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The regulation of hES cell research poses particularly difficult questions for legislatorsaround the world. Some countries have usedexisting regulatory frameworks to oversee hES cell research. Others, recognizing thepotential that hES cell research holds, havecreated exceptions in their existing regulatorystructures, either to accommodate and pro-mote hES cell research, or to restrict it.Yet oth-ers have still to put in place a regulatoryframework. Taken together, these responseswill play an important role in determiningwhere pioneering work will take place andwhere, consequently, investment in thatresearch will flow.

The problem at a glanceThe successful isolation of hES cells was firstannounced in November 1998 by JamesThomson and colleagues at the University ofWisconsin (Madison, WI, USA)1. The subse-quent firestorm of debate over the ethical,societal and political implications of hES cellsand embryo research in general (e.g., geneticmanipulation and reproductive cloning), andthe nature and origin of these cells, presents aunique challenge for regulators and legislatorsaround the globe.

The approach of different national legisla-tors to hES research is influenced by a combi-nation of ideology and science. For manycountries, though, a common distinction isdrawn between using excess embryos fromIVF procedures and creating new embryosexplicitly for the purposes of research (Box 1).Only a few countries—Israel, the UnitedKingdom, Belgium, Singapore and China—

permit the use of cloning techniques to createembryos for research purposes, despite thepotential for autologous transplantation usinghES cells. Others have yet to introduce legisla-tion, but seem poised to ban it, such as theUnited States. A last group, including Ireland,Germany, Austria and Italy, have in place regu-lations that permit no embryo research or der-ivation of hES cells.

In the following article, I attempt to clarifythe diverse national and international posi-tions on regulating hES cells, the extent towhich these positions are likely to change andtheir potential influence on research.

The European UnionA tremendous amount of public and policy

debate on hES cell research has taken place inthe European Union (EU) both at the nationaland the Community level. Member states have taken a variety of positions with respectto the regulation of hES cell research. In gen-eral, national policy reflects each country’shistorical experience and philosophical and religious traditions. Although no gener-alizations can be made, more liberal regula-tion of hES cell research tends to occur incountries with Protestant religious traditionswhereas Catholic countries have more restric-tive regimes. Somewhat surprising is therecent liberalization taking place in much ofthe EU, including in Catholic countries, suchas Spain and France, to permit such researchto take place.

A regulatory patchwork—human ES cell researchoversightLori P Knowles

Permissive regulations in a few regions of the world are dictating where human embryonic stem (hES) cell researchis taking place, but this could change as numerous countries are still formulating policy.

Lori P. Knowles is with the Health Law Institute, University of Alberta, Canada.e-mail: armstrongknowles@juno.com

NATURE BIOTECHNOLOGY VOLUME 22 NUMBER 2 FEBRUARY 2004 157

US President George Bush at his Crawford, Texas ranch after delivering a speech on August 9, 2001limiting US federal funding to existing hES cell lines.

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Part of the regulatory background in Eur-ope that affects the permissibility of hES cellresearch is articulated in the Convention ofthe Council of Europe on Human Rights andBiomedicine2. That convention stipulates notonly that there must be “adequate protection”for the embryos where embryo research is per-mitted, but also that embryos must not be cre-ated for the purposes of research; it alsoprohibits the “creation of a human being by

cloning.” Seventeen countries have ratified theconvention—including Denmark, Greece,Portugal, Spain, the Czech Republic, Hungaryand Slovakia. In these countries, therefore,embryos cannot be cloned or created by othermeans for hES cell research.

Embryo research policy has become one ofthe most fractious issues in the EC, given thewide variety of positions held by member stategovernments. A one-year moratorium on

European funding of embryo research proto-cols ended on December 31, 2003. In anticipa-tion of that deadline, several measures weretaken by the EU. In July 2003, the EU pavedthe way for funding research grants on hEScell research but restricted that funding to theuse of stem cells derived from IVF embryosdonated before June 27, 2002, the date theEuropean Parliament approved the SixthFramework Program for Research and Tech-nological Development. This restriction wasregarded as both too conservative and too lib-eral by various member states. In November2003, members of the European Parliamentvoted to permit public funding for stem cellresearch while prohibiting funding for the cre-ation of embryos specifically to obtain stemcells. It was widely believed that this wouldlead to a successful resolution of the standoffwith respect to the acceptability of fundingembryo research protocols.

