It starts off simple: one cell meets another cell. They make the preliminary introductions, and, taking a liking to each other, they unite and become a new cell, full of promise for the future. The cell divides, divides again, and five days later it is a hollow ball of 200 or so cells, a prodigious result from its humble beginnings of sperm and egg. It is from there that things start to get complicated.

Attached to the inside of that hollow blastocyst are 30 cells that have provoked more impassioned debate than arguably any other scientific development in recent memory. In the midst of the national conversation over these precious embryonic stem cells, one is liable to wonder how something so small ­­— smaller than the period at the end of this sentence — has come to carry so much hope, or fuel so much outrage.

Like vaccines, birth control, or genetic engineering, the march of science has yet again forced society to confront difficult issues or to ignore them at its own peril. In considering the question of conducting research on human embryonic stem cells, scientists, ethicists, legislators, religious leaders, the afflicted and the rest of the country see the need to reach a decision on what it means to be a human, and at what point something is no longer — or not yet — human.

 

Immortal Cells

In every human body there are around 200 different types of cells, all performing their own specific functions and specially equipped to do so. T-cells circulate in the blood ready to engulf microbe intruders; neurons flash electrical signals back and forth inside the brain to communicate with each other. These cells do their jobs well, but age and eventually die.

A few types of cells, however, are more versatile and able to transform themselves into a few other types of cells. These so-called adult stem cells are scattered in isolated clumps around the body — in teeth, bone marrow, umbilical cord blood and other locations.

Research on adult stem cells is currently one of the areas pursued by scientists at the University. The hope is that these adult stem cells can be coaxed to transform reliably into the types of cells that a diseased patient lacks. Controlling this differentiation is a complex matter of balancing an equation of nutrients, growth factors and environmental conditions.

Sean Morrison, an assistant professor in the Department of Internal Medicine, has seen early success in his work with hematopoietic stem cells. These cells are found in bone marrow and eventually give rise to all red and white blood cells.

“We just published a paper in the journal Cell,” Morrison said. For a time, it was the most downloaded paper on Cell’s website. “This indicates we can do stem-cell research that has an impact nationally.”

Deputy General Counsel Edward Goldman said the controversy is centered on embryonic stem cells.

“There is no ethical argument about the use of adult stem cells. The scientific argument is that they are not as useful as embryonic stem cells,” Goldman said.

It is the other variety of stem cells, those harvested from human embryos, which offer greater scientific promise and catch critical attention. Four or five days after fertilization takes place, the embryo has become a blastocyst containing about 30 embryonic stem cells. Unlike adult stem cells, these are pluripotent, meaning each one has the ability to become any of the body’s different types of cells.

“The benefit would be if you created a cell line, instead of testing potentially toxic drugs in human beings you could test them on the cells which are identical to the patient,” Goldman said. The stem cells could also be grown into replacement organs for transplantation.

Scientists are able to extract embryonic stem cells from the blastocyst and to keep them alive in the lab. These stem cells can then give rise to successive generations, forming a stem-cell line. Under the right conditions, stem cells are essentially immortal, given proper care.

The main issue at present is how to acquire these immensely powerful stem cells. One controversial method is somatic cell nuclear transfer, or “therapeutic cloning,” which transfers the nucleus from a skin cell into an egg cell, and activates it in such a way that causes it to multiply like an embryo. A group in South Korea recently announced their success in using this technique to harvest embryonic stem cells.

Another source is from the embryos stored in deep freeze at in-vitro fertilization clinics.

“Currently couples can contract for in-vitro fertilization, create fertilized eggs, store them, decide not to use them, and ask that the fertilized eggs be discarded,” said Goldman. Some couples may instead opt to donate the embryos slated for destruction to researchers.

It is from this source that 71 embryonic stem cell lines were created before the cutoff date of August 9, 2001. On that date, President Bush allowed limited federal funding for the first time to only be used for these stem-cell lines and none derived afterwards.

In a turnaround from his previous stance, Senate Majority Leader Bill Frist (R-Tenn.) recently announced his support for relaxing federal funding restrictions on embryonic stem-cell research, saying that of only 22 lines remaining many were in a deteriorated state and insufficient for research needs.

