The Human Egg Business: California Lawmakers Consider Paying Women for Research Eggs

If you are interested in the buying and selling of human eggs, you might want to take in a California legislative hearing tomorrow in Sacramento.

Up for action in the state Senate Health Committee is a measure that would permit paying women who provide the eggs if they do so for the purposes of research. The compensation is condemned by some because of the risk of providing the eggs, which requires heavy hormonal stimulation. But legalizing payment is sought by others as an aid to science and  as a matter of equality for women.

Currently women cannot legally be paid in California for providing eggs for research but they can be paid for providing them for fertility purposes. Compensation can range upwards of $50,000, according to an analysis by the Health Committee.

The legislation, AB2531 by Assemblywoman Autumn Burke, D-Inglewood, is sponsored by the fertility industry, which is largely unregulated.  A similar measure was vetoed in 2013 by Gov. Jerry Brown who said,

"Not everything in life is for sale nor should it be."

Burke's bill passed the Assembly April 28 on a 65-3 vote. It now requires full Senate approval before going to the governor.

Opposition to the measure includes Dorothy Roberts, a nationally recognized bioethicist who serves on the research standards group of the California stem cell agency. Also opposed is the Center for Genetics and Society in Berkeley. Marcy Darnovsky, executive director of the group, said this spring, 

"Offering large sums of money encourages women in need to gamble with their health. It’s what bioethicists call 'undue inducement.'"

She noted that the proposed law conflicts with the standards of the California stem cell agency and recommendations of the prestigious National Academy of Sciences.

According to the Senate analysis by Melanie Moreno, Assemblywoman Burke says,

"AB 2531 ensures that women are treated equally to all other research subjects - allowing them to actively evaluate their participation in research studies and be paid for their time, trouble and inconvenience when they do participate. Given that compensation is allowed in 47 other states, and there is no evidence of abuse, it’s time to reconsider our ban, just as New York did." 

For more on paying women for their eggs, see here, here, here and here.

California Stem Cell Research and a Super Doc: Inside a $4.4 Million Windpipe Grant at UC Davis

Paolo Macchiarini, Guardian photo 

Headlines around the world once hailed Paolo Macchiarini as a super-surgeon, a stem cell trailblazer who was responsible for the ground-breaking, first-ever stem cell-based trachea transplant.

It was good enough work, indeed, to be cited in 2013 as a starting point in a pitch by a team from the University of California, Davis, for $13 million from the $3 billion California stem cell agency. 

In their application, scientists Peter Balafsky and Alice Tarantal said they would build on the "first-in-human surgical successes with (the) stem cell-based tissue engineered airway implants" pioneered by Macchiarini

Last month, Macchiarini was fired from the prestigious Swedish Karolinska Institute. Six of eight of his patients have died. The institute said,

 "He has acted in a way that has had very tragic consequences for the people affected and their families."

The controversy has stirred up the international stem cell community with blog postings and sharp accusations. And in January, Vanity Fair carried an article that reported Macchiarini falsely claimed he was part of a “highly classified group of doctors from around the world who cater to the world’s VIPs,”including Pope Francis, Bill and Hillary Clinton, Emperor Akihito of Japan and President Obama.

The Italian doctor has denied the charges that led to his dismissal in Sweden and has been working in Russia.

The Macchiarini saga and its California connections offer a peek into the global nature of stem cell research and how scientists must rely on the integrity of others thousands of miles away --  as well as  the sometimes agonizingly slow search for cures. It also provides a deeper look at how the California stem cell agency goes about handing out money.

The California Stem Cell Report queried both Balafsky and Tarantal about their grant along with the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known.  

Kevin McCormack, senior director of communications, replied for CIRM. Asked whether the agency looked into the research by Belafsky as a result of the questions raised about Macchiarini, McCormack said,

"As with all the research we fund we have been carefully following the progress of Professor Belafsky’s project ensuring it continues to meet our rules and regulations."

Peter Belafsky, UCD photo

Belafsky, professor and director of the Voice and Swallowing Center at UC Davis, and Tarantal, professor in the Department of Pediatrics and Department of Cell Biology and Human Anatomy, said Macchiarini is not involved in the CIRM project. The point was stressed in boldface letters in their email response:

"Dr. Macchiarini has had no involvement in this project on any level, in any way, at any time."

(For the full text of the response, see here.)

Macchiarini was not always isolated from UC Davis and Belafsky. Macchiarini served on Belafsky's international team in 2010 when the Belafsky group performed the second-ever larynx transplant. The operation restored the voice of a Modesto, Ca., woman who had been unable to speak for a decade. 

UC Davis issued a press release saying Macchiarini served as an advisor and assisted in the surgery. The statement also said that Martin Birchall of the United Kingdom, a co-leader with Macchiarini on his ground-breaking 2008 transplant surgery, served as a scientific advisor and assisted with the California larynx surgery.

Birchall was identified as a collaborator on the CIRM grant that was approved for Belafsky and Tarantal.  A press release from University College London said that the work in Davis would serve as a "fundamental under-pinning" for two clinical trials in the United Kingdom.

Birchall received a $19,800 planning grant in 2011 to prepare an application for research that appears to be aligned with the current work at UC Davis. Birchall was listed by CIRM at the time as a researcher at the California campus.

Belafsky and Tarantal told the California Stem Cell Report that Birchall is no longer involved with their work. They said,

"Dr. Birchall was involved in our project at the onset, but due to the logistical difficulties of intercontinental collaboration, is not currently an active participant."