Ultimately, however, European ministers,representing individual member states, wereunable to agree on the restrictions to apply tothe funding of embryo research. The issue wasnot, therefore, resolved before the morato-rium expired. Consequently, there will be noconcerted embryo research funding policy inthe sixth framework, requiring individualresearch protocols to be adjudicated on a case-

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Singapore

Embryo research prohibited

IVF embryos can be used for hES cell research

Embryos can be explicitly created for hES cell research and research cloning permissible

Figure 1 Global legislation in response to human embryonic stem cell research.

Box 1 Glossary

Therapeutic cloning. Nuclear transplantation of a patient’s own cells to make an oocytefrom which immune-compatible cells (especially stem cells) can be derived for transplant.Reproductive cloning. Making a full living copy of an organism; requires a surrogatemother.Research cloning. Using somatic cell nuclear transfer to produce a clonal embryo,sometimes called embryo cloning.Reprogenetic. Techniques at the intersection of reproductive medicine and genetics formanipulating gametes and embryos.Parthenogenesis. The development of an individual from an egg without fertilization.Blastocyst. A preimplantation embryo that contains a fluid-filled cavity called a blastocoel. Cleavage. The mitotic divisions of the early embryo that occur in the absence of growth todivide the embryo into many smaller nucleated cells. Inner cell mass. Cells that give rise to the embryo proper and that arise from the inner cellsof an early preimplantation embryo. Trophoblast cells. Cells that contribute to the placenta but not to the embryo itself andthat are required for an embryo to implant into the uterine wall.

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by-case basis. The uncertainty regarding fund-ing for hES cell research may discourage manyapplicants for European funding with theresult that much of the work will continue totake place in countries with a proven record ofbacking hES cell research, such as the UnitedKingdom and Sweden.

Member state regulatory responses. In gen-eral, the regulatory policies of member coun-tries of the EU currently divide along thefollowing three lines3 (Fig. 1).

In Ireland, France, Germany, Austria andItaly, interventions with embryos that are notfor the benefit of the embryo are not per-mitted, thus no embryo research or hES cellderivation is permitted, although substantialchanges to French regulations relating tohuman embryo research are in process.

In the Netherlands, Sweden, Denmark,Finland, Spain and Greece, surplus embryos

from fertility projects may be used for hES cell research. These countries generally require specific consent from the gametedonors and regulatory approval. All of thesecountries forbid the creation of embryos for research purposes, including the procure-ment of hES cells (although The DutchEmbryo Act of 2002 states that theNetherlands will revisit its policy in 2007 andincludes a fast-action clause that would permitthe law to be changed within that five-yearperiod).

Belgium and the United Kingdom areamong the few countries in the world that per-mit the use of both surplus embryos and thecreation of embryos by either fertilization orby somatic cell nuclear transfer (SCNT) forhES cell research. This latter technique is com-monly referred to as ‘therapeutic cloning’ or‘research cloning’ (Fig. 2).

Portugal and Luxemburg have no specificlegislation relating to embryo research or hES cell research, although Portugal has rati-fied the Convention of the Council of Europeon Human Rights and Biomedicine (seeabove).

It is worth noting a few details of the variousconservative and liberal regulatory responsesto get a clearer picture of the variety of res-ponses among member states and the effectthis will have on the primary venues for hEScell research in the next decade.

Conservative European responses. Even insuch countries as Ireland and Germany, inwhich all embryo research is prohibited, therehas been a lively debate over the permissibilityof hES cell research. The much-touted poten-tial of hES cells to eventually save and amelio-rate human lives has pushed some formeropponents of embryo research to revisit theirpositions.

