubon Society). Dresser, who ran a similar
research center at the Cincinnati Zoo before coming to New Orleans,
has long been a leader in applying captive-breeding efforts
and assisted reproductive technologies to endangered species.
She's a brisk, congenial woman, but not easy to get to. ACRES
is tucked away in a sunny new building surrounded by bottomland
forest at the end of a country road outside the city, on the
west bank of the Mississippi River, beneath a towering levee.
The land, 1,200 acres of what once was sugar plantation, is
protected by a fence and a guardhouse with an electric gate.
A sign says "Freeport McMoRan Audubon Species Survival
Center," recognizing the patronship of a mining company
in establishing this compound. ACRES itself was created with
a $15 million appropriation from the U.S. Fish and Wildlife
Service. It resembles the visitor's center of a well-funded
state park, but more private. On a morning in April, the air
is redolent of honeysuckle. I arrive in time to watch surgery
on a domestic cat.
Dr. C. Earle Pope, in a blue smock and mask, is harvesting
ova. Several other figures, also in blue, assist him around
the operating table. The cat has already been anesthetized and
opened, its ovaries exposed. Pope wields a fine forceps in one
hand, a hollow steel needle in the other, his head raised to
view the target area, which is magnified on a video monitor.
He works with easy skill derived from years of experience. The
hollow needle is backed by a suction device that feeds into
a glass vial on a table nearby. With the forceps, Pope gingerly
lifts one ovary so that its follicles (the small, bulbous ovarian
sacs) protrude like grapes on a bunch. With the needle, he punctures
a follicle and sucks out the egg, then moves to another. The
ovary bleeds slightly. Poke, suck, poke, suck, the eggs are
whisked away. They accumulate in the vial. When Pope has emptied
the follicles of both ovaries, an assistant collects two orange-capped
vials and passes them through a window from the operating room
to an adjacent lab.
In the lab, which is darkened and barely larger than a closet,
a technician moves the eggs from a rinsing solution onto a petri
dish. She lifts them, one by one, using an aspirator pipette--that
is, with suction applied by her own gentle breath. Her eyes
are pressed to a scope. The eggs, surrounded by cloudy globs
of ovarian material (called cumulus cells) and air bubbles,
are tiny, but they are conspicuous enough to her. You can tell
the maturity of ova, she says, by the layers of cumulus cells
attached. "These are very good looking." The yield
today is twenty-four eggs, about average from a domestic cat.
Down the hall, she places the petri dish in an incubator. This
afternoon one of Pope's colleagues, Dr. Martha C. Gomez, will
enucleate these eggs and endow each with nuclear DNA transferred
from an African wildcat.
It won't be the first time such a mix is performed. The African
wildcat, Felis silvestris lybica, is a tawny little felid native
to Africa and the Middle East, closely enough related to the
domestic cat, Felis silvestris catus, to have figured in earlier
experiments involving the two subspecies. Using domestic cat
eggs, Gomez, Pope, and their team produced three African wildcat
clones in 2003, the eldest born on August 6 and named Ditteaux.
(That's ditto with Cajun spicing.) The animal from which he
and his--his what? not siblings, not twins--two extremely close
relatives were cloned, known as Jazz, was itself a product of
combined ARTs: the world's first frozen-embryo, thawed-embryo,
embryo-transferred wildcat born to a domestic cat. Gomez, Dresser,
Pope, and several colleagues co-authored a journal paper on
this work, in which they note that the African wildcat "is
one of the smallest wild cats, whose future is threatened by
hybridization with domestic cats." A person might ask:
If hybridization of a wild subspecies with a domestic subspecies
is the threat, in what sense is mixing nuclei from one subspecies
with eggs from the other subspecies a solution?
Another skeptical question, which I put to Betsy Dresser, is
whether this fancy stuff can somehow mitigate the problem of
low genetic diversity in sorely endangered species. If it can't,
what's the point? "Well, indeed it can," she says.
"What we're trying to do is use cloning to bring in the
genetic material from animals that are not reproducing."
Among any population, she notes, there are always infertile
individuals, marginalized individuals, elderly or unlucky individuals,
who fail to breed and so contribute no genes to the next generation.
In a large population (though Dresser doesn't mention this point),
their exclusion represents Darwinian selection, which drives
evolution. But in a very small population (she notes rightly),
their participation could be crucial. "If you can use the
genetic material from those individuals, it helps widen the
genetic pool a bit."
