Stem Cell Experts Discuss the Ethical Implications of Translating iPSCs to the Clinic

Part of The Stem Cellar blog series on 10 years of iPSCs.

This year, scientists are celebrating the 10-year anniversary of Shinya Yamanaka’s Nobel Prize winning discovery of induced pluripotent stem cells (iPSCs). These are cells that are very similar biologically to embryonic stem cells and can develop into any cell in the body. iPSCs are very useful in scientific research for disease modeling, drug screening, and for potential cell therapy applications.

However, with any therapy that involves testing in human patients, there are ethical questions that scientists, companies, and policy makers must consider. Yesterday, a panel of stem cell and bioethics experts at the Cell Symposium 10 Years of iPSCs conference in Berkeley discussed the ethical issues surrounding the translation of iPSC research from the lab bench to clinical trials in patients.

The panel included Shinya Yamanaka (Gladstone Institutes), George Daley (Harvard University), Christine Mummery (Leiden University Medical Centre), Lorenz Studer (Memorial Sloan Kettering Cancer Center), Deepak Srivastava (Gladstone Institutes), and Bioethicist Hank Greely (Stanford University).

iPSC Ethics Panel

iPSC Ethics Panel at the 10 Years of iPSCs Conference

Below is a summary of what these experts had to say about questions ranging from the ethics of patient and donor consent, genetic modification of iPSCs, designer organs, and whether patients should pay to participate in clinical trials.

How should we address patient or donor consent regarding iPSC banking?

Multiple institutes including CIRM are developing iPSC banks that store thousands of patient-derived iPSC lines, which scientists can use to study disease and develop new therapies. These important cell lines wouldn’t exist without patients who consent to donate their cells or tissue. The first question posed to the panel was how to regulate the consent process.

Christine Mummery began by emphasizing that it’s essential that companies are able to license patient-derived iPSC lines so they don’t have to go back to the patient and inconvenience them by asking for additional samples to make new cell lines.

George Daley and Hank Greely discussed different options for improving the informed consent process. Daley mentioned that the International Society for Stem Cell Research (ISSCR) recently updated their informed consent guidelines and now provide adaptable informed consent templates that can be used for obtaining many type of materials for human stem cell research.  Daley also mentioned the move towards standardizing the informed consent process through a single video shared by multiple institutions.

Greely agreed that video could be a powerful way to connect with patients by using talented “explainers” to educate patients. But both Daley and Greely cautioned that it’s essential to make sure that patients understand what they are getting involved in when they donate their tissue.

Greely rounded up the conversation by reminding the audience that patients are giving the research field invaluable information so we should consider giving back in return. While we can’t and shouldn’t promise a cure, we can give back in other ways like recognizing the contributions of specific patients or disease communities.

Greely mentioned the resolution with Henrietta Lack’s family as a good example. For more than 60 years, scientists have used a cancer cell line called HeLa cells that were derived from the cervical cancer cells of a woman named Henrietta Lacks. Henrietta never gave consent for her cells to be used and her family had no clue that pieces of Henrietta were being studied around the world until years later.

In 2013, the NIH finally rectified this issue by requiring that researchers ask for permission to access Henrietta’s genomic data and to include the Lacks family in their publication acknowledgements.

Hank Greely, Stanford University

Hank Greely, Stanford University

“The Lacks family are quite proud and pleased that their mother, grandmother and great grandmother is being remembered, that they are consulted on various things,” said Hank Greely. “They aren’t making any direct money out of it but they are taking a great deal of pride in the recognition that their family is getting. I think that returning something to patients is a nice thing, and a human thing.”

What are the ethical issues surrounding genome editing of iPSCs?

The conversation quickly focused on the ongoing CRISPR patent battle between the Broad Institute, MIT and UC Berkeley. For those unfamiliar with the technique, CRISPR is a gene editing technology that allows you to cut and paste DNA at precise locations in the genome. CRISPR has many uses in research, but in the context of iPSCs, scientists are using CRISPR to remove disease-causing mutations in patient iPSCs.

George Daley expressed his worry about a potential fallout if the CRISPR battle goes a certain way. He commented, “It’s deeply concerning when such a fundamentally enabling platform technology could be restricted for future gene editing applications.”

The CRISPR patent battle began in 2012 and millions of dollars in legal fees have been spent since then. Hank Greely said that he can’t understand why the Institutes haven’t settled this case already as the costs will only continue to rise, but that it might not matter how the case turns out in the end:

“My guess is that this isn’t ultimately going to be important because people will quickly figure out ways to invent around the CRISPR/Cas9 technology. People have already done it around the Cas9 part and there will probably be ways to do the same thing for the CRISPR part.”

 Christine Mummery finished off with a final point about the potential risk of trying to correct disease causing mutations in patient iPSCs using CRISPR technology. She noted that it’s possible the correction may not lead to an improvement because of other disease-causing genetic mutations in the cells that the patient and their family are unaware of.

