How Much Is That Doggy In The Vitro?

Move over, Dolly. Here comes Fido forever. In College Station, deep within the cinder-block bowels of a lab on the campus of Texas A&M University, Madeline the dog waits patiently on a metal table while a veterinary surgeon pulls green sterile scrubs over his pointy cowboy boots. Yesterday, Madeline's blood test revealed the telltale hormonal […]

__ Move over, Dolly. Here comes Fido forever. __

In College Station, deep within the cinder-block bowels of a lab on the campus of Texas A&M University, Madeline the dog waits patiently on a metal table while a veterinary surgeon pulls green sterile scrubs over his pointy cowboy boots. Yesterday, Madeline's blood test revealed the telltale hormonal spike that signals ovulation. It's her turn.

The bathroom-sized preop room is crowded with onlookers, doctors, and nurses. One whispers soothingly in Madeline's ear while another shaves her leg, sucking the fuzz with a Dustbuster. She's a sweet little beagle, and the drugs make her sweeter. Buprenorphine to anesthetize, acepromazine to tranquilize, glycopyrolate to stop her drooling: She looks on passively as the surgeon measures a tracheal tube against her chest.

Deep doggy-sleep overwhelms Madeline in seconds. The tube is in now, her jaws tied around it with a bow of cheesecloth, and the surgeon presses down on her body until she pees into a metal bowl. A man in a surgical mask stabs in from a corner with a Sony digicam for the shot: On his tiny screen, a nurse squeezes an oxygen balloon, and Madeline's body inflates in rigid synchronization.

Under the lights, the nurses have abstracted Madeline's freckled belly to a square of shaved flesh framed by green cloth. The surgeon scalpels a thin red line through the square and stretches the incision with a retractor, O-ing a portal into her belly. Then, as if reaching into a pumpkin with its lid cut free, he pulls out the beagle's uterus and ovaries. Somewhere within his gloved fist are six microscopic dog eggs. For the moment, they are Madeline's.

Madeline is having her eggs harvested, a procedure that's only recently been perfected in dogs. The process is common for humans - the first step in making test-tube babies - but Madeline's surgery is special: The eggs will be used to try to make a clone.

Madeline and 60 other bitches are serving as doggy hens, egg machines that supply the raw materials for the world's only canine-cloning project, a joint venture between A&M and California-based Bio-Arts and Research Corporation (BARC). The $2.3 million effort, called Missyplicity, is privately funded by an anonymous Bay Area billionaire who wants to make an exact copy of his mutt, Missy.

Veterinary researcher Mark Westhusin leads the four-person team of scientists charged with carrying out the science behind Missy's cloning. For the past three years, Westhusin and his colleagues have been laboring at the frontier of canine reproductive biology. Before they could even dream of supplying their anonymous patron with his cloned puppy, techniques like this egg harvest had to be developed. In the process, surgeries like Madeline's have been repeated scores of times on dozens of lab dogs.

After Madeline's eggs are collected, they'll be retrofitted with Missy's DNA, cultured in vitro, and - if the embryo is viable - surgically implanted into another dog's oviduct for gestation. Right now, five Missyplicity dogs like Madeline are pregnant with potential Missy clones. None of their embryos have developed enough to have a perceptible heartbeat, but Westhusin is confident that this pregnancy - or another one soon - will stick. If everything goes perfectly today, Missy 2 will be born in 63 days.

Three years ago, Dolly the sheep was front-page news. Missyplicity was announced soon after, and sounded to many people like a biotech hoax - or, worse, a conspicuous waste of time and money at the expense of lab dogs like Madeline. But despite its cutesy aspects, Missyplicity is important. It brings the reality of cloning closer to home: Dolly was a scientific first, but she's hardly man's best friend. In Dolly's wake President Clinton signed a bill prohibiting the use of federal funds in human-cloning experiments. Four states took the clone ban one step further and made human cloning illegal regardless of who pays for it. The message seemed to be that cloning vegetables, or lab and farm animals is acceptable, but when cloning gets personal, it's illegal. Missy isn't human, but she's no farm animal either. A pet occupies a psychic middle ground. Even if Missy is never successfully cloned - and there's no guarantee that she will be - the very fact that people are trying is an implicit challenge to our legal and ethical comfort zones.

