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Got Silk? GE Goats Turned into
Factories

Got Silk. http://www.nytimes.com/2002/06/16/magazine/16GOAT.html
By LAWRENCE OSBORNE

As soon as I walk into the humid goat shed in my Tyvex suit and
sterilized boots, a dozen Nubians run up to the fence and begin
sniffing at me, their Roman noses dilated with fervent curiosity.
''They're a little frisky,'' a technician explains, shooing them back
toward their playpen toys. ''It's artificial insemination time, you know.''

The technician, a young woman in galoshes named Annie Bellemare,
and two colleagues are playing a trick on a long-bearded billy goat.
Leading him up to a female in heat, they let him mount her; but at the
last moment, they whip out a warmed, rubber-lined bottle and have
him discharge into it.

''There,'' they cry, holding up a phial of goat semen. ''Good boy!''

I look around the pen. Hundreds of sly-looking, inquisitive goats are
staring at me intently. They seem unexceptional enough, but the goats
that are being bred here are far from ordinary. This is a so-called
''transgenic farm'' -- a place where animal species are either cloned or
genetically mixed to create medically useful substances -- owned and
run by a firm named Nexia Biotechnologies. It is housed on a former
maple-sugar farm in rural Quebec, not far from the remote hamlet of
St.-Telesphore. Nexia's facility is one of only three transgenic farms in
the world. (One of the company's rivals, PPL Therapeutics, runs the farm
in Scotland that collaborated in the production of the famous sheep clone,
Dolly.)

Out here in this tough French-speaking farming country, however, hardly
anybody gets worked up about the fact that on the old St.-Telesphore
sugar farm, a new chapter in biotechnology is being written. Nexia scientists
are pursuing a bizarre experiment straight out of ''The Island of Dr. Moreau,''
H.G. Wells's dark science-fiction fable of a mad scientist who breeds
experimental animals on his private preserve.

''Oh, it's not that weird,'' Nexia's president and C.E.O., Jeffrey D.
Turner, says as we walk around the pens, being nibbled constantly by
aroused goats. ''What we're doing here is ingeniously simple,'' he says.

''We take a single gene from a golden orb-weaving spider and put it into
a goat egg. The idea is to make the goat secrete spider silk into its
milk.''

Milk silk?

Turner, a bouncy 43-year-old scientist turned biotech entrepreneur,
makes a sweeping gesture at his bleating production units. ''Spider silk
is practically the world's strongest material,'' he explains. ''It's much
stronger than steel -- five times as strong. We're going to make fishing
lines out of it.''

I raise my eyebrows dubiously.

''Yes. Biodegradable fishing lines. Or maybe tennis racket strings.'' He
grows even more animated. ''You could make hundreds of things out of
spider silk, if only you could produce enough of it. Biodegradable sutures
for surgery . . . replacement ligaments or tendons . . . hemostatic dressings .
. . fashion. We call our product BioSteel.''

Turner isn't simply fantasizing. Nexia foresees tapping into the $500
million market for fishing materials as well as the $1.6 billion market
for industrial fibers in the near future. And the haute-couture world is
already intrigued by a nearly weightless gossamer-like fabric. But the
real gold mine might be body armor: the Pentagon is working with Nexia
to develop a prototype of a new kind of vest that might be made entirely
out of goat silk. The vest would be only a little thicker than nylon, but it
could stop a bullet dead.

''It's nothing short of a revolution,'' Turner exclaims. ''This special
silk is the first transgenic material ever made. The amazing thing,
however, is that we're changing the world from a tiny low-rent sugar
farm, and our only machinery is a goat.''

Turner is very affectionate with his goats. A number of different
species are being tested for the spider-gene project. In one pen a gang
of floppy-eared Nubians frolic and duel, raising themselves on their back
legs and then clashing foreheads. Next door live the Saanens from
Switzerland, all of them white, rather meeker and well mannered, quietly
cocking their heads at the sound of human voices. Across the way stand a
dozen West African Dwarf goats (once used by the Hamburg Zoo as food
for big cats from Africa).

''We use West African Dwarf goats because they're sexually active all
year round,'' Turner says. ''Unlike American goats, which are only active in
the fall and spring.'' He winks. ''The African goats get sexually mature in
three months. This helps reach the output potential quicker.''