Germany’s historical experience and thestrong Church influence on the country hasresulted in a very conservative approach toembryo research and reprogenetic practicesthat might lead to eugenics. In January 2002,despite specific legislation prohibiting embryoresearch, and after much scientific and politi-cal debate, the German government passed alaw that permits, under very strict regulation,the importation of hES cell lines derived bythat date for research protocols. In bothAustria and France, such an importation pol-icy alternative is also being discussed.

Significant administrative hurdles accom-pany the use of imported hES cell lines inGermany, including vetting, reporting andtracking, and it can reportedly take years to getthe authorization necessary to import suchcell lines. This administrative complexity mayprove an impediment to significant scientificcontribution to hES cell research in Germany.In light of the controversy over the use ofhuman embryos in scientific research, Ger-many has articulated its commitment toworking with adult stem cells and promotingthis type of research.

NATURE BIOTECHNOLOGY VOLUME 22 NUMBER 2 FEBRUARY 2004 159

Box 2 International association responses

The hES cell research debate is at the heart of deep disagreements that have thwartedattempts to pass a convention condemning and prohibiting human reproductive cloning atthe UN. At issue is the scope of any such treaty. Although there is consensus amongmember states regarding a ban on reproductive cloning, no consensus exists on theappropriate response to research cloning.

In 2001, Germany and France led a campaign to create a binding treaty banningreproductive cloning. In December of that year, the UN General Assembly passed aresolution to begin that process. Although a majority of countries supported the proposal tonegotiate a ban on reproductive cloning, which was to be followed by a discussion about atreaty on research cloning, a minority of countries, led by Spain and the United States,lobbied to ban both types of cloning in the initial treaty. The decision about the scope ofthe treaty was delayed until September 2003.

In September, the Interacademy Panel on International Issues, comprising more than 60scientific academies from every continent in the world, including the US National Academyof Sciences (Washington, DC, USA), called on the UN to adopt a ban on reproductivecloning, but to permit research cloning. A proposal to ban both types of cloning, put forth byCosta Rica and the United States, was defeated by one vote in November 2003; furtherwork on the convention was postponed for a year despite attempts by Costa Rica and theUnited States to force another vote on the resolution in December. What at one timeseemed an issue of rare consensus at the UN, the banning of reproductive cloning nowseems to have become impossibly mired in the differences between philosophical andethical viewpoints concerning hES cell research among UN members.

a b c d

Nucleartransfer

Oocyte activationand development

Culture and differentiatecells in vitro

Inner cellmass

Nucleus ofadult cell

Enucleatedoocyte Trophoblast Blastocoel

Adult cell

Figure 2 Somatic nuclear transfer for therapeutic cloning. (Reprinted with permission of J. Robertson from ref. 14).

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Ambiguities about the disposition of sur-plus IVF embryos in Spain’s 1988 assistedreproduction law resulted in tens of thousandsof frozen embryos remaining in storage. InOctober 2003, after Spain’s scientific commu-nity lobbied to get access to those embryos,Spain became the first predominately Catholiccountry to permit the use of surplus embryosfor hES cell research. The new law that amendsthe 1988 act permits hES cell research onembryos stored before the law comes intoeffect later this year4. Embryos stored after the law is officially amended must remainfrozen for the duration of the woman’s fertilelife. The new law also prohibits researchcloning and creates a national supervisorycenter, the National Center for Transplantsand Regenerative Medicine, to authorize andoversee the use of frozen embryos and hES celllines.

Defying the trend toward liberalization of embryo research policies and despite anational ethics committee opinion that theuse of excess embryos for hES cell researchwould be appropriate, Italy passed a veryrestrictive assisted reproductive tech-nology bill in mid-December 2003. The lawforbids all research on embryos (and thereforehES cell derivation), but also forbids pre-implantation diagnosis, access to fertility serv-ices for single women and cryopreservation.It does not, however, specifically address the issue of research on imported hES celllines. Some think that the Vatican’s fierceopposition to embryo research was a politi-cal factor in the passage of the bill. If the bill achieves final approval by the ItalianChamber of Deputies in January, many fertility specialists may leave the country sothey can provide the level of care they deemacceptable.

