16 H A S T I N G S C E N T E R R E P O R T March-April 2006

Two myths about eggs figure prominently in thestory of Korea’s national origin. First there is thetale of Pak Hyeokkeose, the first ruler of Shilla,

the ancient Buddhist state that evolved into what is nowNorth and South Korea. According to legend, the sixleaders of the city-states that would eventually becomeShilla decided that they needed a king to rule over them.They gathered in the wilderness and prayed for guid-ance. Suddenly there was a flash of lightning, and on theground appeared an enormous egg. Out of this eggemerged a young boy. The leaders quickly took the childand led him to a secluded temple in the south where hewas raised to be king.

Then there is the story of Seok T’alhae, the son of theking and queen of the Wanha region. He, too, emergedfrom a giant egg. But the king’s advisors warned that thissupernatural event was a bad omen. So the king put hisson on a boat and sent him away. The boat eventuallyreached Shilla. There the boy grew up and becameShilla’s fourth ruler.

These myths provide a fitting metaphor for the recentstem cell scandal involving Dr. Woo Suk Hwang andcolleagues at Seoul National University. Like the story ofKorea’s national origin, this modern tale began with thepurported emergence of another kind of magical Koreanegg—this time human eggs transformed through the

wonder of somatic cell nuclear transfer. It was declaredthat from these special eggs sprang forth entities withenormous potential power—patient-specific pluripotenthuman stem cells that could teach scientists how to treatuncured diseases and injuries. South Korean leaders ea-gerly embraced these magic eggs and their precious con-tents. They created a safe haven to foster this research bybuilding and financing the World Stem Cell Hub inSeoul. Many other world leaders determined that thesemagic eggs were a bad omen and refused to have any-thing to do with them. Korean scientists were left withthe task of developing these unique eggs and nurturingtheir contents alone.

Like the ancient narrative, this modern stem cell storywas supposed to mark the naissance of South Korea, thistime as a world leader in biotechnology and stem cell sci-ence. Scientists with research ambitions shunned by theirown political leaders were to find a refuge for their con-troversial work in Seoul and thus help seal South Korea’snew national identity.

Unfortunately, the parallels do not end there. Like thestory of the country’s origin, the modern stem cell storyalso seems to have been built on an elaborate fiction. Atthe time of this writing, Korean investigators have foundno evidence that Hwang and colleagues ever derivedpluripotent stem cell lines from cloned human blasto-cysts, and the journal Science has editorially retractedHwang’s two landmark papers.1

The Race Ahead

As could have been predicted, the Korean stem cellscandal has provided commentators around the

world ample opportunity to remark on the variouslessons to be drawn from this case. Among researchers,however, the scandal has produced a more surprising re-sponse. After the initial shock of this shameful news hadpassed, scientists began to realize that the playing fieldfor embryonic stem cell research was far more level thanthey had believed. Emboldened by this realization, andperhaps encouraged by the Korean investigators’ reportthat the Hwang team had successfully created clonedhuman blastocysts, many scientists are now reentering

ESSAYS

Magic Eggs andthe Frontier ofStem Cell Science

B Y I N S O O H Y U N

Insoo Hyun, “Magic Eggs and the Frontier of Stem Cell Science,” HastingsCenter Report 36, no. 2 (2006): 16-19.

H A S T I N G S C E N T E R R E P O R T 17March-April 2006

the global race to forge ahead in NT-hESC research—that is,to derive human pluripotent stem cells (hESCs) from em-bryos created via somatic cell nuclear transfer (NT).2 Amongthe illustrious teams planning to pursue NT-hESC researchthis spring are researchers from the Harvard Stem Cell Insti-tute; Advanced Cell Technology; the University of California,San Francisco; the University of California, Los Angeles; theKarolinska Institute in Sweden; Newcastle University; theQueen’s Medical Research Institute at the University of Edin-burgh; and the Institute of Psychiatry, London.3 So, ratherthan dampen scientists’ enthusiasm for NT-hESC research,the Korean stem cell scandal seems to have had exactly the op-posite effect.

But while the Korean debaclehas afforded scientists in othercountries another chance to takethe lead in NT-hESC research,it has also provided a vividwarning that they will be enter-ing an area full of ethical haz-ards. For instance, it is clear thatstem cell scientists and fertilityspecialists must pull together tohelp craft practical yet ethicallyrigorous procedures for volun-tary egg donation. But they mayalso have to guard against theugly possibility of conflict anddeceit among their collabora-tors. The Korean stem cell scan-dal has served as a morality playof sorts. The East has remindedthe West of an age-old morallesson: that with every opportu-nity comes the complementarythreat of danger.

