References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Ethics and Policy

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Why Ethics? Controversy: We respect people’s views about embryos and stem cells while conducting good research. Respect: We avoid infringing on the rights of research donors. Health: We maximize benefits to people and minimize risks. Integrity: We fulfill our duties to the scientific community as a whole. 1

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Origins of Research Ethics NUREMBERG Participation in research must be VOLUNTARY. Research Participants must be INFORMED about the consequences of participating. HELSINKI Certain populations are more VULNERABLE to coercion or harm and should be protected. All research must have independent OVERSIGHT to make sure the benefits are greater than the risks. 2

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Applied Research Ethics How does this effect stem cell research? People who donate embryos, gametes or tissues to stem cell research are research participants. This means they must give informed consent to donate. No one should ever be pressured to donate their tissues or misled about the advantages that may come from donating tissues. If individuals are compensated for their tissues, this must be carefully documented. 3

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Applied Research Ethics Informed consent requires that research participants substantially understand: – How their tissues will be used, – That they will not benefit from the research, – That they have no financial interest in the outcomes, – How much they will be compensated, – That they may withdraw their tissues from the research at any time, – That their participation will be private and confidential. 4

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… International Variation Different countries have different laws and policies about stem cell research. In some countries, embryonic stem cell research is illegal. Others have strict rules concerning research donations. The International Society for Stem Cell Research (ISSCR) is a professional society that issues guidelines for best practices in stem cell research. If all researchers follow the guidelines, international collaboration is possible. 5

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… US Regulations The Common Rule 45 Code of Federal Regulation 46 - Protection of Human Subjects. National Institutes of Health - Office of Human Subjects Research. The Dickey-Wicker Amendment 6

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Applying US Regulations 7 Different organization contribute to the development of US policies. The National Academies of Science (NAS) issues guidelines that are based on the dominant scientific consensus. – These provide guidance to individuals and institutions when there are no clear laws. The National Institutes of Health (NIH) provides most of the Federal funding for stem cell research.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Applying US Regulations 8 The National Institutes of Health (NIH) maintains a registry of all embryonic stem cell lines that can be worked with using Federal grant funds. If you are working with Federal funds, or you want to collaborate with someone who uses Federal funds, you should check the registry before beginning.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Legal Challenges 9 Until the Court reaches a conclusion, existing Federal funding for embryonic stem cell research will most likely continue. In 2010, a Federal judge issued a judgment that ANY Federal funding for work with embryonic stem cell lines may be a violation of the Dickey-Wicker amendment. The question will be decided in Federal court and may go to the Supreme Court.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Funding Sources Because Federal funding for embryonic stem cell research is so uncertain, other sources of funding have been found: – Some US States have begun providing funding using State funds. – Many other countries have provided government funds. – Private companies have invested in stem cell research. 10

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… California 11 This also means that researchers funded by CIRM cannot use stem cell lines where a donor has been compensated. California has its own stem cell research funding agency: The California Institute for Regenerative Medicine (CIRM). In California law, people who contribute eggs or embryos to stem cell research cannot receive any valuable compensation in return.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… New York 12 New York also has its own stem cell regulations: the Empire State Stem Cell Science Board. Under New York regulations it is legal to financially compensate women who give their eggs to stem cell research. This means that researchers in New York can also use lines derived from embryos or eggs where the contributor has received valuable compensation.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Discussion Question 13 You are the head of a small stem cell lab at a public university in California. You want to enter into a research collaboration with another lab located in Iowa. What factors do you need to consider before going forward? What information do you need and where would you go to get it? Discuss these questions with your neighbor and then share with us.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Research Oversight 14 The NAS guidelines recommend that any institution that conducts stem cell research should have a Stem Cell Research Oversight Committee (SCRO). “Ensure that inappropriate research is not conducted and that controversial research is well justified and subject to appropriate oversight” Members are expert in developmental biology, stem cell biology, assisted reproduction, patient advocacy, community relations, law and ethics. Special status of the human embryo demands Scientific rationale for the need to generate new lines and a basis for the number of embryos and oocytes needed Implantation of human embryonic stem cells into nonhuman animals raises ethical concerns

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Research Oversight 15 The NAS guidelines recommend that any institution that conducts stem cell research should have a Stem Cell Research Oversight Committee (SCRO). SCROs are comprised of experts in developmental biology, stem cell biology, assisted reproduction and ethical and legal issues. The job of the SCRO is to provide an outside perspective on research to ensure compliance with policies and help to minimize the unnecessary use of scarce resources.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Research Oversight 16 Most SCROs review research which involves – the use of human embryonic stem cells or their derivatives, – the introduction of human pluripotent stem cells, or their derivatives, obtained from a non-embryonic source, into non-human animals at any embryonic, fetal, or postnatal stage, if an expected effect is that human cells will be integrated into the central nervous system, testes, or ovaries of the animal.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… What do SCROs look for? 17 What is the provenance of the cells? Are they “ethically derived”? Can this research be done with fewer embryos or animal models? Are the research donors adequately protected? Is their personal information ascertainable by the researchers? Did the gamete or embryo donor give their informed consent?