Liberal European responses. In contrast torecent Italian developments, which threaten toclose down that country’s entire embryoresearch enterprise, the United Kingdom hasquickly become known as the destination ofchoice for scientists who wish to conduct hEScell research. Despite a powerful national reg-ulatory body responsible for overseeing alluses of human embryos, the United Kingdomhas a long-standing tradition of promotingscientific freedom.

Recent amendments to the UK’s 1990Human Fertilization and Embryology Act(HFEA) permit the use of embryos for certainpurposes unrelated to reproduction. As adirect result of hES cell technology, thesechanges permit the use of embryos to investi-gate disease conditions and to develop treat-ments for diseases.

The HFEA provides the most liberalnational regulatory framework for embryoresearch to date, permitting not only the use ofsurplus IVF embryos for hES cell research, butalso the creation of embryos by cell nuclearreplacement (known elsewhere as SCNT) forthe purposes of hES cell research. Eight hEScell research protocols have been licensed. Allbut two licenses permit only the use of excessIVF embryos. The other two licenses, includ-ing one granted to the Roslin Institute(Edinburgh, UK), permit researchers to derivehES cells from IVF embryos and to useparthenogenesis to create parthenotes as asource of hES cells.

Parthenogenesis, which occurs frequently ininsects as a means of reproduction, requiresharvesting oocytes from women and thenstimulating in vitro to develop into ‘embryo-like’ entitites that scientists call ‘parthenotes’.In humans, parthenotes may lack the develop-mental potential of embryos but they can be a

source of hES cells. Parthenotes have the iden-tical DNA to the female donor; thus, theyapproximate a type of cloned embryo withoutusing ‘cloning’ techniques5.

Interestingly, the use of hES cell lines is notwithin the purview of the HFEA, nor of the2001 amendments, which only deal with theuse of human embryos, and thus only coverthe derivation of hES cell lines. As a result ofthis lacuna, the Medical Research Council(London) has established an oversight committee for the UK’s new national stem cell bank. This Stem Cell Bank SteeringCommittee will prepare guidelines in the formof a code of practice for the use of bankedstem cell lines and for regulating how they areused. The result of such governmental and sci-entific commitment to hES cell research is aregulated, yet supportive environment that isproving attractive to noted scientists fromcountries with more restrictive policies,including the United States.

European regulatory policies under review.As regulations in this area are constantly beingrevisited, it is likely that some changes to hEScell regulation will have occurred by the timethis issue of Nature Biotechnology reachesreaders. In several European countries, long-held policy positions with respect to embryoresearch are being debated and new regulatoryregimes contemplated to permit hES cellresearch to move forward with varyingdegrees of liberality. Sweden and France havepolicies currently under contemplation; inaddition, new policies are under considerationin Hungary and the Czech Republic.

In Sweden, hES cell research is thriving in arelatively liberal regulatory environment.Sweden’s National Stem Cell Bank was createdbefore the creation of a similar cell bank in theUnited Kingdom. Currently, Swedish law per-

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Table 1 Stem cell line providers with lines for shipping

Location Source Available lines (Number of shipments)

BresaGen, Athens, Georgia, USA Fresh, surplus IVF embryos hESBG01 (8), hESBG02 (3)

2 others not yet available

ES Cell International, Melbourne, Australia Frozen, surplus IVF embryos ES-01(3) ES-02 (8) ES-03 (46) ES-04 (37) ES-06 (0)

ES-05 not available yet

MizMedi Hospital, Seoul National University, Seoul, Korea Surplus IVF embryos M101 (11)

Technicon University, Haifa, Israel Frozen, surplus IVF embryos TE-03, TE-06

6 lines not available yet

University of California, San Francisco, CA, USA Fresh, surplus IVF embryos UC06 (>35)

