SF Lawyer Urges Openness at Stem Cell Agency

Writing in connection with an incident in which two persons were barred from a CIRM meeting, a San Francisco attorney this week called on the California stem cell agency “to return to its commitment to an open and public process.”

Justine Durrell, who is involved in issues dealing with biotech and women's health, made the comment in a three-page letter to the 29 members of the board of directors of the $3 billion research effort. Her letter referred to the item last month in the California Stem Cell Report describing the incident at a San Francisco hotel.

Durrell raised a series of question in connection with the meeting and its implications for procurement of human eggs. Among them were the absence of public notification about the meetings, the justification for exclusion of the public and CIRM's lack of funding for research into the health consequences on women who provide eggs for research.

She wrote,

“Additionally, I emphasize the importance of CIRM's return to its commitment to an open and public process. In the end, openness and transparency will better serve all Californians. Please obviously post in advance all meeting times and locations, the agenda, whether they are open or closed (the justification therefore), and the transcripts/minutes/reports following the meeting.”

You can read Durrell's entire letter here.

Open Meeting Letter -- Justine Durrell to Stem Cell Board

Eggs, Donors, NIH Rules and More This Week

For those of you interested in research standards and rules, the California stem cell agency has posted 28 pages of background material for its meeting in San Francisco this Thursday and Friday.

On the agenda is New York's policy that permits compensation for human eggs to be used for research. CIRM does not permit compensation(valuable consideration), but the agency plans to make some changes in its rules to conform to national standards.

Also available via the CIRM web site is briefing material on proposed changes for donor consent requirements and an update on the NIH rules for human embryonic stem cell research, plus more.

The Associated Press Digs Into Eggs, Money and Stem Cell Research

The Human Egg Debate just racheted up a notch.

Generally confined to scientific journals and websites like the California Stem Cell Report, the issue of scientists paying for eggs for human embryonic stem cell research today clattered onto a broader stage in a thorough-going piece by The Associated Press. The international news service distributes its stories to virtually every newspaper, radio and television station in the country.

Marcus Wohlsen wrote the article out of San Francisco. It began,

"Facing a human egg shortage they say is preventing medical breakthroughs, scientists and biotech entrepreneurs are pushing the country's top funders of stem cell research to rethink rules that prohibit paying women for eggs."

The California stem cell agency was mentioned in the second paragraph. Stemagen, a San Diego stem cell firm, was mentioned in the sixth. Alan Trounson, CIRM's president, Harvard's Kevin Eggan, Cascade LifeSciences, also of San Diego, and the Center for Genetics and Society of Oakland, Ca., were all included.

Sam Wood(pictured), chief executive of Stemagen, said that bans on payments for eggs have kept researchers from making advances that could save lives.

He was quoted as saying,

"You need to have enough eggs to make this thing work, and when you have enough eggs it does work."

"If these guidelines weren't in place, we'd already have many (stem cell) lines and be much closer to a treatment for devastating illnesses for which these are so well suited."

The AP story continued:

"As the country's largest funder of stem cell research by far, California's policy sets the pace for biotech firms and academic researchers nationwide. National guidelines advising against egg payments were developed to ensure any innovations would remain eligible for California funds; any changes to the state's policy would likely have an immediate ripple effect.

"California could also face increasing competition for business and scientific talent as New York prepares guidelines for its own $600 million stem cell research program. A draft report released by the New York program's planning committee said the state may allow payment for eggs."

But Wohlsen quoted Marcy Darnvosky of the Center for Genetics and Society as saying,

"Do we really want to put women at risk to provide raw materials for research a lot of scientists say really isn't the way to go?"

The references to Cascade, Trounson and Eggan all were to events chronicled earlier on the California Stem Cell Report, including the June meeting of CIRM's directors and the February meeting of the CIRM Standards Working Group.

The AP story pulled all of it together for general readers across the nation and perhaps abroad. Wohlsen's article will also attract the attention of editors around the country who may well commission locally written pieces and possibly editorials. It might even trigger a television news story or two.

