New Procedures at CIRM: California Stem Cell Agency Staff Nixes Grant Application

For the first time in its nine-year history, the staff of the $3 billion California stem cell agency this week  formally and publicly weighed in on grant approval actions by its prestigious reviewers, recommending that one application be rejected and another approved with conditions.

The staff, led by CIRM President Alan Trounson and Patricia Olson, the agency’s executive director of scientific activities, made recommendations to the agency governing board on three applications that can be described as “wobblers.” In other words, the board could go either way on the proposals when it considers them at its meeting in La Jolla on Wednesday.

Trounson recommended that the governing board reject one of the wobblers  (No. 6666),  a $2.0 million proposal, even though it received a higher scientific score – 70 – than the other two applications. Trounson recommended approval of two $1.8 million projects (Nos. 6831 with a scientific score of 66 and 6832 with a scientific score of 69), with staff-imposed conditions on one.

 Trounson said the agency is or 

 "will be funding 2 similar approaches to address photoreceptor degenerative disorders so addi-tional investment in an earlier stage project is harder to justify.”

All three fall into a newly defined category, called tier 2, for ranking of applications. The CIRM web site said tier 2 proposals are now ones that possess “moderate scientific quality, or consensus on scientific merit cannot be reached and may be suitable for programmatic consideration by the ICOC(the governing board).”

A fourth application  (No. 6648) for $4.3 million that scored below all three at 64 was approved, however, by reviewers after they imposed a condition on the proposal.  CIRM staff did not publicly address that application. The application review summary said that the researcher – who was not identified – must “demonstrate, within 12 months, the ability to make the hESC–derived 3-D sheets. This is a go no/go milestone for the project.”

The agency’s standard practice is withhold the identities of applicants prior to board action because they might be embarrassed.

In the other instance where conditions are to be imposed, they appeared to deal with an in-kind contribution of “essential services, technology and expertise.”

The new process for evaluating marginal or wobbler applications was established last March in response to an Institute of Medicine study last year that made a host of recommendations for improvements at the stem cell agency.

The staff recommendations on applications came in a $70 million early translational round that is aimed at “proof of concept for development of a therapy candidate and/or studies to select a development candidate.

In all, including staff and reviewer actions, 13 applications were recommended for funding, although the board has almost never rejected reviewer decisions. The 11 grants initially approved by reviewers total $37 million. With the two more recommended by staff, the figure would be about $41 million. A total of 39 applications were considered for funding.

Five applicants filed appeals of reviewer rejections, a CIRM spokesman said today. The  California Stem Cell Report has asked for copies of those appeals and CIRM staff action on them. Appeals are also being conducted under a new staff-dominated procedure, although all applicants have the right under state law to appear before the board to address any subject.

Budgeted grant funds that are unused are available to the board for future grant rounds in any area they so desire.

(An earlier version of this item incorrectly said six applicants had filed appeals, based on information from the agency. The correct figure is five.)

(Editor's note: Kevin McCormick, CIRM's spokesman, later commented on the agency's practice of withholding the identities of applicants to avoid embarrassment to applicants who are not approved. He said,  "Actually they are withheld so that the board doesn't know the identities of the researchers or the institutions whose applications they are voting on." 
(We should note that official CIRM policy is to withhold all applicant names until board action, but it does not release any of the names of denied applicants even after board action. However, it has in the past released in advance of board action the names of applicants when it suits its purposes . Also, the names of many applicants can be discerned based on information provided in the review summaries of the applications. The identities of applicant institutions can also be determined based on which board members are allowed to participate in discussion of specific applications as well as being allowed to vote. For more on the practice of withholding names, see here, here, here and here. )

California Stem Cell Agency's $150,000 Search for Its Financial Future

A San Francisco consultant, who is often known as an “economic therapist,” has been selected to devise a “strategic road map” for the financial future of the $3 billion California stem cell agency.

James Gollub: 'economic therapist'
Gollub Associates photo

James Gollub, managing director of the firm bearing his name, is under a $150,000 contract to lay out by this fall a detailed plan for the agency. The nine-year-old research effort is scheduled to run out of money for new awards in 2017.

Gollub was selected after the agency posted a request for proposals (RFP) last spring. The RFP assumed an additional $50 million to $200 million in a onetime “public investment.” The RFP also assumed additional private funding of a yet-to-be-determined nature.

Gollub is described as a co-founder of the field of cluster-based economic development. One web site said he is known as an “economic therapist.” The website for his current firm says,

“A leading expert in innovation bridge building....
“Global experience assisting universities, institutes, government agencies and public-private partnerships link innovation sources to innovation seekers.
“Committed to the goal of increasing flow of needed solutions, optimizing financial returns and sustainable economic impacts from innovation.”

Gollub's current firm dates back to March of this year. His Linked In profile says,

“James Gollub Associates (JGA) LLC was launched to build on 36 years of Gollub’s professional research and consulting experience. That experience began with 16 years at SRI International, three years at DRI/McGraw-Hill, five years at IDeA, nine years at ICF International and three years with E-Cubed Ventures LLC. During that time Gollub has worked globally to deliver economic strategies for over 30 national, state and metropolitan regions, develop strategies to accelerate growth of new industries (clusters), plan public and private R&D institutes and advise on over 15 science and technology parks.”

The need for a financial transition plan for CIRM was publicly identified as long ago as 2009 by the Little Hoover Commission in its lengthy study and has been reiterated periodically by other bodies since then. Under the terms of Prop. 71, which created the agency, CIRM has only  a 10-year authority to issue state bonds, the borrowed funds that have sustained the research effort. Legal maneuvering blocked the issuance of bonds until 2007.

The California Stem Cell Report asked the stem cell agency on May 31 for a copy of Gollub's response to the RFP. Yesterday we asked for a copy of the contract with Gollub. Those documents will be published when they are received.

New Ties to Big Pharma and Venture Capital Proposed at California Stem Cell Agency

The $3 billion California stem cell agency wants to recruit major biotech and venture capital firms to help provide tens of millions of dollars in research awards to California enterprises.

It's part of a move to “jump start” partnerships in a relatively new, $80 million, business-friendly program that is aimed at pushing therapies into the marketplace. The recruitment plan will come before the agency's governing board at its meeting next Wednesday in San Diego. 