UC01 not available

Wisconsin Alumni Research Foundation, Madison, WI, USA Surplus IVF embryos WA01 (135), WA07 (3), WA09 (22), WA14 (0)

1 line not available

Source: NIH Human Embryonic Stem Cell Registry

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mits the use of surplus IVF embryos for hEScell research; however, a review of the law isunderway. In early 2003, the Committee onGenetic Integrity published a consultationdocument that included the recommendationthat the creation of embryos by fertilization orby SCNT for research purposes not be spec-ifically prohibited. The Committee did rec-ommend that reproductive cloning beunequivocally banned.

A new Swedish law came into effect inJanuary 2004 that affects the use of humanbiological materials in biomedical research.Under this law, research involving identifiablehuman biological material will, among othercriteria, be subject to mandatory ethicsreview3.

After nearly five years of discussion, theFrench Senate passed a new version of itsbioethics law in January 2003. It has not yetpassed the Parliament. Should the law bepassed, it represents a radical shift from thepredecessor law, which prohibits all embryoresearch. The new bioethics law permitsresearch on hES cells taken from spareembryos that donors no longer plan to use.Both gamete donors must give their consentand the research must focus on achievingmajor therapeutic advances that could not beachieved by alternative means. The law createsan oversight body called the Procreation,Embryology and Human Genetics Agency.The agency is responsible for informing thoseresponsible for approving protocols as well asmonitoring and assessing embryo researchprotocols. The same law that creates theagency prohibits human reproductive cloning.

French President Jacques Chirac has beeninstrumental in trying to get the UnitedNations (UN; New York, NY, USA; Box 2) topass a universal ban on human reproductivecloning. On December 2003, the Frenchassembly passed a bill that prohibits all formsof human cloning. Although the senate willnot vote on the bill until sometime inFebruary 2004, it is likely to pass6.

Asian and Pacific Rim regulatoryresponsesUnlike European nations, differences in hEScell regulation in Asia are not so vast.Significant hES research in Asia reflects thegeneral leniency of regulatory provisions inthat part of the world. Singapore, India andChina have liberal regulatory regimes, whereasJapan and South Korea permit hES cellresearch with greater restrictions.

Singapore has no current regulatory regimegoverning stem cell research, but theRegulation of Biomedical Research Act isexpected to pass into law early this year. Thislaw reflects the supportive attitude of theSingapore government to hES cell researchand will permit the creation of embryos usingcloning technology for hES cell research whileprohibiting reproductive cloning. The actreflects the Singapore government’s belief thathES cell research has significant commercialpotential and its commitment to increasingthe scientific training of more Singaporeans7.

In South Korea, embryo research is cur-rently limited to the use of surplus IVFembryos; the creation of human embryos andboth reproductive and research cloning are

prohibited. On December 29, 2003, thenational assembly passed a bioethics andbiosafety law governing hES cell research. Aban on reproductive cloning goes into effectupon the signing of the law in early 2004 andwhen the hES cell research provisions comeinto effect the following year, they will permitthe use of surplus IVF embryos for limitedhES cell research aimed at treating serious dis-eases8. Despite restrictions on the use ofhuman embryos, cloning to create human/bovine embryo hybrids was reported in 2001,and the creation of mice containing humanstem cells was reported in March 2003 (ref. 9).The creation of such animal-human hybrids isstrictly forbidden in most other countries ofthe world.

Since 2001, Japan has permitted the use ofsurplus embryos destined for destruction tobe used as a source of human ES cells.However, both reproductive and researchcloning are prohibited under the LawConcerning Regulation Relating to HumanCloning Techniques and Other Similar Tech-niques. In addition to the law, the Minister ofEducation and Science has published guide-lines to constrain the use of human embryosin research.

