Using Tissue Samples to Make Genetic Offspring after Death

By Yu-Chi Lyra Kuo

Last month, John Gurdon and Shinya Yamanaka were jointly awarded the 2012 Nobel Prize for Medicine for their research on induced pluripotent stem cells (iPSCs).  iPSCs are capturing the public imagination as embryonic stem cells did fifteen years ago, but without the controversy surrounding the destruction of embryos: iPSCs can be garnered instead from living somatic tissue of an organism at any point in its lifespan–even late adulthood.  Yamanaka’s research has shown that somatic cells can be “reprogrammed” to develop into any kind of cell–including an embryo–speaking to the vast research potential of iPSCs.

In light of the research potential of iPSCs, I wanted to highlight the results of a remarkable study (published last month) where scientists induced iPSCs from mice into primordial germ cell-like cells, and aggregated them with female somatic cells to create mature, germinal oocytes. The team was then able to show that these oocytes, after in vitro fertilization, yield fertile offspring. Essentially, the research team created viable mouse embryos from skin cells, and fertilized them using IVF to produce healthy mice, some of which have already produced offspring of their own.

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Twitter Round-Up: What Our Bloggers Are Tweeting About (10/28-11/3)

By Casey Thomson
[Ed. Note: Several of our bloggers are active on Twitter.  In a new feature, we’ll be posting some highlights of their tweets each week so you can stay in the know – or think about following them directly!]
  • Dan Vorhaus (@genomicslawyer) linked to Bloomberg’s article on the current underutilization of genetic tests for Lynch Syndrome, responsible for potentially 3% of all cases of colon cancer. Authors Langreth and Lauerman note that the lack of testing is but one example of the tendency to avoid such tests due to “doctors’ ignorance and financial disincentives.” (10/29)
  • Daniel Goldberg (@prof_goldberg) shared Iona Heath’s article on the problematic nature of current breast cancer screening awareness programs, discussing how women are not given enough information to decide if the potential treatments that follow are indeed worth the psychological devastation often invoked. (10/30)
  • Michelle Meyer (@MichelleNMeyer) retweeted an editorial on medical genetic paternalism. The post by Razib Khan discussed how physicians deciding whether to tell parents about unforeseen genetic test results of their children can be considered not only an act of malpractice, but also morally wrong. (10/30)
  • Einer Elhauge (@elhauge) linked to a new review of his acclaimed book, Obamacare On Trial by the National Law Review. (10/31)
  • Daniel Goldberg also tweeted a review by Boddice of Javier Moscoso’s new book, Pain: A Cultural History. (10/31)
  • Arthur Caplan (@ArthurCaplan) linked to news about China’s promised initiative to reduce the dependence on death row inmates for organs. A new national organ donation system, based on a system previously piloted by the Red Cross Society of China, could take effect as soon as early 2013. (11/2)
  • Arthur Caplan also posted on the Vatican’s announcement to hold its second “International Adult Stem Cell Conference,” revisiting this complicated issue. (11/2)
  • Arthur Caplan additionally linked to a report on the debate and complications regarding feeding tube use, as published by Krieger of Mercury News. (11/2)

Al Roth – Nobel Prize Winner!

Congrats to our blogger, Al Roth, for his Nobel Prize in economics (alongside Lloyd S. Shapley of UCLA)!  Al built on Shapley’s theories about the best ways to match “agents” in markets — for example, students matched with schools or organ donors with patients needing organs — and conducted experiments to further illuminate Shapley’s work.  Al presented a really fascinating paper (with his colleague Judd Kessler) at one of last year’s Harvard Health Law Policy workshops on organ allocation policy and the decision to donate, and you can find lots more about his interesting work over at his Market Design blog.

Congrats again, Al! (Probably the best 4AM wake up call a person could get!)

Commentary from OPTN/UNOS Kidney Transplantation Committee Chair, John Friedewald

Related to Nikola’s post below on the proposed revisions to the deceased donor kidney allocation policy, Al Roth has posted some interesting commentary from OPTN/UNOS Kidney Transplantation Committee Chair John Friedewald (in response to a query on a list serve):

