New Tech, New Rules: Organoids and Ethics at the CJEU

Introduction

Last week, while attending a conference, organized by the Petrie-Flom Center in conjunction with a number of other Harvard institutions, on the ethics of early embryo research and the future of the 14-day rule, I was struck by the presentations on recent developments in stem cell technology. The speakers outlined fascinating developments in human brain organoids. And, since my own cranial organoid is becoming increasingly single track, I started wondering about the potential patentability of such inventions.

An intestinal organoid grown from Lgr5+ stem cells

An intestinal organoid grown from Lgr5+ stem cells

By way of very brief explanation, a human brain organoid is a structure of cells created in vitro through the stimulation of human stem cells. A recent paper has concluded that, given the right conditions for their development, these cell cultures can grow to resemble a 20 week-old human brain in vivo in a number of important respects.

At the conference, Dr John Aach, of the Department of Genetics at Harvard Medical School highlighted the potential of these technologies to form the basis of innovative research and treatments. However, he also highlighted new ethical questions posed by them. In particular, (and I fear I may be grossly oversimplifying his much more subtle presentation) he noted that a sufficiently developed human brain organoid might have the capacity to feel pain. Such technologies might fall to be regulated alongside human embryos created for research. In most jurisdictions, developing an embryo beyond 14 days of gestation is prohibited, whether by law or soft regulation. The rule originally struck a balance between the interests of research and the demands of ethics: day 14 usually marks the appearance of the primitive streak in an embryo and presents a convenient point to place an ethical limitation on research.  Dr Aach noted, however, that a brain organoid does not fall under the traditional definition of embryo. As such, its development is not necessarily subject to the 14-day rule. And yet, the creation of a clump of cells that feels pain is clearly a cause for ethical concern. He argued that the time has come to re-examine the rule in light of technological advancements like organoids. Its replacement, he argued, should not be based on canonical limits but on the underlying moral concerns. Continue reading

THIS AFTERNOON! (11/7): The Ethics of Early Embryo Research & the Future of the 14-Day Rule

egg cells flowing in a blue background

The Ethics of Early Embryo Research & the Future of the 14-Day Rule
November 7, 2016 3:00 – 6:30 PM
Austin Hall, North Classroom (100)
Harvard Law School, 1515 Massachusetts Ave., Cambridge, MA
 

Description

For over 35 years, the “14-Day Rule,” prohibiting in vitro experimentation on embryos beyond 14 days, has stood as an ethical line in the sand for embryo research around the world. Throughout the arc of the rule’s existence it has not been questioned, as scientists have been unable to grow embryos in vitro either up to, or beyond, 14 days; a practical limitation that served as a backstop to the ethical rule. However, in May of this year, labs in the U.S. and the U.K. were the first to report being able to sustain human embryos in vitro for up to 13 days. This development and other advances in in vitro research involving organized, embryo-like cellular structures have raised a number of questions about the rule, its genesis, application, and future scope. This conference will convene experts in bioethics, stem cell research, embryology, and law to discuss the ethical underpinnings and future scope of the rule. Questions to be discussed include:

  • What are the historical, ethical and scientific rationales for establishing the 14-Day Rule?
  • Should the 14-Day Rule be revisited in light of recent advances?
  • Should the 14-Day Rule even apply to research involving the in vitro culture of embryo-like cellular structures?

Agenda Continue reading

Initial Quick Thoughts on the Announcement of the Birth Through Mitochondrial Replacement in Mexico

The science media is abuzz about the birth of a child using mitochondrial replacement techniques in Mexico to Jordanian parents at the hands of NY Doctors. A few quick reactions (I am heading to this unrelated NAS/IOM Committee meeting tomorrow evening so may have some more thoughts when that settles down).

