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And a happy new year to all. --PG

http://www.nytimes.com/2009/01/01/garden/01clones.html

January 1, 2009

Living Together

Beloved Pets Everlasting?

By ERIC KONIGSBERG

Fairfax, Calif.

THE most difficult thing about the cloned puppies 
is not telling them apart, but explaining why 
they don't look exactly alike. This was the 
problem Lou Hawthorne faced on a recent afternoon 
hike with Mira and MissyToo, two dogs whose 
embryos were created from the preserved, recycled 
and repurposed nuclear DNA of the original Missy, 
a border collie-husky mix who died in 2002.

To be sure, they have a very strong resemblance 
to each other and to Missy. It's just that 
sometimes, as soon as people hear that the dogs 
are clones, the questions start coming:

"Why is one dog's fur curlier?"

"Why aren't the dogs the same size?"

"Why is one of them darker?"

"Why does this one have a floppy ear?"

Mr. Hawthorne, who is 48, is highly invested in 
the notion of likeness. With clones, after all, 
what good does similar do? It is Mr. Hawthorne's 
biotech company, BioArts, which is based here in 
the Bay Area but has arrangements with a 
laboratory in South Korea, that performed the 
actual cloning.

He also has particular reason to be sensitive to 
questions that touch on the authenticity of the 
clones, given the history of his chief 
geneticist, Dr. Hwang Woo Suk of the Sooam 
Biotech Research Foundation in South Korea. Dr. 
Hwang is perhaps best known for fraudulently 
reporting in 2004 that a team he led had 
successfully cloned human embryos and stem cells. 
After the false claims were unearthed, he was 
fired by Seoul National University, where he did 
his research as a professor. But he is also 
widely acknowledged for having been involved in 
successfully cloning an Afghan hound in 2005.

"Dr. Hwang's past is obviously controversial, but 
we feel that his lab and his record when it comes 
to dog cloning are the best in the field," Mr. 
Hawthorne said. "He's been very open with me 
about admitting his mistakes. Nobody says he lied 
about cloning animals."

Elizabeth Wictum, associate director of the 
Veterinary Genetics Laboratory at the University 
of California, Davis, said that earlier this 
year, she and her staff had taken sets of DNA 
extracts from Mr. Hawthorne's puppies and 
compared them with stored samples of Missy's DNA, 
and concluded that the results were "consistent 
with clones."

"The puppies had the same nuclear DNA as Missy, 
and different mitochondrial DNA, which is what 
you get from a cloned animal," Ms. Wictum said. 
"If somebody were trying to, say, sneak in two 
samples from the same dog or an identical twin 
and claim that one was a clone's, there would be 
no differentiation between the nuclear and 
mitochondrial DNA."

Missy 1.0 - Mira and MissyToo's "genetic donor," 
as Mr. Hawthorne calls her when he's speaking 
technically - was his mother's dog. To date, he 
said, there are four Missy clones running around, 
all born between December 2007 and June 2008. 
Mira lives at Mr. Hawthorne's house in Mill 
Valley and MissyToo between homes in Mill Valley 
and San Francisco, both owned by his mother's 
boyfriend; clones No. 3 and 4 were given away to 
friends and now live in Phoenix and Boulder, 
respectively. (Two others were produced but died 
of parvovirus as newborns.)

In July, Mr. Hawthorne held a series of online 
auctions, offering his services to four high 
bidders who agreed to pay from $130,000 to 
$170,000 for clones of their dogs. (To offset 
accusations of elitism, Mr. Hawthorne also held a 
search for a fifth, pro bono client.) Over the 
last few weeks, the first three puppies from this 
group were born in South Korea.

Mr. Hawthorne claims Missy's clones are the 
world's first commercially cloned dogs, although 
RNL Bio, a Korean company with which he is 
embroiled in a legal dispute over patent rights - 
and the chance to dominate the dog-cloning market 
- has also made this claim. Between 2004 and 
2006, another company Mr. Hawthorne ran cloned 
cats for a handful of paying customers. Dogs are 
among the most difficult mammals to clone, 
scientists say, because their reproductive 
systems are highly atypical, but Mr. Hawthorne 
thinks that the market is keen.