Imagine you've got a captive population of just five black-footed
ferrets, with no others surviving on the planet. Four of your
ferrets are males, and the fifth is a post-reproductive female.
One young male chokes to death while eating a prairie dog with
reckless gusto. What do you do? Of course you grab the old female
and the dead male, take tissue samples, and clone them. But
wait--in this scenario of five, there are no viable black-footed
ferret ova to receive the clonal DNA. So you use the next best
thing: enucleated eggs from a mink. Then you breed your cloned
female with one of the males, breed any daughters she produces
with other males, get the cloned male's genes into the reproductive
jumble too, and thereby postpone (maybe indefinitely) the doom
of your miserable little population. Whether your ferrets ever
go back into the wild is another question. Do you dare send
them? Do you keep breeding and cloning until you've got a few
dozen, a few hundred? All this would be expensive at best and,
if you hadn't meanwhile solved the root causes of endangerment
(such as insufficient habitat, poaching, or exotic species inflicting
too much predation or competition), ultimately futile. No clones
of an endangered species, and no descendants of clones, have
yet been released to the wild.(*)
What about the money issue? I ask Dresser. Are resources being
diverted that might otherwise pay for habitat preservation?
Her answer is candid: "The money that comes to this kind
of research is primarily from people that are not going to support
habitat." She's a skilled fund-raiser as well as a respected
scientist; she has been through this in Cincinnati, now New
Orleans, and she knows her constituency. Supporting the research
arm of a fine metropolitan zoo is a bit like supporting the
symphony, the conservatory, the opera. These people "don't
want to give their money to Africa, or to Asia, or somewhere.
They don't want their money in political environments where
they're never going to see their name on a plaque." At
the various branches of the Audubon Nature Institute, including
ACRES, there are more than a few grateful plaques.
Back on the city side of the river, I visit the Audubon Zoo
on Magazine Street for a glimpse of Ditteaux the cloned wildcat,
temporarily on display there. For this interlude of public exposure,
he lives in a glass-fronted cage furnished with small boulders,
trees, and a six-foot square of scenery meant to approximate
northern Africa. He's a handsome animal, lanky and lithe, nervous,
his brownish-gray fur marked with pate stripes. As I watch,
his pale green eyes come alert to something--the sight of a
squirrel outside the building, visible through an opposite window.
Groups of schoolchildren pass Ditteaux's cage. A well-fed boy
in an orange T-shirt reads the sign and then asks, "It's
a clone?" Yes. With some vehemence, he says, "Okay,
that's freaky."
Whatever the downside of investing money and time in such an
approach to endangered species, at least one private firm has
also done it: Advanced Cell Technology, of Worcester, Massachusetts.
Founded originally as a subsidiary of a poultry genetics business,
ACT now concentrates mainly on human medical issues. The company's
work with wildlife is an adventuresome sideline, bearing no
such commercial promise as cloning whitetail deer for the trophy
market but offering the possibility of a public good, roughly
equivalent to pro bono work by a law firm. It also offers, when
successful, good publicity.
In early 2001, ACT announced that "the first cloned endangered
animal," an eighty-pound male gaur, had been born to a
surrogate mother. The gaur is a species of wild cattle, Bos
gaurus, native to southeastern Asia from Thailand to Nepal.
Calling it an "endangered animal" was mildly misleading;
the international body that keeps track of such things classifies
the gaur as "Vulnerable," not actually "Endangered,"
with somewhere between 13,000 and 30,000 individuals in the
wild. But the population is declining, and the trend isn't likely
to reverse. Vulnerable or endangered, the species deserves attention.
Two technical points made ACT's gaur work especially notable.
First, the nuclear DNA came from gaur cells, derived from a
tissue sample, that had sat frozen for eight years in a gene
bank at the San Diego Zoo. Second, the enucleated egg cell into
which the gaur DNA had been transferred came from a domestic
cow. So this too was a case of cross-species cloning--in fact,
it was the first recorded case, a precursor to the African wildcat
project in New Orleans. Arguably, the technique could be valuable
in situations when egg cells of an endangered species are unavailable--when
there are no surviving females, say, or so few that you wouldn't
dare cut one open to harvest her eggs.
What made the case less encouraging was that the baby gaur,
named Noah, died of dysentery within two days. Its death fell
hard on Robert P. Lanza, a vice president of ACT, who had led
the cloning effort.