The Belafsky/Tarantal application originally sought $13.3 million. It was trimmed to $4.4 million on the recommendation of the agency's then president, Alan Trounson, who apparently agreed with reviewers that the initial scope and budget were high, but still recommended funding.

The application was given a score of 70 on a scale of 100 by agency's blue-ribbon scientific reviewers, all of whom came from out-of-state. As is their usual practice, the reviewers met behind closed doors and voted on the application. The action then went to the CIRM governing board, which has almost never rejected a favorable decision by its reviewers, whose economic and professional interests are not disclosed publicly.

The score of 70 placed the proposal just below the cutoff line of 75 for routine approval by the board, but the reviewers did not nix application.

The agency publishes a summary of reviewer comments, which does not identify applicants or their collaborators. The summary on the UC Davis application said the research "presents a unique opportunity to bring a world-leading regenerative medicine technology to California." The summary additionally said, without elaboration, "It was also noted that this project is unlikely to be funded by other agencies."

The summary said,

"Reviewers agreed that having already treated human patients (such as those involved with Macchiarini) using this approach is strong proof of concept(for Belafsky's work)."

Reviewers noted that "manufacturing and testing methods were not well described" but "the UK-based collaborators (Barchall and his group) will clearly play an important role in helping to establish the manufacturing process."

The summary added,

"Reviewers were unclear on the relationship between the California- and UK-based team members and whether the relationship and efforts were collaborative or duplicative."

Belafsky appeared before CIRM directors in Los Angeles in December 2013 to ask them to approve his research, saying good treatments for "complex breathing and swallowing problems" do not exist. With little debate, the board voted 8-0 to approve the award.

CIRM's McCormack said that the agency has paid out $3.3 million of the $4.4 million grant. He said, 

"Dr. Macchiarini has never been a part of the UC Davis project or any work that CIRM has funded.... The primary aim of the CIRM project is to determine the scientific reproducibility of research results from previously published studies regarding tissue-engineering for severe airway stenosis. The results are pending."

Belafsky said in his email,

"The translation of high-risk, complex innovation from the laboratory to suffering patient is not an easy road. The controversy surrounding Macchiarini has resulted in the redoubling of our efforts to explore the science behind what saves lives and what does not. This step is essential in order to lay a firm, evidence-based foundation upon which to build.

"Since your primary focus relates to the work of Macchiarini, I would like to re-emphasize that our project is fundamentally different. Our research is focusing on decellularized trachea only, whereas he has utilized synthetic grafts."

Belafsky continued,

"This is a work in progress, and we do not yet have the data to answer all the questions raised by the scientific community. We may apply to CIRM for funds to continue our research, but will not consider human implantation until we are satisfied that the science is sound and the technology is safe."

LA Times on California's Stem Cell Agency, Biotech Gold Rush and Genetically Altering Human Embryos

The Los Angeles Times, which largely ignores the $3 billion California stem cell agency in its news columns, is carrying a piece this weekend that says the agency is considering “work so controversial that the federal government won’t pay for it.”

The reference is to the possibility of the state of California financing research that involves the editing of genes in human embryos, which the agency began to explore at some length at a Feb. 4 meeting in Los Angeles.

The Feb. 12 Times story, written by Melody Petersen, is straight news piece that recaps the controversy about the possibility of making heritable changes in human beings through the use of CRISPR technology. She also covered how the agency intends to proceed with its review.

Peterson described how businesses are embracing CRISPR,

“It has set off a biotech gold rush as scientists imagine its commercial uses and found start-up companies that are attracting hundreds of millions of dollars in venture capital.”

Peterson also wrote about the likelihood of heritable changes in embryos, interviewing Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley. She quoted Darnovsky as saying,

"This is not safe. It's still way too early to try such an experiment on a human being."

Peterson continued,

“The agency's current regulations say that no money can be used to transfer a genetically modified human embryo to a woman to start a pregnancy. But some experts worry that agency-funded researchers could later turn to other sources to finance the reproductive stage of their work.

"'If you have genetically modified embryos in labs around the state,’ Darnovsky said, ‘what's to stop them from being used to initiate a pregnancy?"

Peterson quoted Kevin McCormack, senior director for communications at the stem cell agency, as saying, "So far we have not funded any research that involves CRISPR, nor have we received any proposals for funding using that technology. But that's probably just a matter of time."

The stem cell agency has longed struggled with a lack of news media attention. It would like to spread the word about what it considers its good works, such as the well over $500 million it has pumped into enterprises in the immediate Los Angeles area. The LA Times is an especially important medium because it is the largest circulation newspaper in the state, has an enormous Internet presence and helps to drive what is covered by other outlets.

But given the state of the media nowadays and the shrinkage in science reporting, about all the agency can really expect for now is coverage when something extraordinary happens or when there is the likelihood of something extraordinary happening such as genetic changes being made in human embryos.

California's Stem Cell Agency to Tackle Host of Touchy Issues on Human Genetic Changes

California's stem cell agency yesterday embarked on what is likely to be an exhaustive review of genetic alteration of human embryos with likely recommendations for changes in the $3 billion research effort.

The 11-year-old agency plans to examine a host of issues ranging from inadvertent, inheritable changes in the human race to informed consent on the part of patients.  The move emerged from a day-long review of the far-reaching subject at a meeting yesterday of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

Responding to a request from the California Stem Cell Report, Kevin McCormack, senior director for communications for CIRM, laid out the scope of the agency's future steps and gave his impressions of the session, which suffered from audio quality issues in its audiocast. (See here and here.)

