Two Views About the Gene Editing ‘Breakthrough’ that Are Not Getting Enough Attention (IMHO)

As has now been well-covered in the news, Nature just published a paper from Mitalipov’s lab at the Oregon Health and Science University that used CRISPR/Cas 9 gene editing to correct the MYBPC3 mutation associated with hypertrophic cardiomyopathy — a heart muscle disease that affects 1 in 500 people. The more impressive element of the story is that by doing the alteration simultaneous with the sperm fertilizing the egg (not after fertilization) they were able to avoid the mosaicism that problematized early attempts in China — in mosaicism not all cells are repaired due to failure in the editing. The media coverage thus far, sadly but predictably, has focused on the soundbite of “designer babies” and “hope and hype” (indeed as my friend Hank Greely has suggested perhaps “overhype”.) These are worthy narratives to tell, to be sure, but here are two other narratives that I think are not getting the air time they deserve:

(1) The Importance of Genetic Ties: This use of CRISPR/Cas 9, as with most reproductive technologies, are attempts to allow those with disease-causing genes or other obstacles to reproduce genetically to do so. Investment and development of these technologies reifies the importance of genetic ties, as opposed to the kinds of ties associated with adoption, step-parenting, etc. It confuses a right to be a genetic parent, with a right to be a parent. We might have one right or both, but we should be clear they are different rights claims. Françoise Baylis has written eloquently about this issue in the context of In Vitro Gemetogenesis, and others (myself included) have mused on what claims the infertile have on society to have the state pay for these kinds of technologies instead of adopting. The National Academies report on gene editing suggested that clinical use of gene editing to eliminate disease be restricted to cases where there is an “absence of reasonable alternatives,” but does not take a position on when adoption is a reasonable alternative. Of course, in the U.S. at least, adoption is not easy and not available for everyone and there are a ton of interesting normative questions I have gestured at (including whether it matters for “reasonability” whether the child is of a certain age, race, or lacks developmental delay).

(2) The Importance of Embryo Sparing: A different alternative to gene editing in some cases is to fertilize large numbers of embryos and engage in preimplantation genetic diagnosis to eliminate those embryos that carry the disease-causing genes. There is a lot of obstacles to doing this: the fact that women may not retrieve enough eggs to do this, the cost (physical and financial) of repeated egg retrievals and PGD, the fact that this may not work for all genetic problems, etc. But one problem that vexes some is that this results in the destruction of large numbers of embryos (“discard” is sometimes used as the euphemism). Gene editing may be a solve for this problem. The Mitalipov group in their Nature paper have a line to this effect, “When only one parent carries a heterozygous mutation, 50% of the embryos should be mutation-free and available for transfer, while the remaining carrier embryos are discarded. Gene correction would rescue mutant embryos, increase the number of embryos available for transfer and ultimately improve pregnancy rate” (emphasis mine). This raises to me a very interesting question: some religious conservatives have tended to oppose both attempts to transform the human genome & embryo destruction (especially in the stem cell debate context). Could gene editing offer an olive branch to them as an alternative to the “greater evil” of routine PGD plus discard? Does it matter that to get to a place where we could achieve this we would have to actually destroy numerous embryos to perfect the research? (The Mitalipov embryos were not implanted, it seems under current U.S.  law that they could not be/) Is the right way to think about this consequentialist — destroy some embryos today to develop embryo sparing technologies to save many more tomorrow — or is this a case of complicity where the wrongfulness of the basic research taints what comes later?

Copenhagen Conference: Legal Perspectives on Synthetic Biology and Gene Editing

Join us at the Centre for Information and Innovation Law (CIIR) Faculty of Law, University of Copenhagen on 20 November, 2017 to discuss Legal Perspectives on Synthetic Biology and Gene Editing.

CALL FOR PAPERS

Emerging technologies in Synthetic Biology and Gene Editing offer incredible opportunities and promising solutions to some of the most urgent challenges faced by humanity, such as climate change, environmental protection, growing population, renewable energy and improved health care. But the emerging applications also raise exceptional ethical, legal and social questions.

This conference marks the final phase of the participation of the Copenhagen Biotech and Pharma Forum (CBPF) Research Group at the Centre for Information and Innovation Law (CIIR) in the cross-faculty research project BioSYNergy. In accordance with the goals of this large cross-faculty project on Synthetic Biology, the event explores legal perspectives on synthetic biology, systems biology and gene editing. Dealing with the legal responses to ethical and scientific challenges raised by emerging life science technology. Continue reading

Patenting Bioprinting Technologies in the US and Europe – The Fifth Element in the Third Dimension

By Timo Minssen

I am happy to announce the publication of our new working paper on  “Patenting Bioprinting Technologies in the US and Europe – The 5th element in the 3rd dimension.” The paper, which has  been co-authored by Marc Mimler, starts out by describing the state of the art and by examining what sorts of bioprinting inventions are currently being patented. Based on our findings we then discuss what types of future innovations we can expect from the technological development and how far these would and/or should be protectable under European and US patent laws.