The man with the camera is Lou Hawthorne, an ectomorph with a full head of salt-and-pepper curls and a mischievous streak. A goateed sci-fi fanatic turned college hippie, then techie, and now Bay Area entrepreneur, he lives in Marin County and makes time every day for an hour of yoga. As president of BARC and middleman between Missy's billionaire owner and the Texas A&M cloning team, Hawthorne cuts the checks and manages Missyplicity's PR. Right now, he's shooting a documentary. He's having fun, too; there's a big grin beneath his surgical mask.

Since December 1997, Hawthorne has flown to observe Missyplicity about a dozen times. He's stayed at all the finest hotels and worn out the menus in all the best restaurants between College Station and Houston. But his latest trip is different. This time, Hawthorne is so sure of Missyplicity's success that he's arrived for something even bigger than the world's first dog-cloning project. He's here to launch the world's first dog-cloning company, a gene bank called Genetic Savings & Clone.

A three-way partnership among the scientists, Hawthorne, and the wealthy client, GSC is opening the door to a clone-on-demand future. As little as a thousand dollars puts your doggy's DNA on ice. If today's surgery on Madeline yields a Missy clone, all you'll need to clone your own Fido this year will be the firm's URL (www.savingsandclone.com) and $250,000.

There's no way to predict the demand for cloned puppies, of course, but it's likely to be high. Remember how you cried when you buried your childhood pet in the backyard? Hawthorne can, and right now he has 200 potential clients lined up who never want to endure that loss again. In Hawthorne's vision of the future, people will pass a clone of their beloved family pooch down to their grandchildren. Statistically speaking, a dog lives in every other American household: No wonder Hawthorne wears a grin.

To make Madeline's egg into Missy's clone, Madeline's DNA must be replaced with Missy's in another lab across campus. It's a two-minute drive to the Reproductive Sciences Laboratory, long enough to kill an unheated oocyte, so Madeline's eggs are tucked into a warmed lunch box for the ride.

The RSL is a square gray building. Hawthorne leads me to Westhusin's office to show me the single photograph hanging there. "She's very photogenic, don't you think?" he asks.

The portrait is of Missy, and she is photogenic, a healthy-looking cutie with the pointy ears and snout of a collie and the robust bushiness of a Siberian husky. "We thought Mark should know what he's working toward," Hawthorne says waggishly. "You know, so he won't get it wrong." Hunkered behind a desk littered with grant proposals, Westhusin offers us a resigned smile.

We're here to watch Westhusin insert Missy's DNA into Madeline's eggs. Technically, this is the moment of creation for Missy's clone, and Hawthorne wants to film it. Westhusin dutifully dons a photogenic white lab coat before placing Madeline's fresh ova inside the micromanipulator, a powerful, $60,000 microscope equipped with two hair-thin microsurgical instruments and paid for by Missy's mysterious owner.

__ If Missyplicity succeeds, all you'll need to clone a pet is a tissue sample and $250,000. __

In theory, making a clone is easy: It's only a slight variation on standard sexual reproduction. You take an egg, remove its DNA, replace it with DNA from another cell, and - voilà! - you have a fertilized clone egg that will then split and develop according to those new blueprints.

But in practice many complications arise. Though all the cells of a living creature contain a full set of genetic instructions (in the form of DNA), they don't perform the same functions. A liver is not a nose. A slew of failed frog-cloning experiments in the '60s convinced most scientists that cloning an entire animal from a differentiated body cell - a nasal cell, for example - would at best result in a giant nose. If you wanted to reproduce the entire animal, you'd have to use undifferentiated cells. For 40 years the only source of such cells was fertilized embryos. Scientists could make multiple copies of the unborn - Tetra, the first rhesus monkey clone, was recently created using this technology -but they couldn't produce a clone from an adult animal.

That changed on February 23, 1997, when a team of Scottish researchers trotted out Dolly, a seven-month-old Finn Dorset lamb that was cloned from the mammary cell of an adult ewe. Dolly's creators had cloned an adult by starving the cell - thus apparently tricking it back into an undifferentiated state before placing it inside another sheep's egg.

In attempting to clone Missy, Westhusin's team follows the same protocol used to create Dolly, a process known as somatic cell nuclear transfer. But before the Dolly protocol could even be applied, there was a set of species-specific problems that needed to be solved. For example, dogs have a bursa, or pouch, encasing their ovaries that makes egg harvesting difficult. Sheep don't. And while sheep ovulate regularly - once every 19 days - dogs release ova randomly, once every 6 to 12 months. In undertaking this cloning project, Team Missyplicity had to amass an understanding of canine biology far more comprehensive than dog breeders or vets have ever possessed.

