Our Bodies, Our Cells: FDA Regulation of Autologous Adult Stem Cell Therapies

By Mary Ann Chirba, J.D., D.Sc., M.P.H. and Alice A. Noble, J.D., M.P.H.

Stem cells have been an endless source of fascination and controversy since Dolly the sheep was cloned in 1996. This month’s announcement of a cloned human embryo from a single skin cell [1] came on the heels of Sir John B. Gurdon and Dr. Shinya Yamanaka’s receipt of the 2012 Nobel for Physiology and Medicine for their work with induced pluripotent stem cells. Pluripotent stem cells can be embryonic or induced. Embryonic stem cells (ESCs) can generally be obtained from human embryos or by cloning embryos through somatic cell nuclear transfer (SCNT), as was done for Dolly.  Gurdon and Yamanaka demonstrated that pluripotent cells may also be formed by reprogramming adult cells to an embryonic state, resulting in induced pluripotent stem (iPS) cells without having to use eggs or cloning, or destroy embryos. However derived, pluripotent cells are capable of differentiating into virtually any cell type in the human body. This imbues them with great promise for scientific breakthroughs and medical advances, but also raises serious ethical, legal and safety concerns about their use.

Less controversial are “multipotent” adult stem cells (ASCs) which do not involve embryos or raise as many safety concerns as pluripotent cells.  ASCs are found throughout the body.  Their ability to differentiate is more limited than pluripotent cells but is vast nonetheless. The NIH’s clinicaltrials.gov site lists some 4500 ASC trials as compared with 27 for embryonic stem cells and 21 for induced pluripotent stem cells. Recent announcements of new stem cell treatments usually involve ASCs, such as last month’s news that a toddler born without a trachea received a new one made from her own adult stem cells.  It is therefore no surprise that ASCs have captured the attention of researchers, investors, physicians, patients and – increasingly – regulators, both here and abroad.

A growing number of physicians routinely offer treatments involving ASCs to their patients which can be performed in their offices.  Autologous adult stem cells, used to treat a variety of conditions, are harvested from the patient, processed, and returned to the same patient. It is no surprise that moving ASCs from laboratories to physician offices raises complex questions of law. We consider one of the more pressing ones: to what extent can the FDA regulate a physician’s ability to treat a patient with that patient’s own stem cells?  In the coming months, the D.C. Circuit Court of Appeals will hear oral arguments on this very issue in United States v. Regenerative Sciences.[2]

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An Open Letter From a Genomic Altruist to a Genomic Extrovert (Re-Identification Symposium)

By Michelle Meyer

This post is part of Bill of Health‘s symposium on the Law, Ethics, and Science of Re-Identification Demonstrations. You can call up all of the symposium contributions here. We’ll continue to post contributions throughout the week. —MM

Dear Misha:

In your open letter to me, you write:

No one is asking you to be silent, blasé or happy about being cloned (your clone, however, tells me she is “totally psyched”).

First things first: I have an ever-growing list of things I wish I had done differently in life, so let me know when my clone has learned how to read, and I’ll send it on over; perhaps her path in life will be sufficiently similar to mine that she’ll benefit from at least a few items on the list.

Moving on to substance, here’s the thing: some people did say that PGP participants have no right to complain about being re-identified (and, by logical extension, about any of the other risks we assumed, including the risk of being cloned). It was my intention, in that post, to articulate and respond to three arguments that I’ve encountered, each of which suggests that re-identification demonstrations raise few or no ethical issues, at least in certain cases. To review, those arguments are:

  1. Participants who are warned by data holders of the risk of re-identification thereby consent to be re-identified by third parties.
  2. Participants who agree to provide data in an open access format for anyone to do with it whatever they like thereby gave blanket consent that necessarily included consent to using their data (combined with other data) to re-identify them.
  3. Re-identification is benign in the hands of scholars, as opposed to commercial or criminal actors.

I feel confident in rejecting the first and third arguments. (As you’ll see from the comments I left on your post, however, I struggled, and continue to struggle, with how to respond to the second argument; Madeleine also has some great thoughts.) Note, however, two things. First, none of my responses to these arguments was meant to suggest that I or anyone else had been “sold a bill of goods” by the PGP. I’m sorry that I must have written my post in such a way that it leant itself to that interpretation. All I intended to say was that, in acknowledging the PGP’s warning that re-identification by third parties is possible, participants did not give third parties permission to re-identify them. I was addressing the relationship between re-identification researchers and data providers more than that between data providers and data holders.