 

A felon in the lab

As the U.S. House of Representatives convened to vote on HR 810 at the end of May, passions ran high on both sides of the aisle. Detractors of the Castle-Degette legislation that would allow for increased funding of embryonic stem-cell research saw it as a sanction to destroy human life; supporters argued that these concerns were misplaced and not supporting this research would be an even graver error.

After the dust settled, the bill passed by 238 to 194, overcoming the president’s threat to veto the measure. The bill then moved on to the Senate, where it now awaits a vote after its recess ends in September.

While the national laws on stem-cell research await new developments, the situation in Michigan remains as restrictive as ever. The journal Nature reported that Michigan ranks as one of the most restrictive states in the nation for performing stem-cell research, placing it alongside Arkansas, North Dakota, and South Dakota.

“At a time when this is so scientifically promising, at a time when the state of Michigan is trying to diversify its economic base, and bioscience is one of those areas, it just seems problematic to send out the message that we are a state not favorably inclined towards this line of research,” said Allen Lichter, dean of the medical school.

Robert Kelch, executive vice president for medical affairs at the University and an outspoken advocate for stem-cell research, said what is allowed in most states is illegal in Michigan.

“The private sector can go out and fund new stem-cell lines in other states. In Michigan it’s a felony,” Kelch said.

Kelch is referring to two laws passed in Michigan in 1999 and 1977. They prohibit somatic cell nuclear transfer and research on embryos, respectively.

State Rep. Andy Meisner (D-Ferndale) recently introduced an amendment in the house that would eliminate the word “embryo” in the 1977 bill, which was originally intended to protect fetuses and newborns.

Similarly, the 1999 bill outlawed somatic cell nuclear transfer to prohibit the creation of a human clone.

“That law is not written as carefully as it could have been . . . (somatic cell nuclear transfer) could be used to create a cell line or an artificial kidney, but all of that is banned by the law,” Goldman said.

At in-vitro fertilization clinics, embryos that are carriers of genetic diseases are identified and screened out from being used by the donating couple. At that point, these diseased embryos “clearly can’t be adopted, so they could be donated to make embryonic stem-cell lines to study the diseases that they carry. That’s the sort of research that we are being prohibited from doing,” said Sue O’Shea, a professor of cell and developmental biology in the medical school.

“I personally think the legislation is too restrictive, and it’s not helping us, that’s for sure,” said Alan Saltiel, director of the Life Sciences Institute. “We are trying to formulate a response to it.”

Said O’Shea: “I’m better at educating than at lobbying.”

 

Following the money

As lawmakers trade barbs and forge compromises in the halls of government, University scientists are feeling the hurt at their lab benches.

Morrison, author of the Cell paper on hematopoietic stem cells, expresses the difficulties faced by many local researchers. “The science is hard enough. The last thing we need is to add on top of this all kinds of regulatory hurdles . . . people across the University are universally disgruntled about the extent to which it handicaps us.”

Because of the scientific techniques declared illegal in the state, certain experimental components would have to be acquired from an outside source. “If we decide to study breast cancer, we can’t . . . until someone in California or Boston provides us with the relevant stem cells,” Morrison said.

Several states are jumpstarting major efforts to raise funds to support stem-cell research. California leads the pack with a $3 billion dollar initiative to aggressively push the science over the next decade. New Jersey, Wisconsin and Illinois have also earmarked millions for the construction of dedicated new facilities to research stem cells.

“They’re recruiting vigorously all over the country,” said Kelch.

“If you’re a newly minted Ph.D interested in embryonic stem-cell research, you have a choice of going to a state that has a $3 billion dollar commitment or a state that has laws prohibiting it,” said Goldman.

Already, one stem cell scientist at the University has been lured away. “Mike Clark has already decided to go to Stanford, and that’s a loss for us and a gain for them,” said Lichter.

O’Shea reveals that University scientists “get calls all the time. One guy called me and said if I gave you five hundred thousand dollars would you move to San Diego? It’s all pie in the sky.”

O’Shea, who runs one of the first federally funded human embryonic stem-cell research centers in the nation, adds, “people who stay and work for a long time in Michigan have reasons for staying.”