At this point, Missyplicity scientists have overcome most of the problems, but they're still playing a numbers game that's very hard to win. Egg harvesting, tissue culture, enucleation, renucleation, embryo culture, gestation, birth: Even with the full knowledge of a species' reproductive biology, a clone team needs to make a lot of mistakes before nailing the whole sequence perfectly, which means burning through a lot of eggs. The tally was at 277 before Dolly was born. So far, Missyplicity has renucleated only 77 eggs, plus Madeline's 6 today.

In the RSL micromanipulation room, Westhusin motions Hawthorne's camera toward the scope's cathode-ray tube. The ovum filling the screen resembles a big, fuzzy zero - with Madeline's coiled DNA floating inside the nucleus. Taeyoung Shin, one of Westhusin's postdoctoral students, works a joystick on the scope, and a miniature tool slides into view: a glass pipette, with a blunt mouth only 20 micrometers wide. Shin hits the trigger, and the pipette attaches to the egg like a vacuum hose sucking on a beach ball.

"Now, watch here," Westhusin says to the camera. "It's not as easy as it looks."

Another pipette slides into view on the micromanipulator screen, this one thinner - and sharp. In a single, fluid motion, the sharp pipette pierces the egg, sucks in the nucleus, and pulls out.

"OK," Westhusin says. "Got it."

Click, click: The entire process has taken about five seconds. Genetically speaking, Madeline's egg is vacant. Now it must be retrofitted with Missy's DNA. Hawthorne sets up his camera for the next shot.

One of Westhusin's graduate students pulls a plate of Missy's body cells from a jug of liquid nitrogen, then incubates them back to body temperature under a sterile vacuum hood before Westhusin adds them to the micromanipulator dish. Onscreen, Missy's body cells are tiny and pale next to the giant egg, like moons around Jupiter.

Westhusin points to a small, round cell. "C'mon Shin, you know we're only giving you two more months," he jokes. "We want a dog. I want a dog."

Shin sucks the cell into his pipette, pokes into Madeline's empty egg, and injects. Click, click: done. Loaded with its new nuclear cargo, the egg spins free. It's genetically identical to the fertilized egg that divided and developed into Missy.

Westhusin claps his hands like a director cutting a scene. "OK, Shin," he says. "Great. Are we ready to fuse?"

Right now, Missy's body cell and Madeline's egg cell both have their own membrane. To combine them into a single cell within a single membrane, the final step of today's procedure will be to fuse the cells together with an electric pulse that sends charged ions busting through the cell walls. Afterward the cells should heal into a single whole, like a graft.

The procedure is cutting-edge, but the equipment - a BTX Electro Cell Manipulator - looks like vintage Radio Shack. It's a squat box, resembling a car battery. LCDs show amps and volts. There's a toggle switch marked POWER and an assortment of knobs and dials. The BTX is the perfect lab gizmo - the B-movie bolt of lightning.

Two wires, positive and negative, protrude from the BTX box. Westhusin attaches them with alligator clips to the dish containing the new Missy egg and turns the dials to their proper settings. It's a tasty image, but as Hawthorne pans over for a shot, Shin reflexively pushes out his hand, blocking the camera. "It's secret," he says. "You cannot take a picture." The exact power settings are owned by the project, and they're potentially valuable - patentable. Filming the BTX numbers crosses a line. Hawthorne pushes in for a tight shot of the machine's console anyway.

"Really, really," Shin says. "It's secret - you cannot film."

"Well, I'm paying for it," Hawthorne says. Shin, confused, turns to Westhusin.

__ "You might as well ask if science is for sale. The answer is yes. We try to sell it every day." __

But Westhusin has turned away. He gives the machine a final tweak and steps back to check his work: Everything's right. He flips the switch, sparking the BTX to life. Electricity surges through the renucleated cell, and another potential Missy is created.

"I just decided," Hawthorne announces excitedly. "In the documentary, we're definitely cutting to Gene Wilder in Young Frankenstein: 'It's aliiiiiive!'"

Missyplicity was born in the mind of a dog lover and successful Bay Area businessman who saw the Dolly headlines in 1997. Mr. E, as we'll call him, counted his spayed bitch, Missy, as one of his greatest joys. But she also wasn't getting any younger, a fact no man - not even a rich one - can change.

