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www.sciencemag.org/cgi/content/full/315/5812/603/DC1
Supporting Online Material for
The ISSCR Guidelines for Human Embryonic Stem Cell Research
George Q. Daley,* Lars Ahrlund-Richter, Jonathan M. Auerbach, Nissim Benvenisty,
R. Alta Charo, Grace Chen, Hong-kui Deng, Lawrence S. Goldstein, Kathy L. Hudson, Insoo Hyun, Sung Chull Junn, Jane Love, Eng Hin Lee, Anne McLaren, Christine L.
Mummery, Norio Nakatsuji, Catherine Racowsky, Heather Rooke, Janet Rossant, Hans R. Schöler, Jan Helge Solbakk, Patrick Taylor, Alan O. Trounson, Irving L.
Weissman, Ian Wilmut, John Yu, Laurie Zoloth
*To whom correspondence should be addressed. E-mail:
Published 2 February 2007, Science 315, 603 (2007) DOI: 10.1126/science.1139337
This PDF file includes
Author contact information Conflicts of interest ISSCR Web page links for ISSCR Guidelines and supporting documents The ISSCR Guidelines for the Conduct of Human Embryonic Stem Cell Research Sample consent forms for procurement of human biological research materials for stem cell research Sample Material Transfer Agreement (MTA)
Supplementary Online Materials The ISSCR Guidelines for Human Embryonic Stem Cell Research Daley et al., 2007 1. Author contact information (ii) 2. Conflicts of interest (v) 3. ISSCR webpage links for ISSCR Guidelines and supporting documents (vi) 4. The ISSCR Guidelines for the Conduct of Human Embryonic Stem Cell Research (1) 5. Sample consent forms for procurement of human biological research materials for stem cell research (22)
a. Egg donation; collected for stem cell research purposes only (22) b. Egg donation for stem cell research; in excess of clinical need (30) c. Embryo donation for stem cell research (38) d. Somatic cell donation for stem cell research (45) e. Sperm donation for stem cell research (52)
6. Sample Material Transfer Agreement (MTA) (59)
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AUTHOR CONTACT INFORMATION 1. George Q. Daley, MD, PhD Children’s Hospital Boston Karp 7214 300 Longwood Avenue Boston, MA 02115 617-919-2015 617-730-0222 (f) [email protected] 2. Lars Ahrlund-Richter, PhD Karolinska Institute Department of Lab Medicine Novum Plan 5 Huddinge Stockholm SE-14157 SWEDEN +46-8-5858-3848 +46-8-5858-3870 (f) [email protected] 3. Jonathan Auerbach, PhD GlobalStem, Inc. 6 Taft Ct. Suite 150 Rockville, MD 20850 301-545-0238 301-762-6287 (f) [email protected] 4. Nissim Benvenisty, MD, PhD Hebrew University Department of Genetics Givat-Ram Campus Jerusalem, I-91904 ISRAEL +972-2-658-6774 +972-2-658-4972 (f) [email protected] 5. R. Alta Charo Professor of Law & Bioethics University of Wisconsin Law School Law Building 975 Bascom Mall Madison, WI 53706-1399 608-262-5015 [email protected]
6. Grace Chen Bird & Bird 3614, China World Trade Centre Tower 1 1 Jianguomenwai Dajie Chaoyang District Beijing 100004 CHINA +86-10-6505-6667 +86-10-6505-9469 (f) [email protected] 7. Hongkui Deng, PhD Peking University Department of Cell Biology College of Life Science Beijing, 100871 CHINA +86-10-6275-6474 +86-10-9275-6474 (f) [email protected] 8. Lawrence S. B. Goldstein, PhD University of California San Diego Leichtag LBR 414 9500 Gilman Dr 0683 La Jolla, CA 92093-0683 858-534-9702 858-534-8193 (f) [email protected] 9. Kathy Hudson Genetics & Public Policy Center 1717 Massachusetts Ave., NW Suite 530 Washington, DC 20003 202-663-5971 202-663-5992 (f) [email protected]
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10. Insoo Hyun, PhD Case Western Reserve University School of Medicine 10900 Euclid Ave. Cleveland, OH 44106-4976 216-368-8658 216-368-8713 (f) [email protected] 11. Sung-Chull Junn Institute of Global Management 262-83 Sajiik-dong Jongro-gu Seoul, 110-054 KOREA +82-2-541-2567 +82-2-518-0159 (f) [email protected] 12. Jane M. Love, PhD Wilmer Cutler Pickering Hale and Dorr, LLP 399 Park Avenue New York, NY 10022 212-937-7233 212-230-8888 (f) [email protected] 13. Eng Hin Lee National University of Singapore Division of Graduate Medical Studies 12 Medical Dr. Block MD5 Level 3 Singapore 117598 SINGAPORE +65-6516-4826 +65-6773-1462 [email protected] 14. Anne McLaren, MA, PhD The Wellcome Trust-Cancer Research UK Gurdon Institute University of Cambridge Tennis Court Rd. Cambridge, CB2 1QR UK +44-1223-334-088 +44-1223-334-089 (f) [email protected]
15. Christine L. Mummery, PhD Hubrecht Laboratory Uppsalalaan 8 Utrecht, 3584 CT NETHERLANDS +31-30-212-1942 +31-30-251-6464 (f) [email protected] 16. Norio Nakatsuji, D.Sc Kyoto University Insititute for Frontier Medical Science Department of Development and Differentiation 53 Kawaharacho Shogoin Sakyo-Ku Kyoto, 606-8507 JAPAN +81-75-751-3808 +81-75-751-3890 (f) [email protected] 17. Catherine Racowsky, PhD Brigham and Women’s Hospital Department of Obstetrics and Gynecology 75 Francis St. Boston, MA 02115 617-732-5570 [email protected] 18. Heather Rooke, PhD International Society for Stem Cell Research Karp Research Building, 07216.1 300 Longwood Avenue Boston, MA 02115 617-919-2096 617-730-0222 (f) [email protected] 19. Janet Rossant, BA, PhD Hospital for Sick Children 555 University Avenue Toronto, ON M5G 1X8 CANADA 416-813-7929 416-813-5085 (f) [email protected]
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20. Hans Schöler Max Plank Institute Roentgenstr. 20 Muenster D-48149 GERMANY +49-251-70365-300 +49-251-70365-395 (f) [email protected] 21. Jan Helge Solbakk, MD, PhD University of Bergen Center for International Health Armauer Hansens Hus Haukelandsbakken 28 N-5021 Bergen NORWAY +47-22-84-46-41 +47-55-97-49-79 (f) [email protected] 22. Patrick Taylor Office of General Cousel Children’s Hospital Boston Hunnewell 2 300 Longwood Avenue Boston, MA 02115 617-355-6108 [email protected] 23. Alan Trounson, MSc, PhD Monash University Immunology & Stem Cell Labs Wellington Rd. Bldg. 75 Clayton, VIC 3800 AUSTRALIA +61-3-9905-0771 +61-3-9905-0780 [email protected]
24. Irving L. Weissman, MD Stanford University School of Medicine Department of Pathology 279 Campus Dr B257 Beckman Ctr Stanford, CA 94305-5323 650-723-6520 650-723-4034 (f) [email protected] 25. Ian Wilmut, PhD, DSc The Queen’s Medical Research Institute Center for Reproductive Biology University of Edinburgh 47 Little France Crescent Edinburgh Eh16 4TJ UK +44-131-242-6630 +44-131-242-6629 (f) [email protected] 26. John Yu, MD, PhD Academia Sinica 128 Sec 2 Yen-Chiu Yuan Rd. Nankang Taipei 115 TAIWAN R.O.C. +886-2-2789-9589 +886-2-2789-9588 (f) [email protected] 27. Laurie S. Zoloth, PhD Northwestern University School of Medicine Center for Bioethics 676 N. St. Clair St. Suite 1260 Chicago, IL 60611 312-926-2984 312-926-3023 (f) [email protected]
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Conflicts of Interest L. A.-R. owns stock in Ovacell AB.
R.A.C. is on the Ethics Advisory Committees of the Juvenile Diabetes Research Fund, Howard Hughes Medical Institute, and the California Institute of Regenerative Medicine; is on the scientific advisory board for WiCell Research Institute and the Faculty Advisory Board of the University of Wisconsin Stem Cell Program; is co-chair of NAS/IOM hESC RAC; gets speaker fees from various institutions; and consults for Stem Cells, Inc., and the California Institute of Regenerative Medicine.
G.Q.D. owns stock in Viacell, Inc., is on the scientific advisory board and consults to MPM Capital, and receives speaker fees from various institutions.
K.H. has received speaker fees from Stem Cells, Inc.
E.H.L. is co-chair of the Singapore Stem Cell Consortium and serves on the Bioethics Advisory Committee of Singapore.
A.T. owns stock in Monash IVF Pty Ltd. and is scientific director of Monash IVF.
I.L.W. owns stock in Amgen, is co-founder, consultant to and Director of, and owns equity in Stem Cells, Inc., and Cellerant Therapeutics, and is on the scientific advisory board and consults to MPM Capital.
I.W. owns stock in Geron Corp., is on the scientific advisory board of the Medical Research Council/UK Stem Cell Foundation, and owns two patents with Roslin Institute-Mammalian NT.
L.Z. is a Board Member of ISSCR; a member of the Bioethics Advisory Committee of the Howard Hughes Medical Institute; on the Academic Advisory Board of UCSF Stem Cell Institute and the ESCRO Committee of Northeastern University; and has received speaker fees from Stem Cells, Inc., and various institutions.
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International Society for Stem Cell Research
‘Guidelines for the Conduct of Human Embryonic Stem Cell Research’
and Supporting Documents The following guidelines and supporting documents can be found on the ISSCR Web site: Host page for the Guidelines and related documents and information www.isscr.org/guidelines/index.htm ISSCR ‘Guidelines for the Conduct of Human Embryonic Stem Cell Research’; 12/21/2006 www.isscr.org/guidelines/ISSCRhESCguidelines2006.pdf Consent documents for procurement of human biological research materials for stem cell research
Egg donation for stem cell research; provided directly and solely for stem cell research http://www.isscr.org/guidelines/CFeggsresearch.doc Egg donation for stem cell research; collected during the course of fertility treatment and in excess of clinical need http://www.isscr.org/guidelines/CFeggsexcessofclinical.doc Embryo donation for stem cell research; created for fertility purposes and in excess of clinical need http://www.isscr.org/ guidelines/CFembryos.doc Somatic cell donation for stem cell research http://www.isscr.org/guidelines/CFsomatic.doc Sperm donation for stem cell research http://www.isscr.org/guidelines/CFsperm.doc
Sample Materials Transfer Agreement (MTA) [Adapted and modified from the uniform biological material transfer agreement published in the Federal Register, February 18, 1995]
Sample Materials Transfer Agreement (MTA) document http://www.isscr.org/guidelines/mta.doc
Guidelines for the Conduct of Human Embryonic Stem Cell Research Version 1: December 21, 2006
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Contents: page
1) Justification for stem cell research and goals 3
2) Mission of task force 3
3) Comment on scientific terminology 3
4) Scope of Guidelines 3
5) Responsibility for conduct 4
6) Statement on reproductive cloning 4
7) Issues pertinent to international collaborations 4
8) Recommendations for oversight 5
9) Mechanisms for enforcement 6
10) Categories of research 6
11) Procurement of materials 7
12) Principles for derivation, banking, distribution of human stem cell lines 10
13) Dispute resolution 11
14) Ongoing review of Guidelines 12
15) Acknowledgments 12
16) Appendices 12
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1) Justification for stem cell research and goals
1.1) Stem cell research, with foundations in the fields of cell anddevelopmental biology and genetics, seeks to answer basic questions about the nature of tissue formation and maintenance.The first stem cells to be isolated were from developed tissuesand organs, and are now used in tissue and organ regenerationexperimentally and clinically.
1.2) The rapid growth of the field of stem cell research followsnumerous recent seminal discoveries, including the isolation ofhuman embryonic stem cells and stem cells of various types thathave the potential to generate many different cells and tissues.
1.3) Stem cell research encompasses new approaches for the elucidation of disease mechanisms, offers promise for discoveryof novel drugs that act on stem cells, and may yield cell replace-ment therapies for a multitude of devastating and widespreadgenetic, malignant, and degenerative diseases that are currentlyuntreatable. Stem cell research is certain to advance fundamentalknowledge and to have a profound impact on medicine.The goalsof stem cell research are widely accepted in the biomedicalresearch community and endorsed by diverse scientific societiesworldwide. Long-term goals include improvements in humanhealth and the relief of disease, infirmity, and human sufferingthrough advances in knowledge and new clinical tools that can bemade available and affordable throughout the world.
1.4) The International Society for Stem Cell Research (ISSCR)endorses the goals of stem cell scientists and exists to promoteinnovation in research, education, and the free exchange of scientific ideas and research materials.
2) Mission of task force
2.1) Scientific, cultural, religious, ethical, and legal differencesacross international borders affect how early stages of humandevelopment are viewed, and how research on human embryosand embryonic stem cells is conducted. ISSCR calls for due consideration and appropriate oversight of human stem cellresearch to ensure transparent, ethical, and responsibleperformance of scientific experiments.
2.2) The ISSCR Task Force is charged with formulating guidelinesthat articulate ethical principles and rules of behavior for the performance of human stem cell research.
2.3) These Guidelines are meant to emphasize the responsibilityof scientists to ensure that human stem cell research is carriedout according to rigorous standards of research ethics, and toencourage uniform research practices that should be followed byall human stem cell scientists globally.
3) Comment on scientific terminology
3.1) The ISSCR is dedicated to the use of precise and accurateterminology in stem cell research, and to educating researchersand the public on the meaning of terms and their proper usage inthe discourse on stem cell research. Discussion of the merits ofstem cell research requires that the discussants share a commonunderstanding about the meaning and usage of specific terms, andthe biological implications of the terminology.We also acknowl-edge the limitations of descriptive terminology in the practice ofa fast-moving field of science, and endeavor to apply the most precise terms in the proper context. We have endeavored toemploy the most accurate terms throughout the document, asdefined in an appended glossary.
4) Scope of Guidelines
4.1) Fundamental ethical requirements in research include review and approval of projects by a panel that is independent ofthe investigators, and voluntary and informed consent from anyhuman participants. Well-established guidelines and regulationsgoverning the use of human subjects are already in place throughout the world. These principles have been articulated ininternationally recognized research ethics guidelines including, butnot limited to, the Nuremburg Code of 1947, the Declaration ofHelsinki of 1964 and amendments, the Belmont Report of 1979,the Council for International Organizations of Medical Sciences(CIOMS) International Ethical Guidelines for BiomedicalResearch Involving Human Subjects of 2002, and the UNESCOUniversal Declaration on Bioethics and Human Rights of 2005.Regulations for use of animals and hazardous materials inresearch have also been well established and are in wide use.ThisGuideline document focuses on issues unique to stem cellresearch that involves pre-implantation stages of humandevelopment, research on the derivation or use of humanpluripotent stem cell lines, and on the range of experimentswhereby such cells might be incorporated into animal hosts.
4.2) These Guidelines pertain to the procurement, derivation,banking, distribution, and use of cells and tissues taken from pre-implantation stages of human development; to procurements ofgametes and somatic tissues for stem cell research; and to the useof human totipotent or pluripotent cells or human pluripotentstem cell lines.
4.3) These Guidelines assert that researchers involved in humanstem cell research must adhere to ethical and transparent prac-tices for performing research and sharing research materials.
4.4) These Guidelines assign criteria for defining categories ofresearch that are non-permissible, that are permissible undercurrently mandated review processes, and research that ispermissible yet should be subjected to an added level ofoversight. These Guidelines prescribe the nature of regulatory
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review and oversight for each of the permissible researchcategories.
4.5) These Guidelines do not pertain to research on animal stemcells, or on classes of human somatic stem cells that remainrestricted in tissue potential and are not known to possesstotipotent or pluripotent potential. Research pertaining to theseclasses of stem cells does not raise the same sets of issues asdealt with in these Guidelines.
