BIOLOGY: An immortal cell

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Citing the flood of stories in the media about the anticipated benefits and ethical quandaries posed by stem cell research, the National Institutes of Health complained in a recent report that "the terminology used to describe stem cells in the lay literature is often confusing or misapplied. . . . Even among biomedical researchers there is a lack of consistency in common terms to describe what stem cells are and how they behave in the research laboratory."

In order for a fertilized egg to grow into an adult human body, nature plays a kind of cell game. One master cell ultimately begets 100 trillion (that's 100,000,000,000,000), divided into more than 250 cell families that create life and sustain it day after day, replacing themselves as needed, some noticeably--as with cells of the skin, hair, bone marrow and intestines--and others subtly, as with cells in the brain.

Stem cells are the fire hydrants that stop the system from burning itself up. Paradoxically, they do not divide often and are stored throughout the body in tiny niches next to specialized cells, called nurse cells, that provide the growth factors and other chemical signals that allow stem cells to keep us alive.

"Stem cells are capable of self-renewal, which means that when they divide, they give rise to themselves, kind of like weeds," said Douglas Melton, chairman of Harvard University's department of molecular and cellular biology.

"Most other cells divide once and specialize into something like nerve or muscle cells. Stem cells first ensure their survival by replicating themselves. We biologists say that makes them immortal.

"Second, when they divide they also have the potential to specialize into other kinds of cells, so that a daughter cell can become whatever's needed--a cartilage cell, say, or a blood cell."

Human stem cells, like those of other mammals, come in three main types: totipotent, pluripotent and multipotent, each representing a stage of development.

The fertilized egg is considered a totipotent stem cell. It has total potency, the potential to become an entire individual. In the first hours and days after fertilization, this potential begins to divide into identical totipotent stem cells.

Then, four days after fertilization, the totipotent stem cells begin to specialize, forming what is called a blastocyst--a hollow ball of cells whose inner layer holds tissue-specific embryonic stem cells that will go on to form most of the cells, tissues and organs of the body.

These early stem cells are pluripotent, not totipotent. Their destinies are preprogrammed. They lack the ability to develop into an entire organism. When scientists talk about embryonic stem cells, these are the ones they mean, and these are the ones they want to study.

The only known sources of pluripotent stem cells are those isolated and cultured from early human embryos and from fetal tissue that was destined to be part of the gonads.

Adult cells from mature tissue

Adult stem cells--also called multipotent stem cells--come from mature tissues such as bone marrow, blood, the cornea and retina, skeletal muscle, dental pulp, liver, the skin, nerves, etc. Bone marrow stem cells are the most studied by scientists and have been saving patients from deadly diseases for a long time.

But these multipotent stem cells are rare in humans. They are difficult to identify, isolate and purify. They're considered less robust than embryonic stem cells, biologists say, and their immortality has yet to be proved. "They seem to have a more restricted potential," Melton said.

Moreover, adult stem cells may not exist for every cell type in the body or may be in regions, such as the brain, that are inaccessible.

Scientists hope that's not true. According to Stanford University's Irving Weissman: "There isn't one of us who doesn't wish we didn't need stem cells from embryos. But the adult stem cell story is based mostly on hope."

In stem cell research, an early-stage embryo is killed when the pluripotent stem cells are extracted, although in cellular terms, they just keep dividing. Life goes on. It merely switches locations.

"Nevertheless, we can't pretend that scientists who do stem cell research are in no way complicit in the destruction of embryos," said University of Pennsylvania ethicist Glenn McGee. "That's just wrong, a smoke-and-mirrors game played by proponents, including the NIH.

"It would be much better to take on the issue directly by making the argument that destroying embryos in this way is morally justified. If we can't make that claim, we shouldn't do this research."

Back in 1981, researchers reported that they could grow mouse embryonic stem cells in the laboratory, but it took nearly 20 years before scientists could grow human embryonic stem cells. Most of what is known about them came out of basic research (mouse embryology) and applied reproductive technologies (in vitro fertilization).

In vitro research

IVF research in this country has been strictly private. The federal government was not allowed to fund it, and IVF was left to develop "in a gangly, unsightly way, without federal supervision," writes Chicago lawyer Lori B. Andrews, director of the Institute for Science, Law and Technology at the Illinois Institute of Technology, in her 1999 book "The Clone Age."

After the birth of the first test tube baby in 1978, without federal funds to finance and monitor IVF research, insurance companies considered the technique experimental and refused to cover it. Still, IVF clinics popped up almost overnight as hospitals competed for patients to use as guinea pigs. Desperate infertile couples paid cash for doctors to learn their trade. Instead of the normal progression of research, the procedure was done on women in 1978, but not on baboons until 1979, and chimps until 1983, Andrews reported.

She writes about what she calls the doctrine of unexpected consequences. IVF generally is regarded as a boon. More than a million people worldwide were conceived in laboratory petri dishes and even today a successful pregnancy is considered a miracle.

On the other hand, multiple births used to be uncommon. Not anymore.

Multiple births

Between 1980 and 1997, twin births in the U.S. increased by 42 percent, Laura Schieve of the Centers for Disease Control and Prevention told the 10th International Congress on Twin Studies in London earlier this month. Triplet and higher multiple births increased by 370 percent.

Infertility services in the U.S. are now a $2 billion-a-year business, and specialists are the best-paid doctors, the most experienced earning more than $625,000 annually. But other scientists are warning that the developed world is facing a disastrous "epidemic" of twin and triplet births. "The incidence of multiple pregnancies in Britain is about 25 percent," said fertility expert Robert Winston. "That is a real concern."

A major cause is increased use of IVF, which often results in multiple births because doctors implant more than one embryo to make a pregnancy more likely. Another problem is that the drugs used to induce ovulation often bring on several eggs at once.

One researcher predicted that within a decade or so, if trends continue, almost one-third of all people born in some countries will be a triplet.

Most of the frozen embryos that scientists want to use for stem cell research will come from IVF, though that's not why they were created.

Abandoned embryos

Over the years, Andrews became concerned by the blatant commercialization of IVF and the downside of multiple births--too many sick children, exhausted mothers and damaged relationships with spouses.

She also found herself thinking about all the frozen embryos.

"On the one hand, human embryos are the most revered entities on earth," she writes.

"An entire social movement--the right-to-life movement--is dedicated to protesting, harassing, and even killing in order to protect their right to be born. . . . Infertile couples are willing to spend $16,000 or more per attempt to create an embryo. Researchers see embryos as a Xanadu of research possibilities, as a source of cells that can be used to treat Parkinson's disease or Alzheimer's.

"And yet, in IVF clinics across the country, there are stockpiles of abandoned embryos. How can couples `forget' they have a frozen embryo? Isn't that like a man conveniently forgetting he has a wife?"

Copyright © 2014, Los Angeles Times
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