Second, even as to re-identification researchers, it doesn’t follow from my rejection of these three arguments that re-identification demonstrations are necessarily unethical, even when conducted without participant consent. Exploring that question is the aim, in part, of my next post. What I tried to do in the first post was clear some brush and push back against the idea that under the PGP model — a model that I think we both would like to see expand — participants have given permission to be re-identified, “end of [ethical] story.” Read More

Sperm Donation, Anonymity, and Compensation: An Empirical Legal Study

[Cross-Posted at Prawfsblawg]

In the United States, most sperm donations* are anonymous. By contrast, many developed nations require sperm donors to be identified, typically requiring new sperm (and egg) donors to put identifying information into a registry that is made available to a donor-conceived child once they reach the age of 18. Recently, advocates have pressed U.S. states to adopt these registries as well, and state legislatures have indicated openness to the idea.

In a series of prior papers I have explained why I believe the arguments offered by advocates of these registries fail. Nevertheless, I like to think of myself as somewhat open-minded, so in another set of projects I have undertaken to empirically test what might happen if the U.S. adopted such a system. In particular, I wanted to look at the intersection of anonymity and compensation, something that cannot be done in many of these other countries where compensation for sperm and egg donors is prohibited.

Today I posted online (downloadable here) the first published paper from this project, Can You Buy Sperm Donor Identification? An Experiment, co-authored with Travis Coan, and forthcoming in December 2013 in Vol. 10, Issue 4, of the Journal of Empirical Legal Studies.

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Privacy and Progress and the Deidentification of Whole Genome Sequence Data

[Posted on behalf of Elizabeth Pike and Kayte Spector-Bagdady from the Presidential Commission for the Study of Bioethical Issues – and cross-posted here.]

In the most recent issue of the Hastings Center Report, Drs. Amy Gutmann and James Wagner of the Presidential Commission for the Study of Bioethical Issues (the Bioethics Commission), contributed to the lively debate surrounding the identifiability of genetic data. In Found Your DNA on the Web: Reconciling Privacy and Progress, Gutmann and Wagner, Chair and Vice-chair respectively, argue that the paradigm of identifiability has become less relevant to individual privacy protections than restrictions on access and use.

In their commentary, Gutmann and Wagner continue the public deliberation of the Bioethics Commission’s report, Privacy and Progress in Whole Genome Sequencing, in which the Bioethics Commission took a forward-looking approach to the privacy concerns raised by whole genome sequencing—issues that have come to the forefront of this important science.

Under current law, health information that is deidentified—information for which there is “no reasonable basis” to believe it can identify an individual or that has been stripped of traditional identifiers—is afforded different legal protections than identifiable health information. However, whole genome sequence data are unique to only one person, making them more vulnerable to reidentification.

Recent articles have cast doubt on the extent to which whole genome sequence data can be deidentified. For example, in Identifying Personal Genomes by Surname Inference, published in Science in January, Melissa Gymrek, et. al. successfully uncovered full identities of 50 individuals.

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Transplant Tourism: Hard Questions Posed by the International and Illicit Market for Kidneys, New Article I Wrote

[Cross-Posted at Prawfsblawg]

The Journal of Law, Medicine, and Ethics has just published an article by me on transplant tourism, that discusses the burgeoning international market for buying and selling kidneys. I review the existing data from Pakistan, Bangladesh, and India, which is pretty deplorable. As I show the vast majority of these sellers are poor and using the money (which is a significnat sum in terms of what they earn, even though in the end only 2/3 is paid) to try to buy themselves out of bonded labor, pay off familial debts, or try to mount a dowry. Many are misinformed or decieved about the health consequences for them and the needs of the person who will receive their kidney. Once they have agreed to sell they are often pressured not to renege. They are often released too soon post-transplant compared to what is optimal for a transplant, and their self-reported health post-transplant is worse. Many experience significant social stigma as a “kidney man” (or woman)and the 20-inch scar (the more expensive way of doing the procedure would reduce the scar size) marks them for life and makes it difficult for them to marry. Most express significant regret and would advise others not to undertake the operation.

Despite these grave facts, as I argue in the paper (and in greater depth for many of these arguments in the chapter on transplant tourism in my new book on medical tourism under contract at Oxford University Press), many of the traditional justifications from the anti-commodification literature — arguments relating to corruption, crowding out, coercion, and exploitation — do not make a convincing case in favor of criminalization. If a ban is justified, I argue the strongest arguments are actually about defects in consent and justified paternalism, on the assumption that criminal prohibition is a second best regulation in the face of the impossibility of a more thoroughly regulated market.