McCormack said the issues were "too many and too complex" to produce recommendations immediately. He said,

"In the end it was decided that the most productive use of the day was not to limit the discussion at the workshop but to get those present to highlight the issues and questions that were most important and leave it to the (research standard group) to then work through those and develop a series of recommendations that would eventually be presented to the (agency's governing) board."

Matters to be addressed include the following, McCormack said, 

• Possible changes in language used in getting informed consent from donors in light of the ability of Crispr to make relatively easy changes in human changes. Crispr is a new technique that has brought the whole question to international attention. 
• Use of Crispr on previously donated materials/samples where general consent was given without knowing that these technologies could be available 
• Genetic modification of mitochrondial DNA as well as genetic DNA. 
• The possibility that somatic cell gene editing may lead to inadvertent germ line editing 
• Engaging patient advocates and other community groups such as the social justice and equity movements for their views. McCormack said, "After all, we are a taxpayer-created and funded organization so we clearly have some responsibility to the wider California community and not just to researchers and patients." 
• Financing the use of Crispr and other technologies that can modify the human embryo provided those embryos are not going to be implanted in a human uterus. 

Here is the full text of McCormack's summary, which we suspect is going to be turned into an item for the agency's own stem cell blog, The Stem Cellar.

"The meeting began with the hope that it would produce a strong, robust discussion of the issues surrounding the use of CRISPR to edit human embryos and to result in a series of recommendations that the Standards Working Group (SWG) could then forward to the CIRM Board on whether any changes needed to be made to our existing rules and regulations about funding such research.

"It turned out to be a thoroughly fascinating day with some thought-provoking presentations and equally thought provoking questions from the audience, from scientists, social researchers and members of the public.

"It quickly became clear that the discussion was going to be even more robust than we imagined and the issues raised were too many and too complex for us to hope reaching any conclusions or producing any recommendations in one day.

"In the end it was decided that the most productive use of the day was not to limit the discussion at the workshop but to get those present to highlight the issues and questions that were most important and leave it to the SWG to then work through those and develop a series of recommendations that would eventually be presented to the Board.
"The questions to be answered included but are not limited to:
"1) Do we need to reconsider the language used in getting informed consent from donors in light of the ability of CRISPR and other technologies to do things that we previously couldn’t easily do.

"2) Can we use CRISPR on previously donated materials/samples where general consent was given without knowing that these technologies could be available or can we only use it on biomaterials to be collected going forward.

"3) Clarify whether the language we use about genetic modification should also include mitochrondial DNA as well as genetic DNA.

"4) The possibility that somatic cell gene editing may lead to inadvertent germ line editing

"5) How do we engage with patient advocates and other community groups such as the social justice and equity movements to get their input on these topics – do we need to do more outreach and education among the public or specific groups and try to get more input from them (after all we are a taxpayer created and funded organization so we clearly have some responsibility to the wider California community and not just to researchers and patients)

"6) As CIRM already funds human embryo research should we consider funding the use of CRISPR and other technologies that can modify the human embryo provided those embryos are not going to be implanted in a human uterus.

"This was a really detailed dive into a subject that is clearly getting a lot of scientific attention around the world and is no longer an abstract idea but is rapidly becoming a scientific reality. The next step is for a subgroup of the SWG to put together the key issues at stake here and place them in a framework for another discussion with the full SWG at some point in the future.

"Once the SWG has reached consensus their recommendations will then go to the CIRM Board for its consideration. 

"I hope this captures the flavor and essence of what happened today. It really was a fascinating discussion and the issues raised, and their complexity, highlighted why so many different groups around the world are wrestling with the potential, and pitfalls, of this new technology."

World's First Approval of Genetic Changes in Human Embryo; California Eyes the Issue Thursday

The Guardian newspaper in England did not back away from the big science story today. Its article by Haroon Siddique said flatly in the first paragraph,

“Britain’s first genetically modified human embryos could be created within months….”

Siddique's piece dealt with the approval today by the key regulatory body in the United Kingdom for genetic changes in human embryos, a topic of international controversy and concern but with a special connection to California.

The news came as the state’s $3 billion stem cell agency plans a full-day examination Thursday of the issue and its implication for research in the Golden State. Of particular concern is a gene editing tool called Crispr that makes it much easier to alter genes and raises the possibility of permanent changes in the genetic make-up of the human race.

The journal Nature said the UK action was “the world's first endorsement of such research by a national regulatory authority.”

Kevin McCormack, spokesman for the California stem cell agency, told the California Stem Cell Report that the move demonstrated the timeliness of this week’s conference, which could lead to changes in California stem cell research standards.

Eminent scientists internationally have called for a go-slow approach until the issues are examined more closely. Leading that effort is David Baltimore, a Nobel Prize winner and a former member of the state stem cell agency board. He is scheduled to speak at Thursday’s session.

Baltimore was interviewed today by Nicholas Wade for a piece in the New York Times. Wade wrote that Baltimore “said the proposed experiment appeared to be consistent with the principles laid out by the (scientific) academies.

“Many such experiments are impossible for government-funded researchers in the United States because of the congressional ban (on destruction of embryos in federal research), but ‘luckily, private and state funding sources are available to carry forward such work,’ Dr. Baltimore said.”

The research in the UK is expected to be conducted with embryos donated via an IVF process. The UK rules restrict the length of the experiment to 14 days. None of the embryos will be transplanted to a womb, according to the rules.

In California, the Center for Genetics and Society in Berkeley issued a news release raising questions about the UK action. Marcy Darnovsky, executive director of the center, asked,

“Is today's decision part of a strategy to overturn the widespread agreement that puts genetically modified humans off limits?”