Participating companies will have a special relationship with the state agency, including early input into concept funding proposals prior to their being presented to the agency's governing board. The “industry collaborators” will also be able to attend agency workshops and meetings involving hundreds of grant recipients. Presumably other, non-collaborating firms would be barred.

Other provisions of the plan call for special event-hosting arrangements aimed at creating more collaborations and posting of information from the selected collaborators on the CIRM website.

According to a CIRM staff document, the initiative would be limited to biotech and pharmaceutical firms with a market capitalization of at least $500 million and “qualified venture capital firms.” The document did not define what a “qualified a venture capital firm” is. The document also appeared to bar participation of privately held firms because of the “market capitalization” criteria, which typically uses a formula involving publicly traded shares.

Elona Baum, the agency's general counsel and vice president, business development, said in a statement provided to the California Stem Cell Report,

“This is aimed at trying to jump start the creation of the partnerships that are required to satisfy the commercial validation requirements of the Strategic Partnership Funding Initiative so that timelines are better synced-up as between our review and approval cycles for the Strategic Partnership RFAs and the lengthy time required for investors to conduct due diligence and negotiate an agreement with prospective applicants to Strategic Partnership RFAs.  CIRM's independent review and approval remains the same and is wholly independent. While there may be input given to a particular RFA it only at the high level concept stage and of course CIRM has no obligation to agree. In the context of the Strategic Partnership awards, CIRM wants to fund innovative high quality science that has attracted additional  investors.  Investors will help leverage CIRM fund and will be an important source of future funding to further the project.”  

A $2 Million Bill: Outside Contracting by California Stem Cell Agency

The $3 billion California stem cell agency this week posted a list of its outside contractors, who range from a a $25,000 stem cell licensing consultant to a $550,000-a-year law firm.

The agency expects to spend $2 million during 2013-14 on outside contracting, down from $2.9 million in 2012-13. This week's report covers the 2012-13 year.

Outside contracting is the second largest item in the agency's budget, which is slated to spend $17.4 million this fiscal year for operational expenses, up 5 percent from last year's spending. The largest amount, $12.2 million, goes for salaries and benefits. (For more on the budget, see here, here and here.)

Topping the contractor list is the law firm of Remcho, Johansen & Purcell of San Leandro, Ca., which had the $550,000 contract. CIRM, as the agency is known, reported that Remcho came in under budget by $95,595. That contrasts to some previous years when the firm, which has represented the stem cell agency since its inception, required additional cash on top of its original contract. James Harrison of the Remcho firm is its face at the agency and is designated as the outside counsel to the agency's governing board. In all, the agency is slated to spend $2.2 million on legal expenses, including in-house work.

David Earp is the stem cell licensing contractor. He was paid only $13,125 on his $25,000 contract during 2012-13. It is unclear whether he will be paid the $11,875 balance. Earp was chief patent counsel and senior vice president for business development for Geron before it dropped its stem cell program. Earp was heavily involved in the $25 million loan that CIRM made to Geron in 2011. In February 2008, he testified before CIRM about its then proposed loan program.

The list of contractors included $200,000 to the AlphaMed Press of Durham, N.C., as seed funding for a stem cells translational journal, $156,434 to Hyatt Hotels for the meeting of CIRM grant recipients, $250,000 to Kutir Corp. of Newark, Ca., for informational technology services and $290,000 to the Mitchell Group of Woodland Hills, Ca., also for information technology services.

The list of contractors will be presented to the CIRM governing board at its meeting next week. The list does not usually trigger any significant discussion.

Correction

The stem cell spending item yesterday incorrectly stated that the California stem cell agency would run out of funds for new grants in 2013. The correct year is 2017.

California Stem Cell Agency Spending: Where the Money Is Going

Analysis of CIRM funding by Pat Olson, executive director of CIRM scientific activities July 2013

The California stem cell agency will have committed $472 million to translational research – a key to commercializing stem cell therapies – if it awards the full $70 million in new grants and loans slated to come before its governing board next week.

The nearly $500 million will amount to about 17 percent of its funding so far, according to an analysis last month by Pat Olson, the agency's executive director of scientific activities. The largest percentage of the agency's cash, however, will be going for “development” – 35 percent or $970 million. Olson defined “development” as “essentially our IND enabling, our preclinical development programs and our clinical development programs.”

Basic research is to receive 17 percent or about $469 million with buildings and facilities taking up $443 million or 16 percent. Training and career development has consumed about 15 percent or $414 million.

However, those calculations include $577 million in funds that have been allocated but not yet awarded. Another $491 million is “concept approved” but also not awarded. The agency's governing board could change those allocations or withdraw approval of concepts, although it has not yet shown signs that it might do so.

The agency will run out of money for new grants in 2017 and is examining the possibility of generating more cash through some sort of public-private partnership. To develop support for continued funding, the agency is under pressure to generate results that will resonate with the public and potential private funding sources. Those results are most likely to come from a late stage translational/clinical trial effort.

Here is a link to CIRM's translational portfolio as of September 2012.

(An earlier version of this item incorrectly said that the agency would run out of money for new grants in 2013. The correct year is 2017,.)

Flim-Flam Stem Cell Artists Targeted by CIRM

The California stem cell agency has joined with other prestigious stem cell organizations to help put a stop to the flim-flam artists that prey on desperate people by promising miracle cures from stem cell treatments.

The agency announced the action today on its blog, declaring that it has posted a new patient advisory document that provides a “ robust and detailed set of issues patients should consider when making treatment decisions.”

Don Gibbons, CIRM's senior science and education communications officer and author of the blog item, said the document addresses one of his special concerns: Internet “ads that come up on web searches and seem to be offering everything to everyone.”

Some of those ads can be found on many stem cell-related web sites, including this one, that carry ads that are placed there automatically by Google.

California Stem Cell Researchers to Receive $70 Million Next Week

The California stem cell agency is scheduled to give away $70 million next week as it moves forward on its efforts to turn research into cures.

The awards will be for efforts that will result in proof of concept for development of a therapy candidate and/or studies to select a development candidate.

As many as 20 grants and loans are projected to be awarded in the early translation round. The awards will range up to $3.5 million over a three year period.  The round was open to both businesses and academic institutions. Collaborators from Germany were involved, although funding for research in that country is not provided by the state stem cell agency.

The applications will come before the $3 billion agency's governing board at its Aug. 28 meeting in La Jolla. After next week's awards, the agency, which is known as CIRM,  will have about $500 million left to hand out before cash for new awards runs out in 2017. The agency is currently examining ways to continue its awards with some sort of public-private partnership.

