© 2005 Nature Publishing Group http://www.nature.com/naturebiotechnology
C O M M E N TA R Y
Guidelines for human embryonic stem cell
research
Jonathan D Moreno & Richard O Hynes
Responding to a lack of US government leadership on the conduct of human embryonic stem cell research,
a National Academies panel has proposed the creation of new institutional oversight committees.
The limited federal role in funding and monitoring research involving human embryonic
stem (hES) cells has raised concerns among the
scientific community that the field is progressing without adequate guidance. In response,
the US National Academies set up a committee, which we cochaired, to develop guidelines for the appropriate conduct of hES cell
research. The committee’s report, released in
April 2005, includes both substantive standards
for research and procedures for oversight. It
divides hES cell research into three categories:
research that does not require review beyond
current regulatory mandates, research that
requires more extensive review and research
that is not permissible at this time. We urge
the scientific community and its supporting
institutions to adopt these voluntary guidelines
in order to establish a common framework for
this important field.
The need for guidelines
As the study of hES cells accelerates worldwide,
federal funding for this research area in the
United States has been severely limited by ethical controversy. As a consequence, the normal
leadership role of the US National Institutes of
Health in supporting health-related research
and providing the oversight that comes with
federal funding has been absent. Investigation
of hES cells is being funded increasingly by
individual states and by private foundations
Jonathan D. Moreno is at the Center for
Biomedical Ethics at the University of Virginia.
Richard O. Hynes is at the Massachusetts
Institute of Technology and is a Howard
Hughes Investigator.
e-mail: [email protected]
and [email protected]
Committee co-chairs Jonathan Moreno and Richard Hynes and committee member Marcia Imbrescia at
the release of the National Academies report.
in the absence of universal rules for conduct
of the research. In most states, there are no
regulations; in some, the research is illegal,
either in whole or in part; and, in others, legislation has explicitly legalized research efforts
and even provided public funding. Thus, the
research is proceeding actively but under a
confusing patchwork of regulations. This situation is particularly inappropriate for an area
of investigation that, although offering great
promise, raises ethical issues.
In response to scientists’ concerns about the
lack of federal oversight, a committee of the
National Research Council and the Institute
of Medicine of the National Academies undertook to formulate guidelines for the appropriate
NATURE BIOTECHNOLOGY VOLUME 23 NUMBER 7 JULY 2005
conduct of hES cell research. The guidelines
were released April 26, 2005, after eight months
of deliberations, many meetings and a two-day
public workshop (http://www.nas.edu/).
The committee, composed of scientists, physicians, lawyers, ethicists, a social scientist and
a patient advocate, actively sought to solicit
a broad range of opinions from the international scientific and lay public through public
notices. Among those from whom we received
comments were stem cell biologists, bioethicists, members of the President’s Council on
Bioethics, officials of industry and patient
advocacy groups, and representatives of the US
Food and Drug Administration and the federal
Office for Human Research Protections. We
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© 2005 Nature Publishing Group http://www.nature.com/naturebiotechnology
also reviewed relevant US reports and international guidelines, policies and procedures,
including those of the United Kingdom and
Canada. Fourteen external reviewers from various disciplines provided important critiques of
the penultimate draft.
Summary of the recommendations
A key part of our recommendations is that
all hES cell research protocols be reviewed by
a new institutional panel, an embryonic stem
cell research oversight (ESCRO) committee.
Although we recognized the implications of
recommending another level of bureaucracy, we
concluded that the burden in this case was justified given the novel and controversial nature of
hES cell research and the complexities likely to
be associated with organizing its oversight.
The ESCRO committee does not replace
other research compliance bodies, such as
institutional review boards (IRBs), whose
purview is oversight of research on human
subjects, but is intended to complement and
help coordinate the involvement of IRBs and
other pertinent bodies, including animal care
and use committees, biosafety committees and
radiation safety committees. ESCRO committees should include experts in biology and
stem cell research, legal and ethical experts,
as well as representatives of the public. The
ESCRO committee will be the key point of
contact for all investigators working with hES
cells; they should register their lines with their
institution’s ESCRO committee even if their
research is limited to in vitro studies not subject
to review by existing human subjects or animal care committees. Institutions should also
establish (severally or collectively) stem cell
banks that keep careful records of all aspects
of cell culture and source and assure that all
donor consent and confidentiality rules have
been satisfied. Uniform, industry-wide standards should be adopted by each bank.