When Mr. Hawthorne recalls Missy, he tends to wax 
eugenic. "She was an amazing dog: superior 
intellect, incredibly beautiful, obedient, a 
phenomenal temperament," he said. "I especially 
loved her majestic plume of a tail." And in the 
clones, as he put it matter-of-factly, "all those 
qualities are represented."

As for some of the discrepancies, the clones vary 
in size and color, Mr. Hawthorne said, primarily 
because they were born months apart, and none are 
fully grown yet. "The dark part of their fur 
starts out reddish-black and gets blacker over 
time," he said. "Except on the faces, which start 
out black and go white within the first year."

Each clone's embryo was created by joining 
Missy's nuclear DNA with the enucleated (which is 
to say, DNA-stripped) egg of a different dog. The 
eggs, with their new DNA from Missy, began to 
grow and divide. After that, each was carried to 
term in the uterus of still another dog - a step 
which, though it has no bearing on the dogs' 
genetic makeup, can affect such external traits 
as the waviness of fur and the up-or-down 
pointing of the ears. (It has to do with 
different levels of collagen.)

On his afternoon trek around Lake Lagunitas, Mr. 
Hawthorne did his best to explain these matters 
to his audience, picnicking families who sat 
transfixed as the two dogs he calls "clisters" - 
his made-up word for clone sisters - took turns 
chasing each other off leash.

"Can they clone coconut?" a girl asked.

"Sorry, we don't do vegetables," Mr. Hawthorne said.

A parent clarified: Coconut was the family dog's 
name. "Can you clone a three-year-old housebroken 
dog?"

Mr. Hawthorne went on gamely. "Learned behavior, 
no. But a lot of behavior is hereditary," he said.

While he does acknowledge that when it comes to 
such highly trainable creatures as dogs, it's 
pretty difficult to know where nature ends and 
nurture begins, he said that in the case of his 
dogs, the ambiguities have nothing on the 
essential Missy-ness of the clones.

"The girls love to run after each other," he said 
pointing at the dogs in the distance. "You see 
the speed and athleticism? That's part of what 
made me want to do this. There are dogs that are 
faster on a straightaway, but I'd never seen a 
dog make turns like this until Missy."

Mr. Hawthorne sees himself as a cultivator of 
prodigious talent - from the clones to his team 
of scientists in South Korea to his 8-year-old 
son, Skye, who had accompanied him and the dogs 
on the hike. Skye is in third grade but is 
already studying high school algebra. Mr. 
Hawthorne brought along a notebook with a handful 
of quadratic-equation problems, in case his son 
got restless.

Last spring, Skye completed a science project, 
"Cloning Grandma's Dog" that included a 
behavioral comparison chart. Among other 
findings, the study concluded that Mira shares 
Missy's fondness for broccoli and "lots of 
snuggles" - both dogs scored five out of five 
points in these categories, in addition to the 
one for "likes long walks." ("Most dogs do," Skye 
noted under "comments.") Two key matters of 
variance were "Jumps into cars" ("Clone still 
learning which car is ours") and "Hates camera 
flash" ("Clone did not respond to standard 
flash").

Ultimately, Skye determined that Mira looked a 
lot like Missy but that their behavior was only 
77 percent similar. "But that was April," Mr. 
Hawthorne said. "I think they're a lot more 
similar now."

LIVING with a clone, Mr. Hawthorne claims, is a 
lot like living with the original dog. "It's 
totally as if I've got Missy in my house, once 
you get over the 'wow' factor," he said. He and 
Mira and Skye inhabit a two-story "1950s futurist 
house" built into a hill in Mill Valley (Mr. 
Hawthorne is divorced and shares custody of his 
son with his ex-wife - "an excellent genetic 
donor, by the way," he said of her). At night, he 
said, Mira "puts Skye to bed," which means she 
walks with him to his room and ascends the stairs 
of his loft bed with him, waiting to be told 
"Good night" before she leaves. Mira is an 
outdoor dog, as Missy was, and sleeps on the 
front steps.