  • This is the first time this particular technique has been used to produce a live, but I am not sure from an ethical standpoint the arguments are all that different. That said, for those deeply interested in the more philosophical question of harm to children and the propriety of best interests argument in light of Parfit’s Non-Identity Problem (my take here and here) it may matter whether mitochondrial replacement is done through Pronuclear Transfer or Maternal Spindle Transfer as argued quite well here.
  • The fact that the doctors are from New York, the Patients are from Jordan, and the procedure took place in Mexico is not insignificant. This is a form of medical tourism, a topic I wrote a book on, most similar to cases of fertility and stem cell therapy tourism I cover in the latter half of the book. Absent making domestic prohibitions extraterritorial, something that I argue is permitted by international law and justified in some instances, there is very little that a home country can do about this. The going abroad is likely in part at least a function of some U.S. laws on the subject Eli Adashi and I wrote about for JAMA prohibiting FDA from considering approval of the technology.
  • As I wrote on this blog in February in relation to the IOM report “whatever the US policy in a world where medical tourism is possible and other countries adopt their own systems, so long as not everyone adopts the approach of the US some of these problems will manifest no matter what. So this is about harm reduction not harm avoidance.” This was a bit quicker than even I thought, but is not surprising. More generally if your concern about MRT is harm to offspring and transmission to future generations, people born elsewhere through the technology will inevitably enter the United States and/or marry, and procreate with U.S. citizens who themselves become U.S. citizens. To sound a bit X-Files about it “THEY WILL BE AMONG US!” This is a great example of the limits of unilateral regulation in a world of globalized health care.
  • Interesting that it was a male birth. This may be coincidence or in keeping with the IOM recommendation that only male embryos be transferred (to get rid of germ line transmission). Eli Adashi and I raised some ethical questions in Nature about whether that was an ethically problematic form of sex selection or not but in the reporting I have seen so far it has not been clear that they used only male embryos on purpose.
  • I wish we could stop calling it in the media “Three Parent IVF” or “Three Parent Reproduction.” That assumes the answer to what I think of as a subtle and interesting set of questions — is the mitochondrial donor a “parent” and what sense of the word do we mean.

More soon, I hope!

Stem cell patenting on the other side of the pond

We are pleased to announce a new publication in the International Review of Intellectual Property and Competition Law (IIC). Our paper analyzes new case law in European stem cell patenting and compares these developments with the US situation and International treaties. Further information and an abstract is available below:

Authors: Ana Nordberg & Timo Minssen, University of Copenhagen, Centre for Information and Innovation Law (CIIR)

Title: A “Ray of Hope” for European Stem Cell Patents or “Out of the Smog into the Fog”? An Analysis of Recent European Case Law and How it Compares to the US
Journal: IIC – International Review of Intellectual Property and Competition Law, 47(2), 138-177
DOI: 10.1007/s40319-016-0449-x

ABSTRACT:  Continue reading

Happy New Year: From “Weltschmerz” to Pharmaceutical Innovation

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Dear readers and colleagues, I would like to take this opportunity to wish you all a very happy, healthy and peaceful year 2016. Reaching the end of 2015, I cannot stop thinking about the year that has passed. Being a native German, … Continue reading

NPRM Summary from HHS

As Michelle noted, the Notice of Proposed Rule Making (NPRM) on human subjects research is out after a long delay. For my (and many Bill of Health bloggers’) view about its predecessor ANPRM, you can check out our 2014 book, Human Subjects Research Regulation: Perspectives on the Future.

Here is HHS’s own summary of what has changed and what it thinks is most important:

The U.S. Department of Health and Human Services and fifteen other Federal Departments and Agencies have announced proposed revisions to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects that was promulgated as a Common Rule in 1991.  A Notice of Proposed Rulemaking (NPRM) was put on public display on September 2, 2015 by the Office of the Federal Register.  The NPRM seeks comment on proposals to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. It is expected that the NPRM will be published in the Federal Register on September 8, 2015.  There are plans to release several webinars that will explain the changes proposed in the NPRM, and a town hall meeting is planned to be held in Washington, D.C. in October. Continue reading

GOP Confusion Over Stem Cell Research

Bill of Health Contributor Dov Fox has a new article up on the Huffington Post:

Republican candidates convened last night for the first debates of the 2016 campaign. The presidential hopefuls disagreed on every topic they faced — immigration, health care, foreign policy, gay rights, the economy — all but one, that is. Their differences of opinion disappeared each time they were asked about the controversy over the recent release of an undercover video with Planned Parenthood. On the issue raised by that edited film clip, the candidates came together in a rare consensus.

