Tuesday, November 25, 2014

Bubble Babies, Cures and California's Stem Cell Agency

Alysia Padilla-Vacarro and daughter, Evangelina, on the day
 of the baby's life-saving gene therapy treatment at UCLA.
UCLA photo
Numbers speak loudly in America. We focus intently – sometimes obsessively -- on everything from baseball statistics to the latest count of illegal immigrants. Numbers appear to create certainty and tend to drive discussion of public issues.

Which is where the California stem cell agency comes in.  Executives at the agency point with pride to the 10 clinical trials that it has helped to fund. They do not point to the zero number of therapies that the agency has placed in the public marketplace despite the apparent promises of the ballot campaign that created the research effort 10 years ago this month.

Nonetheless, agency has chalked up some indirect scores that are difficult to quantify but deserve ample consideration when evaluating the California Institute for Regenerative Medicine(CIRM), as the agency is formally known.

One dramatic example gained national media attention last week. The case involves work at UCLA for what appears to be a cure for the fatal “bubble boy” syndrome. The term was coined back in the 1970s when stories involving a youngster in Texas made headlines across the country.  The child had to live inside a plastic bubble because his immune system was compromised. The case even inspired a 1976 movie called “The Boy in the Plastic Bubble” starring John Travolta. (See here, here and here.)

Enter Donald Kohn, many years later.  Kohn is director of the Human Gene Medicine program at UCLA. And last week, the Los Angeles university announced that Kohn and his team have developed a treatment that cures the “bubble boy” syndrome by altering the genes of the afflicted children.  In clinical trials, the UCLA announcement said, the lives of 18 children were saved.

Kohn used a virus delivery system that he first developed in his lab in the 1990s. But the work on the gene treatment began in earnest in 2009 and involved two, multi-year clinical trials.

UCLA's Nov. 18 news release described the treatment simply like this:
“During the trials, the patient's blood stem cells were removed from their bone marrow and genetically modified to correct the defect.”
The stem cell agency did not directly fund Kohn’s “bubble” research, but some of its other funding at UCLA contributed to the effort. Specifically, the work was performed in the stem cell research facility that CIRM helped to finance. Kohn’s lab is in the “shared research lab” space funded by CIRM in still another program. The research was also aided by persons working in two other separate CIRM training programs.

The next step for Kohn will be to use the research in proposed clinical trials involving sickle cell anemia, which are being financed by CIRM to the tune of $13.1 million. They will also be part of the agency’s Alpha clinic program.

Steve Peckman, associate director of the UCLA stem cell center, said the Kohn research “is a perfect example of how CIRM support at all levels is critical to achieve the goal of driving scientific discoveries to the clinic.”

Kohn’s work was cited last week at a Los Angeles media event celebrating CIRM’s 10th birthday. Maria Shriver, the former first lady of California and whose father died of Alzheimer’s Disease, wrote about the research and linked it glowingly to the stem cell agency in an item on the Huffington Post on Nov. 20.  She said,
“The news about 'bubble baby' disease is just the start. I am convinced that stem cell research means we Baby Boomers will be the last generation to have to watch our parents die of Alzheimer's or watch our children die prematurely of sickle cell disease. Proposition 71 (which created the stem cell agency) set this research in motion. Now we have to make sure this research keeps moving forward.” 
While CIRM deserves credit for its role in Kohn’s work, it is only one of 10 entities cited by UCLA as contributing but without providing figures.  Accurately quantifying CIRM’s contribution is difficult if not impossible. That said, it was significant. The agency’s programs do ripple out – not only at UCLA but globally.  They add to the bank of knowledge about stem cells, all of which creates an easier path to the ultimate development of new therapies.
Ironically, one of the CIRM programs -- the "shared labs" -- that helped Kohn has expired despite pleas by some of the state’s top stem cell scientists. News about that program surfaced again a few days after the Kohn announcement. Without mentioning Kohn, Jeanne Loring, head of the stem cell program at Scripps, discussed the importance of the "shared labs" in a piece on the blog of UC Davis stem cell researcher Paul Knoepfler.