In December 2003, a Japanese governmen-tal science panel called the BioethicsCommittee of the Council for Science andTechnology recommended that humanembryos be used and created for research tocombat serious hereditary diseases, provided aregulatory body is appointed to oversee suchresearch. The recommendation made in amidterm report will be followed by a final

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Table 2 Stem cell line providers with no lines for shipping

Location Source Cell lines

Cell Gene and Therapy Research Institute, Not available CHO1, CHO2

Pochon University, Seoul, Korea

Cell Therapeutics Scandinavia, Frozen, surplus IVF embryos SAO1-19

Goteborg University, Sweden

CyThera, San Diego, CA, USAa Frozen, surplus IVF embryos CY12, CY30, CY40, CY51, CY81, CY82, CY91, CY92, CY10

Geron Corporation, Menlo Park, CA, USAa All lines were derived elsewhere GE01, GE07, GE09, GE013, GE91, GE92

Karolinska Institute, Stockholm, Sweden Surplus, fresh IVF embryos KA08, KA09, KA40, KA41, KA42, KA43

Maria Biotech, Maria Infertility Hospital Frozen, surplus IVF embryos MB01, MB02, MB03

Medical Institute, Seoul, Korea (were to be discarded after 5 years)

National Center for Biological Sciences/ Frozen inner cell mass NC01, NC02, NC03

Tata Institute of Fundamental Research,

Banglador, India

Reliance Life Sciences, Mumbai, India Not available RL05, RL07, RL10, RL13, RL15, Rl20, RL21

Source: NIH Human Embryonic Stem Cell RegistryaEligibility criteria for US federal funding for research on human embryonic stem cell lines: (i) The derivation process had to have been initiated before August 9, 2001. (ii) The embryo fromwhich the line was derived must have had no possibility of developing into a human being. (iii) The cells must be derived from an embryo created for reproductive purposes. (iv) The embryowas no longer needed. (v) Informed consent was obtained from the donor. (vi) No financial inducements were used to obtain the embryo.

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report issued by mid-2005 after a publicforum is held on the issue10.

Across the East China Sea, Chinese hES cellresearch is burgeoning, partly as a result of thereturn of Western-trained Chinese scientists,who have repatriated to take advantage of thesupportive research environment for hES cellresearch. As early as 1999, Chinese scientistsused cloning techniques to create embryos as asource of hES cells. Despite recent statementsby the Minister of Health that both reproduc-tive and research cloning will be banned, todate there is no national regulation governinghES cell research. In addition, national guide-lines that were to have been finalized by theend of 2002 have not been forthcoming11.What regulation there is exists at a provinciallevel with guidelines articulated in bothShanghai and Beijing. Shanghai regulationspassed in late 2001 are modeled on the UKregulations, but also permit the creation ofembryos by SCNT using enucleated nonhu-man mammalian eggs and human somaticcells as a source of hES cells for research.

Like Singapore and China, India is support-ive of hES cell research with no specific regula-tions governing its conduct. India has severalNational Institutes of Health approved hES celllines, none of which is currently available forexport. hES cell researchers are subject only tothe constraints applied to human embryoresearch, such as a 14-day limit on the age ofhuman embryos that can be used. Althoughreproductive cloning is prohibited, cloning forresearch purposes is not covered by the sameban. Despite this permissive environment,Indian research priorities have not focused sig-

nificant energies on hES cell research untilrecently. Given India’s scientific strength andliberal regulatory environment, funding will bea crucial factor in determining whether Indiabecomes a site of significant hES cell research.

Down under, Australia recently passed twolaws relating to cloning and the use of embryosfor research. The former, the Prohibition ofHuman Cloning Act 2002, prohibited humanreproductive and research cloning defined as“intentionally creating a human embryo cloneor placing it in a woman’s body.” In addition tothis act, the Parliament passed the ResearchInvolving Human Embryos Act 2002, whichcreates an HFEA-like body and addresses onlythe use of surplus embryos for research pur-poses. hES cell research is permitted under thisact, provided the national oversight body sanc-tions the protocol.Australia has placed a mora-torium on research cloning to be revisited afterthree years. Both acts will be reviewed in 2005.