San Diego Researchers Say No Shortage of Human Eggs

Jeff Sheehy, a member of the board of directors of the California stem cell agency, has brought to the human egg debate a new entry that appears to fly in the face of assertions that scientists cannot get enough eggs for their human embryonic stem cell research.

His comments and information come as the CIRM Standards Working Group plans to dig into the topic again this Friday during a public hearing in Los Angeles. The issue of egg availability, however, goes well beyond California, reaching out to such places as the United Kingdom, where discounted IVF services are being offered to generate eggs for research.

Sheehy, also a member of the Standards Working Group, pointed to work being done by Cascade LifeSciences in San Diego and others to show that the egg shortage concerns of CIRM President Alan Trounson and Harvard's Kevin Eggan may be overstated.

Sheehy's starting point is a letter for reconsideration of Cascade's rejected application for a CIRM grant. Cascade's letter, which can be found here on the California Stem Cell Report, stated that the firm was collaborating with David Smotrich of the La Jolla IVF clinic to obtain eggs. Cascade said that the clinic had a "list of young and healthy volunteers who desire to donate oocytes specifically for this SCNT project. All these donors were pre-tested and demonstrated a high oocyte production (20-25 oocytes per cycle) in response to homornal stimulation."

Last week Sheehy queried Ken Woolcott, who wrote the reconsideration request, about the availability of eggs, which Sheehy recalled as being 100 a year. Sheehy also asked whether they were obtained under circumstances that would make them available for use by CIRM grantees i.e. proper consent, no payment outside of CIRM policy, etc.

In response, Woolcott, Cascade's chief business officer, emailed Sheehy that he checked with Cascade's primary investigator, Dr. Sophia Khaldoyanidi, as well as Smotrich, head of the collaborating La Jolla IVF clinic. Woolcott replied,

"Dr. Smotrich confirmed that the oocyte donors are only reimbursed for their time and medical care expenses.   These donors are not IVF patients that receive discounts or are paid for their eggs.  They tend to be donors that desire to enhance medical research in the Stem Cell  area, are younger and have a track record of high oocyte quality and productivity. 

"I believe that this is consistent with the draft guidelines prepared by CIRM and is consistent with the law in California.    More importantly, any work in this area would be subject to IRB approval."

Sheehy said that Woolcott's information is "very important" if it "confirms that at least one investigator in California is able to obtain sufficient oocytes to conduct research within the confines of CIRM's ethical standards and the provisions of Prop. 71 and SB 1260(the law that deals with non-CIRM funded hESC research)."

But the devil may well be in the details. In this case, does the La Jolla clinic's definition of reimbursement for "time and medical care expenses" match that of CIRM's?

CIRM Reviews the Business of Human Eggs

One week from today, the California stem cell agency is going to dig into the hot topic of human eggs – how many can scientists can get and their cost.

To its credit, the agency has posted background material on the subject well in advance of the July 25 meeting of its Standards Working Group in Los Angeles. Providing the material early is a refreshing change from CIRM's recent dilatory practices. The agency is to be commended.

The egg meeting comes in the wake of complaints earlier this year by researchers and CIRM President Alan Trounson that human eggs were not to be had in sufficient quantities for research. Kevin Eggan(pictured) of Harvard, a member of the Standards group, said that he and his colleagues had spent $100,000 advertising for human egg donors with little success.

The problem is that California and other states bar compensation for eggs for research. But handsome payments -- $15,000 and even more -- are made by IVF clinics for the same egg donation process. So most women take the cash.

Eggan made his comments last February. The ensuing discussion set in motion a review of CIRM policies dealing with compensation of donors. The issue also came up briefly last month at the meeting of the CIRM board of directors.

Trounson said scientists are having a "terrible time" securing eggs. He declared,

"It's all because there's no partnershipping arrangements or because they're using very few oocyte material. They're now trying to use cattle eggs, other species. They're floundering."

CIRM has prepared a draft briefing paper dealing with the egg issue. The agency has not completed all of its work on the subject, but it is surveying funding institutions, interviewing scientists and others and determining whether specific cell lines are not being used by CIRM grantees.

The briefing paper lists the following policy questions.