Loring said the program has had “an enormous impact beyond (its) original intention.” 
In her “open letter to CIRM,” she said,
“Unwittingly, CIRM’s shared lab program jump-started human stem cell research in California, sending it on a trajectory that has led to stem cell clinical trials in just 6 years….CIRM did not expect that there would be interaction among the labs that would make the whole greater than the sum of the parts. The network of shared labs became our means to communicate and share ideas. It sparked new partnerships between institutions throughout the state, and became a conduit for trainees to move from CIRM’s Bridges internships to graduate school. One scientist described the shared labs as ‘the beating heart of California’s stem cell program.’”
She noted that the program was discussed by the CIRM governing board in December 2013 at a time when the directors were being told that the money for new grants would run out in 2017. Today, however, Randy Mills, the new CIRM president, has reexamined the financial assumptions and says the money will be around until 2020.

Loring and 11 other researchers are asking the CIRM governing board at its December board meeting to provide the go-ahead for applications for another round of funding for what they say is the key maintaining the rapid pace of stem cell research in California.

Anything less, they say, would impede the development of stem cell treatments and waste a good portion of the $20 million already spent on the “shared labs” effort.

Perhaps Donald Kohn would agree as well. 

Here is a two-minute CIRM video of Kohn explaining his work.

Friday, November 21, 2014


The "birthday party" item Nov. 20, 2014, incorrectly stated that Anne Holden wrote CIRM blog piece on the "bubble boy" researchat UCLA. It was actually Todd Dubnicoff who wrote the article on the agency's blog, The Stem Cellar.

Thursday, November 20, 2014

Birthday Party for California's 10-year-old Stem Cell Research Program

Fred Lesikar, a heart attack victim aided by
a CIRM-backed cell treatment
CIRM photo
The California stem cell agency today celebrated its 10th birthday with a media event in Los Angeles where its supporters declared that the effort marked “one of the seminal events in the history of medical research.”

Attending the party in Los Angeles were a number of scientists and university officials whose institutions and research have received hundreds of millions of dollars from the program, which is funded by money that the state borrows(bonds).

California voters created the program in 2004 when they approved a ballot initiative that established the California Institute for Regenerative Medicine(CIRM), as the San Francisco-based agency is formally known.

CIRM has awarded $1.8 billion so far out of its $3 billion allotment. Because the money is borrowed, the effort will cost taxpayers about $6 billion, including interest. The agency is controlled by a 29-member board of directors. Eighty-eight percent of the $1.8 billion in awards has gone to institutions linked to current or past directors, according to calculations by the California Stem Cell Report. (For a recent assessment of the agency, see here.)

CIRM Chairman Jonathan Thomas told the gathering at USC, which has received $88.5 million in funding, that the state research effort amounted to a “seminal event.” California began its program when stem cell research was at a low ebb, Thomas said. He said it helped to keep stem cell research alive and  “galvanized” efforts globally.

He and others celebrated the 10 early stage clinical trials that CIRM now expects to be part of this year. None of the speakers mentioned studies that show that only one out 10 potential conventional treatments that enter clinical trials emerges as a therapy that is widely available to the public. The odds for stem cell therapies are unknown because they are so new.

Thomas and others pointed to news this week from UCLA about a genetic treatment that they said saved the lives of 18 children who had an immune deficiency affliction called the “bubble boy syndrome.” The cure involved insertion of a missing gene into the child’s blood stem cells. The work by researcher Donald Kohn received national attention. Oddly, however, the Los Angeles Times has not written about the research, according to a Google search this afternoon. CIRM's Todd Dubnicoff wrote a very nice piece about the research earlier this week.

The stem cell agency did not directly fund the “bubble boy” experiment, although CIRM awards, ranging from training programs to lab construction, did help to make the effort a reality.  The research is expected to be used in devising a sickle cell treatment in a $13 million CIRM program involving Kohn. 

