By David Cyranoski
For someone who had just emerged from a 40-month trial, Byeong-Chun Lee seemed remarkably energetic. "He's pigs; I'm dogs," said the Seoul National University cloning specialist with a smile, distinguishing his presentation from his junior researcher's, which was to follow.
Lee, who was speaking at the Brain Science Institute in Wako, Japan, on 29 October, is Woo Suk Hwang's former student and collaborator, but, unlike Hwang, Lee has maintained his university position. He is known as the force behind Snuppy, the world's first cloned dog1. It was the one major paper from the Hwang laboratory that was not dismissed as fraud in January 2006 (see 'Verdict: Hwang's human stem cells were all fakes').
In May 2006, Lee was charged with embezzlement and fraud for his role in acquiring and using funds during the scandal. On 29 October 2009, when Hwang was handed a suspended prison sentence, Lee, like four others involved in the case, was ordered to pay a fine. The amount of the fine will be decided this month.
But while the trial rolled on, Lee created an impressive list of cloned and transgenic canines. Among them were three female afghan hounds (Bona, Hope and Peace, who Lee calls "Snuppy's girlfriends", though the 10 puppies that Bona and Hope produced with Snuppy, which prove that clone couples can have healthy offspring, were all through artificial insemination); three male wolves using post-mortem cells ("to show that it will be possible to save endangered species, like the wolf"); beagles (because "the dog is the best choice for human disease modelling"); and the first transgenic dog (a beagle, known as Ruby Puppy, or Ruppy, that has red fluorescent protein that makes its nose, paw pads and claws red, even to the visible eye). Lee's team also produced seven golden retrievers -- clones of Korea's best drug-sniffing dog.
"Dogs can communicate and obey," says Lee. "That's why I focus on them."
The team's cloning efficiency has jumped from 1 live clone from 1,195 eggs when they made Snuppy to around 3 per 100 eggs now.
"To be able to produce that many animals, and that many varieties, in such a short time is a tremendous accomplishment," says mouse cloning pioneer Teruhiko Wakayama of the RIKEN Center for Developmental Biology in Kobe, Japan.
Man's best friend
Lee hopes that dogs, which are already used as a model for cardiovascular and other disorders, will become more widely used through cloning and transgenics.
But Wakayama wonders whether dogs will ever catch on as model animals because they are still relatively difficult to clone and carry weighty ethical resistance. "In Japan, at least, it won't happen. It's unfortunate that these great results won't contribute to animal cloning overall."
Alan Colman, who worked on the team that cloned Dolly the sheep, is similarly impressed with the team's productivity, but also sceptical: "For some diseases dogs provide the best animal model for the human disease." But the use of cloned dogs or transgenic dogs could be "somewhat problematic due to the prime place of the dog in human affections," says Colman, now at the A *STAR Institute of Medical Biology in Singapore.
Still, Lee's cloned and transgenic dogs are piquing interest. He is collaborating with both the US National Institute of Allergy and Infectious Diseases to study chronic granulomatous disease, a rare genetic white blood cell disorder, and the University of South Carolina to study Alzheimer's disease.
Brain Science Institute behavioural geneticist Shigeyoshi Itohara is most excited about what the clones could reveal about the function of the brain. "With the differences between species in disposition and cognition, dogs are tremendously valuable to basic genetic studies of higher brain order. By getting rid of the genetic variation among individuals within a species, cloned dogs will significantly raise the value of this data and make a revolutionary contribution to neuroscience." Lee so far has no such behavioural studies underway but is hoping a collaborator will come along.
But as Lee tries to prove the practical value of his animal cloning, he faces fierce competition from his former mentor. In a laboratory funded with private money on the outskirts of Seoul, Hwang is carrying out similar research.
Both laboratories are working on transgenic pigs that can produce tissues for transplant into humans. "What we are doing is really, really similar," says Lee.
The two laboratories are still the only two to clone dogs. Lee has cloned dogs with RNL Bio, a Seoul-based company spun out from Seoul National University and based on the technology developed by Lee and Hwang. Hwang has cloned dogs for Mill Valley, California-based BioArts.
The two companies have been tied up in legal wrangles with each other. BioArts claims that a license it bought in May 2008 from Austin-based Start Licensing, which owns the patents covering the techniques used to clone Dolly the sheep, gives it exclusive rights to clone dogs as well as cats and endangered species. At BioArts' urging, Start Licensing sued RNL for infringement. But in September, with that suit still underway, BioArts withdrew its dog-cloning services.
RNL also claims exclusive dog-cloning rights, based on a license it purchased in June 2008 from Seoul National University. In a separate trial in South Korea, RNL tried to prevent Hwang from cloning dogs by enforcing its patents from Seoul National University. Hwang persuaded the court that tweaks he had made to the cloning procedure constituted a different method, and in August 2009 the court rejected RNL's claim.
Cloning techniques will need to improve if they are to be commercially successful. With the backing of his university position, Lee thinks his team will beat Hwang. "[We] can get the best brains," he says.