I then examine what means might be used to try to crack down on the market if we concluded we should. I evaluate possibilities including extraterritorial criminalization, professional self-regulation, home country insurance reimbursement reform, international criminal law, and of course better organ retrieval in the patient’s home country.

I will keep writing on this topic, including for my new book, so even though this paper is done feel free to email me your thoughts.

Will Your Law Firm (or Other Employer) Pay for Your Egg Freezing? Should It? (Online Abortion and Reproductive Technology Symposium)

As John Robertson mentioned in his post earlier this week, in order to avoid age-related infertility many women are considering or will soon consider using egg freezing, as the technology has dramatically improved. As compared to freezing preembryos, for example, this is an attractive option since many of these women (heterosexual or otherwise) may not yet have chosen a reproductive partner, and also may want to hedge their bets to have options should they divorce. Still, the technology is not cheap.

At least one participant at the the bricks-in-mortar symposium reported to me that they knew of one Am Law 100 firm that will cover egg freezing for its lawyers. I would be grateful if folks in the comments section could indicate whether they knew whether their firm covers it as well. [Ed. Note: If you have any trouble with the comment function on the blog, which is still giving us trouble, send a note and we’ll get it posted for you through the admin account.] My own impression is that this is not yet widespread, but that might change as the practice becomes more common and thus the market converges (perhaps with a push from Above the Law).

Should law firms cover egg freezingt? I have made the argument elsewhere for coverage of reproductive technologies by insurance more generally from a moral and economic perspective. In the case of law firms, I am curious about the PR implications for the firm. Would potential female associates welcome this option knowing that they can work hard early on and still reproduce, if they so desire, later on? Or would they take this as a signal that the firm thinks that working there as an associate and pregnancy are incompatible? Would this option help remedy the deficits faced by women who want to have children on the partnership track or would it in fact exacerbate discrimination against women who do choose to have families early on while at the firm, with the thinking being “she could have waited.” More generally, would this be a blow for or against gender equity at law firms?

Myriad (Gene Patent) Oral Argument and the “Lander Brief”

First, and unrelated to this post, I wanted to say that like everyone here in Boston (and it seems throughout the U.S.) my heart goes out to the folks injured by Monday’s blast and their friends and family.

Now on to the substance. I have participated in a number of Supreme Court amicus briefs  both in my life as a litigator and as an academic. In big name cases the Court is often inundated with them, and one can only hope that the brief is read, let alone put to good use. This is why I was incredibly happy and honored that the Supreme Court devoted a significant chunk of its oral argument time on Monday in the Association for Molecular Pathology v. Myriad Genetics, No. 12-398, the gene patent case,  to discussing the brief I authored with Gideon Schor and Vern Noviel on behalf of Dr. Eric S. Lander. As Nature reported on the argument:

“The justices seemed to have been heavily influenced by a friend-of-the-court brief filed by Eric Lander, genomics whiz and founding director of the Broad Institute in Cambridge, Massachusetts. The brief argued against a lower court’s ruling that a snippet of DNA isolated from its chromosome does not occur in nature and is therefore patentable. To the contrary, wrote Lander, isolated DNA fragments do exist and are found circulating free in the blood. Indeed, a search of two public databases of DNA sequence data obtained from fetal DNA circulating in maternal blood revealed fragments that contained the BRCA1 and BRCA2 genes. “I think that raised a whole new ‘oops’,” said Robert Cook-Deegan, a policy researcher who has studied the case at Duke University in Durham, North Carolina. The justices never heard a proper response to Lander’s argument from Myriad’s attorney, who seemed to have either misunderstood the Lander brief or confused it with another when questioned.”

I reproduce some snippets from the actual transcript below the fold discussing our brief and its significance for how the Court rules.

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John Robertson on Cohen and Adashi on Made-to-Order Embryos for Sale

By John Robertson

Glenn Cohen and Eli Adashi have an interesting Sounding Board piece in the latest NEJM[i] on made-to-order embryos for sale.  A California clinic offering this option has garnered enormous publicity.  It might, however, have stimulated more bioethical thinking than actual demand for its services.