The man sometimes referred to as the father of the California stem cell effort, Robert Klein, was also on hand today.  Klein led the $35 million ballot campaign in 2004 to win approval for creation of CIRM, which functions outside of the normal controls on nearly all state departments. Klein, a Palo Alto real estate investment banker, was also the first chairman of the agency. 

Klein said that a “revolution is underway” in medicine and that CIRM is leading the way. The dream of patients has become a reality, Klein said.

Only one patient appeared along with researchers, Fred Lesikar, a heart attack patient who was treated with his own heart cells at Cedars-Sinai in Los Angeles a few years ago.

Lesikar told the audience that “little by little over the next six months to a year, they (the cells) went in and started replacing the dead tissue.” He said he is now feeling great.

The researcher involved in that treatment, Eduardo Marban, has moved forward with a trial that CIRM is helping to fund through Capricor, Inc., a publicly traded  Beverly Hills firm.

On the podium today were researchers or officials from USC, UCLA, Cedars-Sinai and the City of Hope. All have representatives on the agency’s board. A researcher from ViaCyte, Inc., of San Diego, another CIRM award recipient, also spoke.

Today’s media event, which was available by a telephonic link, represents a major push to generate favorable coverage of the California stem cell program. It was held early enough in the day to meet deadlines for the early TV news shows along with allowing enough time for preparation of fulsome stories. However, Los Angeles is a tough news market. We will be watching later today and tomorrow for coverage of the event and bring you additional information as warranted.

(An earlier version of this item incorrectly said that Anne Holden wrote the CIRM blog item on Kohn's work.)

Wednesday, November 19, 2014


The 10th anniversary media event item today incorrectly said that the news conference will be at UCLA. It will be at USC.

10th Anniversary Media Event Tomorrow in Los Angeles for California Stem Cell Agency

The $3 billion California stem cell agency will celebrate its 10th anniversary with a media event tomorrow in Los Angeles aimed at demonstrating the impact of the Golden State’s research program.

The news conference is scheduled for 11 a.m. PST, and members of the public can listen in by dialing 866-528-2256 with a participant code of 1594399. The event will be at the Broad stem cell center at USC.

A note on the agency’s blog, The Stem Cellar, said,
“(The) money has helped make California a global leader in stem cell research and led to ten clinical trials that the stem cell agency is funding this year alone. Those include trials in heart disease, cancer, leukemia, diabetes, blindness, HIV/AIDS and sickle cell disease.”
The item continued,
“To hear how that work has had an impact on the lives of patients we are holding a media briefing to look at the tremendous progress that has been made, and to hear what the future holds.”
The Los Angeles media market is a tough one. It is also the state's largest. Great competition exists for coverage of events.  Kevin McCormack, the agency’s communications director, is promising to have patients on hand who have benefited from stem cell therapies along with researchers and key figures in the state stem cell effort.

The California Stem Cell Report last Sunday carried a 10th anniversary rundown on the agency.

(An earlier version of this item incorrectly said that the event will be at UCLA. The news conference will be at USC.)

Tuesday, November 18, 2014

A Look at Spinal Cord Injury Treatments from California's Stem Cell Agency

The California stem cell agency today took to the Internet to conduct a nearly hour-long video briefing concerning the state of stem cell treatments for spinal cord injury.

The Google Hangout event featured Jane Lebkowski, president of research and development for Asterias Biotherapeutics of Menlo Park, Ca., which is involved in an early stage clinical trial for a human embryonic stem cell therapy.

The firm is backed by $14.3 million from the stem cell agency. Asterias is carrying forward the Geron spinal cord trial, which that company abandoned for financial reasons. Asterias expects to enroll more patients next year.

She and Kevin Whittlesey, a science officer with the state agency, discussed the multiple stem cell approaches involving spinal injuries that have surfaced since Geron began the first trial with human embryonic stem cells in 2010.

Lebkowski said that first stage of her firm’s trials demonstrated the initial safety of the treatment. She also said it showed some evidence of “preferential restoration” and “prevention of further deterioration.” The patients involved were treated less than a month after their injuries.