What followed was a whim, the sort of wild idea that strikes you as funny in the shower but evaporates by the time you've toweled off. But Mr. E - who declined to be interviewed, even with his anonymity protected - had kibble to burn and, more important, a friend who offered to turn his whim into reality: Lou Hawthorne.

Hawthorne is a professional dabbler - and by his own description, a successful if unsettled one. He has produced interactive multimedia projects for Apple, USWest, and Tandem, as well as a documentary on the ill-fated Biosphere 2. Six months before spearheading the Missyplicity project, Hawthorne was in India chronicling his motorcycle pilgrimage across the subcontinent for a Web site called Hell's Buddhas.

Four months later, armed with Mr. E's checkbook, Hawthorne attended the Transgenic Animals in Agriculture conference in Tahoe City, California, where he met Mark Westhusin. An associate professor at Texas A&M, Westhusin managed a 20-person, multimillion-dollar lab. Before that, Westhusin had worked for five years at Granada BioSciences, developing cattle-embryo cloning techniques. Hawthorne told him he wanted to clone a dog.

At scientific confabs, especially those dealing with new fields like cloning, it's not uncommon to encounter the odd civilian with big ideas but shallow pockets. After meeting Hawthorne, Westhusin wasn't sure what to think. "I listened to him," he remembers. "I told him that trying it would cost money - a lot of money. Millions. That this was fine with him really shocked me."

Westhusin returned to Texas to start building a Missyplicity team. He approached his mentor, Duane Kraemer - a Texas A&M biology professor and an internationally known embryo-transfer specialist - as well as Bob Burghardt, another Aggie faculty member and an expert in isolating, propagating, and characterizing cells for use in nuclear transfer. Lisa Howe, an A&M veterinary surgeon knowledgeable in tissue-collection protocols, was also recruited. Within nine months, the team was on its way to producing a canine clone, and Missy was flown to Texas to have cells harvested from her belly and lips. At mealtime she was brought to a College Station deli and, to Westhusin's amusement, hand-fed broccoli from the salad bar.

Lou Hawthorne and Mark Westhusin make a particularly odd couple. Westhusin has an easy familiarity with guns, cows, and football. With his flannel shirt tucked into neat blue jeans, he looks like a country boy. By contrast, Hawthorne, in silk shirt and supermarket tube socks, looks like an Ivy League yoga geek on a Texas vacation. When I ate dinner with them, Westhusin had cleaned his plate and checked his watch before Hawthorne had even decided on a suitable Sonoma red.

"We butt heads," Westhusin says, "but we've figured out how to work together. He pisses me off, and I pretty much tell him. And I piss him off, and he tells me."

The BBC broke the Missyplicity story in August 1998, well before the cloning experiments had actually started. "They told me they wanted to talk about cloning in general," Westhusin remembers. He agreed on the condition that they not address Missyplicity. "They had this smart-ass reporter who got me on camera and kept asking 'Isn't it true that you just accepted $2.3 million to clone an individual's dog?' Gotcha stuff. I just said 'Nope. Told ya. Not going to talk about that.' But you end up looking guilty anyway."

The story was picked up worldwide, but since the Missyplicity scientists weren't talking, dog cloning was cast as a believe-it-or-not footnote to Dolly. The phone on Texas A&M president Ray Bowen's desk began ringing nonstop. It was the first time he had heard of the project - which was not unusual, as scientific research at A&M is controlled by a separate bureaucracy. Reacting to the bad publicity, Bowen's first impulse was to pull the plug. Cooler heads prevailed, and today Texas A&M stands fully behind the project. But Westhusin still gets the occasional raised eyebrow from fellow researchers who question whether cloning a rich man's dog is serious science.

"We always knew this would be controversial," Westhusin says. "People say, 'This project is so compromised - why would you take this money, why would you get involved in this kind of thing?' You might as well ask if science is for sale. And the answer is yes - yes, it is for sale. We try to sell it every day to NIH and to private industry. As a scientist, you have to weigh what you learn against what the final product is."

Westhusin says he spends much of his time focused on money - raising it, spending it, and then filling out the paperwork. Beakers and test tubes are the small stuff: Micromanipulators cost real money, cryopreservation costs real money. Mistakes - the inevitable by-product of trial and error, the fallen soufflés of scientific knowledge - cost money.

With Mr. E's dollars, the Missyplicity scientists started to learn volumes about dog physiology and, as the email flooded in, almost as much about dog lovers.

First came flames: "This project really stinks. It makes me feel sick. What's wrong with good, old-fashioned breeding? If you make copies, nothing will ever be better."