The paper is forthcoming in: RM Ballardini, M Norrgård & J Partanen (red), 3D printing, Intellectual Property and Innovation – Insights from Law and Technology. Wolters Kluwer, but the working paper is already available on SSRN. Continue reading

Chimeras with benefits? Transplants from bioengineered human/pig donors

By Brad Segal

In January of this year, Cell published a study modestly titled, Interspecies Chimerism with Mammalian Pluripotent Stem Cells. It reports success bioengineering a mostly-pig partly-human embryo. One day before, Nature published a report that scientists had grown (for lack of a better word) a functioning genetically-mouse pancreas within the body of a genetically-modified rat. The latest study raises the likelihood that before long, it will also be scientifically possible to grow human organs within bioengineered pigs.

The implications for transplantation are tremendous. But hold the applause for now. Imagine a chimera with a brain made up of human neurons which expressed human genes. Would organ procurement without consent be okay? That troubling possibility raises  questions about whether manufacturing chimeras with human-like properties for organs is even appropriate in the first place. Here’s what University of Montreal bioethicist Vardit Ravitsky told the Washington Post:

“I think the point of these papers is sort of a proof of principle, showing that what researchers intend to achieve with human-non-human chimeras might be possible … The more you can show that it stands to produce something that will actually save lives … the more we can demonstrate that the benefit is real, tangible and probable — overall it shifts the scale of risk-benefit assessment, potentially in favor of pursuing research and away from those concerns that are more philosophical and conceptual.”

I respectfully disagree. Saving more lives, of course, is good. Basic science is also valuable – even more so if it might translate to the bedside. This line of research, though, is positioned to upend our entire system of transplantation, and so its implications go beyond organ supply. In this post I will argue that to assess this technology’s implications for organ procurement in particular, there is good reason to focus on harms, not benefits. Continue reading

Westworld and Bioethics

By I. Glenn Cohen

[WARNING: Spoilers below]

On Sunday, HBO’s Westworld finished its run. Though I thought some of the early episodes were arguably a bit of a failure as television (and my partner almost jumped off the bandwagon of making this one of “our shows”) IMHO the show finished very strong.

But whatever you thought of it as television, the show is wildly successful at raising a series of bioethics issues. There have been a bunch of other very good treatments of some of these issues in the last couple of decades – A.I., Ex Machina, Humans, Battlestar Galactica all come to mind – that touch on some of these issues. But, what I loved about Westworld is its lack of direct moralizing on these subjects, and how it leaves the viewer puzzling through them in a much more naturalistic way: I have been thrust in this unfamiliar world, and now I am trying to use my ethical compass to get my bearings.

Once upon a time I discussed Bioethics and the Martian, and my aim is to do the same here. I thought one way to share why I think the show is so successful as a text for bioethics exploration was to develop a “mock exam question” on the subject. This is really written more like an oral exam, with follow-up questions. The goal is not entirely fanciful since I do teach a course that uses films as texts to explore bioethics and the law.

Here goes: Continue reading

The Competing Identities of Neuroethics

By Brad Segal

This past week week I attended the International Neuroethics Society’s (INS) annual conference in San Diego, California. Neuroethics is multidisciplinary field that grapples with the implications of neuroscience for—and from—medicine, law, philosophy, and the social sciences. One of the many excellent panels brought together scholars from each of these four disciplines to discuss the diverse approaches to the field. The panel featured; Paul Appelbaum, a Professor of Psychiatry at Columbia University; Tom Buller, Chair of philosophy at Illinois State University; Jennifer Chandler, Professor of law at the University of Ottawa, and; Ilina Singh, Professor of Neuroscience & Society at the University of Oxford.

The panel started by considering the importance of the “competing identities” present in the field of neuroethics. As moderator Eric Racine explained, right from the start, even the term ‘neuroethics’ suggests a tension. Consider the variety of research methodologies employed in the field. For instance, a scholar trained in philosophy might approach neuroscience from a conceptual and purely analytical basis, and yet a social scientist might research the same question by collecting empirical interview data. The interplay between empirical and theoretical work was a theme that defined the discussion.

