Covering stem cells: Background on science, politics and global competition

By Terri Somers, San Diego Union-Tribune

Stem cells are so hot right now, and so promising to scientists and patient advocates, because they are the seeds of all other cells in the body. They can become bone, blood and neurons, leading many to hope they may one day be used to create new and healthy cells to replace those destroyed by disease.

Such miraculous cures are likely a decade away, if they will ever exist at all. More likely short-term discoveries will be tools that help scientists test new drugs, or learn about the progression of disease, by using stem cells as their test subject rather than humans or animals.

There are two general types of stem cells: adult stem cells and embryonic stem cells.

Embryonic stem cells, specifically those extracted, or "derived", from human embryos are currently at the center of the most controversy and hype because of their ability to turn into the more than 200 cell types in the human body.

These cells are found in the embryo just days after fertilization. At this stage, known as the blastocyst stage, the embryo is a cluster of 100 to 200 cells and does not yet have any signs of a nervous system or any other organs. It looks like a tiny gelatinous ball that contains a small brownish cluster of cells – the stem cells.

The process used to derive and grow embryonic stem cells in a Petri dish was patented in 1998 by James Thomson, a researcher in veterinary sciences at the University of Wisconsin. The three patents now held by the University gives it commercialization arm, known as the Wisconsin Alumni Research Foundation, or WARF, control over all human embryonic stem cells used within the United States. That patent is being challenged for a number of reasons, which we'll get to later.

The hope, and the basis for much of the hype around embryonic stem cells, is that they may one day be used to cure diseases like diabetes and Parkinson's by allowing for the creation and implantation of new insulin-producing pancreas cells or new neurons.

However, there is still tons of work to be done before the scientists can actually do all that. For instance, researchers still do not fully understand the mechanisms that make these cells turn into the many different cell types, nor what keeps them from multiplying too much and becoming tumors.

Meanwhile, the science has several political and moral roadblocks to overcome.

Removing stem cells from an embryo destroys that embryo, which some people believe is already a life. And there-in lies the controversy with embryonic stem cells.

The most common defense of embryo destruction is that they are not yet a person. The embryo only has the potential to become a human being if it is implanted into a uterus. Much of the human embryonic stem cell research being done right now involves embryos that were created during the in-vitro fertilization process, and are no longer needed by people trying to start a family. If not used for procreation, many of these cells are thrown out like other medical waste.

ADULT STEM CELLS

Adult stem cells, unlike embryonic stem cells, are pre-programmed to become a certain type of cell, such as bone, blood or tissue. They exist throughout our lives in many different areas of the body, including the blood, brain, heart, bone marrow, umbilical cord and even baby teeth. These cells are fountains of regeneration that allow cells throughout the body to die off and be replaced.

Stem cells found in the fetus and umbilical cord blood are considered adult stem cells, because they have already passed the embryonic stage and are in some way programmed to become a certain cell.

Knowledge of adult stem cells and their regenerative powers is about 30 years old, beginning with the first bone-marrow transplants. But broader research has really heated up in the past decade.

U.S. POLICY

Politics and religion have led to the creation of confusing stem cell policies within the United States.

President George W. Bush, like many Americans, believes that human embryos are lives that should be protected. On Aug. 9, 2001, Bush issued an executive order saying that federal funding would not be used for the further destruction of embryos to create new stem cell lines. Grants from the National Institutes of Health could only be used for research on human embryonic stem cells created before that day.

This order did not affect adult stem cell research in any way. But until that point, the United States had no policy on embryonic stem cells. Bush's edict meant that from this point forward, embryonic stem cell research would be treated differently than adult stem cell research.

At first, scientists were relieved because Bush's order did not ban embryonic stem cell research. And Bush said there were more than 70 different stem cell lines in existence and eligible for federal funding.

Scientists, however, have since found that there are fewer than 20 viable embryonic stem cell lines eligible for federal funding. None of them can ever be the basis of therapies in humans, according to researchers, because they have been contaminated with mouse cells. Scientists also have found that the lines are changing as they get older, and become harder to work with and coax to thrive.

Many scientists have accepted the limitations – at least for now – after determining that there is plenty of basic research they can do on the approved lines, such as trying to determine what make the cells differentiate into various cell types, or even how to grow them more efficiently in petri dishes.