In response, Hawthorne created a PR-minded Web site (www.missyplicity.com). Gradually, the mailbag began filling with a different sort of message.

"My dog died, and I hope that someday he might be clonable. How should I go about preserving what is left of my lovely, perfect creature? His body is in the freezer."

"Personally, I say to hell with 'ethics' that tell us that we cannot preserve those we hold dear. The purpose of religion, in my opinion, is to celebrate life, not death."

"I am interested in cloning my cat, George. How much would it cost?"

The deluge stunned the scientists, especially Westhusin. "Three years ago, I'd have never guessed people were this crazy about pets," he says. "But there are a lot of people out there who think that what we're doing down here is the greatest thing since sliced bread."

Suddenly, without advertising, this quiet enterprise was getting hundreds of requests from pet lovers and potential customers. The Missyplicity team realized that they had their hands on more than just a privately funded research project: Suddenly, they had what looked like a very lucrative startup.

By the time you read this, Genetic Savings & Clone, a "companion-animal DNA storage bank," will be open for business. During my stay in College Station, Hawthorne proudly shows me GSC's 32-page business plan. To open an account, you deposit a tissue sample (preferably, the dog is alive, but a week-old corpse will do). Processing fees range from $1,000 to $3,000, plus $100 per year for cryogenic storage. Six months after Missy's clone is born, Hawthorne claims, the canine-cloning service will be available to the public for about $250,000 per cloned pup - one-tenth the total cost of Missyplicity - and the prices should drop 50 percent every year.

As Hawthorne's plan points out, Americans own and care for 50 million dogs: "Most are beloved members of a family, with one critical difference from the other family members - on average, they live one-seventh as long." If GSC cryo-stores tissue from one-tenth of 1 percent of them, that's an annual gross of $50 million. If GSC also serves one-fifth of 1 percent of the 5 million dogs Hawthorne estimates die each year, his company will be handling 10,000 dead dogs - another $27.5 million. (The partners - Hawthorne, the Missyplicity scientists, and Mr. E - have equity; the prospect of an IPO is mentioned as an enticingly viable possibility.)

Hawthorne figures his customers will find him on the Web. Let's say a prospective client - in the business plan, Hawthorne calls him Joe - wants to bank his dog's genes. Joe logs on to the GSC Web site, where he finds grief-counseling resources and a list of GSC-registered veterinarians. Later, Joe's vet logs on and schedules surgery, choosing from one of four levels of expediency - from "standard" to "emergency" - depending on whether the dog is healthy, sick, or dead. GSC ships the vet its trademarked BioBox, which contains the needed reagents and Tupperware, plus an instructional videotape that gives a step-by-step explanation of the procedure.

On the scheduled day, Joe's vet takes tissue samples from Joe's dog - Rocket, in the business plan - and FedExes them to Texas, where they're cultured for a month in a hormonal medium, checked for DNA viability, and cryo-stored in liquid nitrogen at minus 320 degrees Fahrenheit. Rocket's DNA has now been banked. If Joe later decides to clone his dog, he'll first have to click through several legal contracts. A cloned dog is not a resurrected dog - Rocket 2 won't actually be Rocket, she will be Rocket's identical twin, born well after the original. Rocket 2 will share Rocket's DNA, but the scientific jury is still out as to whether they'll necessarily share personalities. At this point Hawthorne can't contractually guarantee that Rocket and her clone pup will look or act exactly the same. He doesn't want to get sued when Joe discovers that Rocket 2 can't remember his master's voice.

The GSC storage site eventually will have a constantly updated feed - "perhaps cameras trained on the dials and gauges of the liquid-nitrogen controls," Hawthorne says - so Joe can visit Rocket's DNA cylinder as if it were her "gravestone." The virtual DNA "visitation area" will be accompanied by a picture of the deceased and a few paragraphs of canine epitaph. It's a comfort for the grieving dog owner, but keeping the memory of the pooch alive is also good marketing. After cutting that $100 storage check each year, Joe might want to see where his money goes.

The Web interface also transforms what is essentially a giant refrigerator into what Hawthorne calls a "DNA marketplace for famous animals, such as Missy." GSC would take a brokerage fee for any transactions between owner and buyer and perform the actual cloning.