4.6) In their current form, these Guidelines are incomplete intheir potential application to various types of fetal stem cells,which raise a unique set of issues around their procurement.Future revised versions of the Guidelines may incorporate morespecific information pertinent to fetal stem cells.
5) Responsibility for conduct
5.1) International scientific collaboration and mutual trust amongresearchers are vital to the success and advancement of scienceand should be encouraged. Collaborations between scientists indifferent jurisdictions will raise issues due to the differences in thelaws and regulations that govern stem cell research. An underlyingprinciple of these guidelines is that any and all stem cell researchshall be conducted in accordance with any applicable laws andregulations of the country or region where such research takesplace, recognizing and respecting that certain laws and regulationsmay be applicable to individual researchers, regardless of wherethe research will take place.
5.2) Researchers must assume the responsibility for compliancewith local statutes and adherence to guidelines. Institutions sponsoring stem cell research must take steps to ensure that education and appropriate training takes place to makeresearchers aware of regulations and professional guidelines.If warranted, institutions should obtain legal opinions on anyissues of concern on behalf of their researchers.
5.3) Scientists and clinicians must be transparent and truthfulabout issues relating to human stem cell research and its potential to advance medicine. To guard against the creation ofunrealistic expectations of success and to safeguard patients fromserving prematurely as experimental subjects in human stem cellresearch, scientists and clinicians must clearly articulate thedistinct goals of basic research, preclinical studies, and clinicaltrials. Investigators must assume the responsibility to educate thepublic about the many steps required to garner the scientific andclinical evidence to establish treatments as safe and effective.
5.4) Scientific trainees and technical staff who have aconscientious objection to aspects of stem cell research shouldnot be required to participate in research, and should be free ofretribution or undue discrimination in assessments ofprofessional performance. Clinical personnel who have a
conscientious objection to stem cell research should not berequired to participate in providing donor information orsecuring donor consent for research use of embryos, gametes, orsomatic cells; that privilege should not extend to the clinical careof a donor.
6) Statement on reproductive cloning
6.1) Human reproductive cloning is defined as the act of seekingto establish either a pregnancy or the birth of a child by gestatingor transfering into a uterus human embryos that have beenderived in vitro by nuclear transfer or nuclear reprogramming.Given current scientific and medical safety concerns, attempts athuman reproductive cloning should be prohibited.
7) Issues pertinent to international collaborations and the role of ISSCR
7.1) In the context of international collaborations, issues will arisethat relate to ownership and custodianship of intellectualproperty. As a general principle, the ISSCR stands for the openexchange of scientific ideas and materials to maximizeexploration, to promote innovation and to increase theprobability of public benefit through affordable advances madepossible by human stem cell research. Given the need to respectthe varying laws and regulations of different jurisdictions that mayapply to any international collaboration, intellectual propertyissues are best left to be negotiated among the collaboratingparties, taking into consideration the protection regimes or otherrelevant laws and regulations of their respective jurisdictions.Nonetheless, we endorse in the strongest possible terms theprinciple that research with human materials is valuable to all, andthat the proper practice of science requires unhindereddistribution of research materials to all qualified investigatorsengaged in non-commercial research and the dissemination of itsbenefits to humanity at large on just and reasonable terms.
7.2) Pluripotent human stem cell lines are important tools forresearch and replication of experimental data and scientificcollaboration are vital to scientific advancement. The ISSCRrecommends that institutions engaged in human stem cellresearch, whether public or private, academic or otherwise,develop procedures whereby research scientists are granted,without undue financial constraints or bureaucratic impediment,unhindered access to these research materials for scientificallysound and ethical purposes, as determined under theseGuidelines and applicable laws. The ISSCR urges such institutions,when arranging for disposition of intellectual property tocommercial entities, to take all possible care to preservenonexclusive access for the research community, and to promotepublic benefit as their primary objective.The ISSCR endorses theprinciple that as a prerequisite for being granted the privilege ofengaging in human stem cell research, researchers must agree tomake the materials readily accessible to the biomedical research
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community for non-commercial research. Administrative costssuch as shipping and handling should be borne by the receivingparty so as not to pose a severe financial burden on theresearcher providing the cells.
7.3) The ISSCR encourages scientists conducting human stem cellresearch to submit any human stem cell lines they derive tonational or international depositories that allow open distributionin order to facilitate the wider dissemination of these valuableresearch tools across national boundaries. Scientists and stem cellbio-banks should endeavor to work together to harmonizestandard operating procedures to facilitate internationalcollaboration.
7.4) The process of identifying international ethical standards andpractices for the conduct of human stem cell research shouldinclude concerted efforts to engage people throughout the worldin honest and realistic conversations about the science and ethicsof stem cell research and its emerging applications.
8) Recommendations for oversight
8.1) All experiments pertinent to human embryonic stem cellresearch that involve pre-implantation stages of humandevelopment, human embryos or embryonic cells, or that entailincorporating human totipotent or pluripotent cells into animalchimeras, shall be subject to review, approval and ongoingmonitoring by a special oversight mechanism or body equipped toevaluate the unique aspects of the science. Investigators shouldseek approval through a process of Stem Cell Research Oversight(SCRO).
8.2) Review can be performed by an oversight mechanism orbody at the institutional, local, regional, national, or internationallevel, or by some coordinated combination of those elementsprovided that the review as a whole occurs effectively, impartiallyand rigorously. Multi-institutional arrangements for coordinatedreview, which involve delegation of specific parts of this review,shall be permitted as long as they meet that standard. A singlereview rather than redundant review is preferable as long as thereview is thorough and pertains to the uniquely sensitiveelements of human stem cell research. Unless the review isspecifically designed to be comprehensive, the SCRO processshall not replace other mandated reviews such as institutionalreviews that assess the participation of human subjects inresearch, or the oversight for animal care, biosafety, or the like.Institutions engaged in stem cell research must establishprocedures to ensure that research conducted under theirauspices have been subject to appropriate review.
8.3) Review must include assessment of:
i) Scientific rationale and merit of proposal. Research withhuman embryonic material, or totipotent or pluripotent cellsrequires that scientific goals and methods be scrutinized toensure scientific rigor. Appropriate scientific justification forperforming the research using the specified materials isrequired.ii) Relevant expertise of investigators. Appropriate expertiseand/or training of the investigators to perform the statedexperiments must be ascertained in order to ensure theoptimal use of precious research materials. For derivation ofnew human cell lines or experiments that involve use ofhuman embryonic materials, relevant expertise wouldinclude prior experience with embryonic stem cell deriva-tion in animal systems and competence in the culture andmaintenance of human embryonic stem cells.iii) Ethical permissibility and justification. Research goals must beassessed within an ethical framework to ensure thatresearch proceeds in a transparent and responsible manner.The project proposal should include a discussion ofalternative methods, and provide a rationale for employingthe requested human materials, the proposed methodologyand for performing the experiments in a human rather thananimal model system.
8.4) The mechanism or body that provides SCRO function isresponsible for interpreting Guidelines, defining research prac-tices, and monitoring compliance.
8.4a) The SCRO function should assume responsibility formonitoring and periodic review and re-approval of ongoingresearch proposals.
8.4b) The SCRO function has the responsibility for definingwhether a research proposal constitutes permissible or non-permissible research.
8.5) Recommendations for composition of participants to beengaged in providing SCRO function; appropriate expertise,objectivity and responsibility.
8.5a) Scientists and/or physicians with relevant expertise,including representation from scientists that are not directlyengaged in the research under consideration. Relevantexpertise includes areas of stem cell biology, assistedreproduction, developmental biology, and clinical medicine.
8.5b) Ethicists with ability to interpret the moraljustifications and implications of the research underconsideration.
8.5c) Members or advisors familiar with relevant local legalstatutes governing the research.
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8.5d) Community members, unaffiliated with the institutionthrough employment or other remunerative relationships,who are impartial and reasonably familiar with the views andneeds of research subjects, patients and patient communitieswho could be benefited by stem cell research, andcommunity standards.
8.5e) Those responsible for formulating the mechanism orbody to provide SCRO function must be cognizant of thepotential for conflicts of interest that might compromise theintegrity of the review process, and attempt to eliminatesuch conflicts. Potential participants in the SCRO processshould be selected based on the capacity for impartiality andfreedom from political influence.
8.6) Each institution, academic or commercial, that engages inhuman stem cell research shall determine an appropriate SCROprocedure, either internal or external, by which their researcherswill be subject to review, approval, and monitoring of their humanstem cell research activities.
9) Mechanisms for enforcement
9.1) The development of consensus in ethical standards andpractices in human stem cell research through thoughtful andtransparent dialogue is a critical catalyst for internationalcollaboration to proceed with confidence, and for research fromanywhere in the world to be accepted as valid by the scientificcommunity. These standards and practices should beincorporated in a comprehensive code of conduct applicable toall researchers in the field. Senior or corresponding authors ofscientific publications should specifically be charged with theresponsibility of ensuring that the code of conduct is adhered toin the course of conducting human stem cell research and ofsupervising junior investigators that work in their respectiveorganizations or projects. Institutions where such research isundertaken shall strive to provide to researchers working on anysuch projects under their auspices, particularly juniorinvestigators, with up-to-date information on such standards andpractices on an ongoing basis.
9.2) Journal editors should require a statement of compliancewith the ISSCR ‘Guidelines for the Conduct of Human EmbryonicStem Cell Research’ or adherence to an equivalent set ofguidelines or applicable regulations, and a statement that theresearch was performed after obtaining approvals following asuitable SCRO process.
9.3) Grant applicants, in particular the individual scientistsundertaking the research, should undertake to provide fundingbodies with sufficient documentation to demonstrate that theresearch for which funding is requested is ethically and legally inaccordance with relevant local and national regulations and alsoin compliance with the ISSCR ‘Guidelines for the Conduct of
Human Embryonic Stem Cell Research.’ Funding organizationsshould pledge to comply with these Guidelines or theirequivalent and require entities whose research is funded by suchorganizations to do the same.
9.4) In order to facilitate the adoption of uniform standards andpractice of human stem cell research, the ISSCR will makeavailable for download on the ISSCR website examples ofinformed consent documents for obtaining human materials forstem cell research (gametes, embryos, somatic tissues), and aMaterial Transfer Agreement for the sharing and distribution ofmaterials (see appendix).
10) Categories of research
To ensure that stem cell research is proceeding with dueconsideration, to ensure consistency of research practices amongscientists globally and to specify the nature of scientific projectsthat should be subject to SCRO review, we propose specificcategories of research.
10.1) Category 1: Experiments that are permissible afterreview under existing mandates and by existing local committees,and are determined to be exempt from full SCRO review.Thesewill include experiments with pre-existing human embryonicstem cell lines that are confined to cell culture or involve routineand standard research practice, such as assays of teratomaformation in immune-deficient mice. We recommend that allinstitutions pursuing such research establish a mechanism capableof determining that a) these projects can be adequately reviewedby committees with jurisdiction over research on human tissues,animals, biosafety, radiation, etc. and b) that full review by a SCROmechanism or body is not required. This mechanism shouldinclude a determination that the provenance of the humanembryonic stem cell lines to be used has been scrutinized anddeemed acceptable according to the principles outlined in thisdocument, and that such research is in compliance with scientific,legal and ethical norms.
10.2) Category 2: Forms of research that are permissible onlyafter additional and comprehensive review by a specializedmechanism or body established to address the issues pertinent tostem cell research (i.e., the SCRO function). Such forms ofresearch will require provision of greater levels of scientificjustification, consideration of social and ethical aspects of theresearch and justification for not pursuing alternative methods toaddress the same experimental goals. If the research requiresobtaining informed consent from human subjects, the researchwill require review to ensure that treatment of human subjects isconsistent with international norms and local laws, and any otherapplicable regulations or guidelines. Review of such forms ofresearch should consider the protection of genetic and medicalprivacy of donors; such a review is typically done by a localinstitutional review board or its equivalent, but could also be
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performed as part of the SCRO process, with the SCROexercising due regard for the authority of the institutional reviewboard and avoiding duplication of its functions.
10.2a) Forms of research that involve the derivation of newhuman pluripotent cell lines by any means.
10.2b) Forms of research in which the identity of the donorsof blastocysts, gametes, or somatic cells from whichtotipotent or pluripotent cells are derived is readilyascertainable or might become known to the investigator.
10.2c) Forms of research in which human totipotent cells orpluripotent stem cells are mixed with pre-implantationhuman embryos. In no case shall such experiments beallowed to progress for more than 14 days of developmentin vitro, or past the point of primitive streak formation,whichever is first.
10.2d) Clinical research in which cells of totipotent orpluripotent human origin are transplanted into living humansubjects.
10.2e) Forms of research that generate chimeric animalsusing human cells. Examples of such forms of researchinclude, but are not limited to introducing totipotent orpluripotent human stem cells into non-human animals at anystage of post-fertilization, fetal, or postnatal development.
i) We note that chimeric animal research has a longhistory and has been a scientifically essential and validprocedure for understanding cellular, tissue, and organfunction, and has also served as a key pre-clinical stageof research in the evaluation of therapeutics.ii) There are two main points of concern with chimericanimals containing human cells: the degree of theresulting chimerism and the type of tissues that arechimerized.The earlier that human cells are introducedduring animal development, the greater the potentialfor their widespread integration during development.Introduction of a greater number of cells later indevelopment may have an equivalent effect. In general,chimerism of the cerebral cortex or the germ-line areof greatest concern.iii) In reviewing forms of research of this type, theSCRO mechanism or body should communicate withthe appropriate mechanism or body that overseesresearch involving animal subjects, and give specialattention to a number of issues including: A) theprobable pattern and effects of differentiation andintegration of the human cells into the non-humananimal tissues; and B) the species of the animal, withparticular scrutiny given to experiments involving non-human primates. Experiments that generate chimerismof the cerebral cortex or germ-line should be subjected
to especially careful review. Although it is highly unlikelythat any viable fertilization event of an animal gamete bya human gamete generated in an animal would occur,chimeric animals should typically not be allowed toproduce offspring, whether by natural or artificialmeans. If there is a very strong scientific rationale forderiving offspring from such animals, then reviewcommittees should consider whether such anexperiment might be appropriate to pursue. In any case,interbreeding of such chimeras should not be allowed,to preclude the possibility of inadvertent human-humanfertilization events.
10.3) Category 3: Research that should not be pursued at thistime because of broad international consensus that such experi-ments lack a compelling scientific rationale or raise strong ethicalconcerns. Such forms of research include:
10.3a) In vitro culture of any post-fertilization humanembryos or organized cellular structures that might manifesthuman organismal potential, regardless of derivationmethod, for longer than 14 days or until formation of theprimitive streak begins, whichever occurs first.
10.3b) Research in which any products of research involvinghuman totipotent or pluripotent cells are implanted into ahuman or non-human primate uterus.
10.3c) Research in which animal chimeras incorporatinghuman cells with the potential to form gametes are bred toeach other.
11) Procurement of materials
The procurement of human gametes, pre-implantation embryos,and somatic cells are integral to the conduct of human stem cellresearch. The international community of professional scientistsconducting human stem cell research must ensure that humanbiological materials are procured in a manner according toglobally accepted principles of research ethics. Chief among theethical principles applicable to the conduct of human stem cellresearch are that persons should be empowered to makevoluntary and informed decisions to participate or to refuse toparticipate in research. In the case of human embryonic stem cellresearch, the public participates by providing necessary humanbiological materials. Persons should be afforded a fair opportunityto participate in research, and they must be treated justly andequitably. Furthermore, privacy and confidentiality of personalinformation should be protected with the utmost care. Cautionmust also be taken to ensure that persons are not exploitedduring the procurement process, especially individuals who arevulnerable due to their dependent status or their compromisedability to offer fully voluntary consent. Consistent with well-established principles of justice in human subject research, there
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must be a reasonable relationship between those from whomsuch materials are received and the populations most likely tobenefit from the research. Finally, the voluntary nature of theconsent process must not be undermined by undue inducementsor other undue influences to participate in research.