“People are always thinking about moving, it’s just nonstop . . . Money is important to scientists but it’s not the only thing,” said Saltiel. “We have a fabulous scientific environment, great resources, wonderful facilities and a lot of intangibles.”

The trouble is simply that SCNT is not one of those intangibles.

Lichter said, “this work will get done, the discoveries will be made, the new treatments and new procedures will be created. It’s just a question of whether we want to watch while others do this or whether we want to take our place in the forefront.”

Political hurdles are not the only things scientists encounter, but ethical objections from both the scientific and religious communities, as well as the public.

 

Ethics Co-opted by Politics  

In a recent Harris poll, of Americans who had not “seen, heard, or read anything about the use of stem cell research.” Fifty-six percent supported it. This figure rose to 63 percent in the group that had some prior knowledge about the research.

“I think the scientists have been really remiss in educating the public about what stem cells are and where they come from. The conservative right has been really efficient in linking stem cells with abortion,” O’Shea said.

“A large number of people don’t truly understand the potential of stem cell research or the biology of it. Although I disagree with them, I respect the views of individuals who define the origin of life as the moment when a sperm enters an oocyte,” Kelch said.

Father Tom McClain, pastor of St. Mary’s student parish, holds the clearly defined views of the Catholic Church. “To get a stem cell from an embryo means killing the embryo. We believe that life begins at conception. The Catholic Church’s position is that it’s against abortion…artificial insemination, and the creation of life outside the body,” said McClain.

According to a poll conducted by Research America, of those who are opposed to embryonic stem cell research, 57% cite religious objections.

However, out of all Catholics polled, 61% supported the research. A majority of Protestants, Born-Again Christians, and other Christians polled also support the research.

Morrison said the debate over whether embryos are human life was settled decades ago.

“The objection is that embryos are special and sacred but we had that conversation twenty years ago, with in-vitro fertilization. Thousands of embryos are routinely discarded a year,” said Morrison. 

There are about 400,000 frozen embryos in the United States. While rare, some have been adopted by couples, famously called “Snowflake babies” after the Snowflakes Frozen Embryo Adoption program ran by Nightlight Christian Adoptions in Fullerton, California. Some of these families appeared with President Bush when he made his case against embryonic stem cell research on May 24.

“The children here today remind us that there is no such thing as a spare embryo. Every embryo is unique and genetically complete, like every other human being. And each of us started out our life this way. These lives are not raw material to be exploited, but gifts,” Bush said.

The scientific community has vetted a differing criterion for the start of human life.

“There is a proposed scientific definition for when human life begins: when the blastocyst develops a primitive streak, at the 14th day of development,” Goldman said. The primitive streak is the first definition of head and tail directions of the embryo.

“There is a general concern that as we go into new areas of looking at new understandings of biology and human reproduction we have some clear ethical guidelines that are in place,” McClain said.

Howard Markel, the director of the center for the history of medicine in the University’s School of Medicine, finds these safeguards already in place.

“That’s why every medical school and medical research institution has an institutional review board. The idea of the solitary researcher working away… without any interaction or supervision from other colleagues is not accurate,” Markel said.

The National Academy of Sciences has also ironed out a set of guidelines for researchers to follow. Though voluntary, it has already garnered wide consensus in the scientific community. The guidelines prohibit such things as creating human-animal hybrids, or “chimeras,” and reproductive cloning.

Markel views the current debate from a historical perspective. In 1954, the University’s department of epidemiology, in the face of great uproar, ran the field trial for Jonas Salk’s polio vaccine. Previous vaccines had failed to be fully effective, and “they were testing a vaccine on kids, and that’s very emotionally charged,” Markel said.

It turned out to be successful, and the episode is still held to be a paragon of good scientific conduct in doing sensitive research.

“Good medical research in any era… relies on scientists behaving well. We have a social contract here, with the community we live in, and the greater community that we interact with,” said Markel.

McClain posed a question to which he has not yet received a satisfactory answer: “As each new discovery comes to the fore, where is the ethical reflection?”

Goldman said, “Science moves at its own pace, and sometimes it moves quicker than law or ethics.”

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