This heightened sense ofmoral danger has recharged people’s interest in institutionalsafeguards for hESC research. Important work in this area hadalready been initiated last year when the National Academiesissued guidelines for hESC research in the United States.4

Among the report’s main recommendations was that there beEmbryonic Stem Cell Research Oversight committees at allinstitutions conducting hESC research. The primary role ofan ESCRO committee would be to provide an added layer ofethical and scientific review beyond standard IRB approval forall hESC research protocols. More recently, a leading profes-sional organization of stem cell scientists—the InternationalSociety for Stem Cell Research—formed a multinational taskforce of stem cell researchers, bioethicists, and legal and poli-cy experts to draft tough ethical standards for internationalcooperation in hESC research.5 The ISSCR task force is ex-pected to complete its deliberations and present its interna-tional guidelines in June of 2006.

Bioethics at the Stem Cell Frontier

As ESCRO committees begin to materialize in institutionsaround the country—as new international guidelines are

revealed and debated in the global community—and as NT-hESC research moves forward in laboratories around theworld, bioethicists will have important work to do both local-ly and internationally. Initially, much of this work is likely tofocus on the ethics of egg procurement for stem cell research,and it is easy to see why. Many believe that egg procurementis the first and most obvious point at which NT-hESC re-search can conflict with persons’ liberty and welfare interests.

Also, the Korean stem cell scan-dal has underscored what had al-ready become a conventionalview among commentators—that egg procurement issueshang a dark ethical cloud overthe burgeoning field of NT-hESC research. As many will re-call, it was science reporters’ ini-tial suspicions about the Hwangteam’s 2004 egg donations thateventually led to shocking reve-lations of further scientific mis-conduct. In short, it was the eggsthat cracked the case.6

However, those who focustoo narrowly on the ethics of eggdonation risk ignoring otheremerging ethical issues in stemcell research. Here are three un-explored areas that will requireattention very soon.

The first of these unchartedterritories is the ethics of somat-ic cell donation. To conduct

most NT-hESC research today, scientists need two types oftissues: unfertilized eggs and adult somatic cells. While eggdonation has grabbed much of the bioethics spotlight recent-ly, somatic cell donation has gone largely ignored. This is un-fortunate because many of the ethical issues surrounding so-matic cell donation are likely to outlast the currently fashion-able controversies in egg donation. They will have this stayingpower because somatic cells are an essential ingredient in NT-hESC research. The same may not hold true for human eggs.

Stem cell scientists realize there are serious practical andethical limitations standing in the way of procuring all thehuman eggs needed to support the future of NT-hESC re-search. Many of them are seeking alternatives. One of thesepossibilities would be to develop and use artificial eggs createdfrom embryonic stem cells.7 Another alternative may be totransfer human somatic cells into nonhuman eggs to produceNT-hESC lines—not for the purposes of autologous trans-plantation, but to study targeted human diseases at the cellu-lar level. Ian Wilmut and colleagues, for example, have re-

The Korean stem cell scandal has served as a

morality play of sorts. TheEast has reminded the Westof an age-old moral lesson:that with every opportunitycomes the complementary

threat of danger.

18 H A S T I N G S C E N T E R R E P O R T March-April 2006

cently announced plans to use rabbit eggs for NT-hESC re-search to examine the progression of certain human motorneuron diseases.8 A third and more distant possibility wouldbe to learn how the cytoplasm of unfertilized eggs reprogramssomatic cell nuclei to their preembryonic state. If that mysterycan be solved, then stem cell scientists may be able to circum-vent the need for eggs entirely.

In thinking about how to protect the liberty and welfareinterests of egg donors, one ongoing ethical challenge, somehold, is ensuring that women who volunteer to donate accu-rately understand the nontherapeutic and exploratory natureof NT-hESC research, and that they weigh this understandingagainst the remote physical risks associated with egg dona-tion.9 That egg donors could bevulnerable to a kind of “thera-peutic misconception” is a valu-able point. But if this threat in-deed exists in the case of egg do-nation volunteers, then it alsoseems to apply with equal orgreater force in the case of so-matic cell donors. The crux ofthe problem is that NT-hESCresearch aims to producepluripotent stem cell lines thatare patient-specific. Such cus-tomizing is unique to thisbranch of research. Stem cellstudies that use embryos leftover from fertility treatment donot leave behind a person who isa surviving genetic source of thestem cell line. NT-hESC re-search, however, involves theparticipation of existing individ-uals who suffer from serious anduncured medical conditions. Pa-tients who volunteer to donatesomatic cells may do so in thehopes of garnering future healthbenefits either directly or deriva-tively, through downstreamtherapeutic applications of theirstem cell lines. At best, these ex-pectations can only be curbed, not eliminated. In short, thethreat of therapeutic misconception can be introducedthrough the very concept and purpose of NT-hESC research.