Her statement said, 

“The designer-baby question is a social and political question more than a technical one, and we are at a tipping-point moment on it. Now is the time to ensure that gene editing is not used to create GM babies, and that we stay off the high-tech road to new forms of inequality, and to a consumer-driven form of eugenics.”

Stem cell researcher Paul Knoepfler of UC Davis, author of “GMO Sapiens: The Life-Changing Science of Designer Babies,” wrote on his blog,

“It’s frustrating for us biologists that we still know more about the development of other animals (e.g. mice or fruit flies) than that of our own species. Crispr could change that and I believe it could do it in a big way. So with the appropriate oversight, bioethics training, and transparency, I could support this Crispr work in the UK. I need time to read up on what exactly they have planned….”

Thursday’s conference in Los Angeles will be audiocast live via an 800 number. It is also a public meeting at which anyone can make comments. Directions for the audiocast and the specific location are on the meeting agenda. The California Stem Cell Report will be providing live coverage of the day’s discussions.

California CRISPR: Three Golden State Researchers Slated to Explore Gene Editing Directions

Three California stem cell researchers are on tap this week to discuss current and future projects that could involve the state's $3 billion stem cell research agency, CRISPR concerns and the possibility of scientific missteps or worse.

The trio is scheduled to speak at a day-long conference Thursday in Los Angeles which has been convened by the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

The CRISPR technique allows relatively easy changes in genes, including alterations that could be inherited and become part of the human race.

The possibilities have stirred concern internationally, leading many blue-ribbon scientists to call for a moratorium on use of the technique in some cases.

CIRM has promised a full array of bioethicists and others for its conclave. Specifically scheduled to explore research directions in California are Jacob Corn, managing director and scientific director of the Innovative Genomics Initiative at UC Berkeley; Amander Clark, professor and vice chair of the Department of Molecular, Cell and Developmental Biology at UCLA, and Juan Carlos Izpisua Belmonte of the Salk Institute and former director of the Center for Regenerative Medicine in Barcelona.

Clark and Izpisua Belmonte are both recipients of awards from the California stem cell agency.

Juan Carlos Izpisua Belmonte
Salk photo

Izpisua Belmonte has received three CIRM grants totaling $6.6 million, one of which deals with vascular disease. He filed a progress report on the research that said, 

“During the course of this project we have been able to identify novel genetic elements and laboratory conditions facilitating the conversion of human skin cells to vessels comprising the vascular system. The generation of vessels in the laboratory may allow for the treatment of multiple human maladies including ischemic situations.”

Clark received a $1.2 million award from CIRM dealing with human embryonic stem cells. Her CIRM progress report said that the research resulted in development of 15 new hESC lines and will help improve understanding of Down Syndrome.

Amander Clark, UCLA photo

Corn is closely connected to Jennifer Doudna, who is executive director of Berkeley’s Innovative Genomics Initiative. Doudna developed the CRISPR technique at her lab at Berkeley. 

Jacob Corn, UC Berkeley photo

Last month, Corn provided a “translation” of the statement from the widely publicized international conference in December on human gene editing.

Corn wrote, at one point, that the document said “trans-generational gene editing could be very unfair, and might extend ‘rich get richer’ societal problems into our very genes, and trans-generational edits could change our own evolution more than societal influences, and it’s not clear that we actually want to or should do that.”

In addition to the public session in Los Angeles, Thursday's meeting will be available via an audiocast. Directions are on the agenda, but allow some time in advance for setting up your access.

Human Genetic Alteration and Gold Mines: California's Stem Cell Agency Takes a Hard Look at Research Standards

The $3 billion California stem cell agency next Thursday will convene a day-long examination of human gene editing, a field that could be a “gold mine for biotechnology” and perhaps alter the human race permanently.

“Easy DNA Editing Will Remake the World. Buckle Up.” is the way Wired magazine put it in a headline on a lengthy overview article last July.

The piece by Amy Waxmen said that gene editing has “already reversed mutations that cause blindness, stopped cancer cells from multiplying, and made cells impervious to the virus that causes AIDS.”

The key focus is on CRISPR, which is a technique developed at UC Berkeley and which is involved in substantial amounts of the research funded by the California stem cell agency. CRISPR, according to one description, makes changing genes as easy as cutting and pasting changes in this article.

The session next week at Los Angeles International Airport is chock-a-block with big names in

scientific research and ethics, including David Baltimore, a Nobel Prize winner, former president of Caltech and a former member of the stem cell agency board. At an international CRISPR

David Baltimore, Pasadena Now photo

 conclave in December, Baltimore said,

“The overriding question is when, if ever, we will want to use gene editing to change human inheritance.”

The New York Times reported that the group called for what would be, “in effect,” a moratorium on making inheritable changes to the human genome.

In addition to Baltimore, next week’s California conference is scheduled to hear from Alta Charo of the University of Wisconsin and a leading authority on bioethics; Hank Greely, a specialist in bioscience issues at Stanford law school; Jonathan Kimmelman, a bioethicist from Canada’s McGill University, and Charis Thompson, founding director of the Science,

Charis Thompson, UC Santa Cruz photo

Technology, and Society Center at UC Berkeley, along with a number of scientific researchers.

The agenda for the meeting states that the stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), “will continue to support groundbreaking stem cell treatments and technologies, including gamete and embryo research, from their inception to translation.”

“In light of recent science-policy initiatives,” said the CIRM document, the agency’s research standards group has been asked to examine the agency’s policies dealing with human gene editing.