 Should patients or donors be paid for their cells and tissue?

Lorenz Studer said he would support patients being paid for donating samples as long as the payment is reasonable, the consent form is clear, and patients aren’t trying to make money off of the process.

Hank Greely said the big issue is with inducement and whether you are paying enough money to convince people to do something they shouldn’t or wouldn’t want to do. He said this issue comes up mainly around reproductive egg donation but not with obtaining simpler tissue samples like skin biopsies. Egg donors are given money because it’s an invasive procedure, but also because a political decision was made to compensate egg donors. Greely predicts the same thing is unlikely to happen with other cell and tissue types.

Christine Mummery’s opinion was that if a patient’s iPSCs are used by a drug company to produce new successful drugs, the patient should receive some form of compensation. But she said it’s hard to know how much to pay patients, and this question was left unanswered by the panel.

Should patients pay to participate in clinical trials?

George Daley said it’s hard to justify charging patients to participate in a Phase 1 clinical trial where the focus is on testing the safety of a therapy without any guarantee that there will be beneficial outcome to the patient. In this case, charging a patient money could raise their expectations and mislead them into thinking they will benefit from the treatment. It would also be unfair because only patients who can afford to pay would have access to trials. Ultimately, he concluded that making patients pay for an early stage trial would corrupt the informed consent process. However, he did say that there are certain, rare contexts that would be highly regulated where patients could pay to participate in trials in an ethical way.

Lorenz Studer said the issue is very challenging. He knows of patients who want to pay to be in trials for treatments they hope will work, but he also doesn’t think that patients should have to pay to be in early stage trials where their participation helps the progress of the therapy. He said the focus should be on enrolling the right patient groups in clinical trials and making sure patients are properly educated about the trial they are participating.

Thoughts on the ethics behind making designer organs from iPSCs?

Deepak Srivastava said that he thinks about this question all the time in reference to the heart:

Deepak Srivastava, Gladstone Institutes

Deepak Srivastava, Gladstone Institutes

“The heart is basically a pump. When we traditionally thought about whether we could make a human heart, we asked if we could make the same thing with the same shape and design. But in fact, that’s not necessarily the best design – it’s what evolution gave us. What we really need is a pump that’s electrically active. I think going forward, we should remove the constraint of the current design and just think about what would be the best functional structure to do it. But it is definitely messing with nature and what evolution has given us.”

Deepak also said that because every organ is different, different strategies should be used. In the case of the heart, it might be beneficial to convert existing heart tissue into beating heart cells using drugs rather than transplant iPSC-derived heart cells or tissue. For other organs like the pancreas, it is beneficial to transplant stem cell-derived cells. For diabetes, scientists have shown that injecting insulin secreting cells in multiple areas of the body is beneficial to Diabetes patients.

Hank Greely concluded that the big ethical issue of creating stem cell-derived organs is safety. “Biology isn’t the same as design,” Greely said. “It’s really, really complicated. When you put something into a biological organism, the chances that something odd will happen are extremely high. We have to be very careful to avoid making matters worse.”

For more on the 10 years of iPSCs conference, check out the #CSStemCell16 hashtag on twitter.

CIRM’s Randy Mills: New FDA rules for stem cells won’t fix the problem

For the last two days the Food and Drug Administration (FDA) has been holding a hearing in Bethesda, Maryland on new regulations that would tighten control over stem cell treatments. The FDA invited public testimony during the hearing on the regulations that would impact many of the clinics that currently offer unproven therapies

The testimony has been impassioned to say the least. Supporters of the clinics say they offer a valuable service and that patients should be allowed to decide for themselves how they want their own cells to be used. Opponents say the clinics are little more than snake oil sales people, offering bogus, unproven treatments.

One of those presenting was Randy Mills, CIRM’s President and CEO. Randy has been very vocal in the past about the need for the FDA to change the way it regulates stem cell therapies.

In California Healthline Randy explained why he thinks the rules the FDA is proposing will not fix the problem, and may even make it worse:

FDA Must Find A Middle Ground For Sake Of Patients

randy

Randy Mills

We aren’t happy, as a lot of people aren’t happy, with the proliferation of these stem cell clinics — some of which are probably doing good work. But some are clearly making rather outlandish claims for which there’s no real data. 

There are a couple of conditions coming together to create this storm.

One is that the need is very real. These patients are really struggling. They don’t have alternatives. They’re desperate and they need help. It’s not in the realm of possibility to talk to somebody who is suffering as badly as these patients are and to say, ‘You have to wait a few more decades for the science to catch up.’

On the other hand, we have a regulatory paradigm that only provides two pathways to put a cell therapy onto the market. One pathway is the most intense regulatory requirement anywhere in the world for any product — the biologics license application through the FDA, which takes 10 to 20 years and costs over $1 billion.