11.1) Institutional review for procurement of materials:Rigorous review, whether at the local institutional, regional, ornational level, must be performed prior to the procurement of allgametes, embryos, or somatic cells that are destined for use instem cell research.This will include the procurement of oocytesand embryos in excess of clinical need from infertility clinics,fertilized oocytes and embryos generated by IVF specifically forresearch purposes, and oocytes, sperm, or somatic cells donatedfor development of totipotent cells or pluripotent stem cell linesby parthenogenesis, androgenesis, nuclear transfer or othermeans of somatic cell reprogramming. Review at all levels mustensure that vulnerable populations are not exploited due to theirdependent status or their compromised ability to offer fullyvoluntary consent, and that consent is voluntary and informed,and that there are no undue inducements or other undueinfluences for the provision of human materials.
11.2) Contemporaneous consent for donation: Consentfor donation of materials for research should be obtained at thetime of proposed transfer of materials to the research team. Onlyafter a rigorous review by a SCRO mechanism or body canpermission be granted to use materials for which prior consentexists but for which re-consent is prohibitively difficult. Consentmust be obtained from all gamete donors for use of embryos inresearch. Donors should be informed that they retain the right towithdraw consent until the materials are actually used inresearch.
11.3) Informed consent: Researchers should exercise care incommunicating the concept of “informed consent” to ensure thatsuch consent has actually been obtained. The informed consentprocess should take into account language barriers and theeducational level of the subjects themselves. In order to facilitatethe adoption of sound and uniform standards of informedconsent for the procurement of materials for human stem cellresearch, the ISSCR has made sample documents available toresearchers by download from the ISSCR website(http://www.isscr.org). The samples will need to be customizedfor use in specific research studies.
11.3a) The informed consent document and process shouldcover, at a minimum, the following statements (adapted tothe particular research project):
i) that the materials will be used in the derivation oftotipotent or pluripotent cells for research.ii) that the materials will be destroyed during theprocess of deriving totipotent or pluripotent cells forresearch (unless the specific research protocol aims to
preserve the integrity of the research material, as in thecase of embryo biopsy for procurement of blastomeresfor human embryonic stem cell generation. In thiscircumstance, disclosure that the materials “may bedestroyed” rather than “will be destroyed” would beappropriate).iii) that derived cells and/or cell lines might be kept formany years and used for future studies, many of whichmay not be predictable at this time.iv) that cells and/or cell lines might be used in researchinvolving genetic manipulation of the cells or thegeneration of human-animal chimeras (resulting fromthe mixing of human and non-human cells in animalmodels).v) that the donation is made without any restriction ordirection regarding who may be the recipient oftransplants of the cells derived, except in the case ofautologous transplantation.vi) whether the donation is limited to specific researchpurposes and not others or is for broadly statedpurposes, including research not presently anticipated,in which case the consent shall notify donors, ifapplicable under governing law, of the possibility thatpermission for broader uses may later be granted andconsent waived under appropriate circumstances by anethical or institutional review board. The consentprocess should explore whether donors haveobjections to the specific forms of research outlined inthe research protocol.vii) disclosure of what donor medical or otherinformation and what potential donor identifiers will beretained; specific steps taken to protect donor privacyand the confidentiality of retained information; andwhether the identity of the donor will be readilyascertainable to those who derive or work with theresulting stem cell lines, or any other entity or person,including specifically any oversight bodies andgovernment agencies.viii) disclosure of the possibility that any resulting cellsor cell lines may have commercial potential, andwhether the donor will or will not receive financialbenefits from any future commercial development.ix) disclosure of any present or potential future financialbenefits to the investigator and the institution relatedto or arising from proposed researchx) that the research is not intended to provide directmedical benefit to anyone including the donor, except inthe sense that research advances may benefit everyone.xi) that neither consenting nor refusing to donatematerials for research will affect the quality of careprovided to potential donors.xii) that there are alternatives to donating humanmaterials for research, and an explanation of what thesealternatives are (e.g. donation for fertility treatment,discard, etc.).
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xiii) (for donation of embryos) that the embryos willnot be used to produce a pregnancy, and will not beallowed to develop in culture in vitro for longer than 14days from conception.xiv) (for experiments in embryonic stem cell derivation,somatic cell nuclear transfer, somatic cellreprogramming, parthenogenesis, or androgenesis) thatthe resulting cells or stem cell lines derived would carrysome or all of the DNA of the donor and therefore bepartially or completely genetically matched to thedonor.
11.4) Separation of informed consent for research dona-tion from clinical treatment. To facilitate free and voluntarychoice, decisions related to the donation of gametes or creationof embryos for fertility treatment should be free of the influenceof investigators who propose to derive or use human embryonicstem cells in research. Wherever possible, the treating physicianor infertility clinician should not also be the investigator who isproposing to perform research on the donated materials.
11.5) Additional guidelines for procurement of specificresearch materials:
11.5a) For donating embryos or gametes generated in the courseof clinical treatment. Except when specifically authorized bythe SCRO process, no reimbursement of direct expenses orfinancial considerations of any kind may be provided fordonating embryos or gametes that have been generated inthe course of clinical treatment and are in excess of clinicalneed or deemed of insufficient quality for clinical use.Researchers may not request that members of the infertilitytreatment team generate more embryos or harvest moreoocytes than necessary for the optimal chance ofreproductive success. People who elect to donate storedmaterials for research should not be reimbursed for thecosts of storage prior to the decision to donate.Reimbursement for direct expenses incurred by donors as aconsequence of the consent process may be determinedduring the SCRO process.
11.5b) For provision of oocytes for research, when oocytes arecollected outside the course of clinical treatment. In localeswhere oocyte donation for stem cell research is allowed, theSCRO mechanism or body is responsible for conductingrigorous review of any protocol to ensure the safety and thefree and informed choice of oocyte providers, according tothe following principles:
i) There must be monitoring of recruitment practices toensure that no vulnerable populations, for example,economically disadvantaged women, are disproportion-ately encouraged to participate as oocyte providers forresearch.
ii) In locales where reimbursement for researchparticipation is allowed, there must be a detailed andrigorous review to ensure that reimbursement of directexpenses or financial considerations of any kind do notconstitute an undue inducement.iii) At no time should financial considerations of anykind be given for the number or quality of the oocytesthemselves that are to be provided for research.iv) Oocyte procurement must be performed only bymedically qualified and experienced physicians, and non-aggressive hormone stimulation cycles and frequentmonitoring must be used to reduce the risk of ovarianhyperstimulation syndrome (OHSS).v) Due to the unknown long-term effects of ovulationinduction, women should not undergo an excessivenumber of hormonally induced ovarian stimulationcycles in a lifetime, regardless of whether they areinduced for research or assisted reproduction. Thelimits should be determined by thoughtful review duringthe SCRO process, which should be informed by thelatest available scientific information about the healthrisks.vi) There should be a provision to pay for the cost ofany medical care required as a direct and proximateresult of a woman’s provision of oocytes for research.vii) An infertility clinic or other third party responsiblefor obtaining consent or collecting materials should notbe paid specifically for the material obtained, but ratherfor specifically defined cost-based reimbursements andpayments for professional services.
11.5c) For provision of sperm for research. Reimbursement fordirect expenses incurred by donors as a consequence of theconsent process may be determined during the SCROprocess.
11.5d) For provision of somatic cells for research.Reimbursement for direct expenses incurred by donors as aconsequence of the consent process may be determinedduring the SCRO process.
i) In the case that the somatic cell donor is a child or adecisionally incapacitated adult, consent must be pro-vided by a legal parent or guardian or other personauthorized under applicable law.ii) Contemporaneous consent is not necessary ifresearchers procure somatic cells from a tissue bank.However, somatic cells may be procured from a tissuebank only if the tissue bank’s informed consentdocuments specifically designate nuclear transfer orother reprogramming methods for stem cell researchas one of the possible uses of the donor’s tissues, andonly if researchers use somatic cells from tissuesamples whose donors have clearly consented to thispossible use.
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11.6) Steps to enhance the procurement process:Attempts should be made to improve the informed consentprocess for human materials procurement.The informed consentdocument is but one aspect of this process.The purpose of theinformed consent document is to record that all the ethicallyrelevant information has been discussed. The informed consentdocument alone can never take the place of an interactivedialogue between research staff and providers of humanmaterials. Researchers are thus encouraged to focus on enrichingthe informed consent process itself, in addition to ensuring thatthe informed consent document includes all of the ethicallyrelevant information. The informed consent process can beenhanced in the following ways:
i) Whenever possible, the person conducting theinformed consent dialogue should have no vestedinterest in the research protocol. If members of theresearch team participate in the informed consentprocess, their role must be disclosed and care must betaken to ensure that information is provided in atransparent and accurate manner.ii) Empirical research has shown that informed consentis most effective as a dynamic, interactive, and evolvingprocess as opposed to a static, one-time disclosureevent. Thus, researchers should provide ampleopportunities for providers of human materials todiscuss their involvement in the research protocol.iii) Counseling services should be made available uponrequest to any providers of human materials prior toprocurement.iv) Procurement procedures should be revised in lightof a) ongoing studies of the long-term risks associatedwith oocyte retrieval; and b) research on informedconsent for all types of human biological materialsprocurement.v) Researchers should consider on a regular basis,subject to annual review, the possible use of alternativesto hormonally induced oocytes procured solely forstem cell research, such as oocytes derived frompluripotent stem cells, in vitro maturation of oocytesfrom ovariectomy samples, and egg sharing programsoffered through infertility clinics.
12) Principles for derivation, banking, and distribution of human pluripotent stem cell lines
Proposals for derivations of new human pluripotent stem celllines should be scientifically justified and executed by scientistswith appropriate expertise. Hand-in-hand with the privilege toperform derivations is the obligation to distribute the cell lines tothe research community.A clear, detailed outline for banking andopen access to the new lines should be incorporated intoderivation proposals. New pluripotent stem cell lines should be
made generally available as soon as possible following derivationand first publication. The ISSCR encourages researchers todeposit lines early into centralized repositories where the lineswill be held for release and distribution upon publication.
12.1) Derivation of new lines
12.1a) Proposals to attempt derivation of new totipotentcells or pluripotent stem cell lines from donated pre-implantation human embryos, embryonic cells, or via nuclearreprogramming must be approved by a SCRO process. Newderivations by necessity involve procurement of materialsfrom human subjects and, therefore, will need to beapproved by institutional oversight bodies with specificresponsibility for protection of human subjects, as well as bythe SCRO process. In some jurisdictions, the SCRO processwill be formulated in a manner that encompasses all humansubjects and stem cell oversight responsibilities.
12.1b) The scientific rationale for the need to derive newtotipotent cells or pluripotent stem cell lines must beprovided by the researcher, with justification of the numbersof pre-implantation embryos to be used. For proposals thatincorporate nuclear transfer or reprogramming, an explicitscientific justification is needed and the numbers of trials tobe attempted must be justified.
12.1c) Researchers must demonstrate appropriate expertiseor training in the culture and maintenance of existing humanembryonic stem cell lines and expertise or training in thederivation of pluripotent non-human stem cell lines beforebeing granted permission for attempts at derivations of newhuman stem cell lines.
12.1d) Investigators performing derivations should have adetailed, documented plan for characterization, storage,banking and distribution of new lines.
12.1e) Embryos made via nuclear transfer, parthenogenesis,androgenesis, or other in vitro mean of embryo productionshall not be transferred to a human or non-human uterus orcultured in vitro intact as embryos for longer than 14 days oruntil formation of the primitive streak, whichever occursfirst.
12.1f) Investigators performing derivations should propose aplan to safeguard the privacy of donor information.
12.2) Banking of stem cell lines: The ISSCR encourages theestablishment of national and international repositories, whichare expected to accept deposits of newly derived stem cell linesand to distribute them on an international scale. In order tofacilitate easy exchange and dissemination of stem cell lines,repositories should strive to form and adhere to common
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methods and standards; at a minimum, each repository mustestablish its own clear guidelines and make those available to thepublic. Repositories must have a clear, easily accessible materialtransfer agreement (MTA) [a sample MTA is available as anappendix and can be downloaded from the ISSCR website].Each repository may have its own criteria for distribution.The repository has right of refusal if a cell line does not meet its standards.
12.2a) Repository must have clear, publicly availableprotocols for deposit, storage and distribution of hESC linesand related materials.
12.2b) For deposits, repository must receive documentationpertinent to the depositor’s SCRO process. Thesedocuments should be kept on file at the repository.This willinclude, but is not limited to, proof of institutional and/orSCRO approval of the process for procurement of researchmaterials according to ethical and legal principles ofprocurement as outlined in these Guidelines, approval ofprotocols for derivation of new lines, copies of the donorinformed consent documents and what, if any,reimbursement of direct expenses or financialconsiderations of any kind were provided to the donors.
12.2c) Repository should obtain all technical informationfrom depositor. For example, methods used in the derivationof lines, culture conditions, infectious disease testing, passagenumber and characterization data. Repository will make thisinformation publicly available. If repository modifiesdepositor’s protocols or obtains additional data this will alsobe made available.
12.2d) Repository should engage in, but is not limited to,the following:
i) Reviewing and accepting deposit applicationsii) Assigning unique identifiers (catalogue number) to depositsiii) Characterizing cell linesiv) Human pathogen testingv) Expansion, maintenance and storage of hESC linesvi) Quality assurance and quality control of all proceduresvii) Maintenance of website with pertinent characteri-zation data, protocols and availability of hESC linesviii) Tracking distributed cell linesix) Posting a clear cost schedule for distribution ofmaterials. Repositories should distribute international-ly and charge only the necessary costs, which includeshipping and handling.
12.3) Provenance of stem cell lines: Owing to the nature ofthe materials involved in the generation of human stem cell lines,appropriate safeguards should be used to protect the privacy ofdonors and donor information. In order for the stem cell lines tobe as useful as possible and so as not to preclude future potentialtherapeutic applications, as much donor information as possibleshould be maintained along with the cell line, including, but notlimited to: ethnic background, medical history, and infectiousdisease screening. Subject to local laws, donor samples and celllines should be de-identified (anonymized) and coded usinginternationally accepted standards for maintaining privacy.Informed consent and donor information will be gathered andmaintained by the repository, including whatever reimbursementof direct expenses or financial considerations of any kind wereprovided in the course of the procurement. Documentation ofthe provenance of the cell lines is critical if the cell lines are to bewidely employed in the research community, and the provenancemust be easily verified by access to the relevant documents.
12.4) Maintenance of a database of human stem cell linesand verification of provenance: The ISSCR will curate andmaintain a website listing of human stem cell lines that testifies toindependent validation of the provenance of the cell lines. It willbecome the responsibility of the ISSCR Standards Committee toscrutinize the documents relevant to the derivation of stem celllines to vouch for the provenance of the cell lines, according tothe principles laid out in these Guidelines.
13) Dispute resolution
Any conflicts of interest or other conflicts or disputes that mayarise in the course of any international collaboration, for example,disagreements or difference of opinions between researchersfrom different countries involved in common projects, may beresolved in accordance with an agreed-upon dispute resolutionmechanism in a forum with international representation fromcountries doing research and clinical trials in human stem cells.Members of the forum will, as appropriate, seek guidance fromexperts in the fields of science, ethics, law and medicine fromdifferent national, social and religious backgrounds. It isrecommended that all international collaboration agreementsincorporate a dispute resolution provision providing that anydisputes or differences shall be settled through mediation orarbitration by international forum, and this provision shallstipulate whether or not any decision made by the forum will bebinding on the relevant parties.