To expand on this last point, the possibility of future pa-tient-specific stem cell therapies complicates the ethics of so-matic cell procurement in several ways. For instance, if thera-peutic applications were ever discovered using patient-specificstem cell lines in animal models, then the question wouldnaturally arise whether one could permissibly enroll in clinicaltrials cell donors who were the genetic sources of these stemcells. Much hinges on how we now think about this hypo-thetical. On the one hand, if somatic cell donors were permit-

ted in advance to participate in future therapeutically aimedresearch utilizing their genetically matched stem cells, then ei-ther the informed consent procedure for their initial cell do-nation would have to be amended to include this possibility,or a separate informed consent procedure would have to beintroduced later specifically for therapeutic research. In eithercase, it would be very difficult to avoid introducing a thera-peutic misconception during the initial somatic cell procure-ment process for basic research. This is because the possibilityof being involved in future therapeutic studies would have tobe disclosed if it were decided from the outset that this optionshould be made available to cell donors. On the other hand,automatically barring cell donors from enrolling in future

therapeutic studies could be anoverreaction and counterpro-ductive for the later studies.

Nearly everyone hopes for aneventual therapeutic break-through in a disease studiedthrough NT-hESC research. Butif it happened, it would likelycreate a surge of hope in every-body afflicted with a medicalcondition that could, in princi-ple, be addressed by stem cellscience. This might lead to asurge of volunteers for somaticcell donation, all motivated by atherapeutic misconceptionabout their own participation inbasic science studies. (It bearsmentioning here that on just itsfirst day of accepting applica-tions for somatic cell donation,the World Stem Cell Hub re-ceived over 3,500 registrationsfrom patients all over the globe.)But therapeutic misconceptionmakes somatic cell donors forstem cell research vulnerable toexploitation.

A second and closely relatedfrontier issue for bioethical workis the very notion of a “therapeu-

tic misconception” as it relates to tissue donation for stem cellresearch. This term is used loosely in the discussion above as aplaceholder for a whole set of complex issues. Rigorous con-ceptual work is needed to unpack it and assess its usefulnessfor framing the ethical issues. What would it mean, exactly,for egg and somatic cell donors to be under a therapeutic mis-conception about their participation in NT-hESC research?

The notion of therapeutic misconception has traditionallybeen understood in the bioethics and medical literature as aresearch subject’s false belief that “every aspect of the researchproject to which he had consented was designed to benefithim directly.”10 Subjects who operate under this false belief do

The concept of a therapeutic misconceptionmay not provide the best

tool for ethical analysis, butit may serve as the gateway

to more focused debatesabout the kinds of

motivating reasons thatshould be permitted to

affect the decision to donateeggs or somatic cells.

H A S T I N G S C E N T E R R E P O R T 19March-April 2006

so in part because they do not adequately understand ran-domization or double blinding in scientific research. Evensubjects who do cognitively grasp these concepts usually havea hard time genuinely believing that researchers would notnecessarily be acting in their best interests and that there couldbe any major disadvantages to participating in the research.11

In essence, therapeutic misconception is ethically problematicbecause it can translate easily into diminished personal auton-omy and a susceptibility to exploitation.

Does this traditional understanding of the therapeutic mis-conception describe the beliefs that might motivate many po-tential tissue donors for NT-hESC research? It is difficult tosay at this point. It would be troubling, of course, if volunteersdonated their eggs or somatic cells because they were underthe illusion that researchers were ultimately out to promotedonors’ best interests. It would also be problematic if volun-teers falsely believed that there could be no personal disadvan-tage to donating their tissues for NT-hESC research. Either ofthese scenarios could fit the standard definition of a therapeu-tic misconception.

Donors might also be motivated, not by false beliefs aboutthe nature of this research, but by hopes of what the researchcould someday yield for themselves or their loved ones. In thiscase, the concept of a therapeutic misconception may not pro-vide the best tool for ethical analysis. To maintain therapeutichope in NT-hESC research is not the same as having a thera-peutic misconception. Therapeutic hope in this sense is a dif-ferent concept because it is not demonstrably false that NT-hESC research may lead to promising new medical therapies.Perhaps therapeutic hope is less problematic than a therapeu-tic misconception if personal autonomy is not diminishedwhen one acts on beliefs about the future that cannot beproved wrong.