"Should CIRM funded researchers be able to use 'outside' hESC lines if they are derived from IVF-embryos created with paid gametes?

"Should CIRM funded researchers be able to utilize hESC lines derived from IVF-embryos created with paid gametes under an 'authorized authority'?

"Should CIRM funded researchers be be able to utilize IVF-embryos created with
paid gametes to derive new lines?"

Also prepared for next week's meeting is a briefing paper on uses of cell lines derived prior to CIRM regulations.

Fresh Human Eggs and Stem Cell Economics

The price of human eggs and their scarcity, at least for stem cell research, once again have risen as topics, but this time in New York.

The events in the Empire State, however, dovetail nicely with a similar, ongoing issue at the Golden State's $3 billion stem cell agency.

Hawk-eyed Jesse Reynolds of the Center for Genetics and Society in Oakland, Ca., spotted the New York egg issue and reported on it on the Biopolitical Times.

He wrote on June 3,

"One aspect that caught my eye, not surprisingly, concerns the sourcing of fresh human eggs for cloning-based stem cell research (a.k.a. somatic cell nuclear transfer, or SCNT). Although NYSTEM's brief authorizing law is silent on this and related issues, such matters have been deliberated by NYSTEM's Ethics Committee. The draft strategic plan reveals the Committee and the program's governing board are considering offering compensation for women to provide eggs. (pages 26-27)

"This would be an unfortunate deviation to the generally agreed-upon practice of only reimbursing for expenses. I am aware of no ethics committee that has endorsed payments,* and of only one research team which offered them (and that was before the consensus against compensation crystallized in 2004). The good news is that there is still time for input: NYSTEM has not explored the issue in depth, and the Ethics Committee will discuss the topic at its next meeting."

Earlier this year, we reported that the California stem cell agency has embarked on a review of the human egg market and the needs of researchers, some of whom are complaining that they do not have enough raw material.

The study was set in motion after Harvard scientist Kevin Eggan told the CIRM Standards Working Group that he and his colleagues had spent $100,000 advertising for donors and "pursued every option" for collecting eggs with little success.

CIRM President Alan Trounson said "accessing those eggs is no trivial matter." He said scientists are seeking grants from CIRM for research that may not be feasible because of the lack of human eggs.

A wide-ranging review of the issue and related topics is expected to surface publicly at CIRM sometime this year. Issues that may be aired include: availability of eggs and their numbers, researchers' perceptions of the problem, possible reimbursement of IVF treatment, use of eggs by CIRM researchers from other areas where compensation restrictions are not so tight (such as possibly New York) and the grandfathering of cell lines that were derived before CIRM regulations were adopted.

The subject comes under the Standards Working Group, which has a July 25 meeting scheduled in Los Angeles. However, no topic for that session has been announced. We are asking CIRM when the egg issue will come up.

On other related notes:

The Feb. 28 meeting of the Standards Working Group on eggs and other matters carried a reference by CIRM Chairman Robert Klein to an "opinion" by CIRM outside counsel. We queried CIRM about the opinion. Here is the agency's response:

"There is no email or other written legal opinion from James Harrison regarding reimbursements for IVF costs. The transcript from the working group reflects that Bob did query Harrison during the meeting asking him to send a copy of law 1260 (SB1260 by Sen. Deborah Ortiz), which deals with payments for eggs. Harrison did send the bill in an email and that is what is referenced in the transcript. Bob requested that so that he could show a section toward the end of the bill that explicitly states nothing in 1260 is designed to change anything in Prop. 71."

Marcy Darnovsky of the Center for Genetics and Society also has a rundown on writings by feminist scholars on eggs and cloning-based stem cell research. You can find the citations and links to the articles here.

CIRM Seeking Egg Donation Comments

The California stem cell agency has prepared a draft of guidelines for reducing risk in connection with the donation of human eggs for stem cell research and is seeking comments on them from the research community and others.

The draft can be found here. A related document concerning the history of the guidelines and their purpose can be found here.