Also on the board's agenda is a proposed announcement for a CIRM/industry co-funding agreement. No further details on that program were available early today on the agenda. Other matters to be considered include final approval of the changes in the agency's IP regulations, appointment of new members to the grant review group and the latest report on the outside contracts held by the agency. Details on those matters are yet to be posted by the agency.

A tribute to the late Duane Roth, co-vice chairman of the agency, is also scheduled. The board will additionally meet behind closed doors to evaluate the performance of CIRM President Alan Trounson.

The California Stem Cell Report will carry more information on the meeting as it becomes available.

In addition to the La Jolla location for the meeting, other locations where the public can take part in the meeting are in Menlo Park and Duarte. Specific addresses can be found on the agenda.

'Butter and Eggs Money" and a Gubernatorial Veto

Nancy Scheper-Hughes, professor of medical anthropology at UC Berkeley and director of Organs Watch, is one of the opponents of the legislation that would have permitted women to sell their eggs for research. Today she filed the following comment on the “troubling mindset” item on the California Stem Cell Report.

“Jerry Brown's veto of AB926 which would allow young women to be paid for multiple egg extractions for scientific research is one for the gals.  In western Ireland women secreted away their 'butter and eggs' money in anticipation of hard times. In my day every smart girl had her 'mad money' to escape a bad situation. Secret cash for young women is a great idea, but not when it turns on multiple cycles of pumping powerful hormones associated (in other contexts) with ovarian cancer into young women's bodies to produce 30 or 60 eggs a month. That's not promoting gender equity no matter what some of our best Democratic women leaders have to say. Selling sperm and selling eggs are a totally different matter. One  is pleasurable and safe, the other is a complicated and invasive procedure. We need good science and good research and  freedom of choice and action. We also need protection from false advertising. There are no evidence based, long term studies of the effects of these hormone injections on women ten or twenty years after the fact. Let's fund those needed longitudinal and cohort studies and hope for the best. In the meantime, women had best stick to 'butter and eggs' money. It doesn't pay a lot, but it's less painful and a heck of a lot safer.”

Bonilla: Veto of Pay-for-Eggs Bill Shows Troubling Mindset

A Democratic state legislator today assailed Democratic Gov. Jerry Brown's “mindset” as “particularly troubling” in his veto of legislation that would have allowed women to sell their eggs for scientific research.

The statement came from Assemblywoman Susan Bonilla, D-Concord, in response to Brown's action on her fertility-industry sponsored bill, AB926, which would have removed a ban on compensation for women who provide eggs for research.

Susan Bonilla
Photo from California Legislature

Brown cited health risks and other issues and said in his veto message,

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

Alex Matthews, writing on Capitol Weekly, quoted Bonilla as saying,

“It (the governor's veto) shows a glaring inconsistency...The veto statement was very overreaching in the fact that it was making very broad statements about what women should be able to do, and while it's not legislation it certainly goes to a mindset that the governor has that I find particularly troubling.”

Bonilla continued,

“Market-driven compensation of donors by donor agencies and prospective parents continues unchecked.”

In a statement on her website, Bonilla said the governor's veto “is a regressive action that denies thousands of women the prospect of medical fertility breakthroughs.” She said,

“Many women...will be denied hope and the possibility of giving birth to a child because research on their behalf has been halted in California.”

Bonilla has argued that women involved in egg-related research, such as that involving stem cells, should be compensated, just as men are for their sperm. Women who provide eggs for fertility purposes can be legally compensated up to any amount. The current market runs about $10,000 or so per egg cycle but can be much higher.

Bonilla's measure would not have affected a ban on compensation involving research funded by the $3 billion California stem cell agency. It would have taken a 70 percent vote of each house to alter that restriction, compared to a simple majority for Bonilla's bill. The super, super-majority requirement was written into state law by Proposition 71, the measure that created the stem cell agency.

Bonilla did not indicate whether she would attempt to override the governor's veto, which would require a 2/3 vote of each house.

One of the opponents of the bill, the Center for Genetics and Society in Berkeley, called the veto a “welcome development.”

Diane Tober, associate executive director of the center, said,

“It would be unconscionable to expand the commercial market in women’s eggs without obtaining significantly more information about the risks of retrieving them.” 

Here are links to other stories today on the veto of the bill: Los Angeles Times, Sacramento Bee, an additional story from late yesterday on Capitol Weekly, TheAssociated Press and National Review.

California Gov. Jerry Brown Vetoes Pay-for-Eggs Legislation

California Gov. Jerry Brown today vetoed a fertility industry-backed measure that would have permitted women to sell their eggs for the purposes of scientific research.

In his veto message, Brown said,

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

The bill would have repealed a ban on compensation of women who provide their eggs for scientific purposes. The measure would not have changed existing law that allows women to be paid for their eggs for IVF purposes with fees that range up to $50,000. The bill also would not have affected the ban on compensation for eggs for research that is financed by the $3 billion California stem cell agency.

The legislation (AB926) by Assemblywoman Susan Bonilla, D-Concord, was sponsored by the American Society for Reproductive Medicine and easily swept through the Democratic-dominated legislature. Bonilla said the measure would have placed women on an equal footing with men, who are paid for their sperm contributions for research. She also said that it would help to encourage more research into fertility issues.

Some stem cell scientists have complained that not enough women are willing to donate eggs without compensation, but stem cell researchers were not publicly involved in supporting the bill.

The fertility industry group had confidently predicted that Brown, a Democrat like Bonilla, would sign the bill. The governor's action could be overridden by a 2/3 vote of each house of the Legislature. It is not clear whether Bonilla will make such an attempt.

Here is the text of Brown's veto message:

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

"This bill would legalize the payment of money in exchange for a woman submitting to invasive procedures to stimulate, extract and harvest her eggs for scientific research.

"The questions raised here are not simple; they touch matters that are both personal and philosophical.

"In medical procedures of this kind, genuinely informed consent is difficult because the long-term risks are not adequately known. Putting thousands of dollars on the table only compounds the problem.

"Six years ago the Legislature, by near unanimity, enacted the prohibition that this bill now seeks to reverse. After careful review of the materials which both supporters and opponents submitted, I do not find sufficient reason to change course.

"I am returning this bill without my signature."