To really understand GSC's revenue potential, consider the cattle-cloning business, Westhusin's former livelihood. The cattle industry is a $36 billion-a-year enterprise that already traffics in embryo clones, so it's easy to see how highly the beef boys might value a service that lets them store and reproduce infinite genetic copies of their prize bulls - especially if the service is linked with Texas A&M, an aggie institution with a sterling reputation. And Hawthorne says pet dogs aren't the only critters on GSC's radar screen. There are racehorses, racing dogs, cats, and endangered species to think about. GSC's business plan leaves you with the impression that nothing, short of a total failure to clone, stands between the company and world domination. But, of course, as Hawthorne and Westhusin both know, there are pitfalls in the way.

At this point, competition seems to be the least of them, though four other doggy-gene banks are vying for market share: Canine Cryobank, perPETuate, Lazaron, and Clonaid. None of them has the backing of either universities or billionaires. None even has more than a dozen dogs in cold storage. All four are apparently banking on Missyplicity's success: Without the lure of a clone, cryopreservation is a pointless business.

The embryonic canine-cloning industry's real challenge, however, is not cloning a dog - that will happen, sooner or later - it's putting a smiley face on the process of cloning a dog. To that end, Hawthorne has chosen a beautiful bright Wednesday morning to take me to visit the vivisection facility. The kennels lie unmarked at the far end of a dirt road, past fields of frolicking lab bison and NO TRESPASSING signs. They aren't much to look at: several dozen thin, gray sheds arranged in rows like tobacco barns. On one side are the Missyplicity dogs; on the other, the 150 used by Texas A&M for experimental research and teaching.

Only the Missyplicity dogs are visible, romping in a newly constructed yard of fenced gravel. Hawthorne and I put on gray jumpsuits and stroll like shepherds through the surging brown sea of yipping, floppy-eared canines. These are Madeline's sisters, the egg donors and surrogate mothers for Missy's cloned embryo. Except for the telltale squares of pale fur growing over the subdermal microchips used to identify them, they look like any other pack of pups.

"Look at them all," Hawthorne says triumphantly. "Don't they just look - happy?"

__ Dogs alone could make genetic savings & clone $75 million a year. There's more on the way. __

One doesn't usually associate the words lab animal and happy, but resolving this paradox is critical to Hawthorne's conscience - and to his business. This is the paradox of GSC itself. These 61 dogs are being used solely for the Missy clone. To clone other pets, GSC will need hundreds of lab dogs to supply the clone eggs. The Madeline egg that I saw renucleated was a dud, and ended up, like thousands of others will ultimately end up, in a biohazard trash bin. Hawthorne may not have much market competition, but he can count on plenty of ethical opposition from the same dog lovers he's counting on to patronize his cloning business.

Michael W. Fox, a senior bioethicist at the US Humane Society, finds the idea of dog cloning abhorrent. "Dog cloning is a sentimental self-indulgence for those who can afford it," he says. "Those dogs in the Missyplicity dog colony are hormonally manipulated to ovulate faster than normal. Eventually that's going to wear them down to the point that they'll develop diseases earlier and start dying sooner. We've only recently gotten down from the trees, and we're already playing God. We need to think about our responsibilities to animals."

Hawthorne maintains that such thoughts are never far from his mind - or Mr. E's wallet. On my first night in Texas, Hawthorne had given me his card. Predictably, it was whimsical and highly designed, with a photo of Missy at one of its corners. But he was quick to point out the Photoshopped darkness beneath her. "That," he said solemnly, "is the long shadow of biotechnology."

In April 1998, Hawthorne tried to remove that shadow by writing a letter to People for the Ethical Treatment of Animals. ("To whom it may concern: I'm coordinating a multimillion-dollar canine-cloning project.") Each Missyplicity surgery carries the risk of death. Still, he wanted the animal-rights group to understand that he was "designing this project to a very high bioethical standard, involving not just the physical well-being of all animals involved, but also their psychological well-being." PETA responded two weeks later: It hoped his letter was a joke.

Selling PETA on a lab dog-based clone project was a losing proposition, but the rebuke still stung. Hawthorne is an animal lover - in the late '80s he even volunteered for PETA. He considers himself spiritual and, his new biotech business notwithstanding, philosophically opposed to vivisection. To balance his business with his Buddhist conscience, Hawthorne has come up with a kind of karmic spreadsheet, a ledger tallying Missyplicity's ethical red and black.

Central to it is the Missyplicity Code of Bioethics, a binding contract between the project and the scientists that ensures, among other things, preferential treatment for all the dogs in the cloning colony.