Whittlesey gave an overview of other research around the country. He commented on a case in Poland in which one paralyzed man is reportedly now walking with the help of a walker following treatment with cells from his nasal cavity. The cells were extracted by going in through his skull.

Whittlesey said that it is “hard to draw any conclusions from this one patient.” He said the man “enjoyed significant benefit.” However, he said that it is not possible to attribute the benefits entirely to the cell treatment because the experiment was not scientifically controlled.

California’s stem cell agency has put together a healthy portfolio of Webinars, You Tube videos and Google Hangouts involving a wide range of issues. It is all part of its effort to inform the public and spread good news about its $3 billion program.

However, today’s effort demonstrated the difficulty in drawing an audience. Spinal cord injuries affect as many as an estimated 332,000 persons in this country.  Despite promotion online, in the social media and notices in some publications, only 39 persons checked in for today’s Hang Out.

Kevin McCormack, who hosted the event and who is the director of communications for the agency, said that it is pretty much the pattern for these sort of events. The payoff, he said, is the 1,000 or more viewers that are picked up as people go to You Tube to view the video event.   We might add that the information is current, authoritative and useful, although at times a tad technical for non-scientists.

Sunday, November 16, 2014

California's Grand, $3 Billion Stem Cell Experiment: An Evaluation at Age 10

The $3 billion California stem cell agency turns 10 this month, an anniversary that naturally raises the question of what has it done for the first decade of its life.

Today The Sacramento Bee published an anniversary overview of the agency written by the publisher of this blog, David Jensen.  However, as is the nature of the print media, space was at a premium. So the article was limited in what it could cover. Newsprint costs money. Many stories and many topics are competing for space – not unlike the battle for state budget dollars or research funding.

In preparing the article, I asked for comments by email from a number of persons, including some directors of the agency and its executives, and its first president, Zach Hall, and promised to carry the full text of their comments on this Web site. I knew that most of what they had to say would wind up on the cutting room floor and not in the printed piece.  

But for those who follow the agency and its fortunes, what they have to say is important. It is also important for those who may want to tell the tale of California’s Great Stem Cell Experiment some 10, 20 or more years down the road. 

All those who responded to my inquiries were told that the article for The Bee was expected to address generally the questions of whether the agency’s efforts would be worth the $6 billion total cost, including interest, and whether it has fulfilled voter expectations from 2004, when the agency was created. They were also asked about their views on the agency’s achievements and shortcomings and advised to speak freely about any other issues as well.  I would like to thank them all for responding. Their comments contribute significantly to current and future evaluations of this important enterprise.

The agency responded to my request for fresh, pithy quotes from Chairman Jonathan Thomas and President Randy Mills, along with statistics many of which were submitted to The Bee for possible use in an infographic.  

With that said, separate items follow with their statements and more on the topic of the standing of the California Institute for Regenerative Medicine at age 10.  (By the way, the traditional gift for a 10th anniversary is something tin. A romance novel writer working for Hallmark, Stacey Donovan, suggests as a gift “an old-fashioned metal lunch box to take to work.”)

Ten Year Performance of Stem Cell Agency: Top Execs' Comments

Here is the text of what Jonathan Thomas, chairman of the California stem cell agency, and Randy Mills, president of the agency, had to say about its performance over the last 10 years.

Their remarks came after the agency was asked for comments from them for an article that appeared in The Sacramento Bee Nov. 16, 2014. The piece was written by David Jensen, publisher of this blog.   

The agency was told that it was likely that their comments would be severely limited in the piece in The Bee because of the space limitations of the print media. They and others queried were also told that the full text of their comments would be carried on this Web site.

