breakfast of champions Finally. Generic human cells discovered.
REVISED 20 NOV 1998. Deep in your past, there was a group of cells with the amazing capacity to become any kind of human cell. Skin. Nerve. Bone. The lens in your eye. The root of your hair. You name it, and these "embryonic stem cells" could make it.

Researchers have been making embryonic stem cells from mice, hamsters and other animals for several years. In July, 1997, a researcher at the Johns Hopkins Medical Institutions announced that he had human stem cells growing in a lab dish. That's news.

  Coming on the heels of Dolly, the cloned sheep, the announcement represents another step toward a brave new world of high-tech reproduction. But while Dolly developed into a rather normal-looking, and very complete, Scottish sheep, the stem cells in gynecology and obstetrics professor John Gearhart's lab should be able to develop into any cell in the human body.

That same result surfaced for the first time in the scientific literature in November, 1998, when James A. Thomson, a University of Wisconsin-Madison developmental biologist published results in the journal Science.

The ultimate spare part.
Embryonic stem cells are found in early stages of the embryo, after the egg is fertilized and has begun dividing, but before the mass of cells attaches itself to the wall of the uterus. Eventually they differentiate into the various cell types in the body, and disappear. "The nature of embryonic stem cells," says Thomson, "is to quickly develop into other types of cells." The fact that, in nature, embryonic stem cells are ephemeral makes Thomson's achievement singular: What he's done is to capture the cells in their undifferentiated state and keep them in that state in culture. The next step, he says, is to figure out how to direct them to become specific types of cells which would allow scientists to grow an almost unlimited supply of cells for transplant and other aspects of medicine and biology.

Gearhart says, "We clearly had evidence for human stem cells. They've been able to differentiate into several tissue types in a dish." Post-doctoral fellow Michael Shamblott collaborated on the research.

Gearhart says he's confirmed the presence of hematopoietic cells -- cells that can form any blood cell -- among the descendants of the embryonic stem cells. You name it, and these embryonic stem cells could make it.Since the stem cells are the ancestors of all blood cells -- red, white and pink (just kidding) -- one of their first clinical uses could be restoring the blood system after certain cancer treatments. And since blood stem cells can form the CD-4 immune cells that are killed by HIV, the AIDS virus, doctors might be able to replace these essential disease-fighting cells for AIDS patients.

Also on the horizon is a kind of "universal" human donor cell, an in-stock item that could serve as raw material for new liver cells, say, or new spinal cord cells. These donor cells would have to be genetically engineered so they didn't form the cell-surface molecules that incite attack by the recipient's immune system. Under the best of circumstances, Gearhart's "wild guess" is that clinical experiments with stem cells are at least seven years away.

Update 18 MAY 1998
Neurons have now been identified in cultures of cells that are very similar to mouse embryonic stem cells, according to Peter Andrews. He works on the differentiation of embryonic cancer cells and on the biology of testicular germ cell tumors at the University of Sheffield in the United Kingdom. Germ cells are special cells that will become sperm or eggs in the next generation. Testicular germ cell tumors, Andrews says, are the most common cancer in young men, and their incidence has doubled or tripled in the western world over the past 50 years.

The tumor cells that formed the neurons are not embryonic stem cells, but do closely resemble them.

Speaking at a conference sponsored by the Wisconsin Regional Primate Research Center in May, 1998, Andrews explained that neurons "stand out like sore thumbs" in cell cultures derived from testicular germ cell tumors. Using antibodies, he's confirmed that these embryonic tumor cells, have differentiated into neurons. There are even signs that the neurons have some functions, but it's not known if they actually can transmit nerve signals.

A variety of other, unidentified, cell types also appear in the cell cultures, Andrews adds. "We would like to see clear muscle cells or [blood-forming] cells, but we haven't done that yet." Still, neurons are extremely desirable cells since cell transplants already have potential for treating Parkinson's and Alzheimer's diseases. In these diseases, dying neurons cause grave mental impairment and death. "A lot of people are working with embryonic stem cells [derived from mice or primates] as replacement cells," says Andrews, "but they are tumor-derived, and so may not be something you'd want to put into a patient."

The neurons can also be used to study the development of neural cells themselves, as Andrews is doing. He's looking at the signaling process by which genes direct a cell to become a neuron as opposed to, say, a toenail cell. Just one or two days after treating human tumor cells with a chemical that causes them to differentiate, he says, the cells are committed to their fate as specialist cells. No longer can they form multiple cell types.

Is it right?
If the idea of growing a made-to-order pancreatic cells seems weird, check out the far edge of stem cell technology. That's the "chimera" -- an animal that grows from an embryo in which stem cells from another animal have been inserted. That unusual creature, Gearhart says, results from two separate fertilizations -- some of its cells have one set of parents, and some another.

what a knockout!Already, stem-cell technology and this chimeric stage are used to make "knockout" mice -- research animals lacking specific genes.

But Gearhart draws the line at making human chimeras: "We would be designing people, and we wouldn't know what the results would be." Similarly, he argues against human "germ line" research -- allowing the stem cells to reproduce by forming eggs or sperm. In this sense, stem-cell research is an even greater shot in the dark than cloning. With Dolly, the clone of an adult sheep, at least researchers could reasonably know what to expect when she grew up. In stem-cell work, no adult has been seen.

(The Why Files discussed another odd hybrid -- cross-species transplants.)

Although Gearhart has presented the research at an ethical discussion at the International Congress of Developmental Biology, he's not publishing it until he can count just how many cell types emerge from the stem cell culture.

To The Why Files, stem cells sound promising. But they also sound like a Full Employment Act for medical ethicists. Sorry, Dolly, your 15 minutes of fame are up. Now you've got to share the spotlight with the ultimate spare part.

- David Tenenbaum

Related Why Files stories
Scottish sheep shocker!
Cloning ethics
Cloning update
Growing spare body parts -- naturally.

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