A psychiatrist by training, Dr. Applebaum spoke on the medical approach to the field. He argued that a focus on ethical issues in clinical psychiatry and neurology should be viewed as a part (but only a part) of neuroethics. Furthermore, medicine’s empirical approach to neuroethics is one (but not the only) way to advance thinking on neuroethical issues. Continue reading

Kidneys and Livers, Made to Order?

By Seán Finan

Last week, Organovo might just have revolutionised the pharmaceutical industry. The San Diego-based company specialises in producing structures that mimic the behaviours and functions of human tissue, using 3D bioprinting. They announced last week that they were beginning the commercial manufacture and sale of their ExVive Kidney. The product models the proximal tubule of the human kidney and holds significant promise for clinical trials of new drugs. The commercialization of the ExVive Kidney follows the release of ExVive Human Liver Tissue in 2014.

In essence, Organovo is using 3D printing technology to produce samples of “human” tissue that can be used to test the toxicity of new drugs. The printing process, known as 3D bioprinting, involves extracting human cells, culturing them and suspending them in a solution. The resulting “bioink” is fed through a modified 3D printer. Layer by layer, the printer deposits cells, producing a mass with a similar structure and density to a sample of, for example, human liver. Just like “organ on a chip” technology, these synthetic liver and kidney samples present significant advantages over traditional clinical testing.

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NIH Announces Plans for new Rules for Funding Chimera Research (Human-Animal Mixtures)

As reported by Science, today the NIH announced plans to lift a preemptive year long moratorium on funding chimera research – that which mixes human and animal cells, often at the embryonic stage.

Here is a snippet from the Science article about the new proposed NIH process:

According to two notices released today, NIH is proposing to replace the moratorium with a new agency review process for certain chimera experiments. One type involves adding human stem cells to nonhuman vertebrate embryos through the gastrulation stage, when an embryo develops three distinct layers of cells that then give rise to different tissues and organs. The other category is studies that introduce human cells into the brains of postgastrulation mammals (except rodent studies, which won’t need extra review).

These proposed studies will go to an internal NIH steering committee of scientists, ethicists, and animal welfare experts that will consider factors such as the type of human cells, where they may wind up in the animal, and how the cells might change the animal’s behavior or appearance. The committee’s conclusions will then help NIH’s institutes decide whether to fund projects that have passed scientific peer review.

The devil will, of course, be in the details. It will be interesting to see how much NIH takes a more categorical approach as opposed to more case-by-case rule making like in the Institutional Review Board or ESCRO setting. Continue reading

NOW ONLINE! Oxford Union Debating Society DNA Manipulation Debate

DNA fingerprints.The Oxford Union Debating Society at Oxford University has published full video of its DNA Manipulation Debate, filmed on May 26. The Motion under debate was, “This House Believes the Manipulation of Human DNA is an Ethical Necessity.” Oxford billed its DNA Manipulation Debate as “historic” in a year when rapid advances in gene editing and genome synthesis suddenly confront humans with the possibility of being able to write, edit, re-write, and ultimately control their own genetic destinies.

The team supporting the Motion was led by Sir Ian Wilmut, famous for cloning Dolly the Sheep and now Chair of the Scottish Centre for Regenerative Medicine at the University of Edinburgh, and included Oxford’s noted moral philosopher Julian Savulescu and Oxford student debater Lynda Troung, a fast-rising star in RNA research.

The team opposing the Motion included Dr. Norman Fost, professor emeritus of pediatrics and director of the medical ethics program at the University of Wisconsin; Professor Barbara Evans, Director of the Center for Biotechnology & Law at the University of Houston Law Center and a frequent participant in Petrie-Flom conferences; and Oxford student debater Dr. Rahul Gandhi, a young medical doctor and monk focusing on rural healthcare, who is pursuing an MBA at Oxford this year as a prelude to seeking an MPH at Harvard next year.

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Stem cell patenting on the other side of the pond

By Timo Minssen

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

The Testosterone Rule Strikes Again – New Policy to Address Transgender Athletes

New Guidelines issued by the IOC (International Olympic Committee) offer a new policy for the participation of transgender athletes in sports competitions. According to the new policy, transgender athletes should be given the option to compete without having to undergo genital re-construction surgery. Female to Male (F-M) transgender athletes will be allowed to compete without further limitations, however Male to Female (M-F) transgender athletes would be allowed to compete only after receiving hormonal treatment intended to keep testosterone levels under a fixed threshold for at least a year before the competition. This is a significant change to the previous guidelines, which recommended that transgender athletes be eligible to compete only after a genital re-construction surgery and two years of hormonal therapy. The committee explained that the change of policy was due to “current scientific, social and legal attitudes on transgender issues”. The overriding objective of all policies according to the IOC was ‘fair competition’, so whereas genital appearance was not considered to affect fairness, testosterone levels are still understood to generate a competitive edge.