In addition to general remarks, Geoff Lomax, senior officer for the CIRM Standards Working Group, is asking for comments on the following:

"The utility of the guidelines for reviewing studies proposing to obtain oocytes for research

"The consistency of the guidelines with current clinical protocols and standards of care

"General feasibility considerations with the draft guidelines."

The impact of these guidelines will go well beyond California, which is currently in the global forefront of setting standards for human embryonic stem cell research. Seeking comment at early stage and posting the information on its web site serves CIRM well, opening the door to all who are interested or who have something at stake.

An Egg Shortage: Is More Cash the Answer?

The California stem cell agency has embarked on a sweeping review of the human egg market and the needs of researchers, some of whom are complaining that they do not have enough raw material.

The study was set in motion after Harvard scientist Kevin Eggan (see photo on left) told the CIRM Standards Working Group last month that he and his colleagues had spent $100,000 recently advertising for donors and "pursued every option" for collecting eggs with little success.

CIRM President Alan Trounson, a renown Australian stem cell scientist, said "accessing those eggs is no trivial matter." He said scientists are seeking grants from CIRM for research that may not be feasible because of the lack of human eggs.

One answer to the question of scarcity posed during last month's session is increasing the money for women who provide eggs. However, that could be considered the politically fatal "third rail" for hESC cell research. Prop. 71, which created the California stem cell agency in 2004, was approved by voters in a campaign that appeared to promise that women would not be paid for eggs. But the language of the measure is artfully ambiguous. The initiative says that it is up to CIRM directors to set

"standards prohibiting compensation to research donors or participants, while permitting reimbursement of expenses."

Currently CIRM regulations do not allow for compensation other than reimbursement of direct expenses. One suggestion that arose during the meeting of the CIRM Standards Working Group on Feb. 28 was some sort of reimbursement of expenses for women involved in IVF treatments. However, paying for IVF treatments could be construed as cash for eggs.

Not all members of the group were comfortable with the concept of paying women for eggs.

Here is an exchange from the transcript of the Feb. 28 meeting between CIRM Oversight Committee member Jeff Sheehy and CIRM Chairman Robert Klein, who led the campaign for Prop. 71 and claims responsibility for writing it:

Sheehy:

"(Prop. 71) was approved by the voters because the voters thought there wasn't going to be compensation for egg donors when they voted for it, and they didn't know we were going to go back and change it. And so in that context I think this is an issue that would be appropriate for us to study."

Klein:

"Well, I'm in a reasonably good position, Jeff, to discuss the issue of what was presented to the voters. and --

Sheehy:

"I was your average voter, Bob. I was not one of these people that was waving the stem cell flag. I can tell you that if we were going to go out and spend $3 billion buying eggs from women, I wouldn't have voted for it."

Klein:

"Certainly I wouldn't have voted for it either, so we agree. But the key here is medical reimbursement was clearly contemplated. I have gone to James Harrison (outside counsel to CIRM and who wrote portions of Prop. 71) and discussed this issue with him...."

Alta Charo(see photo on right), professor of law and bioethics at the University of Wisconsin and a member of the CIRM standards group, noted the political sensitivity of the issue of cash for eggs. She said changing the CIRM standards worked out in 2005 could be "inviting really quite draconian responses" from unspecified parties, but presumably hostile lawmakers and regulators.

What went unsaid during the Feb. 28 meeting was the fact that some have long regarded the supply of human eggs as insufficient for human embryonic stem cell research. But now that hESC research is enjoying a resurgence, the scarcity is becoming more acutely felt.

The session also did not include a direct discussion of another reality: If eggs are scarce and demand is high, somebody is going to make a business of it. It will be an unregulated business somewhere else in the world. It goes almost without saying that embryonic stem cell research is a global endeavor, a point that Klein made on Feb. 28.

The CIRM Standards meeting ended with a move to investigate the entire subject further. Bernie Lo of the University of California, San Francisco and chairman of the group, indicated the review would include availability of eggs and their numbers, researchers' perceptions of the problem, possible reimbursement of IVF treatment, use of eggs by CIRM researchers from other areas where compensation restrictions are not so tight and the grandfathering of cell lines that were derived before CIRM regulations were adopted.