And who says goodnight to Mira's fellow clone, 
MissyToo? Mr. Hawthorne gave her to his mother, 
Joan Hawthorne, who still misses the original 
Missy. But she has yet to take a liking to 
Missy's progeny, and the dog has lived primarily 
with paid "handlers" in the Mill Valley 
pied--terre of her longtime companion, John 
Sperling.

"They're not at all alike," Ms. Hawthorne said of 
the old Missy and the new one. "In looks, they 
are a little bit, of course. But, I mean, the 
puppy is delicate and aggressive. Missy was 
robust and completely calm." She added, "Missy 
wouldn't come through my home and knock over 
every wineglass."

Besides, she adopted another puppy not long after 
Missy died. "I already have a dog - a real dog."

The idea of trying to clone Missy in the first 
place came from Mr. Sperling, who has been in the 
family picture since Mr. Hawthorne was 4 years 
old - Mr. Hawthorne typically refers to him as 
his stepfather - back in 1997. At the time, Mr. 
Hawthorne was at a sort of career crossroads, 
having worked in the interactive video-production 
business and just returned from five months 
riding a motorcycle across India. Mr. Sperling, 
who would not agree to be interviewed, is a 
billionaire who founded the University of 
Phoenix, the adult-education institution with 
nearly 200 locations. Mr. Hawthorne said that his 
various fruitless attempts at cloning were paid 
for by more than $15 million of Mr. Sperling's 
money, some of which went to purchasing several 
competing and related biotech businesses in what 
Mr. Hawthorne described as an industry roll-up.

"It's kind of weird," Mr. Hawthorne said. "They 
spent 10 years waiting for this to happen and 
then they don't even want the dogs living with 
them." In recent weeks, he added, Mr. Sperling 
has been making an effort to keep MissyToo with 
him at his house in San Francisco. ("He's going 
to have to launch on some serious dog training," 
Ms. Hawthorne said of this new development.)

On the day of the hike around the reservoir, Mr. 
Hawthorne, with a reporter as his audience, 
telephoned Nina and Ed Otto, auction winners in 
July - they paid $155,000 - who were about to 
learn that they were the proud owners of the 
project's first spawn. A clone of Lancelot, their 
late yellow Labrador, had been born a couple of 
days earlier in South Korea.

From the courtyard of a Starbucks, he dialed 
their home in Florida on his cellphone. "Your 
little Lancelot is here," Mr. Hawthorne informed 
Mrs. Otto.

He followed up with date and time of birth, 
weight (540 grams, or 19 ounces), then e-mailed 
two pictures of the newborn as they spoke.

"Breathe, breathe," Mr. Hawthorne said. "How does he look?"

"He looks like Neanderthal Man," Mr. Otto called out from the background.

"No, he doesn't," his wife said.

"I can't say he looks exactly like our other one," Mr. Otto shouted.

"Yes, he does," his wife said.

Several days later - the Ottos will not see their 
new dog face-to-face until he is 10 weeks old, 
when they'll have him flown to the United States 
- Mrs. Otto said they were ecstatic about "having 
the essence of our Lancelot back."

"We can barely contain ourselves," said Mr. Otto, 
the chief executive of a medical-equipment 
company whose father was an early Nascar 
promoter. "We have 8 children and 11 
grandchildren and 9 dogs. Lancelot was the dog 
that was most humanlike in his behavior. He died 
last year - cancer."

Mrs. Otto said: "The only problem with dogs is 
that they have such a short life."

"Cloning means you could have the opportunity to 
have the same dog with you for your entire life," 
Mr. Otto said.