However, even donors’ therapeutic hopes can be exploited,and it is this possibility that requires closer inspection. Un-packing further the notion of therapeutic misconception vis-à-vis NT-hESC research donors could also reveal otherstreamlined ways to frame the core ethical issues underlyingvoluntary tissue donation. Ultimately, the notion of a thera-peutic misconception may serve as the gateway to more fo-cused debates about the kinds of motivating reasons thatshould be permitted to affect the decision to donate their eggsor somatic cells.

A third frontier area for bioethics is the need for empirical,sociological research to enhance the informed consent proce-dures for both egg and somatic cell donation. These proce-dures could be much improved if we had better informationabout those who are interested in donating tissue for NT-hESC research. What are their preconceptions about stem cellresearch, and what are their motivations? What level of infor-mation do they retain throughout the course of the consentprocedure, and would a multistaged consent process improvetheir level of understanding? What are their socioeconomicbackgrounds? When NT-hESC research is conducted in dif-ferent countries, do local cultural traditions significantly im-pact people’s decisions to volunteer their tissues? Do the rele-

vant discussion points for donation volunteers vary fromcountry to country, creating the need for more culturally nu-anced consent documents?

The End of Shilla

If these suggestions are even plausible, the frontier of humanembryonic stem cell research is full of ethical as well as sci-

entific uncertainty. If all goes well, another group of scientistswill author the early chapters of a new stem cell narrative. Likethe stories of the magic Korean eggs that produced Shilla’skings and Hwang’s purported stem cells, the new tales willbegin with declarations about powerful new entities. Their be-ginnings will be the same; how will they end?

Korea’s stem cell story ended abruptly in tragedy. But Shillalasted nearly one thousand years, from 57 B.C. to 935 A.D.The Shilla people enjoyed an affluent and scholarly life untilinternal conflicts led to the suppression of religious and intel-lectual thought and the eventual decline of Shilla itself. If weare to learn a moral lesson from these Korean examples, it isthat all happy stories come to an end when unethical behaviorconverts opportunity into danger.

1. D. Kennedy, “Editorial Retraction,” Science 311 (2006): 335.2. The Seoul National University Investigation Committee stated that

Hwang and colleagues created seventy-one cloned human blastocystsfrom September 17, 2004, to November 8, 2005, with an efficiency rateof 9.99 percent. Seoul National University Investigation Committee,Final Report on Professor Woo Suk Hwang’s Research Allegations, January10, 2006, pp. 10-11 and 38-40, at http://gene.postech.ac.kr/b b s / v i e w. p h p ? i d = j o b & p a g e = 1 0 & s n 1 = & d i v p a g e = 1 & s n=off&ss=on&sc=on&select_arrange=headnum&desc=asc&no=5967.

3. E. Weise, “Cloning Race Is on Again,” USA Today, January 18, 2006; R. Highfield, “Stem Cell Researchers Plan to Create Rabbit-Human Embryos,” news.telegraph, January 13, 2006, at http://news.tele-graph.co.uk/news/main.jhtml?xml=/news/2006/01/13/woosuk13.xml.

4. National Academies, Guidelines for Human Embryonic Stem CellResearch (Washington, D.C.: The National Academies Press, 2005).

5. International Society for Stem Cell Research, “ISSCR to Launchan International Embryonic Stem Cell Research Guidelines Task Force,”at http:/www.isscr.org/press_release/ethics_tf.htm.

6. I owe this apt phrase to Antonio Regalado, science reporter for theWall Street Journal.

7. K. Hubner et al., “Derivation of Oocytes From Mouse EmbryonicStem Cells,” Science 300, 2003: 1251-56.

8. Highfield, “Stem Cell Researchers Plan to Create Rabbit-HumanEmbryos.” This technique was first reported in Y. Chen et al., “Embry-onic Stem Cells Generated by Nuclear Transfer of Human Somatic Nu-clei into Rabbit Oocytes,” Cell Research 13 (2003): 251-63.

9. D. Magnus and M. Cho, “Issues in Oocyte Donation for Stem CellResearch,” Science 308 (2005): 1747-48.

10. P.S. Appelbaum et al., “False Hopes and Best Data: Consent toResearch and the Therapeutic Misconception,” Hastings Center Report17, no. 2 (1987): at 20.

11. P.S. Appelbaum et al., “The Therapeutic Misconception: In-formed Consent in Psychiatric Research,” International Journal of Lawand Psychiatry 5 (1982): 319-29.