On the bioethical side, Glenn and Eli survey the relevant issues and conclude that what is most “new and unique here is the lack of clear legal guidance as to the parentage of the embryos in question.”[ii]  My impression is different– existing laws give sufficient support about parentage, if anyone wants to use them.  The clinic creating the embryos from separate gamete donations will have dispositional control of them, but no parenting questions arise until the embryos are gestated and brought to term.  True, there are few state laws on embryo donation as such. But in states with no specific embryo donation laws, those who have commissioned gestation will most likely have rearing rights and duties once a child is born until they arrange for an adoption.[iii]

Nor would the gamete donors in such states be able to claim rearing rights or be subject to rearing duties after such a birth.   Most states recognize gamete donor relinquishment of rearing rights and duties in resulting children with their consent to donation.  After the birth of a child, the gamete donors ordinarily would have no right to change their mind and acquire rearing rights or be subject to rearing duties, whether the donation was of sperm or egg separately or both combined into an embryo.

One aspect of this transaction that is ethically unique is that divvying up embryos created from the same egg and sperm donor would lead to different recipients giving birth to full rather than half siblings, as is the usual situation with gamete donation (it could happen with excess embryos donated after successful IVF by an infertile couple, but that is rarer). Whether it creates a higher risk of full sibling consanguinity would depend on clinic practices in distributing embryos from the same batch to different recipients.  As Glenn and Eli note, donor registries might solve this problem, but none yet exist in the United States.

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New Paper in the New England Journal of Medicine “Made-to-Order Embryos for Sale — A Brave New World?”

The New England Journal of Medicine just published a new article by me (and my frequent co-author Dean Eli Adashi) entitled “Made-to-Order Embryos for Sale — A Brave New World?”  As we note in the article:

The proliferation of commercial gamete sources (e.g., sperm and oocyte banks) has opened the door to a made-to-order embryo industry in which embryos are generated with a commercial transaction in mind. This prospect of a for-profit embryo bank is no longer theoretical. Indeed, as recently as November 2012, the Los Angeles Times reported on one such clinic that “sharply cuts costs by creating a single batch of embryos from one oocyte donor and one sperm donor, then divvying it up among several patients.” The report went on to state that “the clinic, not the customer, controls the embryos, typically making babies for three or four patients while paying just once for the donors and the laboratory work.

The paper then analyses the legal and ethical issues raised by the development of these kinds of banks. In so doing, a key question we ask is how this practice is similar or different from embryo donation (sometimes called “embryo adoption”), the sale of sperm and eggs for reproductive purposes, and the use of sperm and egg to produce stem cell lines that require embryo destruction.

This one is sure to be controversial, and while this short piece in the New England Journal is now published I would love to hear readers’ thoughts as I may write more on the subject.

Introducing our Online Abortion and Reproductive Technology Symposium

[Editor’s Note: This is Glenn Cohen guest posting on behalf of Kim Mutcherson, what follows below is her post. I will be posting on behalf of several symposium contributors over the next few days.]

On Friday, April 5, a group of almost 30 (mostly legal) scholars gathered at Rutgers Law-Camden to have difficult conversations about abortion and assisted reproduction. The event, sponsored by Rutgers Law and the Law School Initiative of the Center for Reproductive Rights (http://reproductiverights.org/en/our-work/law-school-initiative) sought to initiate discussion about the seeming gulf between those working on issues related to abortion and those working on assisted reproduction and assisted reproductive technology (ART).  Friday’s conversation was the first of at least three planned events with the other two to be sponsored at some future point by the Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics at Harvard Law School and the Program for the Study of Reproductive Justice in the Information Society Project at Yale Law School. If the nature of the conversation at this kick-off event is a harbinger of things to come, I am anticipating that top-notch and cutting edge scholarship related to reproductive rights and reproductive justice will emerge from workshop participants.

While it might seem intuitive that scholars of reproduction would talk often, much of the work in this arena exists in silos. Those writing about abortion have plenty of work to do in keeping up with the flurry of state laws seeking to destroy what remains of Roe v. Wade in a post-Planned Parenthood v. Casey world. And those working in the world of assisted reproduction have to keep abreast of emerging science that is always light years ahead of what the law has done or seems capable of doing. As a consequence, opportunities to study the intertwining and divergence between the right to end a pregnancy and a right to create one are sparse.

And so, in the year that we commemorate the 40th anniversary of Roe, we engaged in a respectful, honest, and richly complex dialogue about the appropriate paradigm for understanding the right to abortion and the right to use assisted reproduction—liberty, equality or some new paradigm that we have yet to fully embrace or articulate.

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