Despite these limitations on the creation ofhuman embryos for hES cell research, theAustralian government has invested signifi-cant money in setting up a central coordinat-ing center for all stem cell research at MonashUniversity (Victoria, Australia).

Middle East responsesAmong Islamic countries, Iran has taken thelead in hES cell research. In Iran and otherIslamic countries, embryo research policiesare influenced by the religious belief that fullhuman life with its attendant rights beginsonly after the ‘ensoulment’ of the fetus. This isgenerally believed by Muslim scholars to takeplace at 120 days after conception (although a

minority belief indicates ensoulment takesplace 40 days after conception)12. This fact, inconjunction with the importance articulatedin the Qur’an of preventing human sufferingand illness, means that the use of surplus IVFembryos for stem cell research is relativelyuncontroversial. What remains controversialin the Muslim world is creating embryos forthe purposes of research.

Israel has been actively involved in hES cellresearch for several years, assuming a leader-ship role in the science. Although a 1998 lawprohibits reproductive cloning, there is littlespecific regulation on stem cell research. hEScell research is currently conducted using sur-plus IVF embryos despite the recommenda-tion in August 2001 by the BioethicsCommittee of the Academy of Sciences andHumanities that research cloning should bepermitted. No cloning protocol has beenapproved yet. A review and renewal of the1998 law is under consideration.

The Israeli government is enthusiasticabout the commercial potential of stem cellresearch. And the Ministry of Industry andTrade announced in July 2003 the creation of aconsortium of hospital research laboratories,academic centers and companies engaged instem cell research in the hopes of developingcommercial products and therapies usingstem cell technology.

North American responsesPolicies in North American countries areunsettled. Existing embryo research regula-tions in Canada and the United States affectthe scope of hES cell research. AlthoughMexico, Canada and the United States havepassed bills addressing research cloning in oneof the legislative houses, no research cloninglaw has been enacted at the federal level in anyof these countries. Most likely Canada willhave legislation in place by early 2004. In theUnited States, the Bush administration is ideo-logically opposed to research on embryos orhES cells.

In Mexico, despite vigorous scientific lobby-ing and differences of opinion about theacceptability of research cloning, the Chamberof Deputies passed a bill prohibiting bothreproductive and research cloning inDecember 2003.

The Canadian regulatory regime that willeventually govern all uses of human embryoshas been a long time coming. After severalattempts to define appropriate and inappro-priate uses of human embryos, the AssistedHuman Reproduction Act passed the Houseon October 28, 2003. It was discussed in theSenate but held over for the new session ofParliament to begin in January. It is likely to

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Box 3 Patchwork within a patchwork—different US stateresponses

In the United States, significant state legislative activity has filled the federal vacuum oncloning legislation, with 69 state bills relating to human cloning introduced in 2003. Ninestates have passed laws pertaining to human cloning. Arkansas, Iowa, Michigan, NorthDakota, Louisiana, Missouri, Rhode Island, California and Virginia prohibit reproductivecloning, whereas several states have prohibitions attached to research cloning, includingArkansas, Iowa, Michigan, North Dakota and Virginia (although Virginia’s Act isambiguously drafted with respect to its definition of ‘human being’).

In addition, in the wake of President Bush’s announcement limiting federal funding forhES cell research, several states have introduced legislation aimed at encouraging localhES cell research. The first state to enact such a law was California in 2002. TheCalifornian law encourages hES and adult stem cell research, including research cloningtechniques and provides state funding for such work. This statute has become a model forother states wishing to support hES cell research. New Jersey recently passed a similarstatute that the governor signed into law in January 2004; Maryland has a statute pending;and a Massachusetts statute was recently defeated. In contrast, Louisiana and SouthDakota forbid all embryo research. Louisiana’s statute expired in July 2003; however, it islikely to be replaced with an equally conservative statute15.