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… What’s off limits? 18 1.Any culture of an intact human embryo for longer than 14 days 2.Research in which hESCs are introduced into nonhuman primate blastocysts or in which any embryonic stem cells are introduced into human blastocysts 3.No animal into which hESCs have been introduced should be allowed to breed.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Case Study: Colonel Sanders 19 Colonel Sanders, MD Research protocol Summary* 1.Sanders plans to put human embryonic stem cells into a chick embryo. 2.wants to study how embryonic stem cells contribute to the development of limbs. 3.Has experience using human embryonic stem cells. 4.Using embryonic stem cells listed on the NIH registry. Should you approve the protocol? What or why not? Would you request any changes to the protocol? Finger Lick’n Good! *Adapted from: Zettler P, Wolf L, Lo B. Establishing Procedures for Institutional Oversight of Stem Cell Research. Academic Medicine, V82, No )

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Human Subjects Research 20 If stem cells will be placed in patients, the research must be reviewed by an Institutional Review Board (IRB). The IRB ensures that participants are adequately informed about the research and that the risks are acceptable. According to Federal policy, participation in human subjects research must be free from coercion. Vulnerable populations must be given extra consideration.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Hwang Woo-Suk 21 Cloning! South Korean scientist Hwang Woo- Suk announces that his team has successfully started a human embryonic stem cell line using the nuclear transfer technique with human eggs. Extracting human eggs is painful and may be dangerous to the woman. She must take high-dose hormones which may have long term effects on her health. Hwang’s paper in Science reports that they used 242 human eggs to get one stem cell line.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Hwang Woo-Suk 22 Fraud! Nature reporter raises questions about where the eggs came from. Junior scientists begin to question specific items in Hwang’s articles. Research actually used 2,061 eggs over a 3-year period. Many women were paid $1500 to give their eggs. Two junior lab members were pressured into giving their eggs. Not all of the women understood the risks of egg extraction procedures. PLUS one of Hwang’s team admits he faked the 9 of the 11 reported lines.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Professional Ethics What does it mean to have scientific ethics? Scientists must have integrity. They must only publish data which they believe to be true. Individuals must be given credit for their work. The assignment of authorship should be fair. Individuals listed as authors on a paper must have contributed significantly to its content. It is wrong to offer credit on a paper in exchange for something else. Scientific conclusions must be supported by the data, not the opinions or goals of the researcher. 23

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Professional Ethics Violating scientific ethics is not against the law in most places BUT it can have serious consequences. – Scientific journals require professional ethics. Hwang’s papers were retracted. – Employers should require professional ethics. Hwang was fired and his lab closed. – Your colleagues require professional ethics. Hwangs collaborators and team members denounced him. 24

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Discussion Question 25 State and federal regulations/policies need to strike a balance between protecting the rights and health of citizens and allowing/supporting scientific research and advancement. At this point in time, do you see the regulations as weighted more to one side or the other? What regulations or policies may be too stringent? Too lax? Explain why. Discuss these questions with your neighbor and then share with us.

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Summary What does this mean for you? You must respect the principles of research ethics in all of your work. You should also maintain professional integrity. Regulations and policies about stem cell research are very different depending on which country and state you are in. When in doubt, you should consult your IRB or SCRO about the relevant regulations and policies. If you do not have a review board, you may try seeking legal counsel. 26

References  Lecture notes (hyperlink)  Activity notes (hyperlink)  More links… Case Study: Professor Plum 27 Professor Plum, PhD embryonic stem cell researcher Research protocol Summary 1.She wants to put neural cells made from human embryonic stem cells into chimpanzees with damaged brains. 2.She plans to study whether the cells can repair or renew the damaged tissue. 3.Plum is a seasoned cell biologist, but has no experience using human embryonic stem cells. 4.Her research plan states the embryonic stem cells came from a German lab, and the Germans got the cells from Israel. Assignment Work with your policy stakeholder partner over the weekend On Tuesday, we’ll deliberate and vote in committee