Here are the comments from Jonathan Thomas: 
"In just a few short years we have helped accelerate the pace of research in California so that we are now funding ten projects that have moved out of the lab and into clinical trials in patients. These include trials in heart disease and diabetes, cancer and blindness, HIV/AIDS and sickle cell disease. By any standards this is a remarkable achievement. But this is really only the start. We have a pipeline of other truly promising therapies that we hope to  move into clinical trials in people in the next few years." 
 "We are a long way from running out of money. We have almost one billion dollars left to award to researchers. At our current rate of spending we'll be able to continue funding new projects until 2020, and we are already working on developing new sources of income to help us keep funding the most promising projects long after that. Without us, without our support, many of the most promising stem cell research projects in California could come to a stop. Those projects are far too important to the millions of people suffering from a wide range of deadly diseases and disorders. We don't intend to let that happen.”
"In ten years and more than 660 grants there have only been a handful of cases where there have been concerns about a conflict of interest and those were all acted upon quickly to remove even the perception of any conflict. The changes we made in response to the IOM report further strengthened the integrity of our process and demonstrated just how seriously we take these matters."  
Here is the comment from Randy Mills: 
"Everything we do centers around the patients, about developing successful therapies for people in need. Our first ten years laid the groundwork and now we are making changes to speed up the way we work, to make it easier for the most promising projects to get the funds they need when they need them, to accelerate the development of effective therapies and to do everything possible to ensure that we live up to the faith the people of California showed in us when they created the stem cell agency.”

The California Stem Cell Agency Numbers

​For today’s 10-year anniversary piece in The Sacramento Bee on the California stem cell agency, the agency was asked for statistics and numbers that would be useful in illustrating what it believes is the progress of the program.

The freelance article was written by David Jensen, publisher of this blog. Given the space limitations of the print media, the California Stem Cell Report is carrying all of the information provided by the agency.

Kevin McCormack, senior director for communications, supplied the following, which has been edited slightly for clarity.  

“One (graphic) is a pie chart that breaks down all the different disease areas where we are funding research at the most advanced levels, the pre-clinical (or translational as the graphic calls it) and the
clinical trial level (shown at right).  As you can see this covers 80 different programs and involves $627 million in funding. Obviously a lot of other money goes to fund other projects such as basic research, developing tools and technologies, etc., but I think this is a graphic that people will be interested in because it highlights the areas where we are closest to developing treatments for patients.

“For other numbers here are some that might be useful: 
“More than 1,750 published discoveries
“Trained more than 1,500 students for future careers in stem cell research
“Lured more than 130 senior scientists, and their teams, to California
“Research facilities helped leverage $543 million for the state 
“Generated more than $280 million in new tax revenues by the end of this year
“Generated more than 38,000 job years by end of 2014

“The second item is our Ten @ Ten list (10 clinical trial investments after 10 years) which shows the ten clinical trials we're funding right now. It's actually a little (off) because we have only been funding research for seven years – it took a couple of years after Prop. 71 was passed for us to get through the legal challenges and set up the infrastructure for the agency, etc., before we began funding – but Ten @ Ten has a much nicer ring to it. 

“HIV, Calimmune 
“Heart disease, Capricor 
“Solid Tumors, UCLA 
“Leukemia, UCSD 
“Sickle Cell Anemia, UCLA
“Solid Tumors, Stanford
“Diabetes, Viacyte
“Spinal Cord Injury, Asterias
“HIV, City of Hope
“Blindness AMD, USC

“We also funded research that led to six other clinical trials and you can find out information about them here: 

“In terms of money there are probably a few things to mention, and as always it gets a little complicated. So far the Board has awarded $1.9 billion in funding but only $1.4 billion has actually been spent. When you talk about our accomplishments to date, as I am sure you will, the $1.4B is the most accurate number to use because it reflects what has gone out the door and been used for research. 

“We also estimate that we'll be able to recover around $100 million of the money that has been awarded through cost savings on projects and on projects that have been cancelled because they failed to meet their milestones. So, if you add that to the $843 million that we still have left to award that means the Board has close to $1 billion left on hand for funding. And that means that, at our current rate of spending, we'll be able to continue funding new projects until 2020, and because those are multi-year awards we'll be continuing to supervise that funding for several more years after that date.”

