FEATURE — Spring 2005

Professor Steven Teitelbaum, past president of the Federation of American Societies for Experimental Biology, says the promise of this research is that patients could use their own cells to ward off serious illnesses.

Stem Cells Hold Great Promise

In the hopes of alleviating diseases such as Alzheimer's, diabetes, and Parkinson's, University scientists urge Missouri legislators not to ban the research procedure "somatic cell nuclear transfer."

by Judy H. Watts

This is the most important issue for medical research and future patient care that I can recall in the 44 years I've been a Missourian!" says research scientist and physician Steven L. Teitelbaum, who left Brooklyn in 1960 to enroll in the Washington University School of Medicine. What Teitelbaum, the Wilma and Roswell Messing Professor of Pathology and Immunology, cares about so deeply are the vast possibilities for healing diseases like Parkinson's and diabetes—cures that could result from research on early-stage stem cells (sometimes referred to as embryonic stem cells).

Throughout the State of Missouri and beyond, scientists, research institutions, patient-advocacy groups, health-care organizations, and individuals strongly support early-stage stem-cell research. Unfortunately, a group of conservative political and religious leaders are attempting to criminalize such research in Missouri, specifically a research procedure to derive early-stage stem cells called "somatic cell nuclear transfer," or SCNT.

The basic state of stem-cell science
Separating reality from hearsay and facts from fears—and understanding what somatic cell nuclear transfer is and is not—begins with basics, and publicized terms are often misleading. Stem cells, then, are basically of two types, adult and embryonic. Both can replicate themselves in the body and differentiate into mature cells.

Adult stem cells—present in fetuses, children, and adults—repair some types of damaged tissue, and each type seems able to develop only a limited number of mature cells into cells such as blood or bone cells. Adult stem cells are not a research substitute for embryonic stem cells, Teitelbaum emphasizes; scientists must study both adult and embryonic stem cells.

Embryonic stem cells are strikingly different from adult stem cells because they are pluripotent—they can differentiate into any type of mature cell. The possibility is strong that they could replace diseased or deteriorated cells and heal different parts of the human body.

To understand SCNT, one must first understand how the process differs from the early-stage human reproductive cycle. Several days after normal fertilization occurs in human beings, and before implantation in the womb, a pinpoint-sized ball called a blastocyst forms. The structure consists of undifferentiated cells including embryonic stem cells. Once the blastocyst implants itself in the womb, its cells begin to differentiate into various organs and structures. SCNT, however, is different and has nothing to do with the process and products of conception.

What somatic cell nuclear transfer offers medical researchers is a way of generating embryonic stem cells without a sperm fertilizing an egg. (The word somatic applies to all the cells in the body with the exception of sperms and eggs, which are called germ cells.)

Teitelbaum explains the SCNT procedure (see graphic at right): "The nucleus of an unfertilized egg is replaced with the nucleus from a somatic cell, such as a skin cell, from the patient who will ultimately be transplanted with the appropriate differential cells. It becomes a structure that looks similar to—but is very different from—a blastocyst produced by a sperm and an egg. Within it are embryonic stem cells but—and this is critical—they are unable to undergo the genetic reprogramming that, after sexual reproduction, permits the development of a healthy baby. And these SCNT-generated embryonic stem cells (ESC) have nothing to do with products of abortion and nothing to do with a sperm fertilizing an egg."

Because the cells produced by SCNT contain the patient's own DNA, there is a strong possibility that they will not be rejected after transplantation, even without the use of anti-rejection medication with its severe side-effects.

Stem-cell research may promise medical breakthroughs
Scientists are enthusiastic about SCNT-based embryonic stem-cell research because it may "lead to cures for people with diseases for which there is currently no hope," says Chancellor Mark S. Wrighton. Among these afflictions that disrupt or obliterate productive and meaningful lives:
• Parkinson's disease, whose progressively worsening movement difficulties are altering the lives of a million people in the United States alone;
• Diabetes, which affects more than one-sixth of the U.S. population, including children—and can produce complications ranging from heart, vascular, and kidney disease to blindness or coma;
• Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), which causes the gradual death of motor neurons and progressive loss of all voluntary muscle movement including breathing;
• Heart attacks, strokes, Alzheimer's disease, severe spinal-cord injuries, and cancer—whose collective ravages are widely known because hundreds of millions of America's loved ones have battled them or are valiantly combating their destructive effects today.

