Religion, politics, morals and stem cells

There was standing room only in the auditorium of the Anlyan Center on April 3, 2003, when actor Christopher Reeve came to speak about stem cells. Famous for playing Superman on screen, he lost the use of all four limbs after a horse riding accident in 1995 and became an activist supporting human embryonic stem cell (ESC) research. In his speech at Yale, Reeve denounced obstacles to ESC research that he believed had the potential to cure his condition.

“It’s morally irresponsible not to allow research to move forward on all of these fronts, with very strict ethical guidelines,” Reeve said. He would not live long enough to see this area of ​​research bear fruit. In October 2004, he died of cardiac arrest.

However, not everyone agreed with Reeve. Ethical, political and religious concerns have plagued stem cell research since at least 1998, when researchers in Wisconsin derived the first human ESC line. This area of ​​science may not only involve the destruction of human embryos to harvest or test stem cells, but it also raises concerns about issues such as human-animal chimeras, cloning, and donor payment or consent. Still, stem cells show promise for treating patients with amyotrophic lateral sclerosis, diabetes, Reeve-like spinal injuries, or other devastating conditions. The result: years of heated debate that resulted in no consensus, leading to a patchwork of ethical and legal statutes for the cells. In the United States, state stem cell laws range from outright prohibition to encouragement and funding. Federal law permits research, but does not fund experiments involving the creation or destruction of embryos. As promising as it is, human embryonic stem cell research in this country has progressed in spurts.

Protecting the embryo and egg donor

The year Reeve spoke, stem cell research in the United States was at half mast. Two years earlier, President George W. Bush had announced that due to concerns about the destruction of embryos, federal funds could only fund research on existing bloodlines.

Although the term stem cell encompasses ESCs as well as other types of stem cells, including adult stem cells found in fully formed organs, concerns about the destruction of embryos have dominated the ethical conversation since stem cells are first appeared in laboratories, summarizing arguments about personality and morality. embryo status. Is the common practice of recovering stem cells from a surplus fertility clinic embryo justifiable, even if that embryo is destroyed in the process? Some say yes, if the knowledge acquired could save lives.

Others, like Daniel Sulmasy, MD, Ph.D., a University of Chicago ethicist and former Franciscan friar who served on the New York State Stem Cell Ethics Board from 2007 to 2009, argue that human rights begin at conception. This view makes embryo destruction unethical and offers a moral distinction between letting embryos die naturally and destroying them in the laboratory.

The creation of new embryos – a practice that made headlines in 2014 when researchers in Oregon announced that they had created patient-specific ESCs via “therapeutic cloning” with human eggs – also troubles Sulmasy. . Anyone who believes that human life deserves respect from conception to natural death, he says, should oppose the creation of new members of humanity just to use those lives. With this in mind, he says, “No good end could justify this means.”

Since 1973 Roe vs. Wade decision that legalized abortion, such embryo-centric ideas influenced federal policy. A two-year moratorium on embryo research funding followed this case in the Supreme Court; even after the moratorium was lifted, no federal funding flowed. In 1979, an ethics advisory committee, spun out of the new Congressional National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, approved experimentation on embryos up to 14 days after conception, when the primitive nervous system appears. But despite this recommendation, Congress quickly blocked federal funding for such research. The 1995 Dickey-Wicker Amendment banned the use of federal funds to create or destroy human embryos, a prohibition that remains in effect today. In August 2000, the Clinton administration issued guidelines that would have allowed scientists to use federal funds to purchase cells extracted from unused frozen embryos. A year later, before the funding was dispersed, President Bush reversed those guidelines with his landmark announcement. Nobody liked it.

“Neither side liked Bush’s attempt to find a compromise solution,” says Stephen Latham, JD, Ph.D., director of Yale’s Interdisciplinary Center for Bioethics, who previously served on the research advisory board on Stem Cells from the State of Connecticut and who is now a member of the Yale Research Committee. Embryonic Stem Cell Research Oversight Committee (ESCRO). Those who opposed embryonic destruction thought the government’s hands were unclean, Latham recalls. Those who supported ESC research pointed out that the existing stem cell lines were of poor quality. Advocates and patients like Reeve were seething, and scientists, spurred on by the Presidential Council on Bioethics, shifted gears and sought nondestructive ways to obtain useful stem cells.