Comments From the First President of the California Stem Cell Agency

The following is the text of what Zach Hall, the first president of the California stem cell agency and who served from 2005 to 2007, had to say about its performance over the last decade.

Hall, who is retired and currently on the board of the New York Stem Cell Foundation, developed the California agency’s strategic plan that largely remained in place until the last couple of years. He commented for a freelance piece written by David Jensen, the publisher of this blog. The article appeared in the Nov. 16, 2014, edition of The Sacramento Bee.

Hall and others queried were told that it was likely that their comments would be limited in the piece in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site.

Zach Hall
NY Stem Cell photo
They were told that the print article would address such questions as whether the work of the agency would be worth its $6 billion cost(including interest), whether it had fulfilled the expectations of voters in 2004 along with discussing the achievements and shortcomings of the agency.

Here is what Hall, former director of the National Institute of Neurological Disorders and Stroke, said via email. 
“CIRM: 10 years after
 “From a scientific standpoint, there is no doubt that CIRM has been an unqualified success. The passage of Proposition 71 in California not only provided much-needed funds for research and training, but gave stem cell scientists around the world a huge psychological boost in a dark time when NIH funds for stem cell research were severely restricted. The funds in California attracted new scientists to the field and supported the training of a new generation of stem cell scientists.  The result has been the establishment of a number of major centers of stem cell research in California and a steady stream of significant results in basic and applied research, some of which now underlie current efforts to develop therapies.  In contrast to some state efforts, CIRM can be proud that it has spent public money in this area wisely and with integrity.  
“CIRM has also clearly played an important role in promoting and encouraging pre-clinical and clinical therapeutic development, breaking new ground in developing ways for government and the private sector to work together. Because this road has been less-travelled, these efforts have been more difficult and CIRM’s ultimate success in promoting therapeutic development remains to be determined.  Nevertheless, CIRM’s attention to this difficult problem is of major significance, since CIRM has been one of the few government entities to try to address the problem in new and creative ways. 
“Are new stem cell therapies available?  The thought that therapies might be developed over the 10 year life-span of CIRM was always more a hope than a realistic outcome, but there is now reasonable expectation, partly because of CIRM, that cell-replacement therapy may be effective for a number of major diseases.  Will the investment of $6 B pay off in terms of economic development?  This question probably will not be answered for another ten years.  Could things have been done differently or better? Undoubtedly.  With such a huge (some would say excessive) budget, not all the money was spent wisely. In addition, the agency was burdened with a cumbersome and conflicted governance structure whose difficulties consumed far too much of the agency’s time and energy.   
“In sum, CIRM is a bold, new initiative that has given new life in California to a field of biomedical research that looks ever more promising for curing disease and saving lives. The visionary investment by California in this burgeoning field will likely pay dividends for decades to come.”    

CIRM Board Member Sheehy on Stem Cell Agency Performance

The following is the text of what Jeff Sheehy, a 10-year veteran of the governing board of the California stem cell agency, had to say about its performance over the last decade.

He commented for a piece written by David Jensen, the publisher of this blog, that appeared in today's edition of The Sacramento Bee. Sheehy and other board members queried were told that it was likely that their comments would be severely limited in the article in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site.

Those queried were given generally free rein but were told that the print article would address such questions as the achievements and shortcomings of the agency along with whether its work would be worth its $6 billion cost(including interest) and whether it had fulfilled the expectations of voters in 2004.

Jeff Sheehy
CIRM photo
Here is what Sheehy, a UC San Francisco communications manager and patient advocate member of
the board, said via email.
“It’s really too early to assess your first question, I believe.  It is ten years since Proposition 71 was passed, but it’s just over seven years since the litigation that blocked access to the bond funding was decided (May 2007).  We did start issuing grants in 2006 with some funds via bond anticipation notes and the Governor did provide $100 million. (I am extremely grateful to those who purchased the BANS and to Governor Schwarzenegger). But, we were obviously slowed down in the beginning by the lawsuit and we could not implement the full program envisioned in our initial strategic plan until we had access to the bond funding.  If one wants to look at our progress at a ten-year mark, I think 2017 or 2018 is a fairer date. And I would note that CIRM funded projects are being approved for clinical trials at an accelerating pace and we should have at least some initial results by then.