The standards group will consider the staff review of the matter at some later date. We have asked CIRM when that is likely to occur.

Needless to say, this subject is complex. We have only briefly touched on a handful of issues discussed during the Feb. 28 meeting. We recommend a close read of the transcript. Most of the pertinent discussion begins on page 91.

Below are some excerpts from the transcript.

Snippets From the CIRM Egg Debate

Here are some excerpts from the transcript of the Feb. 28 meeting of the CIRM Standards Working Group concerning human egg availability.

CIRM President Alan Trounson:

"Accessing those number of eggs is no trivial matter, no matter what the opportunities are. In that circumstance the demand for the oocytes may be way beyond what we can possibly deliver in an outcome. And it may take us five years to do that. If we gave a three-year grant, that would be nonsense because the chance of deriving a cell line might be extremely low.

"That's why we've come because we have these applications sitting in our portfolio which we're questioning about how do we move forward on this, or do we sort of take them off the table and let the other ones proceed. I think it's important for you to understand that it's real-time now. We have to actually know exactly what is appropriate to do."

CIRM Chairman Robert Klein:

"From a legal point of view, I'm very concerned with the use of words here. I don't know anyone that's suggesting you make a $10,000 payment to somebody. If somebody has real cost, and they can document those costs, and they can get reimbursed for part of those costs. What's being addressed here is reimbursement for part of the cost, not a $20,000 payment to someone."

CIRM Oversight committee member Jeff Sheehy:

"If they did not think that they could get the eggs, they should not have submitted the applications. They have submitted applications, so they must believe that they can get the eggs."

Alta Charo, a member of the Standards Working Group and University of Wisconsin professor:

"Prop 71, which itself had this written in to some extent as a political matter, drove the National Academy guidelines which felt like they were already basically having to follow the California lead on the altruistic model here."

Trounson:

"I don't think it drives it forward. That's the problem."

Charo:

"Now we're in a situation, I think, where it's particularly touchy to try and revisit the compromise, putting aside whether or not it's even legally possible given the language of Prop. 71."

Kevin Eggan, Harvard stem cell researcher and member of the CIRM Standards Working Group:

"I have spent countless hours stomping around to different disease advocacy groups, tea circles, knitting circles, trying to find anyone and everyone who would donate their oocytes for our experiments, even out of the goodness of their heart because they had someone that they cared about who was affected by these diseases that we might in the very long term provide hope for.

"We spent more than $100,000 in advertising in the Boston Globe, in the Boston Herald, in the Boston area papers, in the suburbs of Boston. We have literally pursued every option. We've pursued trying to recruit donors from other parts of the United States to come to Boston to donate their oocytes for research. This will not work. In a country where women know that they can be compensated for doing the exact same thing, they simply will not, and in the face of the difficulties, I should add, it's not like they're not doing it solely because of the money, they're doing it because of the money and because it's a very difficult thing to do oocyte donation. And those two things collaborate together to create an environment in which women will not do this in a meaningful way which will allow the research to go forward.

"It was a very reasonable compromise to say we need to give up compensation because we can't afford to be assailed both from the right and the left on this position, but now we know that that compromise position is a failure. So what do we do about that? I think the fact of the matter is that it might as well be against the law if we can't do it. That's one sort of null hypothesis for years. So how to proceed in the face of that? I agree it's risky; but if we don't take the risk, then the outcome will be the same as if we take the risk ..."

Clarification

The "Eggs" item below makes a reference to CIRM regulations concerning reimbursement of expenses for egg donors involving "lost wages" vs. direct expenses. Some persons contend that lost wages should not be reimbursed, arguing that creates a disparity between well-paid and less well-paid women. In California, CIRM regulations include reimbursement for lost wages. So does the proposed policy for ESC research that is not connected to CIRM funding, which is regulated by another state law.

Eggs and Absurd Inconsistencies

Writing in the New England Journal of Medicine, a Harvard business professor says the "politics of egg donation" have obscured the real issues concerning the market for human oocytes.