The other is through the exemptions the FDA has made, which require absolutely no pre-market approval whatsoever. You can be on the market in days, with no data.

The regulatory burden associated with one is massive and the other is almost nonexistent.

So it’s not at all surprising that we’re seeing a proliferation of these stem cell clinics popping up that are operating under the assumption that they fall under the exemption.

What the FDA is doing now is saying, ‘We’re not happy with this. We’re going to define some terms more narrowly than in the past … and make it more difficult to legally be on the market under the less burdensome regulatory pathway.’

That’s what this meeting is about.

The problem with their strategy is twofold. It doesn’t address the patients, or the need side of the equation. And I don’t think it has a chance of actually working because the FDA will acknowledge that they do not have the resources to enforce these types of regulations at the clinic level.

They would have to be essentially regulating the practice of physicians, which is well beyond their capabilities. Even if they were able to enforce it, it would just drive these patients somewhere else.

We’re advocating for the creation of some middle pathway that would bring essentially unregulated therapies into the regulatory fold, but in a manner which could be complied with.

I would rather know these clinics are being regulated and collecting data than have them operating under the radar screen of the FDA. I would like there to be a formal pre-market review of these therapies before they’re put on the market. I would like there to be safety and efficacy data.

I’m going to try hard to get the FDA to see that just plugging this hole won’t make the problem go away.

Thinking that they’re going to strengthen the regulation and that patients are going to be satisfied that there’s absolutely no chance for help is naive.

There isn’t a lot of evidence to suggest these types of procedures are overly risky. It’s not that they don’t have risk, but everything in medicine does. If you’re a patient who has absolutely no alternative, you’re probably willing to take the chance.

Women in Bio on The Influential Paths of Great Visionary Leaders

Powerful women made powerful statements last week at the Women in Bio (WIB) Plenary Event during the 2016 BIO International Convention. A panel of influential women leaders discussed difficult yet critical topics, such as how to brand yourself as a woman in a male-dominated industry, the importance of side hustles, and how to close the gender gap. It was a dynamic and inspiring event that engaged both men and women in the audience in productive conversation about how we can all work together to support women in the life sciences industry.

The panel was moderated by Nicole Fisher, the Founder and CEO of HHR Strategies and Forbes Contributer, and the speakers included Renee Compton Ryan, VP of Venture Investments at Johnson & Johnson and Frances Colón, Deputy Science and Technology Adviser to Secretary of State John Kerry.

Frances Colon, Renee Ryan, Nicole Fisher.

Frances Colon, Renee Ryan, Nicole Fisher.

The panel was more of a fire-side chat with the three woman talking intimately at a small coffee table, first sharing stories about their career paths and the road blocks along the way, and then delving into the controversial topics that women in the life sciences face.

Career Paths of Influential Women

Nicole told her story about how she got into the healthcare space. She started by ghostwriting about healthcare, innovation, and politics for the Congressional Budget Office director. Her passion turned into an opportunity with Forbes where she now runs the Health Innovation and Policy page and eventually into her company HHR Strategies which focuses on healthcare and human rights.

Renee discussed how she started as an investment banker in healthcare and made an investment in a company that benefitted patients. This experience made her want to be a part of the solution for patients, which she described as “a calling we are all fortunate to have,” and ultimately brought her to her current position at J&J.

After completing a Ph.D. in developmental neurobiology, Frances switched gears and found her strengths and assets in science policy and communications. She wanted to bring science into international affairs and shared that her mission now is to “make science cool to political scientists and diplomats to the point where my job becomes irrelevant.”

Other Panel Highlights

Branding

Renee’s advice on branding was, “challenge yourself to know your brand, and revisit your brand”. Everyone builds a resume chronologically, but she forces herself to revisit her resume every two years. Her trick is to flip the resume over to the blank side and list all her skills but do it through a different lens so you can have perspective. This process helps her decide where she wants to grow and learn.

Having Side Hustles

Frances mentioned the importance of having “side hustles”. These are things that you are really passionate about that will also build on your strengths, raise your visibility and help you take your brand to the next level. She mentioned two side hustles in particular, a non-profit she founded that supports the Puerto Rican Diaspora Network and a group she organized called the Science Technology Table, which brings together government and the private sector to discuss trending topics in science, tech and innovation. Nicole chimed in and said that all three of her side hustles have turned into companies or big opportunities that have significantly advanced her career.

Closing the Gender Gap, No More Manels!

The panelists had much to say about closing the gender gap. Renee encouraged women in high-up positions to mentor other women that show promise and to be a hands-on mentor. She also said that everyone in the biotech and pharma industries should be studying the data to see why there are less women in the life sciences and what can be done about it.

