What Stem Cell Researchers Talk About When They Talk About Ethics

This year marks an anniversary that in all probability flew under your radar: The iPSC is 10-years-old.

Great! you say. What's that, some sort of mobile fantasy sports league?

Nooo. Would you guess induced pluripotent stem cells? They're the product of a revolution in stem cell research that helped stem the controversy that was roiling the entire field.

Prior to the development of iPSCs, stem cells were derived primarily from eggs fertilized in clinics in vitro that were donated for research purposes. To some, such as President George W. Bush, this was tantamount to abortion. In 2001 he banned federal funding for research on newly created human embryonic stem cell lines. (President Barack Obama lifted that ban in 2009.)

But iPSCs are normal cells, such as skin or blood cells, which have been tinkered with and reprogrammed to revert to an embryonic-like state. They are then capable of reproducing as stem cells or developing into other types of human cells (pluripotent), such as liver, heart, pancreatic or nerve cells.

So the ability to derive a stem cell without using human embryonic tissue changed the debate about stem cell research ethics.

Plenty of Issues

But there are still plenty of hot-button topics in the field.

At a recent gathering in Berkeley to celebrate “10 Years of iPSCs,” a panel of researchers and leaders kicked off the ethics discussion with comments on how to make sure researchers get proper permissions from human subjects who sign up for clinical trials. Some members of the public might be surprised what a controversial topic “informed consent” can be.

“Everyone wants to avoid a HeLa situation,” said Christine Mummery, of the Leiden University Medical Centre in the Netherlands, referring to the oldest and most commonly used cell line in research.

HeLa cells were taken, without permission, from Henrietta Lacks, a patient who died of cervical cancer in 1951. For reasons no one knows, her cells were the first that could grow “immortally” in a lab, without dying after a few days. Her cells helped test Jonas Salk’s polio vaccine, have been used to research AIDS, cancer, toxic substances, gene mapping, stem cells and much more.

Yet the absence of any consent whatsoever caused immense distress to the Lacks family, once they learned of the appropriation of Henrietta's cells.

“The family has been through a lot with HeLa: they didn’t learn of the cells until 20 years after Lacks’s death, when scientists began using her children in research without their knowledge,” wrote Rebecca Skloot, author of "The Immortal Life of Henrietta Lacks," in the New York Times. "Later their medical records were released to the press and published without consent." (Skloot makes an appearance in a rap ballad about the HeLa cells and the Lacks family, written and performed by Oakland 7th and 8th graders on YouTube this month.)

Adding insult to injury, researchers in 2013 published the HeLa genome without family consent. (This was not illegal but, in the views of modern medical ethics, extremely dicey.)

Panelist Hank Greely, a bioethicist at Stanford University, advised the gathered researchers, “You do not want to be in the position where someone says, ‘I didn't know you were going to do that. I would never agree to that.’

“Not so much for the legal reasons, though those can be significant," he said. "More because of the political fallout that can come to you and your institution. It could also do damage to the whole stem cell enterprise.”

George Daley, of the Children’s Hospital Boston and Harvard Medical School, pointed the audience toward recently revised guidelines from the International Society for Stem Cell Research, which offers templates for informed consent forms.  These include language like this:

Donating your _____ cells for this research project is completely voluntary.  You have the right to agree or to refuse to provide your _____ cells for this project.  The quality of your current or future medical care and your relationship with [name(s) of institution(s)] will NOT change in any way whether you agree or refuse to provide any cells for this research project.

The Issue of Money

“What happens if someone has a drug based on their genes or cells?” the moderator asked.

“That doesn't happen very often,” said Greely. “Most of the time discoveries are the results of work with tens of thousands or more people.”

But, he conceded, every once in a while a patient comes along with unusual cells or genes that can be the basis for a drug. In that case, he said, a researcher must first and foremost follow whatever they said they’d do in the consent forms.

“But even if you didn't promise them anything in the consent process,” he said, “if someone is making lots of money,  I think frankly it’s a good idea to try to return something.” 

He added that this probably doesn't mean offering royalties, which could foster overblown hopes for study participants. Greely likened it to hyping lottery tickets with very bad odds. Instead, he recommends thinking about a person's community, perhaps donating to causes dear to them. Even simple recognition, he says, is important.

“I was involved in the HeLa resolution a few years ago,” he said,  “and the Lacks descendants are really quite proud and pleased that their mother, grandmother and great grandmother is being remembered ... and that they are consulted on various things.”

Continuing on the topic of money, the moderator asked what panelists thought about the ethics of paying tissue donors?

On this, the panel seemed united, “As long as it’s a reasonable reimbursement for the pain and suffering, I think it’s hard to make a case against it,” offered Lorenz Studer, of the Memorial Sloan Kettering Cancer Center. If the amount offered is so high that it becomes an “undue inducement,” said Greely, then it’s a problem.

“Many patients are willing to pay for a treatment that’s unproven. What do you think about the ethics of patients paying to be in a trial?” asked the moderator, acknowledging that many people with serious diseases are desperate to be involved in the latest research and that clinical research is extraordinarily expensive to fund.

No, was the general consensus.

That means people in a control group would be paying for a placebo, Greely noted, and someone desperate to be in a trial might not be making a level-headed decision.

“The simple fact that they’re willing to pay corrupts the informed consent process," he said. "And there is a social justice aspect -- if someone can pay for a trial that’s not an equal distribution of good.”

Someone from the audience chimed in with a question that once would have been relegated to the realm of science fiction: “What are the ethics of designing organs?”

“Think about this with a heart,” said Deepak Srivastava of the Gladstone Institutes and University of California, San Francisco. “It’s just a pump. I think going forward that we should remove the constraints of the design. What we have may or may not be the best thing in evolution.”

But, said Greely, “Many people would be viscerally upset about the idea of changing ourselves, changing our species." So scientists should temper their desire to move quickly.

“If there is one thing I've learned from being around biology for 25 years, it’s that biology is not the same as design," Greely said. "Biology is really complicated! Engineers who design something expect it to work. But if you put something [designed] into an organism, the chances that something odd will happen are extremely high. You have to be extremely careful to avoid making things worse.”