You can read more about the bill and its history here, here, here and here.

Duane Roth: Ecumenical Innovator for San Diego and Biotech

The Xconomy news service today carried a sterling look at the contributions that Duane Roth, co-vice chairman of the California stem cell agency, made before his untimely death as the result of a bicycle accident.

Reporter Bruce Bigelow pulled together a host of comments concerning Roth's involvement in the San Diego community, ranging from biotech to action sports companies. The headline on the piece read, “The Connector Who Wired up a Regional Innovation Economy.”

At the time of his death at the age of 63, Roth was CEO of Connect, a nonprofit organization that supported technology and innovation and one that he was credited with reviving. Bigelow also wrote,

“Once California voters approved a 2004 ballot proposition that authorized the issuance of $3 billion in grants for stem cell R&D, (Mary) Walshok (associate vice chancellor for public programs at UC San Diego) said Roth also played a key role in bringing together UCSD, Scripps, Salk, and Sanford-Burnham to create the Sanford Consortium for Regenerative Medicine. In fact, Walshok doubts whether anyone but Duane Roth could have brought the four major research centers together.”

Another speaker at the memorial services Friday attended by about 1,000 persons was Bill Walton, the former UCLA and NBA great, who grew up in San Diego.

Bigelow wrote,

“Walton, the NBA Hall of Famer who has led San Diego Sports Innovators as a division of Connect since 2010, said Roth became a business mentor to him. In his comments Friday afternoon, Walton said Roth inspired him to be a better person, and he counted Roth among the people who had the biggest influence on his life—a list that included his own father, UCLA coach John Wooden, sportscaster Chick Hearn, author David Halberstam, and Jerry Garcia of the Grateful Dead.”

Bigelow described Roth as an ecumenical and pragmatic advocate for innovation who could work with persons who did not always agree with him on all issues. He was a conservative and active Republican, but his co-vice chair at at the stem cell agency, Art Torres, former chairman of the state Democratic Party, on more than one occasion has lauded Roth's ability to work together.

Bigelow wrote about similar remarks Friday by Don Rosenberg, an executive vice president and general counsel at Qualcomm.

“'Duane and I were as different as two people can be,' Rosenberg said during his eulogy at the Church of the Immaculata. 'Duane was born in Iowa, baptized in the Mennonite church, a Republican. And me, raised in Brooklyn, Jewish, a Democrat. We quickly learned we had more in common. We were kindred spirits. We liked the same things: Bikes, biking, cars, and people.'”

A $6 Billion Question: Progress of the California Stem Cell Agency

The headlines march like legions across the Internet and throughout the world.

“New type of stem cell helps your fingers regenerate”

“Stem cell technology can mass-produce cancer-killing cells to target tumours”

"Stem-cell treatment restores sight to blind man”

“Special stem cells could heal hearts”

But then there is this extraordinarily rare headline that sounds a harshly different note:

“Stem cells: what happened to the radical breakthroughs?”

All these headlines go to address, in one form or another, a request/question posed last month by an anonymous reader of the California Stem Cell Report. The comment came on an item about the California stem cell agency's $70 million plan to establish a network of “Alpha” stem cell clinics in California.

The reader said,

“It would be nice to have an overall update on how much as been spent on California's stem cell research project and what progress has been made.”

On the surface, the answer is easy. The agency has given away $1.8 billion. The agency says it has made tremendous progress and expects to make even more with the about $600 million it has left. The prestigious Institute of Medicine has said the agency has “achieved many notable results.”

However, no thorough, rigorous evaluation has been made of the details of the agency's scientific contributions, specific grant awards or its impact on the field of regenerative medicine. No one has attempted to genuinely assess whether the work of the agency is or will be worth the roughly $6 billion(including interest) that California taxpayers will have paid for the agency's ambitious efforts.

Then there is the question of “progress towards what?” Is the progress to be measured against the promises of the 2004 ballot campaign that resulted in creation of the stem cell agency or more modest goals that eschew the hype of the campaign?

The stem cell agency is burdened in a way that most science is not. The 2004 campaign created a sort of contract with voters. They were led to believe nine years ago that the cures for diseases that the campaign said afflict nearly one-half of all California families were, in fact, right around the corner. Few, if any California stem cell researchers were publicly warning that a hard and long, long slog remained before therapies reached patients.

Last week, however, Simon Roach of the British newspapers, The Guardian and Observer, shed some light on the early, rosy promises of stem cell science compared to the world as it exists today.

He wrote that in 1998,

“(B)iomedical engineer Professor Michael Sefton declared that within 10 years, scientists would have grown an entire heart, fit for transplant. 'We're shooting big,' he said. 'Our vision is that we'll be able to pop out a damaged heart and replace it as easily as you would replace a carburetor in a car.'

“Fifteen years on, however, we've had some liver cells, eye cells, even a lab-grown burger, but no whole human organs. We could be forgiven for asking: where's our heart? It does seem strange that a field stoking so much excitement could be so far off the mark. Speaking last week about the vision that he and his colleagues outlined in 1998, Sefton said they had been 'hopelessly naïve.' As time plodded on and an understanding of the biological complexity increased, the task seemed bigger and bigger. Even now, a cacophony of headlines later, we are not much further ahead.

“Chris Mason is a professor of regenerative medicine at University College London and believes that concentrating on organ regeneration is missing a trick. 'These organs are immensely complex,' he said. 'They've got nerves, blood vessels, in the case of the liver, a bile system – there are huge degrees of complexity. These things take a long time to grow in humans, let alone in the lab without all the natural cues that occur in the growing embryo.'"

The final paragraph in Roach's article said,

“There's a tension in medical research between the glory of the big discovery and the assiduous commitment to real application. 'We're hoping the scope and possibilities of this project will catch the public's imagination,' Sefton concluded in 1998. It did, but perhaps the public's imagination isn't always what science should be vying for.”

Little doubt exists that the California stem cell agency has made a significant contribution to stem cell science, although the size of that contribution – beyond dollars – remains to be measured. For now, the key for the agency and the public is to focus on activities that will generate the greatest value over the next few years and advance the science that has already been financed by the agency.

As the $700,000 Institute of Medicine report said,

“The challenge of moving its research programs closer to the clinic and California’s large biotechnology sector is certainly on CIRM’s agenda, but substantial achievements in this arena remain to be made.”