Although the federal government provides no funding for research, it has not prohibited it. Some states, like Arkansas, Indiana and the Dakotas, have banned research, while others, like California and Connecticut, have created advisory and funding committees. “We had this very heated debate, but no one ever said ‘Let’s make it illegal,'” Latham said.

Money also features in donor ethics. Sulmasy and others are concerned that stem cell research or therapy could result in coercive payments to economically disadvantaged women for their eggs – a concern that becomes more relevant following the completion of therapeutic cloning in 2014, which could lead to a number of patient-specific ESC therapies. The National Academies of Science frowns on payment to egg donors, although the New York State Ethics Board decided (after Sulmasy’s departure) to approve such payment from public research funds .

Stem cells without embryos

In 2007, there was a long-awaited game changer: stem cells that did not require the destruction of embryos. Scientists in the United States and Japan have brought adult human skin cells back to an embryonic state, creating induced pluripotent stem cells (iPS cells), a breakthrough discovery that changed the field. Nine years later, Latham says, researchers are working more with iPS cells, which are cheaper and easier to source than ESCs.

Alas, iPS cells have not eliminated ethical issues. For example, iPS experiments can use ESCs as reference comparisons, meaning the destruction of embryos.

Another line of research attempts to derive sperm and egg cells from iPS cells. In 2012, a Japanese group achieved this near-sci-fi result in mice, announcing that they had created functional sperm from mouse skin cells; the new sperm successfully fertilized an egg, which in turn gave birth to healthy offspring. Needless to say, the prospect of doing such a thing in humans is unnerving.

Additionally, iPS researchers were soon confronted with new issues of consent. A major regulatory change came in 2009, when President Barack Obama revoked Bush’s ban by executive order, reintroducing federal funding for the study of stem cells derived from excess IVF embryos (but not their derivation). ). Proponents of stem cell research hailed this step. The Obama order, however, included strict criteria for informed consent. Were the biological parents of the donated embryos fully aware of what would happen to their donation?

“Some of the lines that Bush’s NIH was willing to fund turned out not to have good consent behind them,” Latham says. New guidelines eventually banned funding for research on older cell lines derived from lab-created embryos, only admitting those derived from supplements from fertility clinics.

The first iPS cells derived from commercially available cell lines are also likely to have been created without donor consent – ​​as with Henrietta Lacks, whose famous and immortal cervical cancer cells became the cornerstone of modern biomedical research, although it never consented to their dispersal before it. died in 1951.

“There are ethical concerns about the derivation of iPS cells,” says Sandra Alfano, Pharm.D., co-chair of Yale’s ESCRO since its founding in 2006. “This idea of ​​examining the provenance and existence proper informed consent is probably the biggest part of ESCRO’s work right now.

Maurice J. Mahoney, MD, JD, the other co-chair, adds: “We are now insisting that people be asked: ‘Is it normal for a cell line from your body to end up all over the world, in many labs, and can be sold, can end up in animal species, meaning animal research continues with cells from your body? … We are pushing these issues now.

These days, according to Latham, ESCRO pays particular attention primarily to research proposals that involve mixing human ESCs with animal embryos in such a way that the animal’s nerve tissue or its sex cells could be affected. This addresses unlikely but nevertheless widespread public concerns that a mouse could be neurologically humanized in a way that could increase its suffering, or that a mouse with altered gametes could escape, reproduce and cause an unpredictable environmental effect. .

No escape from ethical issues

Yale’s ESCRO celebrates its 10th anniversary in June, long before the era of stem cell clinical trials. Dozens are currently underway, despite the thorny issues. For any discussion of ethical restrictions on stem cell research must also consider the human cost of those restrictions, which Reeve made clear in his speech at Yale. Millions of people could die, he said, as scientists search for a way to avoid the moral dilemma of ESC.

“To say that we just have to work on adult stem cells because we will get there [eventually], it’s not fair to people who have conditions like ALS,” Reeve said. “We are going to waste precious time. /yale medicine

Minnie J. Leonard