All 17 — from Ted Cruz to Carly Fiorina — staunchly opposed research that uses tissue cells from aborted or miscarried fetuses. The candidates unanimously called for Congress to end its support of Planned Parenthood over its contribution to that research, with some like Louisiana Gov. Bobby Jindal joining party leaders who would force a government shutdown over that issue. This, after Senate Republicans earlier this week failed to clear a procedural vote to defund. […]

Read the full article here.

Ethics for CRISPR and the Big Leap Forward

By Kelsey Berry

This week, a research group in China published a paper describing a significant step forward in one application of the genome editing technique CRISPR: they used it to modify the genome of non-viable human embryos. Now, the scientific community finds itself grasping for ethical and legal foundations in order to evaluate the implications of this work and its possible extensions. Bioethicists and philosophers have been laying these foundations for years. Yet, the key problem, as always, is in translation: as we shift from science fiction to scientific reality, the robust and rigorous literature on the ethics of human population enhancement must find its way to usefully inform the policy debate and scientific practice. Translation between these camps can be thorny, but it must start with convergence on the issues at stake. Here’s a quick primer on the issue:

The spark: A team out of Sun Yat-sen University in Guangzhou led by Junjiu Huang used the CRISPR technique in non-viable human embryos to modify the gene responsible for a potentially fatal blood disorder. Leading journals Science and Nature denied the group publication on ethical grounds; the paper can be found in Protein & Cell. This is the first time that the CRISPR technique has been used to modify the human germline; however, the team specifically selected non-viable embryos in which to conduct the experiment in order to side step some of the most pressing ethical concerns.

The technology: CRISPR, which stands for “clustered regularly interspaced short palindromic repeats” refers to DNA loci that contain repeated base sequences, separated by other sequences called spacers. These spacers are like memories from previous exposure to a virus, and they tell the biological system which invaders to look out for and destroy – a key part of an adaptive immune system. In 2012, a team led by Doudna and Charpentier showed that CRISPRs could also be used to zero in on DNA sequences of their choosing simply by introducing synthetic guide RNA that matched the DNA sequence they wished to target. The CRISPR system would then slice up the targeted DNA sequence, either knocking out a gene entirely or allowing researchers to insert a “patch,” which if incorporated into the DNA sequence would modify the target gene. Since 2012 this technique has been shown to work in several organisms, including in human cells.

Continue reading

Article III Standing in Patent Law May Be Before the Supreme Court Soon

Who has standing to challenge a patent’s validity? And under what circumstances can Congress define an injury for the purpose of creating Article III standing? Those questions underlie a new petition for certiorari filed by Consumer Watchdog, who is asking the Supreme Court to reverse a Federal Circuit opinion holding that Consumer Watchdog lacked Article III standing to challenge a patent on embryonic stem cells.

Consumer Watchdog, a non-profit consumer organization, requested an inter partes reexamination of a patent on embryonic stem cells held by the Wisconsin Alumni Research Foundation (WARF), alleging that the patent should be invalidated on several grounds. After a lengthy administrative process, the Patent Trial and Appeal Board (PTAB) upheld the patent as valid. Consumer Watchdog subsequently appealed, under sections of the Patent Act that expressly permit third-party requesters (like Consumer Watchdog) in inter partes reexamination proceedings to appeal to the Federal Circuit if they are “dissatisfied” with the PTAB’s decision or if any “final decision [is] favorable to the patentability” of the claims in question. The Federal Circuit held that Article III’s case or controversy requirement imposes a separate, irreducible constitutional minimum requirement on standing — and that Consumer Watchdog hadn’t met that requirement.  Continue reading

Savior Siblings in the United States

By Zachary Shapiro

With the emergence of new techniques in the field of reproductive technology, applications arise that seem more the realm of science fiction than reality. While many have considered stem cells to be the next frontier of modern medicine, reproductive technology may offer hope to many individuals suffering with rare and unique genetic diseases.