Frances said that the gender policies at companies need to change, and that people at companies have to hold each other accountable and have the conversations that can create change. One of her key points that got a laugh from the crowd was getting rid of “manels”, or all men panels, which are prevalent at major conferences in the biotech and healthcare space. She also spoke about how we need to strive for 50/50 representation on boards and executive management.

What the audience had to say

The panel was a hit with the Women in Bio audience. Dr. Leah Makley, a WIB member and Founder and CSO of ViewPoint Therapeutics, had this to say about the event,

Leah Makley

Leah Makley

“The panelists shared candid wisdom from their own career trajectories, passions, and ‘side hustles’ that far surpassed the typical depth of career panels.  Moreover, I thought Nicole Fisher did an exceptional job of framing the conversation and asking provocative questions.”

She also spoke about the importance of the WIB community and the resources they offer:

“WIB is a supportive community of powerful, inspiring women. Both the members and the events tend to be action- and solution-oriented, and I’ve walked away from each event I’ve attended with new insights, perspectives, and energy. I’m so grateful that this resource exists.”

Marco Chacon

Marco Chacon

A moment that really stood out in my mind was a moving speech by Marco Chacon, Founder of Paragon Bioservices, and a WIB sponsor. Marco shared that he recently attended a meeting in Boston and listened in on a few diversity forums. He was appalled to hear the statistics on gender diversity in the executive suite and boards of directors in biotech and pharma. Passionately he said, “This has got to change, and to the degree that I can affect this in some way, I can assure you I will do so.”

Final Thoughts

Influential leaders like Nicole, Renee, Frances, and Marco and organizations like Women in Bio, are laying the groundwork for the career advancement of women in science. This event was a great reminder that the issues facing women in the life sciences industry can be addressed in the immediate future if we continue the conversation and challenge one another to create change.

Brave new world or dark threatening future: a clear-eyed look at genome editing and what it means for humanity

Frankenstein

   Is this the face of the future?

“Have you ever wished that there were something different about yourself? Maybe you imagined yourself taller, thinner or stronger? Smarter? More attractive? Healthier?”

That’s the question posed by UC Davis stem cell researcher (and CIRM grantee) Paul Knoepfler at the start of his intriguing new book ‘GMO Sapiens: The Life-Changing Science of Designer Babies’.

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You can find GMO Sapiens on Amazon.com

The book is a fascinating, and highly readable, and takes a unique look at the dramatic advances in technology that allow us to edit the human genome in ways that could allow us to do more than just create “designer babies”, it could ultimately help us change the definition of what it means to be human.

Paul begins by looking at the temptation to use technologies like CRISPR (we have blogged about this here), to genetically edit or alter human embryos so that the resulting child is enhanced in some ways. It could be that the editing is used to remove a genetic mutation that could cause a deadly disease (such as the BRCA1 gene that puts women at increased risk of breast and ovarian cancer) or it could be that the technique is used to give a baby blue eyes, to make it taller, more athletic, or to simply eliminate male pattern baldness later in life.

Paul says those latter examples are not as ridiculous as they sound:

Paul Knoepfler

Paul Knoepfler

“If you think these ideas sound far-fetched, consider that Americans alone spend tens of billions of dollars each year on plastic surgery procedures and creams to try to achieve these kinds of goals. Some of the time elective cosmetic surgery is done on children. In the future, we might have “cosmetic genetic surgeons” who do “surgery” on our family’s genes for cosmetic reasons. In other countries the sensibilities and cultural expectations could lead to other kinds of genetic modifications of humans for “enhancements”.

While the technology that enables us to do this is new, the ideas behind why we would want to do this are far from new. Paul delves into those ideas including a look at the growth of the eugenics movement in the late 19th and early 20th century advocating the improvement of human genetic traits through higher reproductive rates for people considered “superior”. And there was a darker side to the movement:

“Indiana had instituted the first law for sterilization of “inferior” people in the world in 1907. Astonishingly this state law and then similar laws (the original was revoked, but a new law was passed later) stayed on the books in that state until 1974.

This led to approximately 2,500 governmentally forced sterilizations. The poor, uneducated, people of color, Native Americans, and people with disabilities were disproportionately targeted.”

Paul explores the ethical and moral implications of changing our genetic code, changes that can then be passed on to future generations. While he understands the desire to use these technologies to create positive changes, he is also very clear in his concerns that we don’t yet have enough knowledge to be able to use them in a safe manner.

“CRISPR can literally re-write the genomic book inside of us. However, it remains unknown how often it might go to the wrong page or paragraph, so to speak, or stay on the right page, but make an undesired edit there.”

Tiny errors in editing the genome, particularly at such an early stage in an embryo’s development, could have profound and unintended consequences years down the road, resulting in physical or developmental problems we can’t anticipate or predict. For example, you might remove the susceptibility to one disease only to create an even larger problem, one that is now embedded in that person’s DNA and ready to be passed on to subsequent generations.