At that time, Lanza had nearly sealed an agreement with Spanish
officials toward cloning an extinct Spanish subspecies of mountain
goat, the bucardo. The bucardo (Capra pyrenaica pyrenaica) had
languished at desperately low population levels throughout the
twentieth century, probably because of competition with livestock,
diseases caught from livestock, poaching, and other travails.
The last one died in 2000, clunked by a falling tree, but provident
biologists had arranged to freeze some of its tissue for posterity.
Lanza hoped to clone the bucardo back into existence, using
the frozen sample for nuclear DNA, a domestic nanny goat as
egg donor, and a nanny again as surrogate to carry the fetus.
That plan collapsed with the death of Noah the gaur. Two years
later ACT's cloning team tried again, this time achieving the
birth of two cloned calves from another species of wild Asian
cattle, the banteng, Bos javanicus. The banteng is unambiguously
endangered, with no more than 8,000 individuals in the wild.
The nuclear DNA came from another frozen sample that had been
stored, for twenty-five years, at the San Diego Zoo.
The gene bank in San Diego, loosely known as the Frozen Zoo,
was established three decades ago by a pathologist named Kirk
Benirschke, who was soon joined by a young geneticist, Oliver
A. Ryder. Benirschke and Ryder foresaw that these cell samples
might be useful in genetic studies of relatedness among wild
species. They didn't foresee that the frozen cells might be
cloned back to life. The collection now represents about 7,000
individual animals of 450 different species; about half of those
samples came from animals resident at the San Diego Zoo, the
rest from animals at other zoos and captive facilities, or from
the wild. Ryder is still there, the man to see if you want a
morsel of rare or endangered DNA for some legitimate purpose.
Cloners across the country, from College Station to Worcester
and beyond, point to San Diego's Frozen Zoo as a prescient enterprise
that should be emulated widely, preserving as much genetic diversity
as possible from endangered species before their populations
decline too far. Ryder, for his part, supports the idea of cloning
when it might return a valuable genotype to a breeding population.
The original banteng whose frozen cells went to ACT, for instance,
died in 1980 without offspring, having made no genetic contribution
to the captive banteng population. One of the two clones produced
from those cells was healthy, and that animal has since been
returned to San Diego; its lost genes may eventually be bred
back into the zoo population of banteng, possibly adding some
much needed diversity.
But gene banking is no panacea. Ryder himself says: "I
think it's gonna be a somber day when we realize that the only
thing left of a species is something we've got in the Frozen
Zoo."
Among extinct species and subspecies, the bucardo goat represents
a good prospect for cloning, because the extinction is so recent
and the cell sample was properly preserved. Less propitious
circumstances, though, don't prevent people from trying to resurrect
a lost beast.
Scientists at Kinki University in Japan have begun work toward
cloning a woolly mammoth, using tissue samples from a 20,000-year-old
carcass recently excavated from frozen Siberian tundra. Elephants,
the mammoth's closest living relatives, will serve as egg donors
and surrogate mothers, it the project ever gets that far. Cloning
researchers at the Australian Museum in Sydney hope to re-create
the thylacine, a carnivorous marsupial loosely known as the
Tasmanian tiger, last seen alive in 1936. For that effort, the
starting point is a thylacine pup stored in alcohol since 1866.
Alcohol is a gentler preservative than formaldehyde, and the
Australians have managed to extract some DNA fragments in fairly
good condition--but no complete DNA strands, let alone any viable
thylacine cells with nuclei that could be transferred intact.
The optimistic Aussies aim to reassemble their squibs and scraps
into a full set of thylacine DNA, perhaps patching the gaps
with genetic material from other marsupials. Plausible? Not
very, according to Ryder. "What's the chance that you could
shred the phone book," he asks, "and then drop it
out of a window and have it come back together?" Once they
have reassembled their phone book, if they do, the Australians
will create artificial chromosomes for insertion into an egg
from some related species, such as the Tasmanian devil. Meanwhile
in Hyderabad, India, a team led by Dr. Lalji Singh proposes
to clone an Asiatic cheetah, a subspecies extinct in India for
the past fifty years. They want to use nuclear DNA from a cheetah
loaned by Iran, though Iran itself has only a few dozen cheetahs
in the wild, and none of those has been promised so far. If
the Indians do get their chance to proceed, the eggs and the
surrogate wombs will be furnished by leopards.