The term “savior siblings” refers to the use of pre-implantation genetic diagnosis (PGD) and other forms of in-vitro fertilization (IVF) in order to create a sibling for the purpose of providing biological material (bone marrow, blood, etc.) that can help treat or cure an existing terminally ill child. It is estimated that up to one percent of PGD in the United States is used to create children that are tissue matches for their siblings. See here.

There has been little meaningful discussion about savior siblings in bioethical or legal circles, and there is no formal regulation governing their use or creation in the United States. This stands in stark contrast to other countries, particularly England, France, and Australia, where a regulatory framework for the use of savior siblings has arisen along with debate over their acceptability. These countries are already discussing how to ethically deal with this extremely complicated issue.  Continue reading

Separating Fact from Fiction

By Joanna K. Sax
[Ed. Note: Cross-posted at HealthLawProfBlog]

Rhetoric that misconstrues scientific knowledge to garner support for political positions is troubling. For many years, my scholarship has focused on the debate surrounding embryonic stem cell research.   One of the things that I have experienced is an incomplete understanding about what embryonic stem cell research is, what the starting material is, and why it might be different than adult stem cells. One reason that the public may be confused is because some of the information fed to the public is incomplete or, even, incorrect.

To understand the type of information that the public receives regarding a controversial type of research, in this case, embryonic stem cell research, I conducted an empirical study.  By way of background, in 2001, an intense debate about the federal funding for stem cell research occurred. One of the arguments against federal funding for stem cell research was that there was no need for it because scientists could use adult stem cells (which didn’t have the same ethical concerns) instead of embryonic stem cells. The problem with this proposition, however, was that it had no scientific merit because the scientists had not yet conducted the studies to compare human adult and embryonic stem cells. The call for the need for these studies was loud and clear in the scientific community. But, it seemed that some in the non-scientific community already came to the conclusion that these cell types were interchangeable.

I compared the type of information that was being conveyed to the public in major newspapers to the statements made by scientists in the scientific literature. I confirmed that information in major newspapers was statistically more likely than the scientific literature to say that adult stem cells give the same or similar results as research with embryonic stem cells. A more detailed explanation of the study along with the results is available hereContinue reading

DUE 6/3: Call for Abstracts: Emerging Issues and New Frontiers for FDA Regulation

            PFC_Logo_300x300                    FDLI_Logo_380

The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School and the Food and Drug Law Institute are pleased to announce an upcoming collaborative academic symposium:

Emerging Issues and New Frontiers for FDA Regulation

Monday, October 20, 2014 

Washington, DC

We are currently seeking abstracts for academic presentations/papers on the following topics:  Continue reading

Call for Abstracts: Emerging Issues and New Frontiers for FDA Regulation

PFC_Logo_300x300FDLI_logo_pink

 

 

 

The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School and the Food and Drug Law Institute are pleased to announce an upcoming collaborative academic symposium:

Emerging Issues and New Frontiers for FDA Regulation

Monday, October 20, 2014 

Washington, DC

We are currently seeking abstracts for academic presentations/papers on the following topics:

  • Stem cell therapies
  • Nanotechnologies
  • Genetic (and biomarker) tests
  • Gene therapies
  • Personalized medicine
  • Comparative efficacy research
  • Drug resistant pathogens
  • Globalized markets
  • Tobacco
  • GMO
  • Bioterrorism countermeasures
  • Mobile health technologies
  • Health IT
  • Drug shortages
  • Other related topics

Abstracts should be no longer than 1 page, and should be emailed to Davina Rosen Marano at dsr@fdli.org by Tuesday, June 3, 2014. Questions should also be directed to Davina Rosen Marano.

We will notify selected participants by the end of June.  Selected participants will present at the symposium, and will be expected to submit a completed article by December 15, 2014 (after the event) to be considered for publication in a 2015 issue of FDLI’s Food and Drug Law Journal (FDLJ).  Publication decisions will be made based on usual FDLJ standards.

TOMORROW: Hot Topics in European Bio-Patent Law: Stem Cells, Genes, and More

Hot Topics in European Bio-Patent Law: Stem Cells, Genes, and More

April 2, 2014, 12:00 PM

Langdell, Vorenberg Classroom – North (225), Harvard Law School, Cambridge, MA

Please join us for this esteemed panel of leading patent experts, including members of the European Patent Office. Discussion will address U.S. and European perspectives on patenting stem cells, genes, and medical uses, as well as other ethical and legal issues.