The book includes interviews with key figures in the field – scientists, bioethicists etc. – and covers a wide range of views of what we should do. For example, the Director of the US National Institutes of Health (NIH), Francis Collins, said that designer babies “make good Hollywood — and bad science,” while the Center for Genetics and Society has advocated for a moratorium on human genetic modification in the US.

In contrast, scientists such as Harvard professor George Church and CRISPR pioneer Jennifer Doudna of UC Berkeley, say we need to carefully explore how to harness the potential for these technologies.

For Church it is a matter of choice:

“The new technology enables parents to make choices about their children just as they might with Ritalin or cleft palate surgery to ‘improve’ behavior or appearance.”

For Doudna it’s acknowledging the fact that you can’t put the genie back in the bottle:

“There’s no way to unlearn what is learned. We can’t put this technology to bed. If a person has basic knowledge of molecular biology they can do it. It’s not realistic to think we can block it…We want to put out there the information that people would need to make an informed decision, to encourage appropriate research and discourage forging ahead with clinical applications that could be dangerous or raise ethical issues.”

The power of Paul’s book is that while it does not offer any easy answers, it does raise many important questions.

It’s a wonderfully well-written book that anyone can read, even someone like me who doesn’t have a science background. He does a good job of leading the reader through the development of these technologies (from the basic idea of genetically altering plants to make them disease resistant) to the portrayal of these concepts in literature (Frankenstein and Brave New World) to movies (Gattaca – 4 stars on Rotten Tomatoes  a great film if you haven’t already seen it).

It’s clear where Paul stands on the issue; he believes there should be a moratorium on human genetic modification until we have a much deeper understanding of the science behind it, and the ethics and morality underpinning it:

“This is a very exciting time to be alive and we should be open to embracing change, but not blindly or in a rush. Armed with information and passion, we can have a major, positive impact on how this biotech revolution unfolds and impacts humanity.”

By the way, Paul also has one of the most widely read blogs about stem cells, where you can read more about his thoughts on CRISPR and other topics.

 

How to handle CRISPR: Formulating a responsible approach to gene-editing

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In February 2016, CIRM sponsored a workshop to discuss the impact of CRISPR, a gene-editing tool that is transforming stem cell research. The workshop was designed to enable the Standards Working Group  (SWG) to reflect on policies governing the review and oversight of embryo research support by CIRM.

After the workshop, we wrote a blog about some of the important questions that came up during the discussion. There is also a written and audio transcript of the meeting here.

Since then, the CIRM Team has been working with the co-chairs of the Standards Working Group to develop draft recommendations for how CIRM could address the workshop questions. The draft recommendations may be found here.

As we noted in June 2015, these deliberations and subsequent recommendations are designed to inform the responsible uses of genome editing technologies with CIRM funds. In particular, CIRM continues to place a priority on funding research that does not receive timely or sufficient federal funding – for example research involving human embryos.

As was discussed at the workshop, donors indicated strong support for embryo research for:

  1. Understanding human development and
  2. Creating stem cell lines.

Genome editing may be applied to both types of research.

The draft recommendations are intended to ensure such work may occur under high ethical standards. After the Standards Working Group review, the final recommendations will be forwarded to CIRM’s governing Board, the ICOC, for approval. We hope that will happen this summer.

Timing is everything: could CRISPR gene editing push CIRM to change its rules on funding stem cell research?

CRISPR

Talk about timely. When we decided, several months ago, to hold a Standards Working Group (SWG) meeting to talk about the impact of CRISPR, a tool that is transforming the field of human gene editing, we had no idea that our meeting would fall smack in the midst of a flurry of news stories about the potential, but also the controversy, surrounding this approach.

Within a few days of our meeting lawmakers in the UK had approved the use of CRISPR for gene editing in human embryos for fertility research —a controversial first step toward what some see as a future of designer babies. And a U.S. Food and Drug Advisory report said conducting mitochondrial therapy research on human embryos is “ethically permissible”, under very limited conditions.

So it was clear from the outset that the SWG meeting was going to be touching on some fascinating and fast moving science that was loaded with ethical, social and moral questions.

Reviewing the rules

The goal of the meeting was to see if, in the light of advances with tools like CRISPR, we at CIRM needed to make any changes to our rules and regulations regarding the funding of this kind of work. We already have some strong guidelines in place to help us determine if we should fund work that involves editing human embryos, but are they strong enough?

There were some terrific speakers – including Nobel Prize winner Dr. David Baltimore; Alta Charo, a professor of Law and Bioethics at the University of Wisconsin-Madison  ; and Charis Thompson, chair of the Center for the Science, Technology, and Medicine in Society at the University of California, Berkeley – who gave some thought-provoking presentations. And there was also a truly engaged audience who offered some equally thought provoking questions.