The report recommends that ESCRO committees review all proposals for research involving hES cells from all sources. These sources
include unused blastocysts stored at in vitro
fertilization clinics, blastocysts generated
explicitly for the purpose of generating hES
cells (not eligible for federal funding but legal
in several states) and blastocysts created by
nuclear transfer (again not eligible for federal
funding but legal in several states).
794
IRBs will continue to review aspects of
research that involve human subjects, such as
gamete or blastocyst donors, or patients who
are to receive stem cell therapy. A rigorous
donor consent process must be in place, and
all donors must give explicit, informed consent
for use of their materials in hES cell research.
To avoid financial conflicts of interest, no payments beyond direct expenses should be made
for gametes or blastocysts, either to the donors
or to the in vitro fertilization clinic. Researchers
may not propose that more blastocysts be created by in vitro fertilization clinics than are
intended for reproductive purposes. Only after
reproductive efforts have ceased may potential
donors be asked to consent to the research use
of leftover blastocysts. Many other protections
must also be in place for donors, including confidentiality and protection of privacy.
The guidelines rule out certain experiments.
Following a recommendation from a previous
National Academies report, nuclear transfer
must not be used in attempts to reproduce a
human being, and no human embryos used in
research should be grown in culture for longer
than 14 days or the formation of the primitive
streak. There is no scientific rationale for the
production of a human via nuclear transfer,
and the 14-day standard has been widely recognized since the UK’s Warnock Report of 1984.
Research will require the creation of chimeras—the products of mixing human and
animal cells—both for investigations of the
developmental potential of stem cells (embryonic or adult) or their derivatives and to satisfy
FDA requirements before clinical applications.
Chimeras can involve transfer of human stem
cells and their derivatives into postnatal animals
or into developing embryos. The guidelines
state that an ESCRO committee should review
any proposals to place hES cells into an animal.
Particular consideration and oversight will be
required when it is possible that hES cells could
contribute in a major, organized way to brain
structures. This is perhaps more likely in the
case of transfer into early stages such as blastocysts, and such experiments will require more
careful oversight. Chimeras should not be created if there are alternatives for achieving the
same scientific goal. No hES cells should be put
into nonhuman primate blastocysts, and no animal into which hES cells have been introduced
should be allowed to breed, to avoid the unlikely
possibility that hES cells could contribute to the
germ line in such chimeras. Finally, no animal
embryonic stem cells should be transplanted
into a human blastocyst.
Although the guidelines are directed at US
investigators and institutions, they specify that
international collaboration is permissible if the
ESCRO committee at the US institution finds
that the collaborating institution provides protections consistent with the guidelines.
Finally, our report recommends that a
national independent body be constituted
to review periodically whether the guidelines
should be updated in light of evolving public
attitudes and unforeseen advances in stem
cell science. Although a National Academies
report cannot assign such responsibilities to
the Academies, they would seem to be one
possible host of this important public oversight activity.
The road ahead
In the weeks since their publication, the guidelines have been endorsed by numerous academic and research organizations. Although
our recommendations are not legally binding,
it is our hope and expectation that all interested
parties, including investigators, their institutions, private industry and journal editors, will
voluntarily adhere to them and assist in enforcing them. For example, the guidelines could
be incorporated by reference into university
research rules and industry contracts, foundations could specify adherence to the guidelines
as a condition for awarding of grants and journal editors could require written assurance of
compliance by authors before accepting papers
for publication.
We encourage all those who may participate
in work involving hES cells to familiarize themselves with the guidelines and to commit themselves to the standards they contain. This will
establish a consistent set of rules for the ethical conduct of this important area of scientific
research and provide both a stable scientific
environment and assurance to the public that
the research is being conducted with appropriate oversight. Failure to implement a common
standard would not only make interinstitutional cooperation more difficult but would
also undermine public confidence that the
scientific community is proceeding with care
in this sensitive field.
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