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Classical embryology used the term embryo to connotedifferent stages of post-implantation stages of development(e.g. the primitive streak and onwards to fetal stages).Indeed, Dorland’s Illustrated Medical Dictionary (27thedition,1988 edition,W. B. Saunders Company) provides thedefinition “in animals, those derivatives of the fertilized ovumthat eventually become the offspring, during their period ofmost rapid development, i.e., after the long axis appears untilall major structures are represented. In man, the developingorganism is an embryo from about 2 weeks after fertilizationto the end of seventh or eighth week.” An entry in RandomHouse Webster’s College Dictionary reads “in humans, thestage approximately from attachment of the fertilized egg tothe uterine wall until about the eighth week of pregnancy.”However, the nomenclature is often extended by modernembryologists for the human to include the stages from firstcleavage of the fertilized ovum onwards to seven to nineweeks of gestation, after which the term fetus is used.
Zygote: The fertilized single cell pronuclear ovum (egg),typically observed in humans between 20 to 35 hours afterinsemination with sperm.
Cleavage Stage Embryo (pre-implantation stage):The cleaving or dividing zygote; precise terms include the 2-cell, 4-cell, 8-cell and 16-cell embryo. In humans, eachcleavage division consumes around 18 to 24 hours.
Morula: The compacting grape-like cluster of 16-cells,typically formed 4 days after fertilization.
Blastocyst: The embryonic stage formed from 64 cellsonward, defined by the pumping of fluid into an internalspace.The blastocyst is surrounded by a ring of differentiatedtrophectoderm cells, and encloses a nest of 10 to 25 cellstermed the Inner Cell Mass (ICM).The trophectoderm cellsattach the embryo to the uterine wall, and the ICM formsthe embryo proper. The blastocyst forms 5 to 7 days afterfertilization.The blastocyst hatches from the zona pellucida(glycoprotein shell) around days 6 to 7 after fertilization.Thereafter, and coupled to implantation, which providesrequisite signals for the maturation of the embryo, the ICMof the blastocyst begins to organize itself into a long axiswith anterior and posterior orientation. If isolated from thetrophectoderm, the ICM never adopts an axis, and after thistime it is not possible for the cultured ICM to form anorganism, but instead will form a teratoma (disorganizeddifferentiating cell body) when transplanted.
Gastrula: The embryonic stage of formation of thetrilaminar embryonic disc, leading to the specification ofectoderm, endoderm, and mesoderm.
Neurula: The embryonic stage when the neural plate isclosing to form the neural tube.
Parthenogenetic embryo: Activation of the unfertilizedmammalian ovum can result in embryonic development, andembryonic stem cells can be derived from the ICMs ofparthenogenetic blastocysts. After uterine transfer,parthenogenetic embryos can progress to a fetal stage, butfurther development is compromised by an underdevelopedplacental system that prevents normal gestation.
Gynogenesis: A particular form of parthenogenesis inwhich an embryo is created from the genetic contributions(female pronuclei) of two different fertilized oocytes.
Androgenesis: The creation of an embryo thatincorporates the male pronuclei from two different fertilizedoocytes.
Nuclear Transfer: The insertion of a nucleus of a cell intoan ovum from which the nuclear material (chromosomes)has been removed.The ovum will reprogram (incompletely)the cell nucleus to begin development again. Embryoscreated by nuclear transfer are typically abnormal and oftendie during development, but rarely are capable ofdevelopment to term. ICMs from blastocysts derived bynuclear transfer will form apparently normal embryonicstem cells.
Altered Nuclear Transfer:A process whereby the geneticmaterial of the donor cell is altered prior to nuclear transfer,such that implantation and subsequent development of anembryo is not possible. Pluripotent stem cells can be derivedfollowing the process of altered nuclear transfer.
This technique was employed in the mouse by knock-downof expression of the cdx2 gene. The cdx2 gene product iscritical for the formation of the trophoblast which is criticalfor post-implantation development. When expression ofcdx2 was knocked-down by short hairpin RNAs in thedonor cell nucleus prior to nuclear transfer, thedevelopmental potential of the nuclear transfer embryo wascompromised; the trophoblast was unable to develop andsupport post-implantation development. However, ICMstructures formed, and embryonic stem cells weresuccessfully generated.
Meissner, A., and Jaenisch, R. (2006). Generation of nuclear transfer-
derived pluripotent ES cells from cloned Cdx2-deficient blastocysts.
Nature 439, 212-215.
Fetus: In this document, the term ‘fetus’ is used to describepost-embryonic stages of prenatal development, after majorstructures have formed. In humans, this period is from sevento nine weeks after fertilization until birth.
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16.1b) Terminology relating to developmental potential
Totipotent: The state of a cell that is capable of giving riseto all types of differentiated cells found in an organism, aswell as the supporting extra-embryonic structures of theplacenta. A single totipotent cell could, by division in utero,reproduce the whole organism.
Pluripotent: The state of a single cell that is capable ofdifferentiating into all tissues of an organism, but not alonecapable of sustaining full organismal development, becausefor instance, it lacks competency to generate the supportingextra-embryonic structures of the placenta.
16.1c) The term ‘chimera’ in stem cell research
Trace Chimeras: The simplest form of chimera is one inwhich a limited number of human cells are introduced at anystage of pre-or post-natal development, and whereincorporation into any lineage or tissue is likely to beminimal. An example is the use of an immuno-deficientmouse as a host to study tumor formation from a humancancer cell line. Such chimeras require oversight appropriateto animal use and biosafety (among others as deemedappropriate by local regulatory bodies), and typically will notraise significant concerns unique to human stem cells. Anytrace human/animal chimera that carries human germ-lineage cells bears special concern.
Interspecies Chimeras: Interspecies chimeras are thoseanimals containing extensive and integrated cellularcontributions from another species.There are two types oftrue human/animal chimeras bearing special concern: thoseformed at the earliest stages of development and thoseformed later but contributing a significant degree ofchimerism to the central nervous system and/or germline.Human/non-human primate chimeras formed at any stage ofdevelopment warrant particular attention. Human/non-human chimeras bearing central nervous system chimerismalso warrant particular attention.
Hybrids: Animals formed in which each of the individualcells carry roughly equal genetic contributions from twodistinct species resulting from inter-breeding of species orfusion of genetic material. Examples include the mule (horsebred to a donkey). Hybrids are only likely to survive if thegenetic contributions derive from closely related species.The greatest concern would be for experiments that entailcreation of hybrids between humans and closely related non-human primates.
16.2) Weblinks: international, national and localregulations and reports pertinent to stem cell research
Belmont Report (1979)Ethical Principles and Guidelines for the Protection ofHuman Subjects of Researchhttp://ohsr.od.nih.gov/guidelines/belmont.html
Council for International Organizations forBiomedical Sciences (CIOMS): International EthicalGuidelines for Biomedical Research InvolvingHuman Subjects (2002)http://www.cioms.ch/frame_guidelines_nov_2002.htm
Guidelines for Human Embryonic Stem Cell ResearchAuthored by the Committee on Guidelines for HumanEmbryonic Stem Cell Research, NATIONAL RESEARCHCOUNCIL AND INSTITUTE OF MEDICINE OF THENATIONAL ACADEMIES (USA)http://www.nap.edu/books/0309096537/html
Hinxton Group’s Consensus Statement (2006)http://hinxtongroup.org/consensus/consensus.html
Human Fertilisation and Embryology Authority(HFEA)Home Pagehttp://www.hfea.gov.uk/cps/rde/xchg/hfeaCode of Practicehttp://www.hfea.gov.uk/cps/rde/xchg/SID-3F57D79B-F6DA3CC3/hfea/hs.xsl/411.htmlResearch licence applicationhttp://www.hfea.gov.uk/cps/rde/xchg/SID-3F57D79B-F6DA3CC3/hfea/hs.xsl/376.htmlEU Tissues and Cells Directiveshttp://www.hfea.gov.uk/cps/rde/xchg/SID-3F57D79B-F6DA3CC3/hfea/hs.xsl/493.html
Nuremburg Code (1947)http://www.nihtraining.com/ohsrsite/guidelines/nuremberg.html
Regulations of the California Institute forRegenerative MedicineMedical and Ethical Standards Regulationshttp://www.cirm.ca.gov/laws/default.asp
UNESCO Universal Declaration on Bioethics andHuman Rights (2005)http://portal.unesco.org/shs/en/ev.php-URL_ID=1883&URL_DO=DO_TOPIC&URL_SECTION=201.html
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World Medical Association Declaration of Helsinki(1964 and updates)Ethical Principles for Medical Research Involving HumanSubjectshttp://www.wma.net/e/policy/b3.htm
16.3) Sample consent documents for procurement ofhuman biological research materials for stem cellresearch
Egg donation for stem cell research; provideddirectly and solely for stem cell researchhttp://www.isscr.org/guidelines/CFeggsresearch.doc
Egg donation for stem cell research; collected during the course of fertility treatment and inexcess of clinical needhttp://www.isscr.org/guidelines/CFeggsexcessofclinical.doc
Embryo donation for stem cell research; created forfertility purposes and in excess of clinical needhttp://www.isscr.org/guidelines/CFembryos.doc
Somatic cell donation for stem cell researchhttp://www.isscr.org/guidelines/CFsomatic.doc
Sperm donation for stem cell researchhttp://www.isscr.org/guidelines/CFsperm.doc
Acknowledgments. The sample informed consent documentswere compiled by task force member Insoo Hyun, Ph.D. TheISSCR also wishes to acknowledge the following individuals forreviewing the documents and providing feedback on their content(this acknowledgment does not imply that the individuals listedfully endorse the design and content of the documents, as theseexist as samples that must be modified according to individualresearch protocols and ultimately approved through a process ofStem Cell Research Oversight): Melinda Abelman, Jessica Berg,Bernard Dickens, Kate Heffernan, Jeffrey Jones, Kyu Won Jung, EngHin Lee, Bernard Lo, Patricia Marshall, Alan Meisel, JonathanMoreno, Ralph Nachman, Pearl O’Rourke, John Robertson,Jeremy Sugarman, and Patrick Taylor.
16.4) Sample Material Transfer Agreement (MTA)[Adapted and modified from the uniform biological materialtransfer agreement published in the Federal Register, February 18,1995]
Sample Material Transfer Agreement (MTA) documenthttp://www.isscr.org/guidelines/mta.doc
Acknowledgment. The sample material transfer agreementdocument was prepared by task force member Patrick Taylor,JD.
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ISSCR SAMPLE RESEARCH CONSENT FORM Egg Procurement for Stem Cell Research
(Eggs Provided Directly and Solely for Stem Cell Research) Project Title: Principal Investigator: Participating Institution(s): PROJECT INFORMATION You are being asked to provide eggs for a human embryonic stem cell research project led by [name of principal investigator] at [name(s) of institution(s)]. Embryonic stem cells can be found in embryos around the fifth day of development. These stem cells have the unique ability to turn into any kind of specialized human cell, such as liver cells, heart cells, pancreatic cells, or nerve cells. For this reason, embryonic stem cells can be used to study, and possibly one day help treat, diseases or injuries that have caused patients’ specialized cells to die or become damaged – diseases and injuries such as Parkinson’s disease, heart disease, diabetes, and spinal cord injury. [Name of principal investigator] wants to collect new human embryonic stem cells from embryos that have been created by [as applicable: nuclear transfer; parthenogenesis; the union of sperm and egg.] [As applicable: “Nuclear transfer” is the process by which researchers place donated adult body cells into unfertilized eggs that have had their DNA removed. If successful, this technique can create embryos that contain stem cells which are genetically matched to the body cell donors.] [As applicable: “Parthenogenesis” is the process by which an unfertilized egg is stimulated to begin going through the very early stages of human development. Stem cells that arise from parthenogenesis would be genetically matched to the person who provided the unfertilized egg.] [Insert additional information about this project using very simple language.] VOLUNTARY CHOICE Providing your eggs for this research project is completely voluntary. You have the right to agree or to refuse to provide your eggs for this project. The quality of your current or future medical care and your relationship with [name(s) of institution(s)] will NOT
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change in any way whether you agree or refuse to provide any eggs for this research project. WHAT IS THE PURPOSE OF THIS CONSENT FORM? [Name of person obtaining consent] is authorized to give you information and to answer your questions about this research project. It is very important that you have a detailed conversation with this person so that you can make a careful, voluntary decision about whether or not you want to provide your eggs for this research project. Your signature on the last page of this consent form is meant to show that you have had this conversation and that you freely agree to provide your eggs for this research project. This consent form must not replace actually having this conversation, so be certain you have this conversation. Please take as much time as you need to ask questions and to talk about this project with your family or friends before you decide whether or not to sign this consent form. You may take this form home with you before you decide what to do. Do not sign this form if you feel pressured in any way by any person to provide your eggs for this project. This must be your own decision, not someone else’s. WHAT WILL HAPPEN TO MY EGGS? None of the eggs you provide for this research project will be used to produce a baby or a pregnancy. And no embryos created from your eggs will be allowed to develop for more than a total of 14 days after they have been [as applicable: created through nuclear transfer; created through parthenogenesis]. If any of the resulting embryos are frozen, then the time that they are frozen is not counted as part of the 14 day limit. Researchers will only use your eggs to create embryos from which they will attempt to get stem cells before the 14 day limit. The resulting embryos will be destroyed during the stem cell collection process. There is no guarantee that embryos will be successfully created from your eggs. And there is no guarantee that researchers will be able to get stem cells from any resulting embryos. Researchers will routinely discard as medical waste any eggs which are not used for this research project, as well as any embryos from which they are unable to get stem cells. WHAT WILL HAPPEN TO THE COLLECTED STEM CELLS? It is likely that the retrieved stem cells will be stored for many years. Embryonic stem cells have the ability to self-renew indefinitely, and they are likely to be used by researchers at other institutions and for many other research purposes.
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One possible research use of these stored stem cells might involve changing some of their genes. Another possible research use might be to study some of the stem cells by placing them into laboratory animals. In addition, the stored stem cells might be used in the future for new research related to human stem cell transplantation. These are just three common examples of what might happen to the stored stem cells. But there are many other future possible research uses that are simply unknown at this time. You will have no say as to which institutions or researchers may share the stem cells made from the embryos that were created using your eggs. If stem cell transplantation studies are developed in the future, you will have no say as to who may be a transplant recipient of the collected stem cells [as applicable: except in the case of autologous transplantation after parthenogenesis]. Future uses of stored stem cells must be approved by local ethical and scientific review committees to make sure that they are used in scientifically, ethically, and legally appropriate ways. Please contact the individuals listed on the last page of this form if you have any questions or concerns about the future possible uses of the stem cells collected through this research project. WHAT IS THE EGG RETRIEVAL PROCEDURE? If you decide to provide your eggs for this research project, you will have to undergo several steps. First you will meet with fertility physicians and nurses to discuss in detail the medical procedures involved in egg retrieval. These individuals are qualified to discuss with you in much more detail the procedures and the risks of hormonal stimulation and egg retrieval. You will be asked to sign another consent form for these medical procedures specifically. It is important to emphasize that the consent form you now hold in your hands is not a substitute for these medical consent forms. [As applicable: The person authorized to give you information about this stem cell research project is not authorized to lead you through an informative conversation about hormonal stimulation and egg retrieval.] You will undergo medical testing to screen you for genetic and infectious diseases. [Specify which tests will be conducted and whether the volunteer will have access to these test results.] After your medical tests, you will have to give yourself hormonal injections daily for up to three weeks in order to stimulate your ovaries to produce mature eggs. If you are unwilling to give yourself these shots, you may have another person do this for you.