CIRM Board member Jeff Sheehy highlighted how complex and broad ranging the issues are when he posed this question:

“Do we need to think about the rights of the embryo donor? If they have a severe inheritable disease and the embryo they donated for research has been edited, with CRISPR or other tools, to remove that potential do they have a right to know about that or even access to that technology for their own use?”

Alta Charo said this is not just a question for scientists, but something that could potentially affect everyone and so there is a real need to engage as many groups as possible in discussing it:

“How and to what extent do you involve patient advocates, members of the disability rights community and social justice community – racial or economic or geographic.  This is why we need these broader conversations, so we include all perspectives as we attempt to draw up guidelines and rules and regulations.”

It quickly became clear that the discussion was going to be even more robust than we imagined, and the issues raised were too many and too complex for us to hope to reach any conclusions or produce any recommendations in one day.

As Bernie Lo, President of the Greenwall Foundation in New York, who chaired the meeting said:

“We are not going to resolve these issues today, in fact what we have done is uncover a lot more issues and complexity.”

Time to ask tough questions

In the end it was decided that the most productive use of the day was not to limit the discussion at the workshop but to get those present to highlight the issues and questions that were most important and leave it to the SWG to then work through those and develop a series of recommendations that would eventually be presented to the CIRM Board.

The questions to be answered included but were not limited to:

1) Do we need to reconsider the language used in getting informed consent from donors in light of the ability of CRISPR and other technologies to do things that we previously couldn’t easily do?

2) Can we use CRISPR on previously donated materials/samples where general consent was given without knowing that these technologies could be available or can we only use it on biomaterials to be collected going forward?

3) Clarify whether the language we use about genetic modification should also include mitochondrial DNA as well as nuclear DNA.

4) What is the possibility that somatic or adult cell gene editing may lead to inadvertent germ line editing (altering the genomes of eggs and sperm will pass on these genetic modifications to the next generation).

5) How do we engage with patient advocates and other community groups such as the social justice and equity movements to get their input on these topics? Do we need to do more outreach and education among the public or specific groups and try to get more input from them (after all we are a taxpayer created and funded organization so we clearly have some responsibility to the wider California community and not just to researchers and patients)?

6) As CIRM already funds human embryo research should we now consider funding the use of CRISPR and other technologies that can modify the human embryo provided those embryos are not going to be implanted in a human uterus, as is the case with the recently approved research in the UK.

Stay tuned, more to come!

This was a really detailed dive into a subject that is clearly getting a lot of scientific attention around the world, and is no longer an abstract idea but is rapidly becoming a scientific reality. The next step is for a subgroup of the SWG to put together the key issues at stake here and place them in a framework for another discussion with the full SWG at some future date.

Once the SWG has reached consensus their recommendations will then go to the CIRM Board for its consideration.

We will be sure to update you on this as things progress.

To modify, or not to modify: Experts discuss human germline modification at WSCS15

The question of whether human germline modification, or the genetic modification of human reproductive cells, should be allowed or banned was discussed by a panel of experts in the Ethics, Law and Society session during Day 1 of the World Stem Cell Summit.

On the panel were Aubrey de Grey, Chief Science Officer of the SENS Foundation, Paul Knoepfler, Associate Professor at the UC Davis school of medicine (and a CIRM grantee), and Aaron Levine, Associate Professor of Public Policy at Georgia Tech.

Aubrey de Grey, Paul Knoepfler, Aaron Levine

Aubrey de Grey, Paul Knoepfler, Aaron Levine

What Paul Knoepfler said…

On the basic research side, Paul discussed how CRISPR has revolutionized the way germline modification is being done from the older, costly, time-consuming method using homologous recombination to the faster, more efficient, and cheaper gene editing technology that is CRISPR.

In the big picture, he said that, “people will pursue germline modification with a variety of different goals.” He further explained that because this will likely happen in the future, scientists need to consider the risks (off target effects to name one) and the societal and ethical impacts of this technology. Another question he said we should consider is, whether as a society, we support the modification of the germline for health or enhancement reasons.

He concluded with a recap of last week’s International Summit on Human Gene Editing saying that while the organizers didn’t put forth a definitive statement on whether there should be a moratorium on editing the human germline, he himself believes that there should be a temporary moratorium on the clinical use of this technology since the idea is still very controversial and there is no overall consensus within the scientific community.

What Aubrey de Grey said…

Aubrey began by saying that as a gerontologist, he is interested in all potential therapies that could postpone the effects of old age, many of which could involve genetic modification. He went on to say that it might not seem intuitive that editing the human germline would be applicable to fighting aging, but that:

“Even though the medical imperative to engaging genetic germline modification may seem to be less clear in the case of aging than it is for inherited diseases, which people are unequivocally agreed on that is a bad thing, never-the-less, the potential application to aging may actually play a significant role in the debate, because we’ve all got aging.”