Turner once again admires his flock. ''You could call them Spidergoats,''
he says. ''But that would give people misconceptions. They're only
1/70,000th spider, after all. When it comes down to it, they're just
normal goats with one spider gene in them. They're just goats.'' He pauses.
''Mostly.''

Scientists have been tinkering with the DNA of animals for years.
Researchers have inserted into rhesus monkeys the gene that makes
jellyfish glow in the dark; they've produced chickens that never grow feathers.
But only recently have they begun to develop large-scale industrial plans
for these creatures. For example, a company in Georgia called ProLinia has
cloned cattle and hogs to produce more genetically desirable breeding
stock. After scientists at Johns Hopkins produced enormous ''supermice''
by removing the gene that limits muscle growth, researchers have scrambled
to create the same results in sheep, pigs and chickens.

Inevitably, some bioethicists are alarmed by these projects. And Turner
agrees that some of these experiments are creepy.

''Why do we need cloned sheep?'' he asks. ''What the hell's the use of
millions of cloned sheep? Dolly was a scientific stunt.'' He tells me
that Nexia's project is less about altering nature than harnessing it. The
company's goal isn't to create weird goats; they're merely a means of
producing useful quantities of spider silk, a simple substance created
eons ago by natural evolution. Turner says that what Nexia is really up to
isn't mere genetic engineering, it's ''biomimicry.''

In her 1997 book, ''Biomimicry,'' Janine M. Benyus observed that while
humans create synthetic materials by means of high temperatures and
pressures (''heat, beat and treat'' methods, as they are known), nature
does so under life-friendly conditions. That is to say, in water, at
room temperature and without harsh chemicals. ''Nature's crystals are finer,
more densely packed, more intricately structured and better suited to
their tasks than our ceramics and metals are suited to ours,'' Benyus
observes.

Inspired by this, materials scientists are now looking to merge biology
and engineering -- the natural and human-made.

''In the future, animals will be our factories,'' Turner says as we plod
through the facility. ''Very cheap factories.''

This is a land of silos and bleached cherry-red barns, somewhere between
the St. Lawrence and Ottawa Rivers. ''We need to be where people aren't,''
Turner explains. Nexia's converted cabane a sucre and the surrounding
land, purchased five years ago from a local farmer, look sweetly ordinary.
But the new facilities are meticulously decontaminated. The company's
corporate headquarters are just 15 miles down the road, rising from the
flatlands of Vaudreuil-Dorion like a futuristic castle keep. Inside, the corridors
are freshly carpeted and sunlit; the labs are shiny and uncluttered and
stocked with the latest gadgets. These labs are known as ''Class-100,000
rooms,'' which means that each cubic yard of air contains less than 100,000
motes of dust. Staff members proudly show me the latest P.C.R. (polymerase
chain reaction) machines -- the photocopiers of the gene world -- that look
like high-tech adding machines. Pinned to the walls are some curious images
derived from what is known as FISH analysis. (The acronym stands for
Fluorescent In Situ Hybridization.) These images show the goat genes as
ghostly strands of dark orange, inside which one can clearly see the
bright yellow segments of alien spider silk genes. Nearby are cute pinups of
Nexia's original four transgenic goats, Willow, Bay, Santiago and Zeus.

Nexia used cloning to make its four founder animals, though the descendant
animals are allowed to breed sexually. One pic shows Willow, Canada's
first transgenic farm animal, posing coquettishly on a little orange plastic
bobbin. I am told that she is, in fact, 1/70,000th human. This is
because she has been specifically engineered to manufacture proteins for use
in medical drugs like clot-busters, another source of income for Nexia. I
look at her closely. Am I going mad or do I detect a human gleam in her eye?

How does a spider gene get into goat milk in the first place? Nexia uses
two common spider specimens, Araneus diadematus (the common garden
spider) and Nephila clavipes (the golden orb weaver, native to many tropical
forests). The spiders are frozen in liquid nitrogen, then ground into a
brown powder. Since every cell of a spider contains the precious
silk-producing genes, it's easy to extract them. These genes are then
tested in the ''Charlotte machine,'' what Turner calls a ''synthetic
goat'' that tests whether or not the gene will function inside an actual goat.