Debora Spar discusses the scene nationally and internationally, using the case of woman she calls "Anna Behrens," who Spar says is not a real person. Spar wrote in the March 29 edition of the NEJM:

"The United States, by contrast, maintains the absurd inconsistency illustrated by the case of Anna Behrens: $20,000 for an egg used for reproduction; nothing for the same egg used for stem-cell research. Such a policy would make sense only if we deemed assisted reproduction socially more valuable than research. But this argument is not being made and perhaps could not logically stand, given that the alternative to assisted reproduction would often be adoption. Instead, opponents of egg selling tend to refer to the fears of commodification and the risks to donors — all of which, if valid, apply equally to the reproductive and research uses of eggs.

"What we need, therefore, is a fresh debate on egg donation and a new set of policies. We need to consider the health risks and ways of identifying and mitigating them. We need to ensure that all potential donors are fully informed of these risks and fully protected against them. We need to make clear that the benefits of egg donation, for reproductive or research purposes, are complicated, and that few of these benefits will ever flow directly to the donor. At the moment, though, the politics of egg donation have blinded us to these real issues. We have not thought deeply about what makes sense for science, for women, and for society. Instead, we are only fighting about the price."

Spar, author of "The Baby Business: How Markets are Changing the Future of Birth," does not discuss in her NEJM article the possible growth of a black market for human eggs, which seems certain to arise if eggs have real monetary value and there is a shortage.

As far as California is concerned, Spar reports that researchers using state funds are prohibited from compensating egg donors for anything beyond direct expenses.

The actual language of the CIRM regulations is slightly different. It says that "permissible expenses" are "necessary and reasonable costs directly incurred as a result of donation or participation in research activities. Permissible expenses may include but are not limited to costs associated with travel, housing, child care, medical care, health insurance and actual lost wages."

NEJM has also posted an interview with Spar and Emily Galpern of the Center for Genetics and Society in Oakland on the subject of egg donations.

Uniform ESC Research Standards, More Federal Funding? Lower Your Expectations

The "bizarre patchwork" of embryonic stem cell regulation across the country is not going to disappear regardless of what happens in the presidential election in 2008, several speakers said today at a stem cell conference in San Francisco.

It was not a message that the audience of 500 persons from throughout the world necessarily wanted to hear. Their preference would be for unified standards with ample predictability, ideally at the federal if not global level.

But Nancy Forbes, an attorney with Ropes & Gray of Boston and San Francisco, said "The genie is not going to go back in the bottle." She said she has never seen a governmental body roll back its jurisdiction.

It was a theme echoed by others on the panel discussing "The Un-United States: Cell Lines Border Lines and The Law" at The Stem Cell Meeting, sponsored by Burrill & Company.

Ken Taymor, an attorney with MBV Law of San Francisco and who has followed California stem cell issues closely, also noted that there is little likelihood of a flood of federal ESC research funding following the 2008 election.

He said the NIH, in fact, may look at all the state and private research efforts underway and decide that it does not need to spend its limited funds in the area, an ironic negative effect of state activity aimed at beefing up stem cell research funding.

Russell Korobkin, a UCLA law professor, tackled what he called the "most problematic" aspect of the the stem cell laws across the nation – the bar against compensating women who donate their eggs. He said that compensation is permitted for donation of eggs for in vitro fertilization, which is identical to the process for donating eggs for research.

Korobkin dissected the argument for the compensation ban. He said it does not prevent coercion of women; rather it is actually coercive by limiting what women may do. The argument also assumes that "women cannot make the best decision" concerning egg donation and need to be protected by the state. If the process is too risky, he said, it should be banned regardless of payment or lack of payment. And it is not clear that the ban protects society as a whole, Korobkin argued.

Underlying the argument for compensation prohibitions seems to be "a wish that there were no women so poor that they would be motivated by their eggs," the law professor said.

Korobkin, however, did not deal with the politically touchy nature of repealing the ban on compensation. The subject is freighted with emotions that are fueled by the nightmarish visions of some of egg factories in poverty-stricken corners of the country or the world. Few lawmakers are inclined to support the repeal of compensation lest they get tarred with a brush from that very same vision.