“As for your second question, I am certain that the investment in the California Institute of Regenerative Medicine is a wise one that has benefitted and will continue to benefit the state significantly.  CIRM has led the way in creating in California an impressive research infrastructure in regenerative medicine, a critical, cutting edge biomedical research approach that will lead to cures in several diseases and conditions.   In a period that included the Great Recession, facilities construction funded by CIRM alleviated some of its impact.  In addition, with NIH funding flat, CIRM keeps California researchers working and has brought numerous top and emerging researchers to California.  CIRM funding has helped the San Francisco Bay Area and San Diego sustain their rating as two of the three top biotech clusters in the country.

“And the importance of biotech and healthcare to California should not be underestimated.  In San Francisco, one in four jobs are healthcare related.  The emergence of biotechnology as a driver of the California economy will offer Californians early access to the latest therapies along with the wealth created from developing these therapies. Plus, biotech development and clinical delivery in the regenerative medicine space will be relatively labor intensive and will provide numerous well paying, highly skilled jobs.  These are jobs that will be resistant to outsourcing.

“Ultimately the core value of the investment will be the CIRM funded cures and therapies that improve the health and lives of Californians.”
 After sending the above, Sheehy added the following later:   “I had one other thought, and couldn't figure out how to blend it in.  I wonder if those working on legalizing marijuana would consider deriving revenue (i.e. taxes) and dedicating enough of that revenue to keep CIRM funded.
 “I think that legalizing marijuana has been advanced by the success of Prop. 216 and the medical marijuana movement.  I know Dennis Peron, campaigned with him in 1996, protested with him when (then state Attorney General Dan) Lundgren shut down his dispensary, and observed the benefits of marijuana for people with HIV/AIDS.  The Harvey Milk LGBT Democratic Club held its meetings at the dispensary when it re-opened (I was the club's president then).
 “So from my standpoint, marijuana is now associated with relieving human suffering due to disease and other health conditions.  And, funding research towards cures out of revenue derived from legalization seems sensible.”

Former California Stem Cell Board Member Shestack Comments on the Agency's Record

Jonathan Shestack, a former member of the board of the California stem cell agency, was interviewed by telephone during the reporting for the 10th anniversary article today on the California stem cell agency.

Jonathan Shestack (left) and CIRM Chairman J.T. Thomas
at 2012 board meeting. CSCR photo
Shestack served on the board from 2004 until 2013. A Hollywood producer, he has been a longtime patient advocate for autism. He and his wife co-founded Cure Autism Now in 1995. Here is a link to Shestack's resignation letter from the board.

The 10th anniversary article was written by David Jensen, the publisher of this blog, and appeared in The Sacramento Bee.

Here is a summary of Shestack’s comments, which were trimmed from print article for space reasons.

He said, “CIRM has funded an amazing amount of great projects. It does an amazing amount of good.” He said, however, it should be “more bold going forward.”

Shestack was critical of the senior staff at the agency. He said they did “not like to do what the board wants.” He said, “The staff made a monkey out of the (10) patient advocates (on the board) for eight years.” There was no mechanism by which the board could pressure the staff on “programmatic” issues, he said.

Shestack said he was disappointed in the funding for research funding for autism. He said the agency wants to take credit for more funding on autism than is justified. He suggested that alternative grant-making proposals would been useful, such as creating a round for research on specific diseases.

Shestack was critical of the way in which grant rounds were handled. He said it led to “bloated proposals that people felt they had to approve.” He said the agency could have “more ruthless” on the “big disease” rounds and more willing to spend on basic research. “Ossified” is the way he described the grant-making process. During the review of grant applications, he said the staff “exerted a lot of pressure but in a passive-aggressive way.”