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When your ovaries are ready, doctors will retrieve your eggs by inserting a needle through your vagina and into one or both of your ovaries. Anesthesia and/or sedatives will be used during this process, which will take about thirty minutes. WHAT ARE THE POTENTIAL RISKS OF PROVIDING EGGS FOR THIS RESEARCH PROJECT? There are several risks associated with hormonal stimulation and egg retrieval. [As applicable: A fertility physician who is not a member of the research team will discuss these risks with you in far more detail.] Hormonal stimulation poses a possible risk of severe ovarian hyperstimulation syndrome. This is a serious medical condition that, if left untreated, may lead to kidney failure, infertility, and in extremely rare cases, death. These risks can be greatly reduced if doctors use low doses of hormonal stimulation drugs and if your response to these drugs is monitored daily by health professionals. [As applicable: Therefore, these safety measures will be followed for your care.] Other possible risks include bleeding, discomfort, infection, cramping, mood swings, unintended pregnancy, and complications associated with anesthesia. Hormonal stimulation may also pose some unknown long-term health risks. At this time, scientists do not know for certain what kinds of long-term negative effects, if any, these drugs may have on your fertility or your risk for developing cancer. You should discuss any concerns you may have about these uncertainties with a physician. The egg retrieval procedure carries some risk that the needle used to retrieve your eggs from your ovaries might accidentally puncture one of your organs or blood vessels. There are some psychological risks involved in providing your eggs for this project. Some women who provide eggs for stem cell research might experience feelings of anxiety or regret, especially when considering the possibility that their eggs may result in the creation of embryos that will be destroyed during the stem cell collection process. Some may also feel vulnerable and anxious during the consent process. All egg providers will be asked to undergo medical screening tests for genetic and infectious diseases. While these medical tests involve minimal physical risk, such as from a blood draw, some women may feel anxious about their test results Due care will be taken to help minimize these psychological risks. [Specify how this will be done, e.g. whether counseling services will be provided upon request.] Providing eggs for this project involves some risk to your privacy. Efforts to protect you against this risk are discussed in the section entitled HOW WILL MY PRIVACY BE PROTECTED?
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WHAT WILL HAPPEN IF I GET A RESEARCH RELATED INJURY? We are obligated to inform you about [name of institution(s)’] policy in the event that injury occurs resulting from your participation. [Insert description of the institution’s policy addressing provision of healthcare and/or compensation related to injury resulting from participation.] WHAT ARE THE POTENTIAL BENEFITS OF PROVIDING EGGS FOR THIS PROJECT? This research project is not intended to provide any direct medical benefit to you or anyone else. You would be providing your eggs solely for the advancement of this research project and stem cell research in general. [As applicable: The stem cells that are collected from the resulting embryos may have significant commercial potential in the future. However, by signing this form you understand that there are no plans for you to receive any direct financial benefits from any future commercial development and scientific patents of discoveries made through the use of these stem cells.] WHAT IF I CHANGE MY MIND? You may withdraw your consent for whatever reason at any time before or during the egg retrieval process. Similarly, you may also withdraw your consent after your eggs have been retrieved, but before they are used in research. However, once the resulting embryos are destroyed in the stem cell collection process, you will not be able to change your mind or request that any of the collected stem cells be removed from this research project. If you decide to withdraw your consent after you have signed this form, please contact any of the individuals listed at the end of this document immediately. WHAT ARE THE ALTERNATIVES TO PROVIDING MY EGGS FOR THIS PROJECT? One of your alternatives is to refuse to participate at all in this research project. You may decide to do nothing, or you may decide to undergo hormonal induction specifically to donate your eggs for fertility treatment or another research project. The study staff would be happy to talk with you about other possible alternatives outside of this research project. In the case that your eggs are retrieved but you decide not to participate any longer in this research project, you may (1) have them discarded according to the routine practice of [name of institution], (2) donate your eggs to another research project, (3) donate your eggs to other individuals for fertility treatment, or (4) use them for your own fertility
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treatment, if necessary. Please note that your retrieved eggs will no longer be suitable for reproductive use once they are transferred to Dr. (principal investigator)’s laboratory and prepared for research. Also, if you decide to use your eggs for your own or others’ fertility treatment, you may have to undergo additional screening tests. HOW WILL MY PRIVACY BE PROTECTED? The records of your involvement with this research project will be kept confidential. Identification codes will be used instead of names, and all records will be kept in a private database that can only be accessed by ___________________ (person). The results of your medical screen tests will also be confidentially handled through the use of identification codes instead of names. [Specify how this information will be protected and whether the identification code will be linked to the egg providers and under what circumstances these providers will be identified.] [As applicable: If your eggs undergo parthenogenesis, then the resulting stem cells and any new stem cells that they produce will be a complete genetic match to you. To protect your genetic privacy, only your identification code, not your name, will be discoverable to the researchers who collect these stem cells and the researchers who may later work with the resulting stored stem cells.] [As applicable: Some stem cell researchers working with genetic diseases may want to see genetic information about the egg donors. If you agree to allow these researchers to see this coded information, please check yes. _____ yes _____ no ] [As applicable: Research on the collected stem cells may reveal information that could be important to your health. If you wish to be contacted in the future about any such information, please check yes. _____ yes _____ no ] [As applicable: If you answered “yes” to this question, (name of institution) will, to the extent possible, pass to you any information that it is given from other researchers or other institutions regarding important information received through research on the collected stem cells.] Local and other regulatory agencies, and project sponsors and funding agencies may review the research project records to ensure that your rights as an egg provider were adequately protected. However, your identity will not be readily discoverable to these individuals. Any report that the researchers publish will not include any information that will make it possible for readers to identify you as an egg provider. WILL I RECEIVE PAYMENT?
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You will not receive any cash or payment with goods or services for the number or the quality of the eggs you provide for this research project. [As applicable: Any reimbursements for money you had to spend to participate in the consent process will be decided by local and other relevant review committees.] [As applicable: You will receive a compensation amount of $______ in recognition of your time, effort, and inconvenience. This amount has been decided by local and other relevant review committees based on local community standards for paying other healthy research volunteers for their time, effort, and inconvenience.] DISCLOSURE OF RESEARCHERS’ POTENTIAL FINANCIAL INTERESTS In addition to their scientific interests in this research project, the individuals conducting this stem cell study might profit financially from the research. There may be current or potential financial benefits to the Principal Investigator, [name], the participating institution(s), [names], and other research institutions or researchers arising from discoveries made through this research project and the stem cells collected from your donated embryos. [Disclose using plain language the researchers’ and the institution(s)’ financial interests in the research.] If you have any questions or concerns about these matters, please contact the persons listed below. [As applicable: If you are undergoing fertility treatment, it is important that your physician inform you of any personal benefits he or she may gain by your agreement to provide eggs for this research project. (Disclose here any potential personal benefits the treating physician may receive through this research protocol.)] The person who has been authorized to provide you with information may also have a personal vested interest in this research project. [Disclose here any potential personal benefits this person may have in this research protocol.] CONTACT INFORMATION If you have any questions about this research project, contact: (Principal Investigator)______________________________(phone)_________________ [List any toll-free or reverse-charge line.] (Research Administrator) ___________________________(phone)_________________
[List any toll-free or reverse-charge line.] If you have any questions about your rights as an egg provider, contact:
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(Review Board Member)____________________________(phone)_________________ [List any toll-free or reverse-charge line.]
If you have any questions about the egg retrieval process, contact: (Physician)_______________________________________(phone)_________________ [List any toll-free or reverse-charge line.] CONSENT AND SIGNATURE Please read the statements below, think about your choice, and sign if and when you are ready to agree, or take this form home and discuss it with anyone you wish to and then return it to us later if you wish to participate in this research: [Name of person obtaining consent] has fully explained to me the nature and purpose of this research project in a way that I have understood. [He/she] has encouraged me to be actively involved during the information interview and has responded to all of my questions and concerns in a satisfactory and respectful way. [He/she] has offered me opportunities to consult with an independent person whom I trust, including a counselor or a physician, prior to my making my decision and has given me adequate time to decide. I hereby give my voluntary consent to provide up to __________ (insert number) eggs for the research project entitled [Project Title] conducted by [Principal Investigator] at [Participating Institution(s)]. _____________________________Date:__________ __________________________ Signature of Egg Provider Printed Name _____________________________Date:__________ __________________________ Signature of Person Obtaining Consent Printed Name Copy given to egg provider:_____Yes
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ISSCR SAMPLE RESEARCH CONSENT FORM Egg Donation for Stem Cell Research
(Eggs Collected During the Course of Fertility Treatment and In Excess of Clinical Need) Project Title: Principal Investigator: Participating Institution(s): PROJECT INFORMATION [Name of principal investigator] is conducting a human embryonic stem cell research project at [name(s) of institution(s)]. He/she hopes you will donate any eggs you decide not to use in the course of your own or others’ fertility treatment. [Specify whether the eggs to be used are normal or failed-to-fertilize eggs.] Embryonic stem cells can be found in embryos around the fifth day of development. These stem cells have the unique ability to turn into any kind of specialized human cell, such as liver cells, heart cells, pancreatic cells, or nerve cells. For this reason, embryonic stem cells can be used to study, and possibly one day help treat, diseases or injuries that have caused patients’ specialized cells to die or become damaged – diseases and injuries such as Parkinson’s disease, heart disease, diabetes, and spinal cord injury. [Name of principal investigator] wants to collect new human embryonic stem cells from embryos that have been created by [as applicable: nuclear transfer; parthenogenesis; the union of sperm and egg]. [As applicable: “Nuclear transfer” is the process by which researchers place donated body cells into unfertilized eggs that have had their DNA removed. If successful, this technique can create embryos that contain stem cells which are genetically matched to the body cell donors.] [As applicable: “Parthenogenesis” is the process by which an unfertilized egg is stimulated to begin going through the very early stages of human development. Stem cells that arise from parthenogenesis would be genetically matched to the person who provided the unfertilized egg.] [Insert additional information about this project using very simple language.] VOLUNTARY CHOICE Donating your eggs for this research project is completely voluntary. You have the right to agree or to refuse to donate your eggs for this project. The quality of your current or
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future medical care and your relationship with [name(s) of institution(s)] will NOT change in any way whether you agree or refuse to donate any eggs for this project. WHAT IS THE PURPOSE OF THIS CONSENT FORM? [Name of person obtaining consent] is authorized to give you information and to answer your questions about this research project. It is very important that you have a detailed conversation with this person so that you can make a careful, voluntary decision about whether or not you want to donate your eggs for this research project. Your signature on the last page of this consent form is meant to show that you have had this conversation and that you freely agree to donate your eggs for this research project. This consent form must not replace actually having this conversation, so be certain you have this conversation. Please take as much time as you need to ask questions and to talk about this project with your family or friends before you decide whether or not to sign this consent form. You may take this form home with you before you decide what to do. Do not sign this form if you feel pressured in any way by any person to donate your eggs for this project. This must be your own decision, not someone else’s. WHAT WILL HAPPEN TO MY EGGS? None of the eggs you donate for this research project will be used to produce a baby or a pregnancy. And no embryos created from your eggs will be allowed to develop for more than a total of 14 days after they have been [as applicable: created through nuclear transfer; created through parthenogenesis]. If any of the resulting embryos are frozen, then the time that they are frozen is not counted as part of the 14 day limit. Researchers will only use your eggs to create embryos from which they will attempt to get stem cells before the 14 day limit. The resulting embryos will be destroyed during the stem cell collection process. There is no guarantee that embryos will be successfully created from your eggs. And there is no guarantee that researchers will be able to get stem cells from any resulting embryos. Researchers will routinely discard as medical waste any eggs which are not used for this research project, as well as any embryos from which they are unable to get stem cells. WHAT WILL HAPPEN TO THE COLLECTED STEM CELLS? It is likely that the retrieved stem cells will be stored for many years. Embryonic stem cells have the ability to self-renew indefinitely, and they are likely to be used by researchers at other institutions and for many other research purposes.
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One possible research use of these stored stem cells might involve changing some of their genes. Another possible research use might be to study some of the stem cells by placing them into laboratory animals. In addition, the stored stem cells might be used in the future for new research related to human stem cell transplantation. These are just three common examples of what might happen to the stored stem cells. But there are many other future possible research uses that are simply unknown at this time. You will have no say as to which institutions or researchers may share the stem cells made from the embryos that were created using your eggs. If stem cell transplantation studies are developed in the future, you will have no say as to who may be a transplant recipient of the collected stem cells [as applicable: except in the case of autologous transplantation after parthenogenesis]. Future uses of stored stem cells must be approved by local ethical and scientific review committees to make sure that they are used in scientifically, ethically, and legally appropriate ways. Please contact the individuals listed on the last page of this form if you have any questions or concerns about the future possible uses of the stem cells collected through this research project. WHAT IS THE EGG RETRIEVAL PROCEDURE? After your eggs are retrieved at (fertility clinic facility), with your permission, some of your eggs will be transferred to Dr. (principal investigator)’s research laboratory. The egg retrieval procedure itself at (fertility clinic facility) will involve several steps. First you will meet with fertility physicians and nurses to discuss in detail the medical procedures involved in egg retrieval. These individuals are qualified to discuss with you in much more detail the procedures and the risks of hormonal stimulation and egg retrieval. You will be asked to sign another consent form for these medical procedures specifically. It is important to emphasize that the consent form you now hold in your hands is not a substitute for these medical consent forms. [As applicable: The person authorized to give you information about this stem cell research project is not authorized to lead you through an informative conversation about hormonal stimulation and egg retrieval.] You will undergo medical testing to screen you for genetic and infectious diseases. [Specify which tests will be conducted and whether the volunteer will have access to these test results.] After your medical tests, you will have to give yourself hormonal injections daily for up to three weeks in order to stimulate your ovaries to produce mature eggs. If you are unwilling to give yourself these shots, you may have another person do this for you.
33
When your ovaries are ready, doctors will retrieve your eggs by inserting a needle through your vagina and into one or both of your ovaries. Anesthesia and/or sedatives will be used during this process, which will take about thirty minutes. WHAT ARE THE POTENTIAL RISKS OF DONATING EGGS FOR THIS RESEARCH PROJECT? While there are no additional physical risks posed by your donating (transferring) some of your eggs to this stem cell research project, there are however several risks associated with hormonal stimulation and egg retrieval. [As applicable: A fertility physician who is not a member of the research team will discuss these risks with you in far more detail.] Hormonal stimulation poses a possible risk of severe ovarian hyperstimulation syndrome. This is a serious medical condition that, if left untreated, may lead to kidney failure, infertility, and in extremely rare cases, death. These risks can be greatly reduced if doctors use low doses of hormonal stimulation drugs and if your response to these drugs is monitored daily by health professionals. [As applicable: Therefore, these safety measures will be followed for your care.] Other possible risks include bleeding, discomfort, infection, cramping, mood swings, unintended pregnancy, and complications associated with anesthesia. Hormonal stimulation may also pose some unknown long-term health risks. At this time, scientists do not know for certain what kinds of long-term negative effects, if any, these drugs may have on your fertility or your risk for developing cancer. You should discuss any concerns you may have about these uncertainties with a physician. The egg retrieval procedure carries some risk that the needle used to retrieve your eggs from your ovaries might accidentally puncture one of your organs or blood vessels. There are some psychological risks involved in donating your eggs for this project. Some women who donate eggs for stem cell research might experience feelings of anxiety or regret, especially when considering the possibility that their eggs may result in the creation of embryos that will be destroyed during the stem cell collection process. Some may also feel vulnerable and anxious during the consent process. All egg donors will be asked to undergo medical screening tests for genetic and infectious diseases. While these medical tests involve minimal physical risk, such as from a blood draw, some women may feel anxious about their test results Due care will be taken to help minimize these psychological risks. [Specify how this will be done, e.g. whether counseling services will be provided upon request.]