“One objective of this review is to ensure CIRM research continues to be conducted under the highest medical and ethical standards,” the agency said.

An upshot from next week’s meetings could well be changes in what is permitted to be done by the hundreds of researchers who have funding from the stem cell agency. Beyond that, decisions by the Golden State agency are likely to influence other funding agencies and researchers globally.

CIRM already has alliances with a number of countries, including China, Spain, Israel and Poland. And the agency is closely watched by many from outside California.

Many of the stem cell agency’s meetings of much less import are available live on the Internet. The meeting agenda initially did not list such access. The California Stem Cell Report earlier this week queried the agency about audiocast or Internet access to the session.

Kevin McCormack, senior director of communications, replied late today, 

“When it comes to CIRM, transparent is the new black. Yes, we will be having an audio feed for the standards working group on Feb 4th. Details will be posted on the website shortly.”

The agenda also has links to several useful background pieces along with the names of other invited participants.

California Stem Cell Agency Symposium: 'Vague Fears' vs. Potential Genetic Alteration of Human Race

California’s $3 billion stem cell agency has called a high-level meeting for next fall to examine a
"red-hot" issue that many prominent researchers say could lead ultimately to alteration of the human race.

The topic is a technique that makes it much easier to alter the genetic make-up of individuals in a way that can be inherited by their offspring.

In April, scientists in China reported genetically modifying human embryos in what was regarded as a “world first.” (See here and here.)

That came after a group of leading scientists in March called for a global moratorium on the genome-editing practice, stating that the therapeutic benefits were tenuous.

More recently Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, wrote on May 28 about how the subject was viewed at a meeting called, “Biotech and the Ethical Imagination: A Global Summit.”

Steven Pinker

“The far end of techno-enthusiastic perspectives, both on human germline modification specifically and on biotech in general, was represented by Harvard experimental psychologist and popular science writer Steven Pinker. In his opening remarks, Pinker counseled bioethicists to ‘stay out of the way of progress.’ In his closing comments, he cast ‘vague fears’ as standing in the way of saving millions of lives. In between, he epitomized the ‘bad boy scientism’ that too frequently characterizes the biotech field.” 

Jonathan Thomas, chairman of the stem cell agency, and Geoff Lomax, the agency’s main person on bioethics, wrote on June 1 about the matter and the upcoming meeting. In an item on the agency’s Stem Cellar blog, they said,

“Given CIRM’s support for research activities where genome editing may be employed, we believe it is important to have effective policies to guide our future funding decisions. Therefore, we have charged the CIRM Medical and Ethical Standards Working Group with convening a public workshop to elucidate the scientific and policy considerations surrounding genome editing in the context of CIRM supported research. This workshop is a first step in evaluating whether CIRM should make changes to its existing policies governing stem cell research.”

 CIRM’s standards group consists of some of the top bioethicists in the country. Early on, they developed the agency’s rules for research on stem cells, which were the most advanced in the country at the time. The chairman of the group is Bernie Lo of UC San Francisco.

The genome-editing issue to be discussed in November was originally scheduled to be brought up at an April meeting of the standards group. However, it was put off for a variety of reasons. Thomas subsequently called the meeting for next fall.

At the April meeting, Ted Peters of the Pacific Lutheran Theological Seminary and a member of the stem cell standards group, said the issue was “red hot.”  Jeff Sheehy, a member of the agency board and a communications manager at UC San Francisco, said the agency needed to clarify where it stood.  

Robert Taylor of the Emory School of Medicine and also a member of the standards group, said,

“There are companies that are offering to do this for your cell line, so it's really out there.”

Lo said,

“I think Jeff has raised a really important, complex and breaking topic. I think the idea of having a symposium to deal with both the science, and the ethics policy could be a really important thing to do.” 

 Suggestions regarding the meeting can be sent to Lomax at glomax@cirm.ca.gov. 

California's $70 Million Alpha Stem Cell Clinic Plan Edging Forward

The $3 billion California stem cell agency is predicting that “human healthcare will be greatly improved” by stem cell research by 2024 and this week is fleshing out some of the details of an ambitious plan to help make that happen.

The effort involves what the agency calls “Alpha” stem cell clinics. The agency said its proposed $70 million, Alpha network will support its own projects along with products developed worldwide and brought to California.

The plan will come before the stem cell agency's standards group tomorrow at a meeting in San Francisco. The agency's staff has recommended alteration of some of the agency's regulations to avoid duplication in connection with review and approval of clinical trials.

The staff document said a workshop earlier this year developed a “consensus that it would be beneficial if the CIRM (the stem cell agency) regulations reflected existing state and federal requirements with regard to delegation of responsibility and avoid unnecessary duplication of effort, such as the IRB (institutional review board) responsibility for the risk and benefit assessment.”

The staff is recommending that “CIRM’s regulatory requirements for clinical research should be modified to avoid duplication of IRB’s responsibility for review and approval of clinical trials.”

The staff also said,

“CIRM’s existing regulatory requirements for notification, review and approval of basic and pre-clinical research appear effective at this time without creating undue burdens. In fact, mature systems appear to be in place to efficiently incorporate ESCRO (embryonic stem cell research oversight) operations into institutional compliance programs.”

Also on the standards group agenda are issues dealing with informed consent by providers of somatic cells “obtained under general (biomedical) research protocols" in connection with iPSC (induced pluripotent stem cell) derivation.

Dubbed the “Discuss Project,” its goal is “to initiate a process designed to develop consensus for the use of previously collected specimens for iPSC research" and to publish "final considerations" in early 2014.