Each of these projects, variously dreamy or doable, represents
an effort at cross-species cloning, like the banteng-and-cow
work by ACT. This sort of trick raises further issues. What
are the physiological consequences of mixing nuclear DNA from
a cheetah with mitochondrial DNA (which comes along with the
enucleated egg and helps regulate the cell's biochemistry) from
a leopard ? What are the ecological implications of mixing mammoths
with elephants in a world where the mammoths' ecosystem no longer
exists? What's the merit or demerit of blurring lines between
species (cheetah and leopard, thylacine and devil) by means
of laboratory gimmickry, in order to "preserve" a
vanishing subspecies or "restore" an extinct species
in the wild?
Lines, their integrity or transgression, are exactly what's
at issue: the line between one species and another that defines
biological diversity, the line between one animal and another
that constitutes individuality, the line between living and
dead that gives meaning--as well as poignant temporal limit--to
life. And yet those lines aren't always easy to draw, let alone
to enforce or respect. Even species, even in the wild, sometimes
blur into one another: wolves breeding with coyotes, blue-winged
warblers with gold-winged warblers, barn swallows with house
martins, mule deer with whitetails. True, these natural mongrelizations
represent exceptions to the role of how species are generally
demarcated. But they complicate any effort to think clearly
about drawing other lines, such as the line between Fells silvestris
lybica and Fells silvestris catus, the line between embryo transfer
and nuclear transfer, the line between genetically modified
organisms and heirloom tomatoes (which have themselves been
genetically modified by generations of careful horticulture),
the line between extinct and merely frozen, the line between
what we can do and what we should do, the line between nature
and ART.
Recognizing such complications is not necessarily the same
as surrendering to a paralyzing relativism. Lines that suggest
boundaries of ethical behavior, of judicious balance between
opposing concerns, and of precious entities deserving preservation
are important even when they reveal themselves, at close inspection,
to be smeary zones of gradated gray. The mapping of such boundaries
can't be done by science, which is capable of measuring shades
of gray but not choosing among them. That leaves religion, philosophy,
social consensus, and common sense. Which of those do we rely
on for decisions about assisted reproductive technologies, such
as cloning, when the species being assisted is not the banteng
or the whitetail deer but Homo sapiens?
Consider the prospect of germline genetic engineering--that
is, fiddling with genes in human embryo cells before those cells
are grown into human fetuses. Germline engineering is not yet
available as a consumer option, for medical purposes or any
others, but soon it may be. Select genes would be added to,
subtracted from, or modified in an embryo cell, after which
the cell would be cloned into a customized human child. This
process would permit the correction of genetic weaknesses--bad
eyesight, for instance, or sickle-cell anemia--in advance of
birth. When that starts happening, as Bill McKibben has warned
in his book Enough: Staying Human in an Engineered Age, "the
line between fixing problems and 'enhancing' offspring"
will disappear, at least for any parents who want their kids
to be as bright, robust, good-looking, and competitive as humanly
(that is, technologically) possible. If you can repair your
future child's myopia with preemptive genetic tinkering, you
might also want to increase her I.Q. by a few dozen points.
Will it lead to a world as utopian as Lake Wobegon, where all
the children are above average? Of course not. It will just
add genetic manipulation of embryos and child cloning to the
means by which affluent, fussy people try to distance themselves
from bad luck, disappointment, menial work, death, and poor
people.
McKibben, his ardent humaneness informed by a lot of careful
research and thinking, proposes that we should recoil from such
possibilities and declare "Enough!" He suggests that
somewhere amid the dizzying possibilities of ART as applied
to humans, beyond fertility medicine but short of germline genetic
engineering, we might locate "the enough line"--that
is, the threshold of ugly and corruptive weirdness across which
a wholesome person and a wise society do not go.
As much as I want to agree with him, my own survey of animal
cloning forces me to conclude that his "enough" line,
like any I might try to draw myself, is as subjective as it
is sensible. There is, in fact, no line. There is only a spectrum:
a set of choices among shades of gray. Of course, that's not
to say some choices aren't nuttier than others.
Cloning adult humans, for instance. Any thorough discussion
of assisted reproductive technologies comes eventually to this
topic, which the animal-cloning scientists detest and dismiss
but which other people consider central. The animal guys are
right--it's not central--but, like a parrot in a cage of canaries,
it's too big and noisy to ignore. What if John Sperling or some
other loopy billionaire decides one morning to commission not
the cloning of his lovable mutt but the cloning of himself?