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pass, although it has been very controversial.The law takes a hard line against commercialtransactions in reproductive materials, includ-ing gametes, against commercial surrogacyand prohibits human reproductive cloning.One of the most controversial provisions ofthe act has been the outlawing of cloning forresearch and therapeutic purposes. hES cellresearch will be permitted using surplusembryos from IVF. All research protocolsmust pass through a national oversight bodycalled the Assisted Human ReproductionAgency, which is modeled on the UK’sHFEA13.

In the unlikely event that the bill does notpass the Senate, the Canadian Institutes ofHealth Research articulates the only specificguidelines for hES cell research. These guide-lines apply to any hES cell research conductedin a Canadian institution or in a research facil-ity affiliated with Canadian institutions. Theguidelines limit hES cell research to the use ofsurplus IVF embryos.

South of the Canadian border, cloning billsin the United States have been plagued by con-troversy over their scope (that is, whether theycover both reproductive and therapeuticcloning), which has also blocked the passageof any federal law relating to either reproduc-tive or research cloning. In February 2003, theRepublican-backed Human Cloning Prohib-ition Act of 2003, which sought to criminalizethe nuclear transfer technology itself, passedthe House. It stalled, however in the Senate. Todate, no federal law banning human cloninghas been passed.

Federal law prohibits the use of federalfunds for embryo research; therefore, the deri-vation of hES cells cannot be performed usingfederal funds. On August 9, 2001, US PresidentGeorge W. Bush declared that federal fundscould be used to perform research on hES celllines existing at that time, but not on futurecell lines. Although researchers originallybelieved that there were 60–70 appropriate celllines, it now appears that there are between 10and 15 hES cell lines available for NIH-fundedresearch (Tables 1 and 2). The federal policyremains controversial. There is no federal pol-icy that applies to hES cell research conductedin the private sector, although a number ofstates have taken it upon themselves to pro-mote or restrict hES cell research (Box 3).

ConclusionsSix years since the announcement of the isola-tion of hES cells, countries around the globecontinue to struggle to articulate policies thatwill permit, restrict or limit hES cell researchand research cloning. Although many coun-tries permit the use of surplus IVF embryos

for hES cell research, few permit the creationof embryos for research purposes and evenfewer permit the creation of embryos forresearch purposes using cloning techniques.In the future, such countries as the UnitedKingdom and Israel who are leaders in hEScell science may be joined by other countries,such as Sweden and Singapore, where liberalpolicies are being instituted. The United Statesand Canada appear to be headed down a morerestrictive path. If research cloning becomes atool in the arsenal to fight hereditary diseasesand repair damaged tissue these regulatorypolicies will have a profound impact on wherethe advancement of therapeutic applicationsfor hES cell research takes place.

ACKNOWLEDGMENTSMy sincere thanks to Michael Khair and LoriSheremeta for their research assistance and to LeRoy Walters for his invaluable comments on an earlier draft.

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2. The Convention for the Protection of Human Rightsand Dignity of the Human Being with Regard to theApplication of Biology and Medicine, on theProhibition of Cloning Human Beings (Council ofEurope, Paris, December 1, 1998) http://conven-tions.coe.int/Treaty/EN/Treaties/Html/168.htm.

3. Matthiessen-Guyader, Line (ed.). Survey of opinionsfrom National Ethics Committees or similar bodies,public debate, and national legislation in relation tohuman embryonic stem cell research and use, vol. 1in EU Member States (European Commission, Brus-sels, September 2003) http://europa.eu.int/comm/research/biosociety/pdf/catalogue_stem_cells.pdf.

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8. South Korea to ban human cloning. The WashingtonTimes, December 30, 2003, http://washingtontimes.com/upi-breaking/20031230-121535-4048r.htm

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15. National Conference of State Legislatures. 2003report on embryonic and fetal research legislativeactivity (NCSL, Washington, DC, 2003) http://www.ncsl.org/programs/health/genetics/03embfet.htm

NATURE BIOTECHNOLOGY VOLUME 22 NUMBER 2 FEBRUARY 2004 163

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