Another item on the agenda tomorrow involves an update on the “progress of CIRM iPSC bank and donor consent protocol.”

iPSC Bank and Imaging Technology Sessions Offered by CIRM

The California stem cell agency this spring will be looking into both imaging technology for cellular therapies and ethical/policy questions dealing with reprogrammed stem cells.

The iPSC session April 29 in Los Angeles involves CIRM's Standards Working Group, which makes recommendations for rules for the agency's $3 billion research program. The meeting is a continuation of last year's session dealing with the banking of iPSCs. The goal of the meeting this year is to "recommend operational criteria that will assist CIRM in developing a request for proposal for the iPSC bank."

The draft agenda includes consent standards, withdrawal of subjects from research, transfer of materials and communication of results. The agenda said,

"The generation of iPSCs for disease modeling may results in published findings of interest to donors or individual results on research studies that would alter clinical management of donors. Under what conditions, if any, should information be returned to donors as groups or individuals?"

Coming up on May 26 is a webinar on imaging technology that will feature panelists from the FDA, the NIH and industry. Moderating it will be Ellen Feigal, formerly of Amgen but now the new VP for research and development at CIRM.

The agenda includes the "FDA’s perspective on imaging technology, the use of imaging technology in preclinical studies to assess cell fate" and an overview of existing and new imaging technology.

The webinar, which is part of CIRM's Regenerative Medicine Consortium program, is free but requires advance registration.

CIRM Moving to Hire VP at More Than $332,000

The California stem cell agency may well have a new vice president of research and development by the end of this month and at a salary exceeding the $332,000 allotted for the position.

CIRM directors will meet one week from today to consider raising the existing pay range for the position. CIRM President Alan Trounson obviously has a candidate that wants more than $332,000, and the board is not likely to reject Trounson's choice. To do so would indicate a lack of confidence in Trounson.

CIRM has not disclosed exactly what the new salary will be or explained why it is needed. Don't look for that information until the day of the meeting and probably only if you are in attendance at one of the telephonic meeting locations around the state. CIRM generally has not posted such sensitive salary information in advance of meetings.

Trounson was eager to find someone with industry experience. Last July, Trounson told directors that he wanted “someone with the skill base to have more of a focus in their role with biotech/pharma – translation – clinical applications, which is where we are moving with our translational, disease teams and clinical grants and where we are thin in capacity.”

Trounson hired Levin and Company at a cost of $100,000 to help with the search.

The new position was created by Trounson after Marie Csete resigned suddenly last June as CIRM's chief scientific officer. She said her advice was not respected. Her position will not be filled, but her responsibilities are being parcelled out to the new VP and Patricia Olson, executive director of scientific activities, who has been with the agency since its early days. Under a new structure announced last August, Olson reports directly to Trounson as will the new VP. Previously Olson reported to the chief scientific officer.

The compensation for the new post was scheduled to come up at the CIRM board meeting earlier this month in the State Capitol. CIRM chairman Robert Klein took the matter off the table the day of the meeting, saying negotiations were not at the right stage.

The move came on the same day as The Sacramento Bee carried a front page story that said California state workers received 4 percent less pay last year than in 2008 as a result of the state's financial crisis. Approval of a salary beyond $332,000 creates a public relations risk for CIRM, given the severe cutbacks elsewhere around the state. CIRM's salaries are already quite generous compared to other state agencies.

Salaries are easy for the public to criticize and to understand, especially compared to arcane scientific studies that may not seem immediately relevant to many people. Additionally, boosting a $332,000 salary without telling the public in advance why or specifying the size of the increase plays into the hands of those who are critical of CIRM's lack of transparency and openness.

The new VP will have a financial impact on CIRM beyond the salary. He or she is expected to have at least two or more staffers assigned to work for him or her. They will be new hires at CIRM, which is already chafing under the legal limit of 50 employees. In fact, Trounson has warned that the quality of work could slip unless a way is found to circumvent or repeal the cap.

Another matter is on the table as well next Monday. The item says,

"Consideration of guidance and CIRM’s Medical and Ethical Standards regarding use of previously NIH approved lines in CIRM-funded research and additional lines that are comparable to CIRM’s recommendations to the NIH and/or would be grandfathered or approved under those recommendations.”

No further explanation was offered by CIRM.

Interested parties can take part in the board proceedings at teleconference locations throughout the state including San Francisco(4), Los Angeles(2), La Jolla(2), San Diego, Duarte, Berkeley, Sacramento, Pleasanton and Healdsburg. More locations could be added in the next few days. Specific addresses can be found on the agenda.

CIRM Directors Take Up Revised Research Standards Oct. 27

The Standards Working Group of the California stem cell agency today gave the nod to changes in its standards aimed at achieving consistency with national rules for human embryonic stem cell research.

The proposed regulations now go to the CIRM board of directors at its meeting in Los Angeles Oct. 27-28.

For more on the rules, see the “Research Standards” item on Oct. 11, 2009.

Congressional Bill on hESC Research

A Colorado congresswoman is planning to introduce legislation to codify the president's executive order permitting federal funds to be used for human embryonic stem cell research and to require periodic review of NIH research guidelines.

The Washington Post reported during the weekend:

“Usually, couples who go to in vitro fertilization clinics create more embryos than will be implanted. The remainder are either destroyed or frozen. The NIH regulations and the bill would allow couples to donate their embryos for research as long as they are fully informed of their choices and they are not compensated for the embryos. The guidelines give donors the ability to change their minds 'until the embryos were actually used.'"