Stem Cell Agency's Duane Roth Eulogized at Memorial Services

An estimated 1,000 persons attended services last week for Duane Roth, co-vice chairman of the California stem cell agency, who died at the age of 63 following a bicycle accident.

The San Diego U-T reported,

“A Who’s Who of San Diego’s technology, business and civic community gathered Friday to bid farewell to Duane Roth. The biotech entrepreneur, community leader and director of Connect died last weekend of injuries sustained in a cycling accident.

“Among attendees were Gayle and former Gov. Pete Wilson, who had just celebrated his upcoming 80th birthday with former colleagues and friends in Sacramento, county Supervisor Ron Roberts, former Assemblyman Nathan Fletcher, Chamber head Jerry Sanders, Preuss School benefactors Peggy and Peter Preuss, SDG&E CEO Jessie Knight, and many biotech and high-tech leaders. These included Irwin Jacobs, Ted Waitt and Denny Sanford.”

'Paradigm Shift' -- Researchers as Patient Advocates?

It is not easy for a stem cell scientist to break into “print” in that bastion of American capitalism, Forbes magazine. Much less one from that perceived antithesis of free enterprise, Reed College.

But researcher Paul Knoepfler of UC Davis has done just that.

John Farrell of Forbes wrote about Knoepfler on Friday in the wake of the announcement Knoepfler will be honored with a “national advocacy” award by the Genetics Policy Institute.

Paul Knoepfler -- Advocate for a "new ethos"
UC Davis photo

Knoepfler, who received a degree in English literature from Reed in 1989, is being recognized for his activities as a stem cell blogger since 2009.

Farrell quoted Knoepfler as saying in an email,

“With many stumbles, face plants, land mines, and even a few threats of litigation and career retaliation along the way for the last three and half a years, I turned my crazy idea into a reality.”

Farrell continued,

“But it was only possible, (Knoepfler) added, with guidance from many patient advocates and bloggers in other fields who generously helped him learn the ropes of blogging.

“'I see this award as a validation of the notion that advocacy by scientists has become a valued part of the stem cell field,' he said.

“'My hope is to catalyze a continuing paradigm shift whereby stem cell scientists and biomedical scientists more generally have a new ethos that not just accepts, but also deeply values advocacy.'”

California Stem Cell Agency on Lacks: Informed Consent Cannot Remove All Questions

(Photo and caption from the stem cell agency blog item this morning.)

The $3 billion California stem cell agency today weighed in on the Henrietta Lacks-NIH arrangement restricting the use of her cell lines in research.

Writing on the agency's blog, Geoff Lomax, the agency's senior officer for its standards group, noted that the DNA sequence of her cell line was published without the knowledge of her descendants. Lomax said,

“The family was understandably upset by the lack of consultation and in response the research team removed the genome data from public access.”

Lomax continued,

“CIRM has benefited from these efforts. We are currently supporting an initiative to collect tissue samples from thousands of people with a range of incurable diseases and create reprogrammed iPS cells from those tissues (here's more about that initiative). These cells will be a resource for scientists worldwide working to understand and treat diseases. Part of this initiative includes a consent process to make sure people who donate fully understand how their cells will be used. (This process is formally called informed consent.) 

“The informed consent process includes a form that identifies the purposes of the research and describes the way cells will be used. We are also developing education materials that will help potential donors quickly and easily understand the basic aspects of research that will be conducted with those cells. The end result of this collaboration with our grantees will be a process that is truly informative to donors.

“The informed consent process can’t entirely eliminate all future questions on the part of the donor, but it does ensure that donors have a chance to understand how their cells will be used and what information will be made public—something Henrietta Lacks and her family never had.”  

Skloots, Collins and More on Henrietta Lacks' Cell Line Deal

More details about the unprecedented arrangement involving Henrietta Lacks' cell line emerged today in a wide range of publications, including a Nature journal piece that said it was not a precedent.

The article was co-authored by Francis Collins, head of the NIH, and Kathy Hudson, deputy director for science, outreach and policy at the NIH.

“It is important to note, however, that we are responding to an extraordinary situation here, not setting a precedent for research with previously stored, de-identified specimens. The approach we have developed through working with the Lacks family is unique because HeLa cells were taken and used without consent, and gave rise to the most widely used human cell line in the world, and because the family members are known by name to millions of people.”

The restrictions on use of the cell lines came about after a flap erupted about their recent use without the knowledge of her descendants. (The California Stem Cell Report carried a commentary on it yesterday.) Rebecca Skloots, author of the best-seller, “The Immortal Life of Henrietta Lacks,” wrote about the controversy in a March 23 op-ed piece in the New York Times. She said,

In the article, Skloots said,

“Imagine if someone secretly sent samples of your DNA to one of many companies that promise to tell you what your genes say about you. That report would list the good news (you’ll probably live to be 100) and the not-so-good news (you’ll most likely develop Alzheimer’s, bipolar disorder and maybe alcoholism). Now imagine they posted your genetic information online, with your name on it. Some people may not mind. But I assure you, many do: genetic information can be stigmatizing, and while it’s illegal for employers or health insurance providers to discriminate based on that information, this is not true for life insurance, disability coverage or long-term care.

“'That is private family information,” said Jeri Lacks-Whye, Lacks’s granddaughter. “It shouldn’t have been published without our consent.'”

Nature also carried a Q&A with Collins in which he said,

“This has wrapped in it science, scientific history, ethical concerns, the bringing together of people of very different cultures, a family with all the complications that families have.”

In the Wall Street Journal this morning, Ron Winslow described the arrangement with the NIH like this.

“Under the pact, two descendants of Ms. Lacks will serve on a six-member panel with scientists to review proposals from researchers seeking to sequence the DNA of cell lines derived from her tumor or to use DNA profiles of such cells in their research. That gives family members a highly unusual voice in who gets access to personal health information.

Terms call for controlled access to the genomic data and credit to the Lacks family in papers and scientific presentations based on the research done with the DNA data.”

In an interview in The Scientist, Skloots, who was involved in the Lacks-NIH negotiations, said the Lacks family asked for her participation.

“The only reason I was involved in this is because scientists did this without the family’s consent and then it got all of this press coverage, and no one asked the question, 'Did the family give consent?' So I sort of waded back in.”

She continued, 

“That OpEd that I wrote was the first time I’d ever publicly expressed an opinion, which was, 'Really?!? Are we going to continue to not ask the Lacks family questions?' I was kind of shocked in a sense that nobody thought to raise that issue.”