"As a precedent it's a big deal," Hawthorne explains as several confused beagles hump his leg. "I wouldn't have even considered a cloning project if I didn't feel that we could commit to seeing it through in a humane manner. This dog colony could have been an ethical disaster."

Ethics don't come cheap, but Mr. E's money covered the cost of that too, buying the canine equivalent of a luxury condo complex. It comes staffed with a dog trainer named Jessica Harrison, who gives out treats.

Westhusin and Hawthorne haven't always seen eye-to-eye on the necessity of pampering experimental dogs. "Initially," Hawthorne says, "I think Mark considered animal-rights folks all the same and all trouble - well-meaning, but fundamentally deluded. But this dog colony is pretty obviously a cool thing. I've even noticed that Mark sort of shifts gears mentally when he's around the colony: He slips into the persona of Dog Owner rather than Scientist."

If Hawthorne's dogs could consider, they might consider themselves fortunate indeed. Like their yelping brethren in the sheds, the Missyplicity dogs were bred for experimentation. But unlike the regular lab dogs, which live out their lives inside cages, the Missyplicity dogs have names and an hour of daily exercise. Here on the gravel, they gallop around their jumpsuited obedience trainer, who housebreaks them for home adoption after their eight-month stay.

"Ours are the lucky ones," Hawthorne says, scratching a beagle's tattooed ear. "Sometimes, walking through here, I feel like Schindler."

Genetic Savings & Clone does have a Spielbergian air about it, albeit less Schindler's List than Jurassic Park. Hawthorne is hoping that his own movie, the Missyplicity documentary, will be picked up by HBO, driving people to the GSC Web site. He has the cloning biz all planned out, from the science to the PR, from the design of the BioBox right down to the logo that goes on top of it. But there's something obviously missing from the plan: GSC's address.

That's why, five days after Madeline's surgery, I find myself cruising in the Corinthian-leather confines of Westhusin's cherried-out Chevy Suburban. Westhusin and Hawthorne are looking for a suitable office to house GSC's reception area, cryotanks, hot room, and computers. Steve Pittman is the real estate agent. He'll find them an office, he tells them. He has, after all, "the equivalent of a PhD in real estate."

Like urban sprawl zones all over the country, College Station is a blur of Applebee's and Taco Bells and minimalls named for the trees plowed under. We've been driving past them all morning.

"Uh, you'll want to hang a right right here, Mark," Pittman drawls. Westhusin squints intensely at the oncoming traffic and wheels the SUV into another strip mall. He's out the door, ready to examine the structure, before the engine starts to tick. In the backseat, Hawthorne readies his digicam.

Hawthorne and Westhusin lean against the tinted windows, peering in at the drop ceiling. Around us, cattle ranchers in pickups hunt for parking spaces. "I don't know," Hawthorne says. "It's going to be hard to put Genetic Savings & Clone between a Solar Tan and a Yogurt Plus. It just seems wrong."

__ Ethics don't come cheap, but Mr. E's money covered that too - his lab animals live first-class. __

Westhusin steps back and surveys the masonry. "Well, it's expensive," he says, swaggering up next to Hawthorne. He's thinking about GSC's bottom line. The two men stare at the brickwork in silence.

Hawthorne had told me earlier that, in the beginning - when GSC was just another idea - he had discovered that video documentaries and bioethics weren't his only concerns that Westhusin found irrelevant; the researcher also had no taste for making money. "Sure," Hawthorne had said, "he knew on some level that he should want to make money - but he didn't want to." Hawthorne smiled knowingly. "Now he's a convert."

Back in the car, Pittman is reassessing their needs. What sort of traffic does a cloning business create? What does a gene bank look like? What sorts of zoning, parking, and toilets does it need? Even with his real estate qualifications, Pittman has no reference: GSC breaks the mold.

"Uh, I hear ya on the high-speed Internet wires," he says. "Think y'all are gonna need a loading dock?"

"Probably," Westhusin says. "We might have some freight."

"Ah, OK. A loading dock or a dolly dock?" Pittman's wondering whether they need a ramp, but the unintended Dolly association sends secret smiles through the car.

The smiles fade fast as we pull into the next driveway - a series of corporate office spaces with a shared elevator. As Pittman fumbles for the key, we stare at our feet, trying to imagine the future GSC with this public, industrial-carpeted setting. Down the hall, a door opens. Then another - neighbors uneasily eyeballing the prospective tenants. We are, it must be said, an eclectic bunch for College Station: Hawthorne, overdressed in a suit and holding a camcorder, Westhusin in his rugged flannel, Pittman, and me. What sort of business could we possibly be in?