The newspaper continued:

“Congress already prohibits federal funding for collecting stem cell lines from human embryos, which are destroyed in the process. But the NIH rules make it clear that taxpayer money will not be used on lines from embryos created solely for research.”

Rep. Diana DeGette, D-Colo., plans to introduce the measure soon, according to the Post. The CIRM Standards Working Group meets this morning to consider revising California regulations to achieve consistency with federal rules.

CIRM Acts on Revised Research Standards This Week

The California stem cell agency Monday takes up changes in its research standards aimed at achieving consistency with national rules for human embryonic stem cell research.

The changes appear to be non-controversial although researchers and other interested parties would be well-advised to listen in on the audiocast proceedings of the 10 a.m. meeting of the Standards Working Group. Its discussions often shed light on questions that may pop up later when the standards are to be applied.

If you can't tune in, CIRM has posted the regulations along with additional details and the Powerpoint briefing slides to be used at the meeting. The documents are also necessary if one wants to follow the audiocast.

The rules being considered by CIRM apply only to research that is funded by the agency. Stem cell research in California that is not funded by CIRM is regulated by the state Department of Health.

From day one, CIRM has banned the use of stem cell lines if they are derived in a process that provides compensation – “valuable consideration” – for eggs or embryos. One of the proposed changes that caught our attention involves an exception to the ban on “valuable consideration” in the case of embryos created in reproductive IVF. The proposed rule states:

“For embryos originally created using in vitro fertilization for reproductive purposes and were no longer needed for this purpose 'valuable consideration' does not include payments to original gamete donors in excess of 'permissible expenses.'”

Having watched laws and regulations formulated for several decades as a journalist, creation of exceptions piques my interest. In this case, I wondered whether money could be made by using the proposed exception. What happens if human eggs have real economic value at some point in the future in terms of research i.e. a high demand and a supply shortage? Is it possible that crafty entrepreneurs could use the cover of IVF to generate eggs to meet that demand?

CIRM firmly believes that will not happen under its proposed rules. Their intent is clear plus CIRM also reviews its grantees' research protocols and audits the institutions, the agency says.

We also asked Hank Greely, a Stanford law professor familiar with stem cell issues, about the matter. Greely, who is not involved with the CIRM regulations, offered this quick and informal response that basically supports the CIRM regulation.

“I think that's a defensible interpretation. She is being paid to 'donate' ('paid to donate' is odd wording, in itself) her eggs for reproductive purposes. She cannot be told, in advance, that not all of her eggs will be used to make embryos for reproductive purposes, because no one knows, in advance, how many eggs she will provide, how many embryos will thrive, and how many the recipient will need for reproductive purposes. She doesn't get any money because of the research use and she doesn't 'donate the eggs for research use' - the woman/couple who pay her for her eggs ultimately donate the embryos made from those eggs for research use. The egg donor gets the same amount of money whether the recipient ends up using all of the embryos created with the donated eggs for reproductive use or none. No more or less money changes hands depending on whether all the eggs are used for reproduction or some of the eggs are used for research.

“Assume I pay you $3 for a six pack of Coke Zero and I tell you I plan to drink as many as I need, which may or may not be all of them. I end up giving one of the cans to my wife. Have you received 'valuable consideration' for donating the can to my wife?”

For an earlier discussion of the regulations, you can see the transcript of the standards group meeting on Sept. 18.

Directions for hearing the audiocast can be found on the standards group agenda.

(Editor's note: An earlier version of this item incorrectly said that the proposed regulations will be considered by the CIRM board Friday. They will be heard by the board at its meeting in Los Angeles Oct. 27-28.)

CIRM Looking for Closer Conformity on Egg Rules

SAN FRANCISCO --As part of its effort to achieve consistency with national standards, the California stem cell agency is moving towards allowing the use by CIRM researchers of embryos created through IVF that originally involved payments.

The CIRM Standards Working Group last week approved the move although specific language is yet to be worked out. Bernie Lo, co-chairman of the group and director of the medical ethics program at UC San Francisco, said the language would be narrowly focused.

Jesse Reynolds of the Center for Genetics and Society of Berkeley, Ca., said he was
“encouraged” by the CIRM direction. Earlier, the group had expressed concern that CIRM might be creeping towards possible creation of a loophole in the Prop. 71 ban on compensation for egg donors.

CIRM hopes to present specific language soon for its proposed rule to the Standards Working Group in a telephonic meeting. The proposal would then go to the CIRM board and from there into the official state regulation process.

In other matters involving the standards group, Alta Charo, a professor of law and bioethics at the University of Wisconsin, who has been a member of the group since its beginning in 2005, is leaving the panel because of her new position as a senior advisor at the FDA,

CIRM hopes to approve a replacement at the board meeting that begins Oct. 27.

Reynolds also praised CIRM staff for the early posting of background material on matters to be discussed at the meeting last week. Additional material has been posted as well on the research standards issues facing CIRM. It all can be found here.

Egg Donor Proposal Stirs Concern; CIRM Says Language is 'Placeholder'

The Center for Genetics and Society Thursday raised “serious concerns” about some of the matters to be discussed at today's meeting of the research standards group of the $3 billion California stem cell agency.

CIRM, however, said the center has “misconstrued the intent of the proposed changes.”

In a letter to CIRM, the Oakland, Ca., organization center referred to preliminary language contained in a briefing paper for the group that dealt with compensation for egg donors, which is banned by CIRM. The draft language, which is intended to conform CIRM rules to others nationally, would “limit the payment restriction to donation of oocyctes provided specifically for research purposes.”