The Henrietta Lacks Story and Eggs, Money and Motherhood

The legacy of Henrietta Lacks popped up again today in a piece in the New York Times that should resonate among stem cell researchers and within the stem cell industry.

It even has a current hook involving California legislation to permit women to sell their eggs for the purposes of scientific research – a bill that is now on the desk of Gov. Jerry Brown.

The issues in the Lacks saga involve ownership of human cells, trafficking in them and informed consent, all of which surface in one form or another in the state legislation.

But first a refresher on Henrietta Lacks. She was an African-American woman who died in 1951 of cervical cancer at the age of 31. Shortly before her death, physicians removed some of her tumor cells, and, as recounted in today's NYTimes article by Carl Zimmer,

“They later discovered that the cells could thrive in a lab, a feat no human cells had achieved before.

"Soon the cells — nicknamed HeLa cells — were being shipped from Baltimore around the world. In the 62 years since — twice as long as Ms. Lacks’s own brief life — her cells have been the subject of more than 74,000 studies, many of which have yielded profound insights into cell biology, vaccines, in vitro fertilization and cancer.”

But Lacks never consented to her cells' being studied, a situation not uncommon at the time, nor did her family know about the situation until 1973. The complete story was chronicled in 2010 in a best-selling book, “The Immortal Life of Henrietta Lacks," by Rebecca Skloot.

Zimmer noted in today's article,

“For 62 years, (Lacks') family has been left out of the decision-making about that research. Now, over the past four months, the National Institutes of Health has come to an agreement with the Lacks family to grant them control over how Henrietta Lacks’s genome is used.”

The particulars involving her genome are in Zimmer's story. But the article implicitly raises anew questions that make many scientists uncomfortable. Often they contend that the situation involving Lacks could not occur today because of higher ethical standards. Standards ARE higher today. But problems continue to arise in the scientific community, including the sale a few years ago of willed body parts at UCLA for $1.5 million to private medical companies.

Development of products based on human stem cells promises even greater rewards, with billion-dollar blockbuster therapies not out of the range of possibilities. Profit and the desire to record a stunning research triumph are powerful motivators. They can lead to short cuts and dubious practices, such as seen in the Korean stem cell scandals of 2006.

So we come to whether women who donate their eggs for stem cell research can give truly informed consent when they surrender all rights to whatever products may result from parts of their bodies, as is common on such consent agreements. Or for that matter, what about the men who give up adult cells for reprogramming to a pluripotent state? Can they really understand the likelihood of a billion dollar product being generated with the help of their contribution? On the other hand, can the donors also truly understand that they are probably more likely to be struck by lightning than have their body parts result in a medical blockbuster?

These considerations may seem insignificant to some in science. But to grasp their full implications, one only has to read a few of the nearly 200 reader comments today on Zimmer's article today. Here is a sample.

From Frank Spencer-Molloy in Connecticut:

“(T)the Lacks family was robbed. Scores of companies profited to the tune of tens of millions of dollars from products they made derived from Henrietta Lacks' cancerous cells. Maybe this will provide some impetus to a wider consideration of the rights patients are entitled to when their tissues are cloned and disseminated to other researchers and ultimately put to use in profit-making ventures.”

From Robbie in New York City:

“At the very least, this family needs to be financially compensated for the anguish of their discovery and for the time and energy they've put into pursuing their rights. In my opinion, they also deserve a portion of any commercial gain that's been made using the HeLa cells. It is only through having to give away money that the powerful learn manners.”

From Julia Himmel in New York City:

“It is absolutely true that scientists have had a blind spot when it came to the human element of the HeLa cells.”

The pay-for-eggs legislation (AB926) now before Gov. Brown requires informed consent from those who provide eggs. Opponents of the measure, however, argue that truly informed consent from some women could be actually impossible because of economic pressures felt by the women. Writing in The Sacramento Bee last month, Diane Tober and Nancy Scheper-Hughes said,

“Allowing a market in eggs for research would reach beyond the current pool to target women who may be motivated by dire need. How many low-income women might consider selling their eggs, multiple times, to feed their children or pay the rent?”

Even the fertility industry group sponsoring the legislation acknowledges that informed consent can be problematic. A 2012 news release from the American Society for Reproductive Medicine said, 

“Prospective egg donors must assimilate a great deal of information in the informed consent process, yet it remains difficult to determine the extent of their actual understanding of egg donation and its potential risks.”

The story of the treatment of Henrietta Lacks and her descendants is a poor commentary on science and medicine. Yet it resonates with the public, which is keenly sensitive to scientific and medical abuses, even in situations that did not appear to be abuses at the time.

Stem cell research already is burdened by its own particular moral and religious baggage. With commercialization of new, pluripotent stem cell therapies coming ever closer, the last thing the field needs is contemporary version of the Lacks affair. It would behoove researchers and the stem cell industry to walk with more than normal care as they manipulate products that are tied inextricably to visions of both motherhood and money.  

Californians Top List of Stem Cell Honorees

Californians dominated the list of those to be honored at the World Stem Cell Summit coming up in San Diego this December.

They include fellow blogger Paul Knoepfler, a stem cell scientist at UC Davis, and Roman Reed, the San Francisco Bay Area stem cell activist and son of another stem cell advocate, Don Reed. Both are among the 2013 Stem Cell Action Award honorees for this year.

Others include Denny Sanford, a philanthropist whose name now adorns the Sanford-Burnham Institute in La Jolla, and Malin Burnham, who is also linked to the institute. Also being honored is Mary Ann Liebert, whose firm publishes peer-reviewed journals in science and biomedical research.

Malin is a San Diego businessman who joined with an anonymous donor in 1996 to contribute $10 million to the La Jolla Cancer Foundation. It was renamed to reflect that contribution. In 2010, Sanford pledged $50 million to the organization, and it was renamed again.

Memorial Services Friday for Duane Roth, Co-vice chairman of the California Stem Cell Agency

A memorial service for Duane Roth, co-vice chairman of the California stem cell agency, will be held Friday at 11 a.m. at Immaculata Church at the University of San Diego.

Roth died Saturday from injuries suffered in an accident last month while bicycling in the mountains east of San Diego. He was 63.