Panelists:

  • Aliki Nichogiannopoulou, Director, Biotechnology, EPO
  • Anja Schmitt, Examiner, EPO
  • Maaike van der Kooij, Examiner, EPO
  • Tom Kowalski, US Patent Attorney
  • Moderator: Benjamin N. Roin, Hieken Assistant Professor in Patent Law, Harvard Law School; Co-Director, Petrie-Flom Center for Health Law Policy, Biotechnology & Bioethics; Associate Member, Broad Institute

This event is free and open to the public, but space is limited and registration is required. Register here.

Lunch will be served. For questions, contact petrie-flom@law.harvard.edu or 617-496-4662.

Cosponsored by the Broad Institute of MIT and Harvard.

4/2: Hot Topics in European Bio-Patent Law: Stem Cells, Genes, and More

Hot Topics in European Bio-Patent Law: Stem Cells, Genes, and More

April 2, 2014, 12:00 PM

Langdell, Vorenberg Classroom – North (225), Harvard Law School, Cambridge, MA

Please join us for this esteemed panel of leading patent experts, including members of the European Patent Office. Discussion will address U.S. and European perspectives on patenting stem cells, genes, and medical uses, as well as other ethical and legal issues.

Panelists:

  • Aliki Nichogiannopoulou, Director, Biotechnology, EPO
  • Anja Schmitt, Examiner, EPO
  • Maaike van der Kooij, Examiner, EPO
  • Tom Kowalski, US Patent Attorney
  • Moderator: Benjamin N. Roin, Hieken Assistant Professor in Patent Law, Harvard Law School; Co-Director, Petrie-Flom Center for Health Law Policy, Biotechnology & Bioethics; Associate Member, Broad Institute

This event is free and open to the public, but space is limited and registration is required. Register here.

Lunch will be served. For questions, contact petrie-flom@law.harvard.edu or 617-496-4662.

Cosponsored by the Broad Institute of MIT and Harvard.

An interview with I. Glenn Cohen on law and bioscience

With the first issue of Journal of Law and Biosciences now available, the Oxford University Press blog has published an interview with I. Glenn Cohen discussing the journal’s focus and format. From the blog:

There are huge changes taking place in the world of biosciences, and whether it’s new discoveries in stem cell research, new reproductive technologies, or genetics being used to make predictions about health and behavior, there are legal ramifications for everything. Journal of Law and the Biosciences is a new journal published by Oxford University Press in association Duke University, Harvard University Law School, and Stanford University, focused on the legal implications of the scientific revolutions in the biosciences. We sat down with one of the Editors in Chief, I. Glenn Cohen, to discuss the rapidly changing field, emerging legal issues, and the new peer-reviewed and open access journal.

Read the full interview.

TOMORROW: Frances Kamm’s Bioethical Prescriptions: Book Talk and Panel Discussion

Please join us on February 27 at 2:00pm in Wasserstein 1019 at the Harvard Law School as we launch Professor Frances Kamm’s latest book, Bioethical Prescriptions: To Create, End, Choose, and Improve Lives (Oxford University Press, January 2014). The book showcases Professor Kamm’s articles on bioethics as parts of a coherent whole, with sections devoted to death and dying; early life (on conception and use of embryos, abortion, and childhood); genetics and other enhancements (on cloning and other genetic technologies); allocating scarce resources; and methodology (on the relation of moral theory and practical ethics).

Panelists include:

  • Frances Kamm, Littauer Professor of Philosophy & Public Policy, Harvard Kennedy School of Government; Professor of Philosophy, Faculty of Arts & Sciences, Harvard University; Former Senior Fellow, Petrie-Flom Center
  • Norman Daniels, Mary B. Saltonstall Professor of Population Ethics and Professor of Ethics and Population Health, Harvard School of Public Health
  • Thomas (Tim) Scanlon, Jr., Alford Professor of Natural Religion, Moral Philosophy, and Civil Polity, Faculty of Arts & Sciences, Harvard University
  • Moderator: Christopher T. Robertson, Visiting Professor of Law, Harvard Law School; Associate Professor, James E. Rogers College of Law, University of Arizona

This event is free and open to the public. For questions, please contact petrie-flom@law.harvard.edu or 617-496-4662.