The center said,

“We were startled to see this for two reasons. As you know, both Proposition 71 and California law prohibit paying women to provide eggs for research. This proposed policy would mean that a woman undergoing egg extraction could be compensated or receive other valuable consideration as long as research is not the specifically stated purpose of harvesting her eggs. Diverting eggs for which payments have been made from the reproductive to the research context would be contrary to Proposition 71 and state law.

“We sincerely hope that this is an oversight. We ask the Standards Working Group to reject the proposed language and to clarify that paying women for eggs that will be used for research (beyond reimbursing their expenses) is contrary to law, and will not be done in California.”

CIRM posted a response to the CGS letter on the agency's website. In the response, CIRM referred to National Academy of Sciences guidelines and said,

“The language 'specifically for research' is a placeholder taken directly from the NAS Guidelines. The SWG (standards group) has consistently drawn from the NAS guidelines to provide a model for our regulations. This example is no different. This placeholder language is designed to support policy development. Any proposed regulatory language is subject to SWG review, ICOC approval, OAL review and public comment to ensure the regulatory language is consistent with the intent of the policy.”

Our take? We think CIRM's intent is clear. However, whether the proposed regulatory language achieves that goal is another question. We suspect more artful language will be developed as these proposed changes work their way through the regulatory process during the next few months.

CIRM is to be lauded for posting its 28-page briefing paper well in advance of today's meeting. That allows time for such parties as the Center for Genetics and Society and others to comment thoughtfully on the matters to be considered. It also allows time for CIRM to respond publicly in advance of the meeting. The upshot is likely to be better policy and better regulations and enhance CIRM's image as responsive to the public.

We should also note that the center's letter also raised concerns about the “prospective use for research of paid-gamete IVF embryos could create conflicts of interest for the physician attending an egg provider, and thus put her at increased risk.”

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.

CIRM Takes on Federal Chores

The California stem cell agency will be dealing with federal stem cell and biotech matters over the next couple of weeks, including the proposed NIH rules on hESC research.

The agency has created a task force that will meet publicly this Thursday to hear comments on the rules. The panel is preparing a report that will be submitted to the full CIRM board on May 12 with the intent of getting the comments to the NIH later this month.

You can find CIRM's preliminary work on the subject here and our report here. Comments for CIRM can also be submitted via email at info@cirm.ca.gov.

Also on tap for the May 12 board meeting is consideration of a statement of principles dealing with federal legislation on production of biosimiliars, which would be copies of biotech drugs following expiration of their patents.

Teleconference locations are available for the May 12 meeting in San Francisco, Los Angeles(2), Sacramento, La Jolla(2), Pleasanton, Berkeley, Elk Grove, Healdsburg, and Irvine(2). Specific addresses can be found on the agenda.

Five teleconference locations exist for Thursday's meeting: San Francisco Elk Grove, Los Angeles, Healdsburg and Duarte. You find the addresses on the agenda.

Public CIRM Hearing Next Week on NIH hESC Rules

If you are interested in the proposed NIH regulations for hESC research and California's reaction to them, put a May 7 meeting of the California stem cell agency on your calendar.

Not long after the CIRM directors Legislative Subcommittee Monday approved creation of a task force on the subject, a meeting with teleconference locations in San Francisco, Elk Grove, Los Angeles, Healdsburg and Duarte was scheduled for next week. Specific addresses can be found on the agenda.

Comments on the proposed rules must be submitted by May 24 to the NIH. You can read more on what CIRM has done so far here, but keep in mind that this is very much a work in progress.

Stanford's Weissman Flays Proposed NIH hESC Regs

The NIH's proposed hESC regulations were hardly off the presses today before they came under fire from an eminent stem cell researcher for flying in the face of President Obama's March proclamation on stem cell research.

Irv Weissman(pictured), director of stem cell research at Stanford, took on the NIH in a news release from the Stanfod School of Medicine.

Weissman said,

"Instead of facts, the NIH placed its own version of ethics in place of the president’s clear proclamation. As head of the National Academy of Sciences' panel that unanimously endorsed research using SCNT, and as a drafter of the guidelines for the International Society for Stem Cell Research, I know that this suggested ban on federal funding of SCNT-derived human embryonic stem cell lines is against our policies and against President Obama’s March 9 comments. The NIH has not served its president well."

The news release continued,

"'I am happy that these are draft guidelines,” said Weissman, who noted that the NIH did not solicit input from either the National Academy of Sciences or the International Society for Stem Cell Research during the consensus process. 'I’d like to remind the NIH of the principles enunciated by the president on March 9. Research in this area is moving very fast, and it’s not possible to say whether advances will come from work on adult-derived iPS cells or from embryonic stem cells created by nuclear transfer. Policy needs to be developed as the field develops, rather than precluding something based on ideology.'"

Across San Francisco Bay in Oakland, the Center for Genetics and Society praised the regulations,

Its news release said,

"Cloning-based stem cell research lays the technical foundation for human reproductive cloning - which the U.S., unlike dozens of other countries, has not yet prohibited - and requires enormous numbers of human eggs, whose extraction poses health risks to women. Despite years of work, no researcher has created a clonal human embryo viable enough to yield stem cells," said Jesse Reynolds, policy analyst at the Center. "In contrast, alternative methods of cellular reprogramming have largely achieved the goals of cloning-based work. The NIH was wise in leaving such risky work outside the domain of federal funding."

The group did not address CIRM's position on the proposed rules, but it has been an advocate of strong national standards.