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Does the NAM Recommendation of Sex Selection for Mitochondrial Replacement Therapy Violate the Equal Protection Clause (Part III on my take on the NAM report)

As I said in one of my earlier posts today one of the most interesting parts of the NAM report on mitochondrial replacement therapy was its recommendation that only male embryos be implanted and not female ones. The argument is that this will eliminate the risks of germ-line transmission of anything untoward. I will leave it to others more versed in the risk factors to discuss whether this is an over-reaction (the UK did not adopt this in their recommendation) or reasonable. In the last post I discussed why politically/ethically this may get them in some hot water, but here  I want to raise a different question. Would such a recommendation be unconstitutional?

If FDA were to adopt this rule it would clearly be state action. It seems to be a state-law that favors one gender (males) over another (females) in that only males can be produced in this way. If that is right, under existing Supreme Court precedent it would be judged under “intermediate scrutiny.” To pass intermediate scrutiny, the challenged law must further an important government interest by means that are substantially related to that interest. Would this rule satisfy that test? Continue reading

Breaking News: NAM Releases Report on Mitochondrial Replacement Therapy (Part I Summary)

By I. Glenn Cohen

As readers know I’ve written on mitochondrial replacement therapy and its attendant ethical and regulatory issues. Today the National Academy of Medicine (formerly known as the IOM) released a terrific report today with its recommendations. I’ll have a second post with my reactions but here is a summary from the report of their recommendations. The big headline is they have recommended FDA largely move towards allowing it to go forward under a regulatory pathway with restrictions, the most important of which is the transfer only of male embryos (to avoid germ-line issues).

In the NAM’s own words:

Recommendation 1: Initial clinical investigations of mitochondrial replacement techniques (MRT) should be considered by the U.S. Food and Drug Administration (FDA) only if and when the following conditions can be met: Continue reading

The Testosterone Rule

Dutee Chand is an Indian athlete that has been in the focus of a recent drama in elite sport. Chand, a gifted athlete and champion, was suspended from participating in competitions by the International Association of Athletics Federations (IAAF), after she was found to have high levels of testosterone. A biological condition called “hyperandrogenism” caused Chand to have three times more testosterone than an average woman athlete, similar to that of men. Chand was given the unappealing alternative of undergoing surgery and hormonal treatments meant to “normalize” her so she could race again, or turning to the Court of Arbitration for Sport (CAS), she chose the latter.

One would think that in a world in which men and women’s sports are so profoundly separated, distinguishing between male and female athletes would be a no-brainer.  Well, it’s not like that at all. Chand’s case can be traced along a history of similar episodes in which female athletes (like South African runner Caster Semanya and others) were suspected for not being “true females,” having to undergo medical scrutiny in order to conclude on the matter. This ambiguity is not special to athletes. It even has a name – “intersex,” an umbrella term describing a range of conditions in which the person’s sex cannot be conclusively determined. To read more on intersex variations click here.

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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.

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HLS Health Law Workshop with Matt Lamkin

HLS Health Law Workshop: Matt Lamkin

November 3, 2014 5:00 PM
Griswold Hall, Room 110 (Harvard Law School)
1525 Massachusetts Ave., Cambridge, MA [Map here.]

Download the paper: “Regulating Identity: Medical Regulation as Social Control”

Matt Lamkin is Assistant Professor of Law at the University of Tulsa College of Law. He previously was a Fellow at Stanford Law School’s Center for Law and the Biosciences. Prior to entering academia, he was in private practice in Chicago and Indianapolis, served as a law clerk to a federal judge, and worked as a policy advisor to the Mayor of Indianapolis. Matt’s scholarship explores the intersection of health care, law, and ethics, with a particular focus on how the increasing commercialization of medical care is reshaping our understandings of disease and disability, informed consent and personal responsibility, and the role of government in regulating medical care.

Harvard Effective Altruism: Nick Bostrom, September 4 at 8 PM

[This message is from the students at Harvard Effective Altruism.]

Welcome back to school, altruists! I’m happy to announce our first talk of the semester – from philosopher Nick Bostrom. See you there!

Harvard College Effective Altruism presents:
Superintelligence: Paths, Dangers, Strategies
with Nick Bostrom
Director of the Future of Humanity Institute at Oxford University

What happens when machines surpass humans in general intelligence? Will artificial agents save or destroy us? Professor Bostrom will explore these questions, laying the foundation for understanding the future of humanity and intelligent life. Q&A will follow the talk. Copies of Bostrom’s new book – Superintelligence: Paths, Dangers, Strategies – will be available for purchase. RSVP on Facebook.