If that decision hasn't already been made, quietly in a penthouse
somewhere, it probably soon will be; and whatever unique technical
difficulties or scientific scruples have so far prevented the
consummation of such a desire will soon be overcome. Some people
view the prospect of human cloning with great alarm. Bill Clinton
labeled it "morally reprehensible." His presidential
ethics commission recommended federal laws to prohibit human
cloning. Finding myself less certain than Clinton or those advisers
about the moral or legal verities against which human cloning
should be measured, I'd simply call it perniciously stupid.
Then again, many things people do nowadays are, in my opinion,
perniciously stupid. Not all of them are illegal, and so, I
suppose, human cloning needn't be either.
Down in College Station, I'm reminded of all this during my
chat with Duane Kraemer, when we bounce from the subject of
endangered species back to companion animals. Isn't there something
misguided, I ask Kraemer, about cloning your pet? Doesn't it
reflect an inclination to deny mortality?
Deny mortality? "We do that every day!" he says brightly.
"We get up and brush our teeth. Why do we do that? Because
we want to live as long as we can. So denial of mortality is,
yeah, it's in our being. And it's not only natural. It's necessary."
Two other voices of wisdom echo through my head, addressing
aspects of the question why. One of these voices belonged to
J. Robert Oppenheimer, the physicist and founding director of
the Los Alamos nuclear-weapons laboratory. Trust me on this
seeming digression. Having helped build the first atomic bomb,
Oppenheimer resisted the notion that America should rush ahead
to build a thermonuclear superbomb. It was fission versus fusion,
uranium versus hydrogen, kilotons versus megatons, and the global
political context of 1943 versus the context of 1951. His resistance
was swept aside by a clever design principle concocted by two
other physicists, one of whom was Edward Teller. Asked later
by an inquisitorial panel about how the H-bomb decision was
made, Oppenheimer declined to speak about technical details.
"However," he said mordantly, "it is my judgment
in these things that when you see something that is technically
sweet, you go ahead and do it and you argue about what to do
about it only after you have had your technical success."
This scary truth, which might be thought of as Oppenheimer's
Axiom, explains many controversial gambits in whizbang scientific
engineering. Why do some scientists crave to clone animals?
Not just because they can but because they can do so--with an
elegant medley of ingenious laboratory moves--in a way that
is technically sweet. And therefore irresistible.
The other voice comes from Louis Armstrong, as recorded in
1931:
Oh, when skies are cloudy and gray,
They're only gray for a day,
Bay-bay-bay-bee ...
So wrap your troubles in dreams,
And dream your troubles away.
Duane Kraemer is right in noting that this methodology isn't
unique to assisted reproductive technologists.
On the morning after our conversation, Dr. Kraemer welcomes
me to his home, in a neighborhood just north of the A&M
campus, to meet the famous cloned house cat, CC. As we enter,
she crosses a living room of draped-over furniture and leaps
onto a carpeted cat perch, presenting herself for Kraemer's
gentle petting. She's no longer a kitten. She arches her back
to my touch, then carefully sniffs my hand. Her fur is soft
and clean. She looks like any normal cat. The most striking
aspect of her appearance, which I wouldn't notice if I hadn't
read some background, is that she's a tiger-tabby shorthair,
mottled black-and-gray with a white breast and legs. It's striking
because she was cloned from a calico.
CC's color pattern is utterly different from that of Rainbow,
her DNA donor. The cause of this difference is complicated (involving
random inactivation of one of her two X chromosomes, which in
a female such as CC are redundantly paired, though each may
carry a distinct gene for color), but it can be simplified in
a single word: random. Cloning isn't resurrection, as the man
said. It's not even, quite, duplication.
On CC's right cheek, otherwise white, I notice a small patch
of tan fur, like a birthmark. Yes, says Kraemer, that wasn't
present in Rainbow either. The genotype may be identical in
a clone, but it gets expressed differently. Maybe one day when
she was a fetus, inside the surrogate mother, CC rubbed her
little face against the wall of the womb. A smudge. Things happen.
(*) It bears noting, though, that other ART methods have yielded
some returns to the wild, such as the hundred Mississippi sandhill
cranes, additions to an endangered subspecies, that were bred
at ACRES using artificial insemination and released on a refuge
near Pascagoula.
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