Next, the gene is altered. A ''genetic switch'' is added, which programs
the gene to ''turn on'' only inside the mammary gland of its new female
host during lactation. The altered gene is then pushed on a fine glass
pipette into a goat egg. The baby goat will have a spider gene present
in each of its cells (its eyes, ears and hooves will all be part spider),
but only in the mammary glands of female goats will the silk gene actually
spring to life. The goat will eventually start lactating a kind of
silk-milk mixture, which looks and tastes just like normal milk.

This milk is first skimmed of fat, and salt is added to make the silk
proteins curdle into thin whitish particles that promptly sink to the
bottom. After the residue has been removed from the milk, a little water
is added to this sediment until it turns into a golden-tinged syrup. This
silk concentrate is known to scientists as ''spin dope'' and is more or less
identical to what is inside a spider's belly. Now completely stripped
from its milky context, the syrupy raw silk is ready for spinning.

Nexia's labs are packed with odd machines that replicate a spider's
anatomy. First there is an extrusion machine, a strange-looking
three-foot-tall apparatus bristling with aluminum pipes, designed to
force the raw silk material through a tiny hole. As the silk comes out
through this aperture, it is immediately stretched inside a long steel
bathtub -- at full tilt, roughly a hundred yards of it an hour.

Then the silk, which is transparently shiny with a white tinge, is taken
to a spinner and strung out between two spindles a yard apart, which
stretch the threads out as finely as possible. The idea is to do what a spider
does naturally: subject the silk to tremendous stretching, or ''shearing.''
This not only elongates it but actually strengthens the material as well.
After being spun and wound around a plastic bobbin, some of the threads are
then passed to a tensile tester, which measures their strength. In the
production room, Turner hands me a few 20-micron-wide strands, frail as
gossamer. The difficulty, he says, is making the silk as evenly as a
spider does.

As we pass through yet more rooms filled with liquid nitrogen tanks
where frozen goat semen and ova are stored, Turner explains to me the
enigmatic inner world of spiders and their miraculous silk and their connection
to modern needs.

Four hundred million years ago, he begins excitedly, spiders were doing
just fine as ground hunters until one day bugs started flying. ''The
spider's evolution comes out of a kind of arms race between spiders and
bugs. The bugs start flying to get away from the spiders, so the spiders
have to come up with a new weapon.'' Most spider species died out, but a
few developed a new talent, namely, spinning webs. The silk had to both
be invisible to a bug's vision and virtually indestructible. Only spiders
capable of making superfine, powerful silk survived -- a perfect example
of evolutionary pressure.

What's special about spider silk, as opposed to silk from worms, is that
it is a unique liquid crystal. And that's what's magical, says Turner.
''Liquid crystals are the Holy Grail of material sciences. They make for
incredibly tough, light, strong materials with phenomenal properties.
It's way beyond anything we humans can make. Milled steel pales next to it.''

But the complexity of arachnid silk is also what is problematic about
it, from the point of view of biomimicry. Spider-silk proteins consist of
very long strings of amino acids that are difficult to decode, and little is
known of how spiders actually unravel them and spin them into threads.
A spider, moreover, constructs its web methodically out of different kinds
of silk. It builds diagonal support lines called ''dragline silk'' (which
it also uses to hoist itself around its web) and then inner wheels called
''the capture spiral'' made from a more viscid, sticky silk. Dragline
silk, says Turner, is the ''best stopping material you've ever seen,'' but
how it's actually made inside a small orb weaver's abdomen remains
mysterious.

And whereas spiders produce up to seven kinds of silk proteins, BioSteel,
as yet, contains only one.

As a result, BioSteel doesn't have all the resistant strength of spider
silk -- yet. Part of the mystery of spider silk's tremendous strength,
current research suggests, lies in the spinning rather than in the
internal chemistry of the silk itself. It seems that the silk proteins
self-assemble as they are squeezed out of the spider's glands much like
toothpaste being squeezed out of a tube. The stretching spontaneously
causes the proteins to line up and lock into each other. ''That's why we've
spent so much money on these extrusion machines,'' Turner says. ''The
secret is in the spinning.''