San Diego has seen an outpouring of tributes in the wake of Roth's death for his contributions to the community in the life sciences, philanthropic and technology areas. He had served on the stem cell agency board since 2006 and had been scheduled to become of chairman of the Sanford-Burnham Institute this fall. He was CEO of Connect, a non-profit organization aimed at support entrepreneurship in the technology field.

Ted Roth, Duane's brother, remembered him in a piece in the San Diego U-T as the oldest of five sons growing up in Wayland, Iowa. Ted Roth wrote that their parents relied on Duane "to set an example for his brothers, and he was the one they called upon in their later years. He was a lifelong mentor and friend to his brothers, someone that was always there to share in life’s experiences." 

Ted also wrote about his brother's involvement in technology and business.

 "Duane was captivated by the possibilities that innovation provides in improving the world in which we live." 

The family has suggested that in lieu of flowers that donations be made to the Otterson Fund at Connect, Challenged Athletes Foundation or the Copley-Price Family YMCA.

Here are links to some of the other recent articles on Roth: San Diego U-T (see here and here), La Jolla Patch, La Jolla Light.

CIRM's Roth Dies Following Bike Accident

Duane Roth, co-vice chairman of the California stem cell agency, died yesterday from brain injuries suffered in a bicycle accident two weeks ago.

Duane Roth, Connect photo

Roth, CEO of Connect, a San Diego organization aimed at fostering technology entrepreneurship, succumbed yesterday afternoon at the UC San Diego Medical Center, the San Diego U-T reported. He was 63.

An avid bicyclist, Roth was injured while biking in the mountains east of San Diego July 21. Roth hit an outcropping and his helmet was broken in the accident.

Roth was a long-time member of the 29-person governing board of the $3 billion California stem cell agency and was a strong advocate for industry. He chaired the agency's loan task force, was vice chair of the Intellectual Property and Industry Engagement Subcommittee and a member of the executive committee.

J.T. Thomas, chairman of the stem cell agency, released the following statement this morning.

“On behalf of all the CIRM family, we mourn the loss of our colleague and dear friend Duane Roth.  Throughout his tenure with us, he was one of the true stewards of the mission, offering countless insights on the role of industry in the world of regenerative medicine and how best and efficiently to drive therapies through to patients.  He was unfailingly a voice of reason and optimism and always sought to find ways to make things happen, refusing to take 'no' for an answer.  Though one of 29 Board members, his extensive participation as co-Vice Chair of the Board, co-chair of Intellectual Property and Industry Engagement Subcommittee and a member of our Executive Committee gave Duane a singularly important and resonant voice in our organization.  His passing will be deeply felt by all of us as well as by the many patients and other CIRM stakeholders whom he touched over the years.  We send our deepest sympathies to Renee, Duane's brothers and the rest of the Roth family.”

Roth recently was involved in raising funds for cancer, and reporter Bradley Fikes wrote in the San Diego U-T,

“Contributions in Roth’s name can be made to Pedal the Cause, a fund-raiser for cancer research that Roth supported. More than $10,000 has been raised since Roth's accident."

Pay-for-Eggs Legislation: A Comment on Risk

The author of the Forbes piece cited in the eggs legislation item today has responded to a comment filed by two persons opposed to the measure that would remove the ban in California on paying women for their eggs for scientific research.

Here is the text filed by Jon Entine, executive director of the Genetic Literacy Project.

“Diane and Nancy, I'm shocked that you are either unaware or do not acknowledge that there are studies of oocyte retrieval surgeries that show very persuasively that the potential harm from this procedure is manageable. While you refer to 'stories' of women being harmed--that's called anecdotal evidence and is the antithesis of science--you ignore the established research in this area, which makes it clear that you are reacting hysterically rather than responding to empirical evidence. I would suggest that you read the National Academies Press workshop report: Assessing the Medical Risks of Human Oocyte Donation for Stem Cell Research (http://www.nap.edu/catalog.php?record_id=11832). It cites numerous studies, including a German study that examined the outcome of approximately 380,000 oocyte retrieval surgeries during 2000-2004. For the procedures for which there was information, the rate of complications was very low: only 0.002 percent—2 in every 100,000—had complications that required surgery to correct.

“Studies have also examined the potential risks of retrieval for a woman's future fertility.
“According to one large study, the rate of infection after oocyte retrieval was about 1 in every 200 IVF cycles, and surgery is needed to treat pelvic abscesses in less than 1 in 1,000 IVF cycles. 

“About five hundred egg donations take place in Canada each year, according to the Canadian Fertility and Andrology Society.The CFAS told me that, between 2001 and 2010, only two donors in Canada, out of a total of 4,177 donations, suffered from “severe” OHSS, which usually involves hospitalization. Fourteen others had “moderate” OHSS. These numbers are collected in a database called the Canadian Assisted Reproductive Technologies Registry.

“So sure, you can find your 'stories' but they do not represent a scientific review of the available data--you are trying to legislate based on fear. That's not science; that's the dark ages, and it's exactly the tactics used by anti-abortionists (and indeed by organizations like the Center for Genetics and Society which opposes such beneficial advances as mitochondrial replacement surgery).

“Furthermore, because women have a set of two ovaries and two fallopian tubes, they can remain fertile even if one set is damaged, and there is no evidence that both might be threatened simultaneously by the side effects of retrieval surgery. 

“Today doctors have had two decades of experience with the use of hormone treatments to maximize the number of eggs that can be harvested from a woman, and they have become quite proficient in the production of oocytes. During that time they have also worked to improve the safety of the procedure and decrease the potential risks. Despite these improvements some risk will remain, because hormones have a powerful effect on the body—they could not increase egg production so dramatically if this were not true—and anything with a powerful effect on the body has the potential for harmful side effects as well. 

“Egg donations are done for a reason. There are risks and benefits. For you to exaggerate the risks based on 'stories' and ignore the evidence is unconscionable. It's exactly what anti-abortion groups do and what opponents of genetically modified foods do--you promote fear around manageable (or in the case of GMOs, negligible) risk. 

“Your call for 'further studies' is the age old technique of reactionaries trying to control other people and impose their values on other people. You know darned well, because of your fundamental ideological opposition to this procedure, no study results could ever meet your standard of acceptability. 

“You are trying to control other women's bodies, claiming you have superior knowledge and wisdom--those are pro-life talking points. Your views, and that of the organizations that you represent, are illiberal.”

