Last week, researchers from Oregon Health & Science University reported that they had created embryonic stem cells via somatic cell nuclear transfer (SCNT), with a high enough efficiency to bring the creation of patient-specific embryonic stem cell lines into the realm of the possible.

Successful medicine, though, takes more than scientific progress. And embryonic stem cells have always been the poster child for that fact.

The scientific challenges are formidable in their own right. The hope of therapeutic cloning is to produce patient-specific stem cells. That approach is by its nature more complicated than the cells now in clinical trials by companies including StemCells, Inc., Advanced Cell Technology and ReNeuron plc. (See BioWorld Insight, Nov. 12, 2012.)

And not only are such cells individualized to each patient. There are two individuals involved in generating the therapy, the patient and the egg donor. And that has consequences ranging from regulation to production.

Getting Fresh Eggs

For non-patient specific stem cells currently in clinical trials, getting source cells is a one-time issue. "Once you have them, [non-patient-specific stem] cells will replicate without limit, at least for the foreseeable future," Michael West told BioWorld Insight. West is now CEO of BioTime Inc., was a co-founder of Geron Inc. and later, the CEO of Advanced Cell Technologies, both companies that pioneered the commercial use of embryonic stem cells.

Egg donation, on the other hand, is in some ways similar to organ donation. "We worry about that in transplantation in general . . . the cells have to come from someplace." And one of the lessons of the new research was that time is of the essence. The success rate of the Oregon team literally declined by the hour if SCNT was not initiated almost immediately after eggs were retrieved from donors.

Ultimately, West does not think that getting eggs will be an insurmountable obstacle. "People will donate a kidney for a loved one," he pointed out, and egg donors will still have plenty of eggs left over after a donation. The procedure, though neither pain- nor risk-free, is also far less involved for the donor than having a kidney removed.

Additionally, eggs and patients do not need to be immunologically matched. And, unlike organ donors – but like blood and sperm donors – egg donors can be compensated. The women who donated the eggs for the current studies, which appeared in the May 15, 2013, issue of Cell, were paid $5,000 each.

The real sticking point is likely to be regulatory. Having a ready supply of eggs "doesn't get you around the regulatory issues," West said.

Clinical trials involving personalized cellular therapies are closely supervised by the FDA, because while small-molecule drugs are static, destined to have a certain efficacy and safety profile, cellular therapies intrinsically vary between patients – and that variation is magnified by having not just a different patient each time, but a different egg donor for each patient.

Such variation is also a chance for constant improvement. At the Annual Meeting of the American Association for Cancer Research in April, a Novartis scientist involved in the clinical trials for autologous engineered T cells for the treatment of leukemia noted that "our product can be improved in real time," and that the manufacturing process is constantly adjusted in response to patient data. But such real-time improvements also require ongoing close interaction with the FDA.

The agency, which in 2001 asserted its jurisdiction over "human cells used in therapy involving the transfer of genetic material by means other than the union of gamete nuclei," told BioWorld Insight that no cells created by such methods have been approved to date.

FDA spokesman Curtis Allen told BioWorld Insight that "this area of research involves many complex issues, and appropriate discussions with FDA are strongly advised . . . The need for FDA clearance for every patient would be necessary for single patient or emergency INDs. For INDs that contained the appropriate clinical protocol for multiple patients, FDA would not need to interact with a sponsor for each patient enrolled in the clinical protocol."

Two Individuals? Or Even Three?

Policy and ethics, too, will affect how the work proceeds.

One of the key findings of the study was that eggs harvested for fertility procedures are not useful for SCNT. Shoukhrat Mitalipov, the leader of the team that announced success in cloning human embryonic stem cells with high efficiency, told BioWorld Insight that "donors should not have fertility problems."

And that finding puts SCNT "on a collision course" with some people's ethics, as well as with the current policy on federal funding of such research, Josephine Johnston told BioWorld Insight.

The ethics of their use has been vigorously debated, and guidelines for embryonic stem cell research – and the federal funding for such research – have changed with the political climate. (See BioWorld Insight, Nov. 12, 2012.)

Federal funding of embryonic stem cell research has been expanded under the Obama administration, but is still limited, and under litigation, though currently, proponents of broadening stem cell funding have the upper hand in the courts. (See BioWorld Today, Aug. 27, 2012.)

But federal sources "did not and would not fund the kind of research" done by Mitalipov and his team, Johnston, a bioethicist at think tank The Hastings Center, said. The Dickey-Wicker Amendment forbids federal funding of research that could destroy or harm a human embryo.

More broadly, "many people support embryonic stem cell research only when it uses cells from discarded embryos."

She added that the realization that medical progress cannot be achieved with such discarded embryos means the decision about the ethical justifiability, or lack thereof, of such research will need to be re-thought.

Her prediction was that for many people's opinion about whether creating embryos specifically for SCNT is ethically justifiable, "it might become relevant to what's gained." Although the most extreme position is that such embryos should have the same moral standing as a baby would after birth – in essence, that there are three individuals involved in any medical procedure involving embryonic stem cells.

But the more common view is that an early stage embryo is an early human life that is not yet a person, and is not the moral equivalent of a baby. If the method can prevent significant suffering or cure fatal illnesses in full-fledged persons, many people might feel that those gains justify the sacrifice of such early human life.

Still, whether creating human life that has no chance to develop into a person for research or medical purposes is acceptable, she said, is a "deeply personal" decision, and one on which there is no full consensus on even among bioethicists.

Many prominent bioethicists feel strongly that stem cell research is not only ethically justified, but should be allowed to proceed with fewer restrictions than are currently in place. But, she added, "there are dissenters as well."