In any case, the properties of spider silk have long been recognized.
Fishermen in India have always prized it for the making of their nets;
American Civil War soldiers frequently used it as a surgical dressing.
The problem lay always in getting sufficient quantities of it. Whereas
silkworms are peaceful herbivores and can easily be farmed, spiders are
aggressive territorial carnivores that need plenty of space and
solitude. In farm conditions, they moodily attack and eat each other.

Farming zillions of spiders, then, is far too tricky. But farming
peaceable goats is a cinch. Yet how to get the desirable material from a
rather nasty predator like a spider into the reproductive system of a kindly
animal like a Nubian goat? Enter the odd subject of mammary glands.

The mammary gland is a perfect natural factory for the synthesizing and
production of proteins. It occurred to Turner, who had been working on
lactation at McGill University's animal sciences department in the
mid-to-late 80's, that, theoretically, one could introduce foreign genes
into an animal's mammary gland and get any given protein out of the
animal without killing it, much as one milks a cow. Given the enormous
expense of manufacturing drugs artificially, transgenic animals offered a
brilliant way to make dirt-cheap drugs; $50,000 worth of proteins could be
extracted from a few buckets of milk at a cost of about $12 of hay! The logic
seemed irresistible: the udder as factory outlet.

In 1993, Turner was approached by the two venture-capitalist godfathers
of Canada's budding biotech industry, Bernard Coupal and Ed Rygiel. They
had heard of his work at McGill and were interested in finding a way to
create a transgenic goat. But where most transgenics is concentrated on making
drugs, Turner, Coupal and Rygiel eventually wondered if it might not be
more practical, and less risky, to concentrate on materials. For one
thing, they realized, it's almost impossible for small companies to manufacture

drugs. But a simple material that doesn't need F.D.A. approval is quite
another thing. And when they considered the possible uses of spider
silk, they were astounded.

''Humans never think about size,'' Turner says. ''If an animal doesn't
make stuff on a scale we understand, we just ignore it. But insects and
marine animals, although they're tiny, make incredible materials that we could
use. Who's to say we can't?''

Nexia doesn't only farm goats in St.-Telesphore. It also has ambitious
plans to turn an old Air Force base on the American side of the border
into its mass-production facility for Bio-Steel. As I approach this
decommissioned base just outside Plattsburgh, N.Y., I look through the
miles of lonely fencing at the old concrete bunkers where nuclear
missiles were most likely housed. They rise from the ground like ancient tombs
covered with grass. A few floppy-eared Nubian goats stand incongruously
on top of them, wagging their tails and bleating.

Nexia's sympathetic farm manager, Thomas Ballma, tells me that the goats
just love rolling down the grassy sides in summer. ''We can't hardly
control them,'' he says as he shows me the inside of a newly refurbished
bunker coated with epoxy paint. Inside the 80-foot-long cave our voices
echo ominously as he points out with some pride the new ventilation
ducts and electric cables. Nexia is trying to breed as many goats here as it
can.

From the present 302 goats they hope to have 1,500 a year from now.

We wander into one of the inhabited bunkers, where dozens of mop-haired
Angoras jump to attention. Then they come trundling over to us en masse,
licking our hands and cocking their heads inquisitively. I remark that
the country music playing on the loudspeakers is rather loud. Is that Dolly
Parton?

''Oh, they love Dolly Parton,'' Ballma says. ''Country music has the
steadiest beat. It keeps them calm and happy. Heavy metal, though, gets
them agitated.''

A shipment of goats has just arrived from Georgia, and as we stroll
around the gigantic half-abandoned base, Ballma tells me how Nexia has
revitalized the sagging post-cold-war economy of Plattsburgh. ''It's been a
godsend,'' he admits. ''Even though it seems a little improbable. I've been
raising goats for years, I love them, so at first the idea of making them
secrete spider silk kind of weirded me out. But now I understand it. It's not
what people think.''

''Not Dr. Moreau?'' I ask.

''No! We're just making fishing nets here. It's pretty normal, really.''

As we stand in the old air-control tower overlooking the base I can hear
a faint bleating of happy goats. From nuclear bombs to transgenic goats,
it seems a strange progression, I say.

''Sure,'' he replies. ''But perhaps it's just our own cleverness that
weirds us out.''


Lawrence Osborne is a frequent contributor to the magazine.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~



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