The Fall of the House of Hwang:
Reflections of a Stem Cell Enthusiast
With Dr. Hwang’s house of cards now flattened, what lessons are there for those who have seen hope and hype in the embryonic stem cell (ESC) dance.The Science Lesson. The Hwang debacle, while an embarrassment to science, is also a vindication of science. Fraud gives a temporary advantage but fraud, like murder, will out. Methods that don’t work won’t last. In this case young Korean scientists who suspected fakery pointed out the smoking gun. But if they hadn’t, the inability of other scientists to replicate the feat would have soon outed him. Like all pyramid schemes, short-run success leads to long-run failure.
The Biology Lesson. The lesson about the state of stem cell biology is that learning and then controlling the developmental steps that will turn embryonic progenitor cells into useful therapies will be a long and arduous journey. We knew that, but in the fight against right-to-life attacks, often glossed over it. Well, not the scientists themselves, but the support structure of science on which science itself rests.
The Hwang fraud has also forced us to revise the timetable for nuclear transfer cloning. Proof of principle in humans is still lacking, but excellent labs in the U.K. and the U.S. are on the case. Nuclear transfer cloning, however, is but one part of the puzzle, and one that in the immediate future is not as key as uncovering the gene and protein systems that control differentiation. Nuclear transfer will help obtain disease specific genotypical cells for studying those diseases and targeting treatment to them, but it will be some time before a real clinical need for histocompatible ESCs.
More pressing is the need to uncover the developmental signals that control differentiation. Scientists have turned human ESCs into endoderm pancreatic tissue, a key progenitor for islet cells, but there is much to be learned before clinical applications occur. If we have done the prior work, nuclear transfer cloning may at some point have clinical significance, but that’s further done the road.
The Egg Donation Lesson. The most important ethical lesson in the Hwang debacle is the spotlight now cast on egg donation practices. Human eggs are a precious commodity, and not easily obtained. Women must be willing to provide them. It is imperative that we not abuse or exploit women in the process.
This means that the rights and welfare of egg donors be protected. In the case of women going through IVF for infertility, there should be no alteration in the procedure such as increasing hormone dosages to obtain eggs for research or therapy. It also means getting free and informed consent at the time of donation.
Women who volunteer to undergo ovarian stimulation and retrieval in order to donate eggs need protection and respect. This means fully informing them of the risks, benefits, uses, and other consequences of their participation. It also means using procedures that minimize medical harm, providing treatment in the case of injury, and covering medical and work losses if injuries occur from donation. Until we have more experience, review by an independent review body, such as the ESCROs recommended by the National Academy of Science, is justified.
Dr. Hwang broke every one of these rules. Laboratory workers were pressured to donate. Outsiders were recruited without a full account of the risks and benefits of the science or what they were getting into. There was no independent review. Dr. Hwang’s people also paid egg donors, which many persons think is undesirable or per se wrong.
Money in Hwang’s program payment may have functioned in an unethical way, but even without payment the program would not passed ethical muster. Some would go further and ban compensation beyond expenses, as California and Massachusetts and the United Kingdom have done, but there are strong arguments on the other side, as I noted in an earlier guest posting.
Ah Hubris! Dr. Hwang’s drive for fame and fortune led him to lie and cheat and hurt people along the way. This is an old story, more sad than tragic, an unneeded reminder that pride and greed still work haunt the human heart. Dr. Hwang had the skill to clone a dog and the drive to fool a sophisticated international audience. He is now a monument of the unethical scientist, a negative archetype for the field.
L’affaire Hwang contains a rich lode of lessons for all touched by the ESC endeavor and the temptations it has spawned. A useful corrective for overenthusiastic proponents, it gives opponents only a short leg up. It changes nothing about the basic dynamic of ESCs—societal support within reasonable ethical limits—nor about the steepness of the climb ahead.
On the political front, the Hwang debacle should not produce any permanent set-back. Occurring before the Senate considers whether to enact the Castle-DeGrette bill overriding Bush’s limitations on federal funding of ESC research, there is sufficient time to digest the events and realize that they have no direct bearing on that issue, though no doubt opponents will try to use it to that end. A more important threat comes from the attention being paid to non-embryonic sources for ESCs. While further research in that direction should occur, the mere prospect that such alternatives may exist is not a good reason to keep federal funds from research involving stem cells derived from embryos.
Nor will it affect the battle over stem cells occurring in the several states. It has not undermined the effort to get a constitutional amendment in pro-life Missouri to protect nuclear transfer cloning nor the efforts of Michigan’s governor to repeal the ban on research cloning that Michigan adopted in 1997. The major player here is California, but its rules and funds will not be affected by Hwang’s fall. If anything, it will give added impetus to have a California be the first to successfully clone human ESCs.
[Hwang might have gotten credit as the first one there, and may have patented a technique, but would not have gotten usuable stem cells line. Some harm to egg donors in his lab or elsewhere. 20 eggs per donor, which suggests much stimulation and thus risks. Plus coercion. Plus recruiting on false grounds of who was being helped, and not a review by an ESCRO to make sure that needed.]
Hwang might have gotten a temporary advantage, but could not have maintained it for long. Maybe could have gotten one as an early founder. Would have drawn more people to him from other programs and led more women to donate than the field was ripe for. But could not have lasted.
We pay women to donate eggs for infertility treatment, and on the whole the practice has been done reasonably well. Donation for ESC research is as important. As long as full information, coverage, etc. are there, there is no reason per se why some financial compensation is not provided. However, some clear procedures or guidelines will be needed. With the National Academy and California taking the lead, the main elements of such a system are coming into focus, and should prove sufficient to guide the field for some time to come.