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Donating eggs for this project involves some risk to your privacy. Efforts to protect you against this risk are discussed in the section entitled HOW WILL MY PRIVACY BE PROTECTED? WHAT WILL HAPPEN IF I GET A RESEARCH RELATED INJURY? We are obligated to inform you about [name of institution(s)’] policy in the event that injury occurs resulting from your participation. [Insert description of the institution’s policy addressing provision of healthcare and/or compensation related to injury resulting from participation.] WHAT ARE THE POTENTIAL BENEFITS OF DONATING EGGS FOR THIS PROJECT? This research project is not intended to provide any direct medical benefit to you or anyone else. You would be donating your eggs solely for the advancement of this research project and stem cell research in general. [As applicable: The stem cells that are collected from the resulting embryos may have significant commercial potential in the future. However, by signing this form you understand that there are no plans for you to receive any direct financial benefits from any future commercial development and scientific patents of discoveries made through the use of these stem cells.] WHAT IF I CHANGE MY MIND? You may withdraw your consent to participate in this research project for whatever reason at any time before or during the egg retrieval process. Similarly, you may also withdraw your consent after your eggs have been retrieved, but before they are used for research. However, once the resulting embryos are destroyed in the stem cell collection process, you will not be able to change your mind or request that any of the collected stem cells be removed from this research project. If you decide to withdraw your consent after you have signed this form, please contact any of the individuals listed at the end of this document immediately. WHAT ARE THE ALTERNATIVES TO DONATING MY EGGS FOR THIS PROJECT? One of your alternatives is to refuse to donate any eggs to this research project. In the case that you agree to donate some of your eggs but change your mind after your eggs are retrieved, you may (1) use them for your own fertility treatment, (2) donate your eggs to other individuals for fertility treatment, (3) donate your eggs to another research
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project, or (4) have them discarded according to the routine practice of [name of institution]. Please note that once your eggs have been transferred to Dr. (principal investigator)’s laboratory and prepared for research, they will no longer be suitable for reproductive use. HOW WILL MY PRIVACY BE PROTECTED? The records of your involvement with this research project will be kept confidential. Identification codes will be used instead of names, and all records will be kept in a private database that can only be accessed by ___________________ (person). The results of your medical screen tests will also be confidentially handled through the use of identification codes instead of names. [Specify how this information will be protected and whether the identification code will be linked to the egg providers and under what circumstances these providers will be identified.] [As applicable: If your eggs undergo parthenogenesis, then the resulting stem cells and any new stem cells that they produce will be a complete genetic match to you. To protect your genetic privacy, only your identification code, not your name, will be discoverable to the researchers who collect these stem cells and the researchers who may later work with the resulting stored stem cells.] [As applicable: Some stem cell researchers working with genetic diseases may want to see genetic information about the egg donors. If you agree to allow these researchers to see this coded information, please check yes. _____ yes _____ no ] [As applicable: Research on the collected stem cells may reveal information that could be important to your health. If you wish to be contacted in the future about any such information, please check yes. _____ yes _____ no ] [As applicable: If you answered “yes” to this question, (name of institution) will, to the extent possible, pass to you any information that it is given from other researchers or other institutions regarding important information received through research on the collected stem cells.] Local and other regulatory agencies, and project sponsors and funding agencies may review the research project records to ensure that your rights as an egg donor were adequately protected. However, your identity will not be readily discoverable to these individuals. Any report that the researchers publish will not include any information that will make it possible for readers to identify you as an egg donor.
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WILL I RECEIVE PAYMENT? You will not receive any cash or payment with goods or services for the number or the quality of the eggs you donate for this research project. [As applicable: Any reimbursements for money you had to spend to participate in the consent process will be decided by local and other relevant review committees.] DISCLOSURE OF RESEARCHERS’ POTENTIAL FINANCIAL INTERESTS In addition to their scientific interests in this research project, the individuals conducting this stem cell study might profit financially from the research. There may be current or potential financial benefits to the Principal Investigator, [name], the participating institution(s), [names], and other research institutions or researchers arising from discoveries made through this research project and the stem cells collected from your donated embryos. [Disclose using plain language the researchers’ and the institution(s)’ financial interests in the research.] If you have any questions or concerns about these matters, please contact the persons listed below. If you are undergoing fertility treatment, it is important that your physician inform you of any personal benefits he or she may gain by your agreement to provide eggs for this research project. [Disclose here any potential personal benefits the treating physician may receive through this research protocol.] The person who has been authorized to provide you with information may also have a personal vested interest in this research project. [Disclose here any potential personal benefits this person may have in this research protocol.] CONTACT INFORMATION If you have any questions about this research project, contact: (Principal Investigator)______________________________(phone)_________________ [List any toll-free or reverse-charge line.] (Research Administrator) ___________________________(phone)_________________
[List any toll-free or reverse-charge line.] If you have any questions about your rights as an egg donor, contact: (Review Board Member)____________________________(phone)_________________
[List any toll-free or reverse-charge line.]
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If you have any questions about the egg retrieval process, contact: (Physician)_______________________________________(phone)_________________ [List any toll-free or reverse-charge line.] CONSENT AND SIGNATURE Please read the statements below, think about your choice, and sign if and when you are ready to agree, or take this form home and discuss it with anyone you wish to and then return it to us later if you wish to participate in this research: [Name of person obtaining consent] has fully explained to me the nature and purpose of this research project in a way that I have understood. [He/she] has encouraged me to be actively involved during the information interview and has responded to all of my questions and concerns in a satisfactory and respectful way. [He/she] has offered me opportunities to consult with an independent person whom I trust, including a counselor or a physician, prior to my making my decision and has given me adequate time to decide. I hereby give my voluntary consent to donate up to __________ (insert number) eggs for the research project entitled [Project Title] conducted by [Principal Investigator] at [Participating Institution(s)]. _____________________________Date:__________ __________________________ Signature of Egg Donor Printed Name _____________________________Date:__________ __________________________ Signature of Person Obtaining Consent Printed Name Copy given to egg donor:_____Yes
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ISSCR SAMPLE RESEARCH CONSENT FORM Embryo Donation for Stem Cell Research
(Embryos Created for Fertility Purposes and in Excess of Clinical Need) Project Title: Principal Investigator: Participating Institution(s): PROJECT INFORMATION You are being asked to donate embryos for a human embryonic stem cell research project led by [name of principal investigator] at [name(s) of institution(s)]. Embryonic stem cells can be found in embryos around the fifth day of development. These stem cells have the unique ability to turn into any kind of specialized human cell, such as liver cells, heart cells, pancreatic cells, or nerve cells. For this reason, embryonic stem cells can be used to study, and possibly one day help treat, diseases or injuries that have caused patients’ specialized cells to die or become damaged – diseases and injuries such as Parkinson’s disease, heart disease, diabetes, and spinal cord injury. [Name of principal investigator] will attempt to collect new human embryonic stem cells for research from embryos that are no longer required for reproductive purposes. [Insert any additional information about this project using very simple language. Specify whether the embryos used will be PGD embryos, frozen embryos, poor quality embryos, or fresh and good quality embryos.] VOLUNTARY CHOICE Your embryo donation is completely voluntary. You have the right to agree or to refuse to donate embryos for this project. The quality of your current or future medical care and your relationship with [name(s) of institution(s)] will NOT change in any way whether you agree or refuse to donate any embryos for this research project. Embryos can be donated for this research project only if the sperm and the egg donors and the people for whom the embryos were created each give their permission by signing their own copies of this form. None of these other individuals who must provide permission for embryo donation will be told about your decision. If you are undergoing fertility treatment, your treating physician will not know what you have decided, unless you choose to provide this information.
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WHAT IS THE PURPOSE OF THIS CONSENT FORM? [Name of person obtaining consent] is authorized to give you information and to answer your questions about this research project. It is very important that you have a detailed conversation with this person so that you can make a careful, voluntary decision about whether or not you want to donate embryos for this research project. Your signature on the last page of this consent form is meant to show that you have had this conversation and that you freely agree to donate embryos for this research project. This consent form must not replace actually having this conversation, so be certain you have this conversation. Please take as much time as you need to ask questions and to talk about this project with your family or friends before you decide whether or not to sign this consent form. You may take this form home with you before you decide what to do. Do not sign this form if you feel pressured in any way by any person to donate embryos for this project. This must be your own decision, not someone else’s. WHAT WILL HAPPEN TO THE DONATED EMBRYOS? None of the embryos that are donated to this research project will be used to produce a baby or a pregnancy. And no embryos will be allowed to develop for more than a total of 14 days after conception. [If using frozen embryos, add: “The time period that the embryos are frozen does not count toward this 14 day limit.”] Researchers will only use your donated embryos to attempt to get new embryonic stem cells before the 14 day limit. The donated embryos will be destroyed during the stem cell collection process. Your agreement to donate embryos does not guarantee that the embryos will actually be used for this research project. Nor is there any guarantee that researchers will be able to get stem cells from the embryos you donate. Researchers will routinely discard as medical waste any donated embryos which are not used for this research project. WHAT WILL HAPPEN TO THE COLLECTED STEM CELLS? It is likely that the collected embryonic stem cells will be stored for many years. Embryonic stem cells have the ability to self-renew indefinitely, and they are likely to be used by researchers at other institutions and for many other research purposes. One possible research use of these stored stem cells might involve changing some of their genes. Another possible research use might be to study some of the stem cells by placing them into laboratory animals. In addition, the stored stem cells might be used in the future for new research related to human stem cell transplantation. These are just three common examples of what might happen to the stored stem cells. But there are many other future possible research uses that are simply unknown at this time.
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As an embryo donor, you will have no say as to which institutions or researchers may share the stem cells made from the embryos. If stem cell transplantation studies are developed in the future, you will have no say as to who may be a transplant recipient of the stem cells derived from your embryos. Future uses of stored stem cells must be approved by local ethical and scientific review committees to make sure that they are used in scientifically, ethically, and legally appropriate ways. Please contact the individuals listed on the last page of this form if you have any questions or concerns about the future possible uses of the stem cells collected through this research project. WHAT IF I CHANGE MY MIND? You may withdraw your consent for whatever reason at any time before stem cells are removed from your embryos. However, if you withdraw your consent after the embryos have left the fertility clinic, then the embryos will no longer be suitable for reproductive purposes and will have to be destroyed. Also, once stem cells are collected from your embryos, you will not be able to change your mind or request that any of the collected stem cells be removed from this research project. If you decide to withdraw your consent after you have signed this form, please contact any of the individuals listed at the end of this document immediately. WHAT ARE THE ALTERNATIVES TO DONATING EMBRYOS FOR THIS PROJECT? You have the right to refuse to participate in this research project. If you refuse, then the embryos will not be used for this project. The person or persons for whom the embryos were created (if not you) will then have to decide whether to (1) donate them to other people for fertility treatment, (2) keep them stored for their own future use, (3) keep them stored to donate to a different research study, or (4) have them discarded according to the routine practice of [name of institution]. WHAT ARE THE POTENTIAL BENEFITS OF DONATING EMBRYOS FOR THIS PROJECT? This research project is not intended to provide any direct medical benefit to you or anyone else. Your embryo donation should be made solely for the advancement of this research project and stem cell research in general. [As applicable: The stem cells that are collected from your donated embryos may have significant commercial potential in the future. However, by signing this form you understand that there are no plans for you to receive any direct financial
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benefits from any future commercial development and scientific patents of discoveries made through the use of these stem cells.] WHAT ARE THE POTENTIAL RISKS OF DONATING EMBRYOS FOR THIS PROJECT? If you donate all of these embryos for this research project, none of them will be available for future fertility uses. This means that if you later decide that you want to have a child via in vitro fertilization, you will have to undergo a completely new in vitro fertilization cycle. Furthermore, there are some psychological risks you need to consider. Some people who donate embryos for stem cell research might experience feelings of anxiety or regret. Some may also feel vulnerable and anxious during the consent process. Due care will be taken to help minimize these psychological risks. [Specify how this will be done, e.g., whether counseling services will be made available on request.] [As applicable: Persons who had provided the eggs and sperm used to create the embryos will be asked to undergo medical screen tests for these genetic diseases: _______ (specify). Although this screen test carries no foreseeable physical risks, some donors may feel anxious about their test results.] Donating embryos for this project involves some risk to your privacy. Efforts to protect you against this risk are discussed in the next section. HOW WILL MY PRIVACY BE PROTECTED? The records of your involvement with this research project will be kept confidential. Identification codes will be used instead of donors’ names, and all records will be kept in a private database that can only be accessed by ___________________ (person). [Specify how this information will be protected and whether the identification code will be linked to the embryo donors, including the sperm and egg donors, and under what circumstances these donors will be identified.] If your sperm or eggs were used to create the donated embryos, then the resulting stem cells and any new stem cells that they produce will be a partial genetic match to you. To protect your genetic privacy, only your identification code, not your name, will be discoverable to the researchers who collect stem cells from your donated embryos and the researchers who may later work with the resulting stored stem cells. The results of your medical screen tests will also be confidentially handled through the use of identification codes instead of names. [As applicable to the embryos’ sperm and egg donors: Some stem cell researchers working with genetic diseases may want to see genetic information about the
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embryo’s sperm and egg donors. If you agree to allow these researchers to see this coded information, please check yes. _____ yes _____ no ] [As applicable to the embryos’ sperm and egg donors: Research on the collected stem cells from your donated embryos may reveal information that could be important to your health. If you wish to be contacted in the future about any such information, please check yes. _____ yes _____ no. [As applicable: If you answered “yes” to this question, [name of institution] will, to the extent possible, pass to you any information that it is given from other researchers or other institutions regarding important information received through research on the stem cells collected from your donated embryos.] Local and other regulatory agencies, and project sponsors and funding agencies may review the research project records to ensure that your rights as an embryo donor were adequately protected. However, your identity will not be readily discoverable to these individuals. Any report that the researchers publish will not include any information that will make it possible for readers to identify you as an embryo donor. WILL I RECEIVE PAYMENT? You will not receive any cash or payment with goods or services for the embryos you donate to this research project. You will not be reimbursed for the cost of embryo storage for the time period before the embryos are donated for this research project. [As applicable: Any reimbursements for money you had to spend to participate in the consent process will be decided by local and other relevant review committees.] DISCLOSURE OF RESEARCHERS’ POTENTIAL FINANCIAL INTERESTS In addition to their scientific interests in this research project, the individuals conducting this embryonic stem cell study might profit financially from the research. There may be current or potential financial benefits to the Principal Investigator, [name], the participating institution(s), [names], and other research institutions or researchers arising from discoveries made through this research project and the stem cells collected from your donated embryos. [Disclose using plain language the researchers’ and the institution(s)’ financial interests in the research.] If you have any questions or concerns about these matters, please contact the persons listed below. If you are undergoing fertility treatment, it is important that your physician inform you of any personal benefits he or she may gain by your agreement to donate embryos for this
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research project. [Disclose here any potential personal benefits the treating physician may receive through this research protocol.] The person who has been authorized to provide you with information may also have a personal vested interest in this research project. [Disclose here any potential personal benefits this person may have in this research protocol.] CONTACT INFORMATION If you have any questions about this research project, contact: (Principal Investigator)______________________________(phone)_________________ [List any toll-free or reverse-charge line.] (Research Administrator) ___________________________(phone)_________________
[List any toll-free or reverse-charge line.] If you have any questions about your rights as an embryo donor, contact: (Review Board Member)____________________________(phone)_________________
[List any toll-free or reverse-charge line.] CONSENT AND SIGNATURE Please read the statements below, think about your choice, and sign if and when you are ready to agree, or take this form home and discuss it with anyone you wish to and then return it to us later if you wish to participate in this research: [Name of person obtaining consent] has fully explained to me the nature and purpose of this research project in a way that I have understood. [He/she] has encouraged me to be actively involved during the information interview and has responded to all of my questions and concerns in a satisfactory and respectful way. [He/she] has offered me opportunities to consult with an independent person whom I trust, including a counselor or a physician, prior to my making my decision and has given me adequate time to decide. I hereby give my voluntary consent to donate _______ (insert number) embryos for the research project entitled [Project Title] conducted by [Principal Investigator] at [Participating Institution(s)].
