Scientists today have access to increasingly sophisticated research tools, including capabilities that allow them to culture embryos and create embryo models. These tools have opened the door to new possibilities in biomedical research. We can now explore early human development and answer questions that were previously impossible to address.
Naturally, these advances have drawn the attention of the media and the general public, reinforcing a need to ensure the use of stem cell technologies in the lab meets an established standard of scientific rigor. Recently, a team convened by the International Society for Stem Cell Research (ISSCR) published a paper in Stem Cell Reports that offers a detailed set of practical recommendations to help review boards, regulators, and researchers around the world evaluate and justify the application of these powerful new technologies. While the paper was written by members of the ISSCR Ethics Committee at the request of ISSCR, it is not an official ISSCR document and is not legally binding.
Erica Jonlin, PhD, is the lead author of the paper. Dr. Jonlin is a member of the ISSCR Ethics Committee, which produced the recommendations. She is also a member of the UW Embryonic Stem Cell and Research Oversight Committee (ESCRO) and she is the Regulatory Manager for the Institute for Stem Cell and Regenerative Medicine.
The following is an edited and abridged interview with Jonlin.
Your article responds to a need for clear guidance for researchers using new stem cell technologies. How would you describe the advances in the field that are discussed in your paper?
The field has evolved very quickly. And science always evolves faster than the ethics can keep up. For example, we can now culture human embryos past 14 days (the conventionally accepted stopping point for in vitro culture of a human embryo). That extended culture used to be impossible. Moreover, we can make a human stem cell embryo model from induced pluripotent stem cells (IPSCs). We can make a chimeric creature that has animal cells and human cells, including human reproductive cells, and we can theoretically put it in a uterus of an animal and allow it to grow until the pregnancy is over. We are able to do all this technologically, but just because we can doesn’t mean that we should. A crux of this paper is what is appropriate scientifically? And then what is appropriate scientific justification in these areas of research?
What are some of the potential clinical improvements and important ethical questions to balance?
If someone is studying the reasons for miscarriage, and if these stem cell technologies can help us understand the black box of post-implantation development, I think it’s well recognized that there’s a lot of good to be gained. And there are upsides from a clinical standpoint. For example, we don’t have enough organs for the millions of patients who need transplants. Stem cell and embryo research is incredibly useful because it enables us to learn more about how to regenerate organs, so that maybe we can make organs in the lab, in addition to exploring more profound mysteries about human development.
But the questions remain, what about human life? What about human dignity? What are these entities that we are capable of creating? This is something that ethicists are discussing and something that people on the street are discussing, and it’s important for scientists to discuss as well. The public is watching us.
What are the goals of the paper?
The International Society for Stem Cell Research (ISSCR) Guidelines for Stem Cell Research and Clinical Translation (written in 2016 and updated in 2021) stated there needs to be adequate and appropriate scientific justification for performing stem cell research. Those guidelines cover a lot of topics, including issues about informed consent, establishment of embryonic stem cell research oversight committees and what they do. One area that they really did not elaborate on was the meaning of scientific justification. Our paper aims to address that.
ISSCR leadership asked the Ethics Committee to write this paper to unpack what “appropriate scientific justification” means. Some of the elements in this paper, which was written by a team of researchers, social scientists, and ethicists, and informed by discussions with researchers in the field, delve deeper into how a researcher would justify why and how they’re doing the research.
The paper also addresses a gap in the review infrastructure. Some stem cell research doesn’t always involve humans or animals. It may just involve human cell lines, which means it may not be reviewed by a human subjects committee, or by an animal care and use committee. Although many universities do have stem cell research oversight committees, they are advisory only, and they look to the ISSCR guidelines to provide clarity on what research may be permissible.
Another issue has to do with funding sources. Many stem cell research studies are not funded by the government and therefore are not peer-reviewed. Just because a scientific investigation is not funded by the government doesn’t mean researchers can do anything. They still have to answer to all the usual parameters of how you do research.
By unpacking what “scientific justification” means for pluripotent stem cell research, we hope to meet the goal of informing researchers and regulators and government officials. And we want to ensure that the public knows that we’re doing this research thoughtfully and with good reason.
How did you approach writing this paper for scientists all over the world operating under many different legal systems?
That’s one of the motivations behind the paper: to really bring together a lot of ideas in one place so that researchers can go to this and realize this is what they’re going to be asked to address no matter what country they’re in when they’re designing their research experiment. Box 1 in the paper explains how various countries legislate stem cell research at different levels of government. Different countries have different regulations. Some are much more constrained. Some have laws that prohibit certain things that aren’t prohibited in other places. One of our goals was to try to summarize it all in one paper.
Talk about the review process proposed in the paper and how it was developed.
In some cases, we recommend that there be a stepwise approach to the research, with a more collaborative relationship between the reviewing entity and the investigator in designing the experiments. That’s not something that is usual in a review process for grant funded research. So, let’s say somebody wants to grow the human embryos to 28 days. They would go the committee, and the committee would say, well, we’ll let you go until 21 days right now and then come back to us with your results and we’ll discuss going to 28.
Much of the process we propose in the paper was informed by our committee discussions and by workshops we held with researchers who are in the trenches doing this kind of work. We asked, if you could gestate a chimeric creature, why would you do it? What are the issues? They told us how they would explain that, and those answers informed the paper. Our mindset was we want to respect scientific autonomy of the investigators, but we do have to set limits. Because we are accountable to the public.
What do you hope comes about as a result of this paper?
We as a committee wrote this with the hope that this will be helpful to people who are on review committees and to researchers designing research studies. There’s a table in the paper that offers specific considerations for a list of topics that might be helpful for a review committee to consider when they are assessing proposed research. At the same time, that could be useful to researchers too, because they will know what criteria reviewers will be using. And we hope is that by giving this kind of guidance to reviewers and to researchers, we will address concepts that the public is concerned about.