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?

Harley's next big discovery came in 1994, after he had joined Geron Corp. He and a team of scientists made the first connection between telomerase and the abnormal growth patterns of cancer cells. It goes like this: Cancer cells don't respond to normal growth signals. They grow when and where cells aren't supposed to grow. Harley likens it to a car with no steering wheel and a stuck gas pedal. The cancer cells careen all over the place. And, aggressive cancer cells are immortal, which is like the same crazy car with an endless tank of gas (this is why cancerous tumors can grow indefinitely).

So, Harley started thinking about some kind of on-off switch. If you could turn off the telomerase in cancer cells, they'd stop dividing, and therefore stop growing. Conversely, if you could turn on the telomerase in normal cells, they'd keep growing, and the body could repair itself.

But how? It would seem to require some kind of gene transfer. The scientific community was skeptical, but scientists are a skeptical bunch.

The enzyme telomerase has two known components: a protein and a regulating (RNA) component. In 1995, Harley and Geron researchers successfully cloned the RNA component of telomerase. A race to find the missing pieces began. There were about four groups of scientists around the globe working on this, and over the next two years many were close to finding the answer.

On May 9, 1997, at about 2 a.m., following years of experiments, the answer finally appeared on a computer screen at Geron's Menlo Park lab. Scientists had been refining the sequences of DNA strands again, and again, and again. And there it was: 1,132 amino acids with no gaps, or stops along the way. Yessssss! They had cloned the protein component. They had cloned the whole thing. They had found the recipe for telomerase, the key to making cells divide infinitely!

This was big. But there was more yet to do. Immediately, Harley's group and collaborators at the University of Texas, Southwest Medical Center in Dallas put the newly cloned telomerase into normal cells of skin, retina, and blood that they had in the lab. This was the final piece of the puzzle. They had to prove that Geron's cloned enzyme made cells immortal, or it wasn't worth the dish it was in.

Days went by. And then weeks. Something was happening.
The control cells -- those cells without Harley's telomerase -- were dying off. But all of the cells with telomerase were still alive.

After two months had passed, the lab was starting to buzz with excitement. True, some of the scientists remained skeptical. More time, they feared, might reveal a flaw in their discovery. Geron installed locks on all the tissue labs to prevent intentional or accidental sabotage. These cells were precious gems.

As time passed, the control cells continued to die. The cells with telomerase continued to live. The proof was getting stronger. In fact, it was becoming undeniable.

In December 1997, the journal Science accepted a paper reporting Geron's results for peer review, the first official step in claiming discovery. Telomerase had increased the life span of cells by 30 percent. In fact, some of those original cells are still growing in Geron's lab, having divided into six times the population of the normal cell.

In 1998, Geron announced to the world that it was now certain telomerase was capable of immortalizing normal cells without becoming cancerous. Geron patented the technology, and is still testing and improving the process to the point where it might be used routinely. But that's all cleanup work.

Harley and his band of scientists at Geron had figured out how to recharge cells, literally how to jump-start one of the most basic processes of growth and survival.

And that was just the beginning.

Menlo Park is not the only place where Geron-funded scientists are taking apart the body's building blocks. The company also bankrolls research at academic laboratories across the country.

Last year, Geron-backed researchers at the University of Wisconsin-Madison (led by Dr. James Thornton), and at Johns Hopkins University in Baltimore (led by Dr. John Gearhart), delivered the second of the major pieces that would become Geron's transplant technology triumvirate.

Working with embryonic tissue, the scientists successfully extracted something called human pluripotent stem cells.

In short, the pluripotent stem cells are the beginning of anything and everything in the human body. Pluripotent stem cells are "undifferentiated," meaning they exist so early in the development of the human embryo that they have not yet been assigned a job specialty. Depending on what signals a pluripotent stem cell receives later in the embryo's development, it could just as easily become skin as blood, heart as brain.

As an added bonus, it turns out that these cells are capable of endless replication.

So, in theory, a scientist could take a pluripotent stem cell and tell it to become, say, skin tissue for a patient who needs grafts, or heart tissue for a patient with a damaged heart. It's a gross simplification, but in effect doctors would be able to custom order replacement parts for their patients.

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