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_____________________________Date:__________ __________________________ Signature Printed Name I am an _____ Embryo Donor _____ Egg Donor _____ Sperm Donor _____________________________Date:__________ __________________________ Signature of Person Obtaining Consent Printed Name Copy given to donor:_____Yes
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ISSCR SAMPLE RESEARCH CONSENT FORM Somatic Cell Donation for Stem Cell Research
Project Title: Principal Investigator: Participating Institution(s): PROJECT INFORMATION You are being asked to donate _____ (insert type) cells to create embryos for a human embryonic stem cell research project led by [name of principal investigator] at [name(s) of institution(s)]. You are being invited to participate in this project because __________ (identify participants’ medical condition). The purpose of this project is to collect embryonic stem cells that have _____________ (identify characteristic). Embryonic stem cells can be found in embryos around the fifth day of development. These stem cells have the unique ability to turn into any kind of specialized human cell, such as liver cells, heart cells, pancreatic cells, or nerve cells. For this reason, embryonic stem cells can be used to study, and possibly one day help treat, diseases or injuries that have caused patients’ specialized cells to die or become damaged – diseases and injuries such as Parkinson’s disease, heart disease, diabetes, and spinal cord injury. [Name of principal investigator] wants to collect new human embryonic stem cells from embryos that have been created using _____ cells. To do this, researchers will put _____ cells into unfertilized eggs that have had their DNA removed. If successful, this process, called nuclear transfer, can create embryos that contain stem cells which have the same DNA as the _____ cell donors. [Insert additional information about this specific project using very simple language.] VOLUNTARY CHOICE Donating your _____ cells for this research project is completely voluntary. You have the right to agree or to refuse to provide your _____ cells for this project. The quality of your current or future medical care and your relationship with [name(s) of institution(s)] will NOT change in any way whether you agree or refuse to provide any cells for this research project. WHAT IS THE PURPOSE OF THIS CONSENT FORM? [Name of person obtaining consent] is authorized to give you information and to answer your questions about this research project. It is very important that you have a
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detailed conversation with this person so that you can make a careful, voluntary decision about whether or not you want to donate your _____ cells for this research project. Your signature on the last page of this consent form is meant to show that you have had this conversation and that you freely agree to donate your _____ cells for this research project. This consent form must not replace actually having this conversation, so be certain you have this conversation. Please take as much time as you need to ask questions and to talk about this project with your family or friends before you decide whether or not to sign this consent form. You may take this form home with you before you decide what to do. Do not sign this form if you feel pressured in any way by any person to donate your _____ cells for this project. This must be your own decision, not someone else’s. What Will Happen To My _____ Cells? None of the _____ cells you provide will be used to produce a baby or a pregnancy. And none of the resulting embryos will be allowed to develop for more than a total of 14 days after they have been created using nuclear transfer. If any of the resulting embryos are frozen, then the time that they are frozen is not counted as part of the 14 day limit. Researchers will only use your _____ cells to create embryos from which they will attempt to get stem cells before the 14 day limit. The resulting embryos will be destroyed during the stem cell collection process. There is no guarantee that embryos will be created from your _____ cells. And there is no guarantee that researchers will be able to get stem cells from any resulting embryos. Researchers will routinely discard as medical waste _____ cells or embryos they do not use for this research project. WHAT WILL HAPPEN TO THE COLLECTED STEM CELLS? It is likely that the retrieved stem cells, which would be genetically matched to you, will be stored for many years. Embryonic stem cells have the ability to self-renew indefinitely, and they are likely to be used by researchers at other institutions and for many other research purposes. One possible research use of these stored stem cells might involve changing some of their genes. Another possible research use might be to study some of the stem cells by placing them into laboratory animals. In addition, the stored stem cells might be used in the future for new research related to human stem cell transplantation. These are just three common examples of what might happen to the stored stem cells. But there are many other future possible research uses that are simply unknown at this time. You will have no say as to which institutions or researchers may share the stem cells made from the embryos that were created using your _____ cells. If stem cell
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transplantation studies are developed in the future, you will have no say as to who may be a transplant recipient of the collected stem cells [as applicable: except in the case of autologous transplantation]. Future uses of stored stem cells must be approved by local ethical and scientific review committees to make sure that they are used in scientifically, ethically, and legally appropriate ways. Please contact the individuals listed on the last page of this form if you have any questions or concerns about the future possible uses of the stem cells collected through this research project. HOW WILL MY _____ CELLS BE COLLECTED? [As applicable: You will be asked to provide a _____ sample.] [As applicable: With your approval, your stored _____ sample will be transferred by [name of institution] to the research team.] WHAT IF I CHANGE MY MIND? You may withdraw your consent for whatever reason at any time before your _____ cells are used to create embryos for this project. However, once the resulting embryos are destroyed in the stem cell collection process, you will not be able to change your mind or request that any of the collected stem cells be removed from this research project. If you decide to withdraw your consent after you have signed this form, please contact any of the individuals listed at the end of this document immediately. WHAT ARE THE ALTERNATIVES TO DONATING MY _____ CELLS FOR THIS PROJECT? One of your alternatives is to refuse to participate at all in this research project. In the case that your _____ cells are retrieved but you decide not to participate any longer in this research project, you may (1) have your _____ cells discarded according to the routine practice of [name of institution], (2) donate your _____ cells to other research project, or (3) [as applicable: return your _____ sample to storage]. WHAT ARE THE POTENTIAL BENEFITS OF DONATING MY _____ CELLS FOR THIS PROJECT? This research project is not intended to provide any direct medical benefit to you or anyone else. You would be donating your _____ cells solely for the advancement of this research project and stem cell research in general.
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[As applicable: The stem cells that are collected from the resulting embryos may have significant commercial potential in the future. However, by signing this form you understand that there are no plans for you to receive any direct financial benefits from any future commercial development and scientific patents of discoveries made through the use of these stem cells.] WHAT ARE THE POTENTIAL RISKS OF DONATING MY _____ CELLS FOR THIS PROJECT? There are no foreseeable physical risks for you in donating _____ cells for this research project. However, there are some psychological risks you need to consider. Some people who donate _____ cells for stem cell research might experience feelings of anxiety or regret, especially when considering the possibility that their donation may result in the creation of genetically-matched embryos which will be destroyed during the stem cell collection process. Some may also feel vulnerable and anxious during the consent process. [As applicable: As a cell donor for this project you will be asked to undergo medical screen tests for these genetic diseases: _______ (specify). Although this screen test carries no foreseeable physical risks, some donors may feel anxious about their test results.] Due care will be taken to help minimize these psychological risks. [Specify how this will be done.] Donating _____ cells for this project involves some risk to your privacy. Efforts to protect you against this risk are discussed in the next section. HOW WILL MY PRIVACY BE PROTECTED? The records of your involvement with this research project will be kept confidential. Identification codes will be used instead of donors’ names, and all records will be kept in a private database that can only be accessed by ___________________ (person). [Specify how this information will be protected and whether the identification code will be linked the cell donors, and under what circumstances these donors will be identified.] If your _____ cells are used to create embryos, then the resulting stem cells and any new stem cells that they produce will be a complete genetic match to you. To protect your genetic privacy, only your identification code, not your name, will be discoverable to the researchers who collect stem cells from the resulting embryos and the researchers who may later work with the resulting stored stem cells. The results of your medical screen tests will also be confidentially handled through the use of identification codes instead of names.
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[As applicable: Some stem cell researchers working with genetic diseases may want to see genetic information about the _____ cell donors. If you agree to allow these researchers to see this coded information, please check yes. _____ yes _____ no ] [As applicable: Research on the collected stem cells from the resulting embryos may reveal information that could be important to your health. If you wish to be contacted in the future about any such information, please check yes. _____ yes _____ no ] [As applicable: If you answered “yes” to this question, (name of institution) will, to the extent possible, pass to you any information that it is given from other researchers or other institutions regarding important information received through research on the stem cells collected from the resulting embryos.] Local and other regulatory agencies, and project sponsors and funding agencies may review the research project records to ensure that your rights as a _____ cell donor were adequately protected. However, your identity will not be readily discoverable to these individuals. Any report that the researchers publish will not include any information that will make it possible for readers to identify you as a _____ cell donor. WILL I RECEIVE PAYMENT? You will not receive any cash or payment with goods or services for the _____ cells you donate to this research project. [As applicable: You will not be reimbursed for the cost of your _____ sample storage for the time period before your _____ cells are donated for this research project.] [As applicable: Any reimbursements for money you had to spend to participate in the consent process will be decided by local and other relevant review committees.] DISCLOSURE OF RESEARCHERS’ POTENTIAL FINANCIAL INTERESTS In addition to their scientific interests in this research project, the individuals conducting this stem cell study might profit financially from the research. There may be current or potential financial benefits to the Principal Investigator, [name], the participating institution(s), [names], and other research institutions or researchers arising from discoveries made through this research project and the stem cells collected from the resulting embryos. [Disclose using plain language the researchers’ and the institution(s)’ financial interests in the research.] If you have any questions or concerns about these matters, please contact the persons listed below.
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If you are a ______ (specify medical condition) patient, it is important that your treating physician inform you of any personal benefits he or she may gain by your agreement to donate _____ cells for this research project. [Disclose here any potential personal benefits the treating physician may receive through this research protocol.] The person who has been authorized to provide you with information may also have a personal vested interest in this research project. [Disclose here any potential personal benefits this person may have in this research protocol.] CONTACT INFORMATION If you have any questions about this research project, contact: (Principal Investigator)______________________________(phone)_________________ [List any toll-free or reverse-charge line.] (Research Administrator) ___________________________(phone)_________________
[List any toll-free or reverse-charge line.] If you have any questions about your rights as a _____ cell donor, contact: (Review Board Member)____________________________(phone)_________________
[List any toll-free or reverse-charge line.] CONSENT AND SIGNATURE Please read the statements below, think about your choice, and sign if and when you are ready to agree, or take this form home and discuss it with anyone you wish to and then return it to us later if you wish to participate in this research: [Name of person obtaining consent] has fully explained to me the nature and purpose of this research project in a way that I have understood. [He/she] has encouraged me to be actively involved during the information interview and has responded to all of my questions and concerns in a satisfactory and respectful way. [He/she] has offered me opportunities to consult with an independent person whom I trust, including a counselor or a physician, prior to my making my decision and has given me adequate time to decide.
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I hereby give my voluntary consent to donate my _____ cells for the research project entitled [Project Title] conducted by [Principal Investigator] at [Participating Institution(s)]. _____________________________Date:__________ __________________________ Signature of Cell Donor Printed Name _____________________________Date:__________ __________________________ Signature of Parent or Legal Guardian Printed Name If Cell Donor is a Minor or Decisionally- Incapacitated _____________________________Date:__________ __________________________ Signature of Person Obtaining Consent Printed Name Copy given to donor:_____Yes Copy given to parent or legal guardian (if applicable):______ Yes
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ISSCR SAMPLE RESEARCH CONSENT FORM Sperm Donation for Stem Cell Research
(Includes Sperm Donation Specifically for Stem Cell Research and Sperm in Excess of Clinical Need)
Project Title: Principal Investigator: Participating Institution(s): PROJECT INFORMATION You are being asked to donate sperm to create embryos for a human embryonic stem cell research project led by [name of principal investigator] at [name(s) of institution(s)]. Embryonic stem cells can be found in embryos around the fifth day of development. These stem cells have the unique ability to turn into any kind of specialized human cell, such as liver cells, heart cells, pancreatic cells, or nerve cells. For this reason, embryonic stem cells can be used to study, and possibly one day help treat, diseases or injuries that have caused patients’ specialized cells to die or become damaged – diseases and injuries such as Parkinson’s disease, heart disease, diabetes, and spinal cord injury. [Name of principal investigator] wants to collect new human embryonic stem cells from embryos that have been created with your sperm [as applicable: created through androgenesis]. [As applicable: “Androgenesis” is the process by which a sperm cell is stimulated to begin going through the very early stages of human development. Stem cells that arise from andogenesis would be genetically matched to the person who provided the sperm.] [Insert any additional information about this project using very simple language. Specify whether the investigator plans to use donated cryopreserved sperm, fresh sperm, or both.] VOLUNTARY CHOICE Donating your sperm for this research project is completely voluntary. You have the right to agree or to refuse to provide your sperm for this project. The quality of your current or future medical care and your relationship with [name(s) of institution(s)] will NOT change in any way whether you agree or refuse to provide any sperm for this research project.
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WHAT IS THE PURPOSE OF THIS CONSENT FORM? [Name of person obtaining consent] is authorized to give you information and to answer your questions about this research project. It is very important that you have a detailed conversation with this person so that you can make a careful, voluntary decision about whether or not you want to donate your sperm for this research project. Your signature on the last page of this consent form is meant to show that you have had this conversation and that you freely agree to donate your sperm for this research project. This consent form must not replace actually having this conversation, so be certain you have this conversation. Please take as much time as you need to ask questions and to talk about this project with your family or friends before you decide whether or not to sign this consent form. You may take this form home with you before you decide what to do. Do not sign this form if you feel pressured in any way by any person to donate your sperm for this project. This must be your own decision, not someone else’s. WHAT WILL HAPPEN TO MY SPERM? None of the sperm you donate for this research project will be used to produce a baby or a pregnancy. And no embryos created from your sperm will be allowed to develop for more than a total of 14 days after they have been [as applicable: created through the union of sperm and egg; created through androgenesis]. If any of the resulting embryos are frozen, then the time that they are frozen is not counted as part of the 14 day limit. Researchers will only use your sperm to create embryos from which they will attempt to get stem cells before the 14 day limit. The resulting research embryos will be destroyed during the stem cell collection process. There is no guarantee that embryos will be successfully created from your sperm. And there is no guarantee that researchers will be able to get stem cells from any resulting embryos. Researchers will routinely discard as medical waste any sperm or embryos they do not use for this research project. WHAT WILL HAPPEN TO THE COLLECTED STEM CELLS? It is likely that the collected embryonic stem cells will be stored for many years. Embryonic stem cells have the ability to self-renew indefinitely, and they are likely to be used by researchers at other institutions and for many other research purposes. One possible research use of these stored stem cells might involve changing some of their genes. Another possible research use might be to study some of the stem cells by placing them into laboratory animals. In addition, the stored stem cells might be used in the future for new research related to human stem cell transplantation. These are just three
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common examples of what might happen to the stored stem cells. But there are many other future possible research uses that are simply unknown at this time. You will have no say as to which institutions or researchers may share the stem cells made from the embryos that were created using your sperm. If stem cell transplantation studies are developed in the future, you will have no say as to who may be a transplant recipient of the collected stem cells [as applicable: except in the case of autologous transplantation after androgenesis]. Future uses of stored stem cells must be approved by local ethical and scientific review committees to make sure that they are used in scientifically, ethically, and legally appropriate ways. Please contact the individuals listed on the last page of this form if you have any questions or concerns about the future possible uses of the stem cells collected through this research project. HOW WILL MY SPERM BE COLLECTED? [As applicable: In the routine practice of fertility clinics, you will be asked to return a sample of your ejaculate in a sterile container, which will be provided for you.] [As applicable: With your approval, your frozen sperm will be transferred by (name of institution) to the research team.] WHAT IF I CHANGE MY MIND? You may withdraw your consent for whatever reason at any time before your sperm is used to create embryos for this research project, or before researchers attempt to collect stem cells from embryos created from your sperm. However, once the resulting embryos are destroyed in the stem cell collection process, you will not be able to change your mind or request that any of the collected stem cells be removed from this research project. If you decide to withdraw your consent after you have signed this form, please contact any of the individuals listed at the end of this document immediately. WHAT ARE THE ALTERNATIVES TO DONATING MY SPERM FOR THIS PROJECT? One of your alternatives is to refuse to participate at all in this research project. In the case that your sperm is retrieved but you decide not to participate any longer in this research project, you may (1) have your sperm discarded according to the routine practice of [name of institution], (2) donate your sperm to other individuals for fertility treatment, or (3) store your sperm for your own fertility treatment, if necessary. Please note that these alternatives are possible only if your sperm has not already been prepared
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by researchers to create embryos for this project. Also, using your sperm for your own or others’ fertility treatment may involve additional screening tests. WHAT ARE THE POTENTIAL BENEFITS OF DONATING MY SPERM FOR THIS PROJECT? This research project is not intended to provide any direct medical benefit to you or anyone else. You would be donating your sperm solely for the advancement of this research project and stem cell research in general. [As applicable: The stem cells that are collected from the resulting embryos may have significant commercial potential in the future. However, by signing this form you understand that there are no plans for you to receive any direct financial benefits from any future commercial development and scientific patents of discoveries made through the use of these stem cells.] WHAT ARE THE POTENTIAL RISKS OF DONATING MY SPERM FOR THIS PROJECT? There are no foreseeable physical risks for you in donating sperm for this research project. However, there are some psychological risks you need to consider. Some people who donate sperm for stem cell research might experience feelings of anxiety or regret, especially when considering the possibility that their sperm may result in the creation of embryos that will be destroyed during the stem cell collection process. Some may also feel vulnerable and anxious during the consent process. [As applicable: As a sperm donor for this project, you will be asked to undergo medical screen tests for these genetic diseases: _______ (specify). Although this screen test carries no foreseeable physical risks, some sperm donors may feel anxious about their test results.] Due care will be taken to help minimize these psychological risks. [Specify how this will be done.] Donating sperm for this project involves some risk to your privacy. Efforts to protect you against this risk are discussed in the next section. HOW WILL MY PRIVACY BE PROTECTED? The records of your involvement with this research project will be kept confidential. Identification codes will be used instead of donors’ names, and all records will be kept in a private database that can only be accessed by ___________________ (person). [Specify how this information will be protected and whether the identification code will be linked the sperm donors, and under what circumstances these donors will be identified.]