Comment re Pay-for-Eggs Item and Forbes Article

One of the authors of an op-ed piece in The Sacramento Bee has filed a comment in connection with an item today on the California Stem Cell Report. The item dealt with the California pay-for-eggs bill, which was also the subject of an op-ed piece in The Sacramento Bee as well as an article yesterday on the Forbes magazine website that discussed the op-ed piece critically.

A quotation from the article was contained in this item earlier today.

Here is the text of the comment from Nancy Scheper-Hughes, a professor of anthropology at UC Berkeley and director of Organs Watch.  Diane Tober, associate executive director of the Center for Genetics and Society of Berkeley, was the other author.

“Dr. Diane Tober and Prof. Nancy Scheper-Hughes  are 'pro choice'  social scientists who are concerned about the absence of any evidence-based medicine on the long term effects of hyper-stimulation for oocyte (egg) production in young women research subjects. We are not concerned about abortion, right to life, or obstructing  needed and valuable research on stem cells. We are concerned about the safety for potential research subjects who are being actively recruited to participate in  invasive medical procedures without any medical research studies on the possible risks and consequences of egg multiplication and extraction. We are on record that we  fully support stem cell research but not at the expense of unprotected egg donors.”  

Pay-for-Eggs Legislation Now Before California Gov. Jerry Brown

California's pay-for-eggs bill is now officially on Gov. Jerry Brown's desk, awaiting his signature or veto.

The measure, AB926 by Assemblywoman Susan Bonilla, D-Concord, was sent to the governor at 4:45 p.m. PDT yesterday. On July 1, it easily won legislative approval and has been held in legislative processing since then. The governor has 12 days to act on the measure or it becomes law without his signature.

The legislation would remove the state ban on payment to women for their eggs for scientific purposes. Currently women who provide their eggs for fertility purposes can be compensated. Fees run as high as $50,000 in some cases, depending on the characteristics of the woman providing the eggs, but generally are in the $10,000 range or less. The bill does not affect the ban on the use of funds from the California stem cell agency to compensate egg providers.

Bonilla's bill is sponsored by the $5 billion-a-year fertility industry, which is backing it on motherhood and sexual equity grounds. Supporters say women should receive payment for their eggs just as men are paid for their sperm. They also argue that more eggs are needed for research into fertility problems. In the stem cell field, scientists have also said it is nearly impossible to find women who will provide eggs unless they are paid.

Opponents contend that the process of stimulating production of eggs can be risky or dangerous. They say that the longterm effects of the process have not been studied well. They also argue that it will lead to exploitation of low income and minority women to produce eggs that then can become a profitable commodity for the largely unregulated fertility industry. (For more informationon on the bill, see here, here and here.)

In one op-ed piece in The Sacramento Bee, opponents cited the late philosopher Ivan Illich, who was much admired by Jerry Brown, who considered him a friend. Illich was quoted as warning "against the processes of medical industries which 'create new needs and control their satisfaction and turn human beings and their creativity into objects.'"

The industry group says, however, that Brown is committed to signing the bill.

The measure surfaced in the news yesterday in an article on the Forbes magazine website by Jon Entine. He wrote,

“Should activist groups, working through legislators, exercise their control over women’s reproduction? Do we really 'own' our own bodies? Or does that tenet only hold when nanny groups say it’s okay?”

(One of the authors of The Sacramento Bee op-ed piece criticized in the Forbes article later filed a comment concerning their position.)

The egg legislation may have implications for regulation of stem cell research by the state Department of Public Health(again not involving the California stem cell agency). Last month the California Stem Cell Report asked Hank Greely, a Stanford law professor and chair of the state department's Human Stem Cell Research Advisory Committee, about the measure. He replied,

“Well, if (when?) AB 926 is signed, I think our committee should meet to consider what recommendations we would make to the (the department) as a result of the bill.  Those recommendations could lead, if the committee and the department agree, to a revision of the state guidelines.  As a matter of law, a statute, particularly a subsequent statute, trumps a guideline where they are in conflict, but basically I expect we'll see what the committee thinks and what the department decides.  I don't wish to guess at the results of either process.”

Another question that was not discussed publicly during the debate on the legislation deals with whether human eggs provided with compensation would be subject to state sales tax at any stage in the process. A check of the tax code, however, makes it clear that eggs are tax free. The code states that “any human body parts held in a bank for medical purposes, shall be exempt from taxation for any purpose." The definition of “bank” includes research facilities, and "medical purposes" includes research.

CIRM's Roth Remains Hospitalized

Duane Roth, a co-vice chairman of the $3 billion California stem cell agency, is displaying no apparent brain damage following a bicycle accident 11 days ago in the mountains east of San Diego.

Bruce Bigelow of Xconomy reported this morning,

“MRI diagnostic imaging showed no apparent brain damage, but he remains sedated, according to his brother, Ted Roth. While doctors see nothing that would prevent Duane Roth from a good recovery, told me by phone yesterday his caregivers are moving slowly to give him time to heal.”

Roth is also CEO of Connect in San Diego, a technology industry assistance organization.

Skimpy Coverage of Alpha Clinic Concept Approval

News coverage of approval of the California stem cell agency's ambitious, $70 million Alpha clinic plan has been quite light but does include one article in the Los Angeles Times, the state's largest circulation newspaper.

The concept proposal was ratified last week by the agency's board with RFAs scheduled to be posted in October. The agency is seeking to build a basis for a robust stem cell clinic business in California that would have an international reach and give the state dominance in the industry.

Karen Kaplan's story in the Times last week quoted CIRM President Alan Trounson as saying in 2010 about agency's goals.

“If we went 10 years and had no clinical treatments, it would be a failure. We need to demonstrate that we are starting a whole new medical revolution.”

The stem cell agency was created by voters in 2004 and funded with $3 billion in borrowed money. It will run out of funds for new grants in 2017.

Outsourcing-Pharma.com caught up with the plan this week in a story that said,

“The opportunity to run trails under the well-funded CIRM could be a boon for CROs (contract research organizations)....But the difficulties of handling the stem cells and gathering enough patients to enroll in a trial may prove daunting for whatever company tries to conduct the trials.”

The article also quoted CIRM spokesman Kevin McCormack as saying,

 “No one has reached out to us yet because the specific details of what we are looking for in the clinics have not yet been decided.”

That said, considerable information is available here, here, here, here and here.)

Also reporting on board approval of the Alpha clinic plan was GenNews.