He gave an example of the ApoE4 gene. If you have two copies of this form of the gene instead of the normal ApoE3 gene, then you have a very high risk of getting Alzheimer’s disease and atherosclerosis. He posed the question to the audience, asking them whether if they knew that they had this disease causing gene, would they consider genetically altering their fertilized eggs back into the safe ApoE3 version to prevent their offspring from inheriting disease even if the therapy wasn’t approved by the FDA. It’s a hard question to answer and Aubrey further commented that if we begin using genetic modification to prevent one disease, where would we draw the line and where would modification end?

He ended with saying that the real question we need to consider is “whether people will want to do germline modification against aging, even though the modifications may really be more in the way of enhancements than genuine therapies.”

What Aaron Levine said…

Aaron Levine began with saying that the question of human germline modification is an old question with new twists. By new twists he meant the recent advances in gene editing technologies like CRISPR and Zinc Finger Nucleases. He further commented that the baseline question of this debate is whether we should modify the DNA of the germline, and that how we do it isn’t as significant.

He played devil’s advocate by saying that germline editing would greatly benefit single gene disorders, but that we should think of the full spectrum. Many traits that we might want, we don’t know enough about and attempting to add or remove these traits using gene editing would be like shooting in the dark.

On policy side, Aaron commented that international policy harmonization would be nice, but that we should treat it skeptically. He said that not everyone is going to agree or follow the same rules and we need to consider this going forward. As for the FDA, he said that its role and regulations regarding germline editing aren’t clear and that these need to be defined.

One really interesting point he made was the issue of unproven stem cell clinics. They exist and pose a huge risk to human health. The real question, he said, is could this turn into unproven CRISPR clinics around the world? He ended with saying that someone will claim to offer this technology soon and asked what we should do about it.

From the peanut gallery…

One of the questions asked by the audience was whether it’s just a matter of time that one of the world’s governments might go forward with human germline modification because of the huge medical implications.

Paul responded first saying that there was a consensus at the gene editing summit that it’s more of a question of when, rather than if this would happen. Aaron agreed and said that he believed it would happen but wasn’t sure when, and followed with saying that the more important question is how it will be done, overseen, and what reasons the editing will be done for.

Bernie Siegel, who is the co-Chair of the World Stem Cell Summit, spoke at the end and said that the panel delivered exactly what he hoped it would. He emphasized a theme that I didn’t mention in this blog but that was brought up by each of the panelists: the voice of patients.

“One of the things missing from the [International Summit on Gene Editing] meeting was the voice of the patient community. Do they understand the concepts of CRISPR technology? Patients are a major stake holder group, and they have the most influence on creating change in policy. When we talk about a moratorium, the patients see it as a five-alarm fire. All they want is to see a few drips of water, and they can’t get it. From a societal and popular culture standpoint, these are a whole group of people that will be experiencing the sweeping changes of biotech today. When those voices that are receiving these technologies enter the conversation, it will be a full debate.”

How do you know if they really know what they’re saying “yes” to?

How can you not love something titled “Money, Mischief and Science.” It just smacks of intrigue and high stakes.

And when the rest of the title is “What Have We Learned About Doing Stem Cell Research?” you have an altogether intriguing topic for a panel discussion.

Sue and Bill Gross Hall: Photo by Hoang Xuan Pham/ UC Irvine

Sue and Bill Gross Hall: Photo by Hoang Xuan Pham/ UC Irvine

That panel – featuring CIRM’s own Dr. Geoff Lomax, a regular contributor to The Stem Cellar – is just one element in a day-long event at the University of California, Irvine this Friday, November 13.

Super Symposium

The 2015 Stem Cell Symposium: “The Challenge of Informed Consent in Times of Controversy” looks at some of the problems researchers, companies, institutions and organizations face when trying to put together a clinical trial.

In many cases the individuals who want to sign up for a clinical trial involving the use of stem cells are facing life-threatening diseases or problems. Often they have tried every other option available and this trial may be their last hope. So how can you ensure that they fully understand the risks involved in signing up for a trial?

Equally important is that many of the trials now underway now are Phase 1 trials. The main goal of this kind of trial is to show that the therapy is safe and so the number of cells they use is often too small to have any obvious benefit to the patient. So how can you explain that to a patient who may chose to ignore your caveats and focus instead on the hope, distant as it may be, that this could help them?

Challenging questions

The symposium will feature experts in the fields of science, law, technology and ethics as they consider:

  • Does informed consent convey different meanings depending on who invokes the term?
  • When do we know that consent is informed?
  • What are human research subjects entitled to know before, during and after agreeing to participate in clinical trials?
  • How might the pushback on fetal tissue research impact the scientific development of vaccines, research on Alzheimer’s disease or other medical advancements?

