Science of the Lambs

Buying Dolly the duplicated sheep has brought researchers at the Bay Area's Geron Corp. to the threshold of remarkable frontiers in transplants and cloning. Do we want to follow their lead?

It was a stunning discovery. Needless to say, it also has become hugely controversial.

Stem cells must come from embryos, and there are two ways to obtain them. Thornton's research team in Wisconsin took the cells from leftover, would-be embryos originally produced through clinical in vitro fertilization and later donated by the patient.

Gearhart and his team at Johns Hopkins got their stem cells from aborted fetal tissue (early stage tissue), which was also donated by the patient. Neither method is without controversy -- stem cell research is a cousin of both the abortion debate, and debate about creating embryos for research. And, it's a bit reminiscent of scenes in Brave New World.

Nonetheless, by bringing together the stem cell research with Harley's work on the telomerase enzyme, Geron's scientists were two-thirds of the way to an ability, in theory at least, to grow unlimit-ed amounts of transplantable tissue in the laboratory.

What they lacked was a way of inserting a specific person's DNA into the process so that tissue grown in the lab would match the intended recipient.

That part of the puzzle would come from a Scottish celebrity named Dolly.

Before the human stem cell discovery was even yesterday's news, Geron hit the headlines again, last month, when the corporation acquired a new pet -- Dolly, the famous cloned sheep.

Technically, Geron purchased Roslin Bio-Med Ltd. (now Geron Bio-Med Ltd.), a commercial arm of the Roslin Institute in Scotland and owner of the technology used to clone Dolly. Geron also made an agreement to fund further cloning research at Roslin for the next six years.

The technology, called nuclear transfer, works like this:
Roslin scientist Dr. Ian Wilmut and his group in Scotland figured out how to remove the genetic material from an egg cell, replace it with genetic material from virtually any body cell (like, say, a skin cell) of another being, and then make the egg grow. Of course, genetic material (DNA) is the program that makes people who they are, good, bad, or ugly, and so the egg grows into an exact copy of whomever the cell came from. To cite the irresistible Hollywood reference, it's kind of like how scientists brought back Ripley in Alien Resurrection.

The process is far from perfect. It took more than 250 tries to make one Dolly, and scientists later discovered that Dolly was physically a few years older than her birth date decreed -- Dolly's telomeres are shorter than they should be for a sheep her age. Scientists hypothesize that there are a few things at play here: Dolly was cloned from an adult sheep, whose cells would have been older to begin with. And, those cells continued to age in the laboratory while scientists worked on cloning. Both of which suggest, according to Geron, that the addition of telomerase to the cloned cells would have avoided the problem by making cells grow and divide.

Dolly was cloned in the first place as part of the Roslin Institute's research on producing genetically modified animals for agriculture. It's a couple of steps beyond pedigreed breeding -- herds cloned from high-performance or desirable animals that might be free of disease or produce high-grade meat.

But the technology the Roslin lab developed promises a wide range of uses, and dovetailed nicely with the emerg-ing transplant sciences under way at Geron.

One of the possible commercial applications for these nuclear transfers, for instance, is to produce herds of pigs genetically modified to grow certain organs for transplant into humans. For whatever reason, pigs are the closest to humans in the size and shape of their organs. Scientists are not quite envisioning a pet pig in the back yard growing its owner a new liver, however. It would be more like altering pig genes to remove things that the human body wouldn't recognize and might reject, thereby making pig organs compatible to human patients.

Telomeres and pluripotent stem cells might have been difficult for the general public to grasp, but Dolly was there for everyone to see. As quickly as photographs of Dolly popped up on front pages and news broadcasts around the world, a wave of controversy and soul-searching followed.

Almost immediately, most countries agreed to an international ban on human cloning, the prospect that most struck fear in the hearts and souls of politicians, religious leaders, and ethicists.

By the very nature of its work, Geron has found itself swept up in the debate. When the British government last week banned the cloning of human embryos for scientific research, reporters called Geron for comment.

But Geron insists it is not trying to make people. The real value of the nuclear transfer technology Geron purchased, in the human context, is to figure out how to reprogram cells so that they might grow into perfectly matched replacement tissue and organs -- like ordering a particular part for a specific make and model car. The nuclear transfer technology makes the promise of the telomerase and stem cell discoveries even greater.

The stem cell technology allows scientists to make cells and grow tissue in the laboratory. Telomerase makes those cells live on and continue to divide indefinitely, without becoming cancerous or dying on the job. Finally, with the addition of the cloning technology, Geron scientists hope that they will be able to make their lab-grown tissue a perfect match, since that tissue would be grown from a cloned cell. The body would not likely reject a graft or transplant if it were a genetic match.

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