Hawthorne's starting to get nervous. He finds Texas hard to take on a good day, but this is too weird - he needs a reality check. In desperation, he turns to the only other non-Texan, non-PhD in the hall: me.

"What do you think?" he asks.

"I don't know," I say. Pittman can sense our displeasure: His ears prick up.

"No, really," Hawthorne says. "Serious. I'm asking."

"Well," I say, "this just doesn't seem like the sort of place where, you know, folks will want to schlepp their frozen, rotting dogs."

Pittman's eyes go wide.

Back in the passenger seat, he nods to himself, reassessing. "OK," he says finally. "I'm getting a better sense of what y'all need." He cranes around from his seat. "What I'm thinking is that you guys need a place which is - well, I don't want to say secret, but ..."

"Well, how about private?" Hawthorne volunteers.

"OK," Pittman agrees. "Private. Y'all need a location that offers ... privacy."

About 10 miles down the road from the university, where the urban sprawl has finally trickled to an end, we hit Main Street, Bryan, Texas. It's a big-shouldered, windblown main drag, with abandoned storefronts reminiscent of Steinbeck's Salinas. And there, on a corner across from a Western hat shop, is Hawthorne's dream location: an abandoned, old-timey bank - the real thing - a big federal building with columns and everything. It's earnest as hell, the sort of stone strongbox they used to build when knocking over a bank wasn't just a turn of phrase.

Hawthorne is thrilled. He prances on the pavement, filming the building. He loves the blond concrete facade; he loves the idea of buying a real bank, just as he loves the cute names - Missyplicity and BARC and Genetic Savings & Clone.

Westhusin, meanwhile, just hangs back, hands on his hips. He couldn't care less about the facade. In his lab back on campus, Westhusin shares a can of Lysol and a single, squalid toilet with another professor and a half-dozen grad students. What Westhusin cares about are tools. He wants ventilation, a loading dock, enough electrical juice to freeze nitrogen.

Hawthorne cares about tools, too, but his have to do with PR and the media. He's already turned down story requests from The New York Times Magazine, The Tonight Show, Dateline NBC, Primetime Live, The Roseanne Barr Show, and The Oprah Winfrey Show. I'm the first, but there will be others, writers and TV people who come to see the clone business with the cute name. And they'll want to see his gene bank. Maybe this bank. He knows the future that causes apprehension is the one in which biotech is a blank door in the minimall, symbolized by a little sign that reads CLONATEK or some other hybrid name - words and images mashed monstrously together.

But a bank. You can trust a bank. It's sacred: There's something cathedral-like about its grandiose appearance, something solid about Main Street. The answer to GSC's real estate quandary had been hiding in plain sight. A gene bank stores something more important than money. Hawthorne sees this, and he knows the public will too.

"What does Mark think?" asks Hawthorne.

Westhusin isn't sure. The implications of putting a gene bank in a real bank - like much of what he's taken on with Missyplicity - well, it's just not his department.

Westhusin told me that, when he first met Hawthorne and Mr. E, "the way they thought and saw the world" struck him as "rather silly." He still remembers when they started the project, after the contracts were signed and they flew Missy out on a Learjet. Westhusin was just trying to get things done: Sneak the dog into surgery and get her out of there - in secret. But Hawthorne wanted Westhusin - a scientist! - to organize a band of Texas A&M cadets, wanted them lined up in full uniform on the road from the airport, holding banners that said WELCOME, MISSY! Right there, in front of everybody. "I'm like, this is nuts!" he remembers.

At first he felt that way about the Missyplicity Code of Bioethics, and Hawthorne's video, too, but he's gradually come around to a different viewpoint. The way Westhusin sees it now, cloning is no longer only for scientists: Ready or not, the future is here, and he owns a piece of it.

On the sidewalk, Hawthorne's got his digicam in Westhusin's face, fishing for a reaction. "Hey," he says, "find out if we can put a sign out front."

"A sign?" Westhusin squints up at the bank's facade. "You want a sign?"

"Yeah. You know, like a bank."

Westhusin shuffles over to Pittman and stuffs his hands in his pockets. "Whatcha think, Steve?" he asks. "Think they'd let us put a sign out front?"

Pittman looks at the two men and scratches his head. "Yeah, well, I'll talk to the guy," he says, walking back to the Chevy. "I betcha we can work something out."