Thursday, September 4
8 pm
Emerson 105

Rational Actors and Happy Actors

By Nathaniel Counts

Politics, theoretically at least, is a process designed to enhance the sense of wellbeing of its citizens.  The success of this process, the amount of wellbeing that can be created, is hamstrung by biology – we have basal levels of felt wellbeing that are determined through some amount of nature and nurture, and that are independent of our present circumstances.  Because there is a biological component to it, we may be able to alter an individual’s basal wellbeing before they reach adulthood.  For example, if hypomania, a psychological condition where the individual only experiences the manic part of bipolar disorder, were found to have a definitively genetic etiology, gene therapy could be used on embryos so that they would grow up to experience the constant heightened state of wellbeing associated with the condition (for an interesting article on hypomania and wellbeing, see here).

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The Neuroethics of Unintentional Memory-Modification

By Matthew L Baum

At least since the publication of the President’s Commission on Bioethics’ report in 2003, “Beyond Therapy: Biotechnology and the Pursuit of Happiness”, there has been an ongoing debate about the ethics of using drugs to modify emotional memories.  Rather than focus on the Hollywood-type total memory erasure featured in the Eternal Sunshine of the Spotless Mind, many ground the debate in the molecular neuroscience of memory reconsolidation (for an excellent overview, see here). In the process of memory reconsolidation, a newly reactivated memory triggers certain molecular events that are necessary for it to return to long-term storage; during these events, the memory is temporarily susceptible to disruption by certain drugs like the beta-blocker, propranolol. Further work with people with Post-Traumatic Stress Disorder (PTSD) suggests that using propranolol in this way doesn’t erase a memory, but may blunt the reconsolidation of the memory’s negative emotional content. In the ethical discussion, most agree that 1) it should usually be acceptable to use drugs to modify memories in cases of PTSD where the emotional content of memories becomes debilitating, but 2) the use of memory modifying drugs is usually morally problematic when the target is everyday unpleasant memories, disappointments, and rejections.

Existing debate has focused on intentional memory modification. But what about those who modify memories in these problematic ways unintentionally? Conspicuously under-discussed is the ethics of continuing to use drugs with potential memory-modifying properties for the treatment of other medical conditions. Propranolol, for example, is on the Department of Veterans Affairs (VA) National Formulary for treatment of patients with severe liver disease (liver cirrhosis). This (not-small) population of people, in theory, risks unintentionally (and pre-emptively) modifying memories every day!

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Inaugural Issue of the new Journal of Law and the Biosciences Now Online (Free Access)

I am very pleased to announce the the first-ever issue of The Journal of Law and the Biosciences is now online. I serve as one of three Editors In Chief (along with Nita Farahany and Hank Greely). The journal is a co-production of Harvard, Duke, and Stanford Law schools and Oxford University Press and is the first peer-reviewed journal of its kind.

Here is the table of contents for the first issue:

Edward S. Dove, Bartha M. Knoppers, and Ma’n H. Zawati, Towards an ethics safe harbor for global biomedical research, J Law Biosci (March 2014) 1 (1): 3-51 doi:10.1093/jlb/lst002

Rebecca Dresser, Public preferences and the challenge to genetic research policy, J Law Biosci (March 2014) 1 (1): 52-67 doi:10.1093/jlb/lst001

Hannah Maslen, Thomas Douglas, Roi Cohen Kadosh, Neil Levy, and Julian Savulescu, The regulation of cognitive enhancement devices: extending the medical model, J Law Biosci (March 2014) 1 (1): 68-93 doi:10.1093/jlb/lst003

Timothy Caulfield, Sarah Burningham, Yann Joly, Zubin Master, Mahsa Shabani, Pascal Borry, Allan Becker, Michael Burgess, Kathryn Calder, Christine Critchley, Kelly Edwards, Stephanie M. Fullerton, Herbert Gottweis, Robyn Hyde-Lay, Judy Illes, Rosario Isasi, Kazuto Kato, Jane Kaye, Bartha Knoppers, John Lynch, Amy McGuire, Eric Meslin, Dianne Nicol, Kieran O’Doherty, Ubaka Ogbogu, Margaret Otlowski, Daryl Pullman, Nola Ries, Chris Scott, Malcolm Sears, Helen Wallace, and Ma’n H. Zawati, A review of the key issues associated with the commercialization of biobanks, J Law Biosci (March 2014) 1 (1): 94-110 doi:10.1093/jlb/lst004

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