Sponsored by the Petrie-Flom Center for Health Law Policy, Biotechnology, and BioethicsEdmond J. Safra Center for Ethics at Harvard University; and the Countway Library of Medicine at Harvard Medical School; with support from the Oswald DeN. Cammann Fund.

2/27: Frances Kamm’s Bioethical Prescriptions: Book Talk and Panel Discussion

Please join us on February 27 at 2:00pm in Wasserstein 1019 at the Harvard Law School as we launch Professor Frances Kamm’s latest book, Bioethical Prescriptions: To Create, End, Choose, and Improve Lives (Oxford University Press, January 2014). The book showcases Professor Kamm’s articles on bioethics as parts of a coherent whole, with sections devoted to death and dying; early life (on conception and use of embryos, abortion, and childhood); genetics and other enhancements (on cloning and other genetic technologies); allocating scarce resources; and methodology (on the relation of moral theory and practical ethics).

Panelists include:

  • Frances Kamm, Littauer Professor of Philosophy & Public Policy, Harvard Kennedy School of Government; Professor of Philosophy, Faculty of Arts & Sciences, Harvard University; Former Senior Fellow, Petrie-Flom Center
  • Norman Daniels, Mary B. Saltonstall Professor of Population Ethics and Professor of Ethics and Population Health, Harvard School of Public Health
  • Thomas (Tim) Scanlon, Jr., Alford Professor of Natural Religion, Moral Philosophy, and Civil Polity, Faculty of Arts & Sciences, Harvard University
  • Moderator: Christopher T. Robertson, Visiting Professor of Law, Harvard Law School; Associate Professor, James E. Rogers College of Law, University of Arizona

This event is free and open to the public. For questions, please contact petrie-flom@law.harvard.edu or 617-496-4662.

Sponsored by the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics; Edmond J. Safra Center for Ethics at Harvard University; and the Countway Library of Medicine at Harvard Medical School; with support from the Oswald DeN. Cammann Fund.

DC Circuit Upholds FDA Authority Over Stem Cells

Earlier this week, the D.C. Circuit upheld the FDA’s authority to regulate stem cells (for a good news report see here). The company in question, Regenerative Sciences, had received a warning letter from FDA, which the company challenged claiming that its use of stem cells as therapy was not prohibited by existing federal law and that the FDA lacked authority to regulate it. They lost before the district court and appealed to the D.C. Circuit.

In a unanimous decision (by judge Griffith for himself, Judge Srinivasan and Edwards) the D.C. Circuit affirmed this decision. Here are some key passages: Continue reading

Technological Solutions to Moral Problems

By Matthew L Baum

When we consider our society’s tough moral questions, like whether it is acceptable to use embryonic stem cells for research and medicine, we often look towards governmental leaders, policy makers, lawyers, and ethicists to find solutions. But should we look more often towards engineers?

This week in Nature, a research group from the RIKEN institute in Kobe, Japan described a new and simpler way to induce cells from differentiated tissues to return to a pluripotent-stem-cell-like state. The method is not only scientifically interesting, but also a member of a class of what I have come to think of as Morally Modifying Technologies.

Morally Modifying Technologies represent an under-incentivized means through which scientists and engineers could help us disentangle our society’s most controversial moral issues and have three key components. The first is that they neither resolve a moral debate (in this case, the acceptability of embryonic stem cells for research and medicine) nor do they comment on the validity of the reasons on each side of an issue; the moral questions raised are equally problematic before and after the invention of the technology. The second is that, even though the issue itself is unaffected, the importance of our resolving it seems to matter less. That is, morally modifying technologies make a moral dilemma less practically problematic. The third is that the new technology often does not perform the desired function empirically better than existing technology (it might even be worse), but does so in a morally less problematic way – that is, if it were not for the moral advantage, the technology might be thought of as redundant.

Continue reading