Think what ESC research by means of nuclear transfer could mean, says Teitelbaum. "As a physician, I could NOT sit across from a patient with Parkinson's disease and say to that father or mother or neighbor: 'Investigating a promising way to save your life is just not worth using a pinpoint-sized ball of undifferentiated cells derived from an unfertilized egg and a simple skin cell.'" Instead, Teitelbaum says he'd prefer to say that medical science is investigating Parkinson's disease with promising new treatments, thanks to SCNT.

David I. Gottlieb, professor of neurobiology, is among those researching the most effective ways to encourage embryonic stem (ES) cells to generate into specific cells. In his lab, the focus is on turning ES cells into neural stem (NS) cells.

Challenges of the new science
Because ESC research is so new, understanding the fundamental processes of the biology is the first mission. "We can't get to cures until we do the science, moving forward on all possible fronts," says Teitelbaum. "Science is standing in front of 20 doors and knocking on each of them. Behind 19 you may find nothing, in spite of all your hard work—but behind the 20th you may find gold."

Just a few of the labor-intensive realities researchers face are learning the best, most efficient way to encourage ES cells to generate the specific cells needed to treat different diseases, ensuring that the new cells will not become tumors, and learning how and where to deliver the cells effectively to sites in the body.

SCNT: A fundamental force for good
A bill may go before the Missouri legislature that supports criminalizing "human cloning"; however, language embedded in this legislation would also criminalize research using SCNT. While Washington University and research institutions throughout the region emphatically oppose cloning human beings (reproductive cloning), they urge lawmakers to authorize somatic cell nuclear transfer for medical research.

"SCNT—which is aimed not at making people but at curing people—has to be separated out of the legislation," says Teitelbaum. A national leader in his profession, and past president of the Federation of American Societies for Experimental Biology, he adds: "I know of no scientist who favors reproductive cloning of people."

Two weeks before 2005, leaders of four Missouri research institutions wrote to legislators in Jefferson City in support of SCNT: Chancellor Emeritus William H. Danforth, chairman of the Donald Danforth Plant Science Center, in St. Louis; Elson Floyd, president of the University of Missouri System, in Columbia; William Neaves, president and CEO of the Stowers Institute for Medical Research, in Kansas City (and member of Washington University's Board of Trustees); and Chancellor Mark Wrighton. They pointed out that SCNT works entirely with the ordinary body cells of already-living persons and does not create new life—and urged legislators to follow other states' examples by criminalizing cloning human beings (reproductive cloning) but authorizing somatic cell nuclear transfer for medical research.

"Banning research with nuclear transfer would undermine Missouri's efforts to build a strong life sciences industry," the letter read in part. "It would damage our ability to attract and retain scientists, entrepreneurs, and life science companies. Very importantly, the medical care for Missouri's citizens would be harmed. As new treatments and cures emerge from this promising research conducted elsewhere, many of our state's citizens would not have access to cutting-edge medicine and would be forced to settle for second-class health care."

Continuing to build the region's brilliant research community will benefit not only the region but the world, Wrighton says. St. Louis is at the heart of a rapidly developing BioBelt, in which thousands of scientists in dozens of academic and other research institutions—including companies that take discoveries to the community—are working on behalf of the plant and life sciences.

The free and open inquiry so essential to scientific strides is vital to the University as well. "Banning this research would have a chilling effect on our faculty," says Wrighton. Washington University's climate of academic freedom, protected by research guidelines consistent with the laws of the state and federal government, "has been essential to our ability to recruit and retain the most talented faculty—including people not necessarily focused on stem-cell research."

"We must maintain our welcoming environment for scientists," Teitelbaum continues. "My colleagues in California, in a sense, are hoping that the bill will pass, because we have this great University—and they're looking to pick off our faculty."

At the heart of it all
"I believe in medical research," says Chancellor Emeritus Danforth. "Old cemeteries are full of the graves of babies and graves of young women, who died during or after childbirth. That is no longer true.

"During my internship at Barnes Hospital, a polio epidemic struck St. Louis. I helped put young people into iron lungs; some never came out. Others were paralyzed permanently. Today's house officers don't see such things.

"But house officers today see other serious diseases that cause suffering, pain, and premature death. I can't imagine anyone wanting to stop medical research. Of all human undertakings, medical research is one of the most noble, and moral." Danforth concludes with an admonition to encourage SCNT, not to ban something that holds such great promise for our future health and well-being.

Judy H. Watts is a free-lance writer and former editor of this magazine.

For more information, please visit the Web site for the Missouri Coalition for Lifesaving Cures: www.MissouriCures.com.