So if you are looking for something thought provoking and engaging to do this Friday, here you are:

“The Challenge of Informed Consent in Times of Controversy,” Friday, Nov. 13, 9am – 4:30pm, at the Sue & Bill Gross Stem Cell Research Center on the University of California, Irvine campus.

The symposium will be livestreamed, and a video recording will be available on www.law.uci.edu following the event.

REGISTER: The symposium is free to UCI student, staff and faculty. There is a $20 registration fee for non-UCI attendees. Visit the event page to register.

CRISPR cluster: How the media spotlight is focusing on gene editing tool

Illustration by Ashley Mackenzie: from New York Times Sunday Magazine

Illustration by Ashley Mackenzie: from New York Times Sunday Magazine

Getting in-depth stories about science in general, and regenerative medicine in particular, into the mainstream media is becoming increasingly hard these days. So when you get one major media outlet doing a really long, thoughtful piece about a potential game-changing gene-editing technology it’s good news. But when you get three major media outlets, all reporting on the same technology, all in the space of less than one week, and all devoting lots of words to the pieces, then it’s really a cause for celebration.

That’s what happened in the last few days with features on the gene editing technology CRISPR in the New York Times Sunday Magazine,  the New Yorker Magazine,  and STAT, a new online health and life-sciences publication produced by the Boston Globe.

Making the story personal

Feng Zhang: photo courtesy of the Broad Institute

Feng Zhang: photo courtesy of the Broad Institute

Each takes a similar approach, focusing on the individuals behind the new approach – Feng Zhang at Harvard/MIT and Jennifer Doudna at the University of California, Berkeley. The fact that the two are involved in a fight over patent rights for the process adds an extra element of friction to a story that already has more than its share of drama.

In the New Yorker, Michael Specter neatly summarizes why so many people are excited about this technology:

“With CRISPR, scientists can change, delete, and replace genes in any animal, including us. Working mostly with mice, researchers have already deployed the tool to correct the genetic errors responsible for sickle-cell anemia, muscular dystrophy, and the fundamental defect associated with cystic fibrosis. One group has replaced a mutation that causes cataracts; another has destroyed receptors that H.I.V. uses to infiltrate our immune system.”

Jennifer Doudna: Photo courtesy of iPSCell.com

Jennifer Doudna: Photo courtesy of iPSCell.com

Sharon Begley in STAT, writes that this discovery could bring cures to some of the deadliest health problems we face, from cancer to Alzheimer’s, but that it also comes with big ethical questions hanging over it:

“He (Zhang) has touched off a global furor over the possibility that a genetics tool he developed could usher in a dystopian age of designer babies.”

Jennifer Kahn in the New York Times Sunday Magazine follows up on that thought, writing about Doudna:

“But she also notes that the prospect of editing embryos so that they don’t carry disease-causing genes goes to the heart of CRISPR’s potential. She has received email from young women with the BRCA breast-cancer mutation, asking whether CRISPR could keep them from passing that mutation on to their children — not by selecting embryos in vitro, but by removing the mutation from the child’s genetic code altogether. ‘‘So at some point, you have to ask: What if we could rid a person’s germ line, and all their future generations, of that risk?’’ Doudna observed. ‘‘When does one risk outweigh another?’’

Each article makes for fascinating reading. Collectively they highlight why CRISPR is such a hot topic, on so many different levels, in science right now.

The topic is going to be the focus of a conference, featuring scientists from the US, Europe and China, being held at the National Academy of Sciences in Washington DC the first week of December.

CIRM is also getting involved in the debate and is holding a science-policy workshop on February 4th, 2016 in Los Angeles to consider the future use of genome editing technologies in studies sponsored by CIRM.

A call for scientists to speak out for Stem Cell Awareness Day

SCAD campaign

The International Society for Stem Cell Research (ISSCR) and the journal Cell Stem Cell, are asking stem cell scientists to take part in a social media campaign with the hashtag #AStemCellScientistBecause between October 1 and October 14.

“We want to share with the world our pride and excitement to be a part of a worldwide effort to transform human health,” the association states on a web page created for the event, calling the effort a “campaign to give a voice to the scientists behind the research.”

ISSCR suggests several ways to take part:

  • Tweet a brief statement about why you entered the field,
  • Record a 10-20 second video to accompany the Tweet,
  • Talk to peers about taking part,
  • Share and retweet favorites posts.

The journal’s October issue will include an article with contributions from all the first authors of papers in the issue stating why they entered the field as well as contributions from other authors in the issue.

As always, CIRM is facilitating getting researchers we fund into high school classrooms on October 14th to give guest lectures. We expect to reach more than 50 classrooms including several school-wide assemblies this year.

Several institutions in California will be hosting special events to commemorate Stem Cell Day this month. And if you are across the border, the MaRS center in Toronto is hosting the children’s museum exhibit we helped develop, “Super Cells: The Power of Stem Cells.”

All the events con be found at http://www.stemcellday.com/