However, many scientists want the freedom to work on unapproved stem cell lines. New lines offer scientists broader genetic diversity in cells, to help them determine how specific diseases occur and progress in different people. Diversity also will be needed if the cells are going to eventually be used for testing how different people will respond to novel therapies.

Many scientists said Bush's order not not specific in how it was to be implemented. That left the National Institutes of Health to figure out how to carry out the policy, creating a culture of chaos and fear, said Mahendra Rao, formerly the head of the embryonic stem cell program at the NIH's Institute on Aging. Rao has since left his coveted federal job to run the embryonic stem cell program at Invitrogen, an international biotechnology company which has labs in Europe and Asia, where scientists can work on embryonic stem cells unfettered by U.S. policy.

Scientists in the United States operate under the assumption that they cannot do any embryonic stem cell work on lines not approved for federal funding in buildings that are paid for even in part by federal grants, nor on equipment purchased with federal dollars.

Some of the bureaucratic nightmares created by the policy include the need for two sets of equipment – the microscopes and expensive cell sorters that were paid for at least in part with federal funding, and those bought wholly with state or private money, on which they can use all stem cell lines. Most labs have had to create a system in which they mark the equipment with stickers, to remind them of who paid for it.

The policy has required scientists to spend more time trying to raise money from state grant sources and private sources, which include organizations such as the Juvenile Diabetes Research Foundation, the Gates Foundation and the Howard Hughes Institute.

STATE INITIATIVES

The outcry from scientists that federal policy has stymied their research prompted a quick reaction from politically powerful patient advocacy groups. Together, scientists and patient advocates created a grass-roots movement that has made stem cell research a hot button political issue and fueled a number of state initiatives.

California was in the forefront of this movement. In 2003, a group of scientists, patient advocates and politicians set out to persuade state voters that they should fund human embryonic stem cell research because it offered the potential of new therapies that would ease human suffering while also cutting health care costs.

Such discoveries could create more jobs in the biotech sector, an industry in which California already holds 50 percent of the world's jobs, according to those campaigning for what became known as Proposition 71.

In November 2004, by a 17 percent margin, California voters approved the bond measure that would pour $3 billion into stem cell research over the next decade, with preference going to human embryonic stem cell research. In the end, Californians will pay $6 billion to pay back the bond debt.

That level of investment is something entire countries cannot match. It prompted politicians and patient advocates in several other states, including New Jersey, Maryland and Connecticut, to propose their own initiative.

MEANWHILE, IN THE REST OF THE WORLD

The United States has been the global leader in the life sciences industry. That may not be true when it comes to stem cell research, Countries around the world see the moral debate in the United States an creating an opportunity to get a head start, or at least make in-roads into an industry from which they might be shut out.

The United Kingdom is widely considered to be one the leaders in human embryonic stem cell research. Singapore has poured millions into all stem cell research, particularly embryonic stem cell research. China, Japan, the Netherlands, Sweden, Australia and even Iran are pushing ahead with all stem cell research.

WARF

Researchers outside the United States have another advantage – they are not bound by patent restrictions on human embryonic stem cell research.

The patents held by the University of Wisconsin Alumni Research Foundation extend to anyone doing research using human embryonic stem cells. U.S.-based scientists claim WARF seeks licensing fees and restrictions that are just too limiting to their work, and make it unattractive for companies to want to get involved in anything involving embryonic stem cells.

In January, WARF announced that it would be easing some of its licensing policies, theoretically making it easier for researchers at nonprofit institutes to work with human embryonic stem cells.

Although greeted with excitement by researchers, the policy changes do not erase all concerns with the patent.

Two taxpayer advocacy groups – The Foundation for Taxpayer and Consumer Rights in Santa Monica and the New York-based Public Patent Foundation – challenged the validity of the patents. Also joining in the challenge is Jeanne Loring, a stem cell researcher at the Burnham Institute in La Jolla, Calif.

They claim that the patent never should have been issued, because the research it covers is not unique.

In March, the U.S. Patent and Trademark Office issued a preliminary rejection of WARF's patents. On May 31, 2007, WARF formally challenged the decision.

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Note: At the time this piece was written, Terri Somers was a biotechnology writer for the San Diego Union-Tribune. She has since taken a position as the director of communications for BIOCOM , an association for the Southern California life science community.