“The current proposal for kidney allocation from the UNOS kidney committee is what it is not because it was the first thing we thought of, and “wow, it’s perfect” but rather it is the product of 8 years of trial and error, consensus building, and compromise.  To state that EOFI takes into account both equity and efficiency would seem to suggest that the current UNOS proposal does not.  How could this be?  We have tried over 50 different methods of allocation and simulated them (which has not happened yet with EOFI).  And with each simulation, we view the results and how the system affects all sorts of different groups (NOT just age, but blood type, ethnic groups, sensitized patients, the effects on organ shipping, the effects on real efficiency in the system (the actual logistics).  And we have seen that some methods of allocation can generate massive utility (or efficiency in your terminology).  We can get thousands of extra life years out of the current supply of organs.  But in each instance, we have made concessions in the name of equity.  The current proposal does not increase or decrease organs to any age group by more than 5% (compared to current).   This has been our compromise on equity.  What we see in utility/efficiency is an extra 8000+ years lived each year with the current supply of organs.  So the current policy has done a tremendous amount to balance equity and utility.  And we have left thousands of life years lived on the table in the name of equity.  Now you may argue that we have not done enough in that regard, but rest assured, we have given equity hundreds of hours of consideration.

UNOS Proposes a New Kidney Allocation System

By Nikola Biller Andorno

The Kidney Transplantation Committee of the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) has put forward a proposal that would substantially revise the existing national allocation system for kidneys from deceased donors. It would also dissolve alternate local kidney allocation systems, which were put in place to study various allocation methods, some of which have been incorporated into the new proposal.

The proposal contains a number of provisions. Whereas the current allocation system is focused on the time a patient has been on the waiting list for a kidney, the new proposal suggests a tiered system: The 20% of kidneys that are ranked highest with regard to the likely duration of functioning once transplanted will be matched with the 20% of candidate recipients who are expected to have the longest time to benefit from a transplant. The logic behind this suggestion – like many others driving health policy considerations these days – is an attempt to maximize utility. Although the attempt to extract the most benefit out of a precious, scarce resource is certainly in keeping with good stewardship, the proposal raises concerns about fairness: What about patients who have a lower life expectancy due to age, disability, coexisting conditions, or socioeconomic status? Will they be deprioritized, with an increased risk of either dying before they get a transplant or of receiving a transplant that may not last for long? This would mean a departure from current policy, which focuses on waiting time, and it would also diverge from policies for other organs, such as livers, in which urgency is of primary concern and very sick patients are prioritized. On the other hand, stratifying organs for transplantation is not entirely new: in an attempt to reduce the number of discarded organs, several European countries have established so-called ‘old-to-old’ programs, which match the kidneys of donors 65 years of age or older with recipients of a similar age.

At the same time, the OPTN/UNOS proposal aims to promote equality of opportunity for the remaining 80% of potential recipients, by calculating their waiting time from the onset of end-stage kidney failure rather than from the date when they were added to the waiting list and by correcting for biological factors such as uncommon blood type or high immune-system sensitivity.

The proposal can be expected to undergo careful scrutiny by the different stakeholders. There is a period for public comment running through December 14, 2012. Have a look at http://optn.transplant.hrsa.gov/news/newsDetail.asp?id=1579 and contribute to the debate.

TODAY – Deceased Organ Donation and Allocation: 3 Experiments in Market Design

Sorry for the late notice, but we just learned that Al Roth will be giving a talk with this title TODAY @ 3:30 at Stanford.  More info here.

Al has also pointed us to two relevant posts over at his Market Design blog:

Allocating deceased donor kidneys for transplant: problems, some proposed changes, and how can we get more donors?

Two recent NY Times stories discuss the allocation of deceased donor kidneys:

A few different things are intertwined here: the long waiting lists, the congested process of offering kidneys and having them accepted or rejected and offered to the next person on the list, and the ordering of the list, which in turn might influence how often people need a second transplant, which comes back to how long the waiting lists are…There are lots of interesting and important questions about how to most efficiently allocate the scarce supply (see e.g. Zenios et al.)But organ allocation has an unusual aspect: how organs are allocated may also influence the supply, by changing donation behavior. [And this is the topic of Al’s talk today.]

Older kidneys work fine (thank you for asking:)

Older Kidneys Work Fine for Transplants“Using data from more than 50,000 living donor transplants from 1998 through 2003, researchers at the University of British Columbia concluded that the age of the donor made no difference to the eventual success of the transplant — except for recipients ages 18 to 39, who were more likely to succeed with a donor their own age. Patients in this group accounted for about a quarter of all the patients studied. The scientists also analyzed lists of people waiting for a kidney from a deceased donor and found that the probability of becoming ineligible for donation within three years was high, varying from 21 percent to 66 percent, depending on age, blood group and severity of disease. Waiting can be fatal, the authors contend, and an offer of a kidney should not be rejected simply because of the donor’s age.”