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If your sperm is used to create embryos for this project, then the resulting stem cells and any new stem cells that they produce will be a partial genetic match to you [as applicable to androgenesis: will be a complete genetic match to you]. To protect your genetic privacy, only your identification code, not your name, will be discoverable to the researchers who collect stem cells from the resulting embryos and the researchers who may later work with the resulting stored stem cells. The results of your medical screen tests will also be confidentially handled through the use of identification codes instead of names. [As applicable: Some stem cell researchers working with genetic diseases may want to see genetic information about the embryo’s sperm donors. If you agree to allow these researchers to see this coded information, please check yes. _____ yes _____ no ] [As applicable: Research on the collected stem cells may reveal information that could be important to your health. If you wish to be contacted in the future about any such information, please check yes. _____ yes _____ no ] [As applicable: If you answered “yes” to this question, [name of institution] will, to the extent possible, pass to you any information that it is given from other researchers or other institutions regarding important information received through research on the stem cells collected from embryos created using your sperm.] Local and other regulatory agencies, and project sponsors and funding agencies may review the research project records to ensure that your rights as a sperm donor were adequately protected. However, your identity will not be readily discoverable to these individuals. Any report that the researchers publish will not include any information that will make it possible for readers to identify you as a sperm donor. WILL I RECEIVE PAYMENT? You will not receive any cash or payment with goods or services for the sperm you donate to this research project. [As applicable: You will not be reimbursed for the cost of sperm storage for the time period before your sperm is donated for this research project. [As applicable: Any reimbursements for money you had to spend to participate in the consent process will be decided by local and other relevant review committees.]
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DISCLOSURE OF RESEARCHERS’ POTENTIAL FINANCIAL INTERESTS In addition to their scientific interests in this research project, the individuals conducting this embryonic stem cell study might profit financially from the research. There may be current or potential financial benefits to the Principal Investigator, [name], the participating institution(s), [names], and other research institutions or researchers arising from discoveries made through this research project and the stem cells collected from embryos created using your sperm. [Disclose using plain language the researchers’ and the institution(s)’ financial interests in the research.] If you have any questions or concerns about these matters, please contact the persons listed below. If you are undergoing fertility treatment, it is important that your physician inform you of any personal benefits he or she may gain by your agreement to donate embryos for this research project. [Disclose here any potential personal benefits the treating physician may receive through this research protocol.] The person who has been authorized to provide you with information may also have a personal vested interest in this research project. [Disclose here any potential personal benefits this person may have in this research protocol.] CONTACT INFORMATION If you have any questions about this research project, contact: (Principal Investigator)______________________________(phone)_________________ [List any toll-free or reverse-charge line.] (Research Administrator) ___________________________(phone)_________________
[List any toll-free or reverse-charge line.] If you have any questions about your rights as a sperm donor, contact: (Review Board Member)____________________________(phone)_________________
[List any toll-free or reverse-charge line.] CONSENT AND SIGNATURE Please read the statements below, think about your choice, and sign if and when you are ready to agree, or take this form home and discuss it with anyone you wish to and then return it to us later if you wish to participate in this research: [Name of person obtaining consent] has fully explained to me the nature and purpose of this research project in a way that I have understood.
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[He/she] has encouraged me to be actively involved during the information interview and has responded to all of my questions and concerns in a satisfactory and respectful way. [He/she] has offered me opportunities to consult with an independent person whom I trust, including a counselor or a physician, prior to my making my decision and has given me adequate time to decide. I hereby give my voluntary consent to donate my sperm for the research project entitled [Project Title] conducted by [Principal Investigator] at [Participating Institution(s)]. _____________________________Date:__________ __________________________ Signature of Sperm Donor Printed Name _____________________________Date:__________ __________________________ Signature of Person Obtaining Consent Printed Name Copy given to donor:_____Yes
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ISSCR SAMPLE FORM
Uniform hESC-related Materials Transfer Agreement I. Definitions: 1. PROVIDER: 2. PROVIDER SCIENTIST: 3. RECIPIENT: 4. RECIPIENT SCIENTIST: 5. ORIGINAL MATERIAL: 6. MATERIAL: ORIGINAL MATERIAL, PROGENY, and UNMODIFIED DERIVATIVES. The MATERIAL shall not include: (a) MODIFICATIONS, or (b) other substances created by the RECIPIENT through the use of the MATERIAL which are not MODIFICATIONS, PROGENY, or UNMODIFIED DERIVATIVES. 7. PROGENY: Unmodified descendant from the MATERIAL, such as virus from virus, cell from cell, or organism from organism. 8. UNMODIFIED DERIVATIVES: Substances created by the RECIPIENT which constitute an unmodified functional subunit or product expressed by the ORIGINAL MATERIAL. Some examples include: subclones of unmodified cell lines, purified or fractionated subsets of the ORIGINAL MATERIAL, proteins expressed by DNA/RNA supplied by the PROVIDER, or monoclonal antibodies secreted by a hybridoma cell line. 9. MODIFICATIONS: Substances created by the RECIPIENT which contain/incorporate the MATERIAL. 10. COMMERCIAL PURPOSES: The sale, lease, license, or other transfer of the MATERIAL or MODIFICATIONS to a for-profit organization. COMMERCIAL PURPOSES shall also include uses of the MATERIAL or MODIFICATIONS by any organization, including RECIPIENT, to perform contract research, to screen compound libraries, to produce or manufacture products for general sale, or to conduct research activities that result in any sale, lease, license, or transfer of the MATERIAL or MODIFICATIONS to a for-profit organization. However, industrially sponsored academic research shall not be considered a use of the MATERIAL or MODIFICATIONS for COMMERCIAL PURPOSES per se, unless
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restricted by third party rights that may govern the material, or unless it grants intellectual property rights in excess of a nonexclusive internal research license and the right to review (but not own) research data. II. Terms and Conditions of this Agreement: 1. The RECIPIENT and the RECIPIENT SCIENTIST agree that the MATERIAL: (a) is to be used solely for teaching and academic or other noncommercial internal research purposes; (b) will not be used in human subjects, in clinical trials, or for diagnostic purposes involving human subjects without the written consent of the PROVIDER; (c) is to be used only at the RECIPIENT organization and only in the RECIPIENT SCIENTIST's laboratory under the direction of the RECIPIENT SCIENTIST or others working under his/her direct supervision; (d) will not be transferred to anyone else within the RECIPIENT organization without the prior written consent of the PROVIDER. (e) will be used only in compliance with applicable treaties, laws and regulations, as they are amended from time to time, and only after securing such review and approval as such treaties, laws and regulations require; (f) will be used ethically, in substantial compliance with the review procedures and ethical guidelines of the International Society for Stem Cell Research or, where those are superseded by authoritative, higher national standards, in substantial compliance with such standards; and (g) recognizing that third parties may have contractual and intellectual property rights related to receipt and proposed use of the MATERIALS under the laws of diverse countries, will be used consistent with rights of such third parties; 2. (a) The RECIPIENT acknowledges that the MATERIAL may be the subject of a patent application or covered by patent rights in one or more countries. Except as provided in this Agreement, no express or implied licenses or other rights are provided to the RECIPIENT under any patents, patent applications, trade secrets or other proprietary rights of the PROVIDER or any third party, including with respect to any altered forms of the MATERIAL made by the PROVIDER. In particular, but without limitation, no express or implied licenses or other rights are provided to use the MATERIAL, MODIFICATIONS, or any related patents of the PROVIDER for COMMERCIAL PURPOSES.
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(b) RECIPIENT represents that, based on adequate exercise of due diligence, it has verified the extent to which third-party rights, treaties, laws and regulations may restrict its receipt of the MATERIALS or the use of the MATERIALS in research, including commercially sponsored research, and that it has satisfied all such requirements, including by entering into such third party agreements and licenses, and securing such regulatory and institutional approvals, as are required. RECIPIENT will provide adequate documentation of its compliance with this term upon PROVIDER request. (c) RECIPIENT hereby agrees to indemnify and hold harmless PROVIDER, its trustees, officers, employees, agents and medical and research staff, including without limitation SCIENTIST, against any claim arising from RECIPIENT’s use of this Agreement, including without limitation any claim that RECIPIENT’s use of the MATERIAL violates any of intellectual property or other rights of the third party, or violates any provision of law, or arises from a breach of this Agreement. 3. The PROVIDER retains ownership of the MATERIAL, including any MATERIAL contained or incorporated in MODIFICATIONS. 4. Subject to any third-party rights, the RECIPIENT retains ownership of: (a) MODIFICATIONS (except that, the PROVIDER retains ownership rights to the MATERIAL included therein), and (b) those substances created through the use of the MATERIAL or MODIFICATIONS, but which are not PROGENY, UNMODIFIED DERIVATIVES or MODIFICATIONS (i.e., do not contain the ORIGINAL MATERIAL, PROGENY, or UNMODIFIED DERIVATIVES). If either 4 (a) or 4 (b) results from the collaborative efforts of the PROVIDER and the RECIPIENT, such material will be jointly owned. 5. The RECIPIENT and the RECIPIENT SCIENTIST agree to refer to the PROVIDER any request for the MATERIAL from anyone other than those persons working under the RECIPIENT SCIENTIST's direct supervision. The RECIPIENT and/or the RECIPIENT SCIENTIST shall have the right to distribute, nonexclusively, substances and materials created by the RECIPIENT through the use of the ORIGINAL MATERIAL, provided that (a) those substances are not PROGENY or UNMODIFIED DERIVATIVES, (b) such transfer is not otherwise restricted by unlicensed third party rights or otherwise; (c) the RECIPIENT, in documents effecting such distribution, reserves the right to deposit the substances and materials in banks and depositories providing reasonable public and scientific access on ethical terms in accordance with guidelines and standards of the International Society for Stem Cell Research; (d) the RECIPIENT reserves all rights necessary to transfer nonexclusively such substances and materials, and sufficient rights to use them, to other academic and governmental research institutions for internal research purposes at nominal cost, and will implement arrangements to effect such transfers; (e) the RECIPIENT agrees that upon request it will also provide such materials to
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PROVIDER at nominal cost; and (f) the RECIPIENT conditions transfer of such materials to further recipients on terms substantially similar to the terms of this paragraph 5, and does not acquire commercial, monetary or other rights directly or indirectly for itself or others under such agreements or arrangements that are greater than the rights received by PROVIDER under this agreement. 6. Without written consent from the PROVIDER, the RECIPIENT and/or the RECIPIENT SCIENTIST may NOT provide or license MODIFICATIONS for COMMERCIAL PURPOSES. It is recognized by the RECIPIENT that such COMMERCIAL PURPOSES may require a commercial license from the PROVIDER and/or third parties and the PROVIDER has no obligation to grant a commercial license to its ownership interest in the MATERIAL incorporated in the MODIFICATIONS. RECIPIENT may grant commercial licenses under the RECIPIENT's intellectual property rights claiming such MODIFICATIONS, or methods of their manufacture or their use, if not subject to third party rights and restrictions. 7. If the RECIPIENT desires to use or license the MATERIAL or MODIFICATIONS for COMMERCIAL PURPOSES, the RECIPIENT agrees, in advance of such use, to negotiate in good faith with the PROVIDER to establish the terms of a commercial license, subject to any pre-existing rights held by others. It is understood by the RECIPIENT that the PROVIDER shall have no obligation to grant such a license to the RECIPIENT, and may grant exclusive or non-exclusive commercial licenses to others, or sell or assign all or part of the rights in the MATERIAL to any third party(ies), subject to any pre-existing rights held by others and obligations to governmental authorities and funding agencies or bodies. RECIPIENT is responsible for timely procuring all necessary licenses from all third parties. 8. Subject to third party rights or restrictions in the MATERIAL, the RECIPIENT is free to file patent application(s) claiming inventions made by the RECIPIENT through the use of the MATERIAL but agrees to notify the PROVIDER upon filing a patent application claiming MODIFICATIONS or method(s) of manufacture or use(s) of the MATERIAL. 9. Any MATERIAL delivered pursuant to this Agreement is understood to be experimental in nature and may have hazardous properties and that its use may require acquisition of rights from third parties. The PROVIDER MAKES NO REPRESENTATIONS AND EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESSED OR IMPLIED. THERE ARE NO EXPRESS OR IMPLIED WARRANTIES OF THE MATERIAL, ITS SOURCE, MERCHANTABILITY, TRANSFER OR FITNESS FOR A PARTICULAR PURPOSE, OR THAT THE USE OF THE MATERIAL WILL NOT INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER PROPRIETARY RIGHTS.
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10. Except to the extent prohibited by law, the RECIPIENT assumes all liability for damages which may arise from its use, storage, disposal or transfer of the MATERIAL. The PROVIDER will not be liable to the RECIPIENT for any loss, claim or demand made by the RECIPIENT, or made against the RECIPIENT by any other party, due to or arising from the use or transfer of the MATERIAL by the RECIPIENT, except to the extent permitted by law when caused by the gross negligence or willful misconduct of the PROVIDER. 11. This agreement shall not be interpreted to prevent or delay publication of research findings resulting from the use of the MATERIAL or the MODIFICATIONS. The RECIPIENT SCIENTIST agrees to provide appropriate acknowledgement of the source of the MATERIAL in all publications. 12. This Agreement will terminate on the earliest of the following dates: (a) when the MATERIAL becomes generally available from third parties without restriction, for example, though reagent catalogs or public depositories or (b) on completion of the RECIPIENT's current research with the MATERIAL, or (c) on thirty (30) days written notice by either party to the other. Upon the effective date of termination, or if mutually agreed, any deferred effective date of termination, RECIPIENT will discontinue its use of the MATERIAL and will, upon direction of the PROVIDER, return or destroy any remaining MATERIAL. The RECIPIENT, at its discretion, will also either destroy the MODIFICATIONS or remain bound by the terms of this agreement as they apply to MODIFICATIONS. 14. Paragraphs 2, 3, 9, and 10 of Article II shall survive termination. 15. The MATERIAL is provided at [no cost] [with a transmittal fee of ____ solely to reimburse the PROVIDER for its preparation and distribution costs]. 16. This agreement will be construed so as to comply with the laws of both the PROVIDER and the RECIPIENT, except that to the extent they conflict and cannot be harmonized, the contractual provisions of this agreement shall be construed in accordance with the laws of the PROVIDER, and ethical restrictions and prohibitions on uses of the MATERIALS shall be construed in accordance with the laws of the location where research is being conducted. ________________________________________ [PROVIDER Scientist] ________________________________________ _______________ [PROVIDER Institution] Date [Title – Authorized official]
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ACCEPTED BY RECIPIENT: ________________________________________ [RECIPIENT Scientist] ________________________________________ [RECIPIENT Institution] [Title - Authorized Official] ________________________________________ _______________ Title Date ________________________________________ Institution ________________________________________ Address ________________________________________ "This Material Transfer Agreement was adapted and modified from the uniform biological material transfer agreement published in the Federal Register, February 18, 1995."