On conflict of interest issues, he said, “Trying to legislate away all conflict is a way to install permanent idiocy.”  Knowledgeable people in a small field such as stem cell research are nearly always going to have conflicts. He said the key is to manage them properly.

Shestack remarked on the impact of the state laws concerning open meetings. Compared to the private sector, they were “incredibly onerous” and made it difficult to do things, although he recognized they were necessary.

Shestack said the board is one of the best he has ever served on.  He said all the members were “pulling incredibly hard for the success of the agency. None of them had a hidden agenda.”

CIRM Board Member Prieto on 10-year Performance of Stem Cell Agency

The following is the text of what Francisco Prieto, a 10-year veteran of the governing board of the California stem cell agency, had to say about its performance over the last decade.

He commented for a freelance article written by David Jensen, the publisher of this blog, that appeared in today's edition of The Sacramento Bee. Prieto and other board members queried were told that it was likely that their comments would be severely limited in the article in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site.

Francisco Prieto
CIRM photo
They were additionally informed that the print article would address such questions as whether the work of the agency would be worth its $6 billion cost(including interest), whether it had fulfilled the expectations of voters in 2004 along with discussing the achievements and shortcomings of the agency.

Here is what Prieto, a Sacramento physician and patient advocate member of the board, said via email.
“Has the agency fulfilled the promises of the 2004 campaign? 
“I think that largely, yes, it has. The principal promise of the prop 71 campaign was that here in California, we would not abandon or throttle this incredibly promising avenue of research, as the Federal administration was threatening to do at that time, and instead would try to push it forward. The promise was that we would aggressively push towards finding cures for the debilitating chronic diseases that are responsible for most of our chronic illnesses, premature death and healthcare expenses. CIRM has made that push, and has made California probably the preeminent site for stem cell research in the world. 
“Will its efforts be worth the $6-$7 billion that will have been spent, including interest? 
“This will be hard to judge until we see what the results are of some of the stem cell related treatments that are just now entering or about to enter clinical trials. If even 1 or 2 of the major ones result in a cure for something like diabetes or one of the major cancers that some of our CIRM funded researchers are working on, I think we will have to consider that it was a bargain. 
“What are its current achievements and shortcomings? 
This one could go on much longer and I'm afraid I don't really have the time right now. I think to some extent I answered this above.  California has become one of if not the Center for stem cell research in the world. We could have done better, especially early in the history of the agency in terms of transparency, and could have perhaps involved the public more in the discussions of our priorities. Some of the conflict of interest issues and events that came up particularly in the recent past caught us by surprise, and I wish we could have foreseen them, but I'm glad once they happened that CIRM and our new Pres. responded appropriately. 
“I think our understanding of this field is going to some day (soon, I hope) transform medicine and make the things I do every day look as primitive as leeches and blood letting.  Speaking of which, I have patients waiting so I’m afraid I need to go find those leeches.”

Comments From a Former Communications Director at CIRM

The following is the text of what Dale Carlson, who served the California stem cell as its chief communications officer from 2005 to 2007, had to say about its performance over the last decade.

He commented at the request of the California Stem Cell Report for a piece written by David Jensen, the publisher of this blog. The article appeared in the Nov. 16, 2014, edition of The Sacramento Bee. Carlson and others queried were told that it was likely that their comments would be severely limited in the piece in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site.

Those queried were given generally free rein but were told that the print article would address such questions as whether the work of the agency would be worth its $6 billion cost(including interest), whether it had fulfilled the expectations of voters in 2004 along with discussing the achievements and shortcomings of the agency.

Here is what Carlson, a San Francisco publicist, said via email.
“Hard to know where to begin on CIRM. We were fortunate to attract such talented, dedicated professionals to the staff, particularly in the early days when funds were so limited, though they were a pretty beleaguered bunch by the time I arrived. The press coverage was dominated by the lawsuit. Seemed every story talked described the agency as ‘moribund,’ ‘mired’ or ‘stillborn.’ Most of them had come from labs and agencies that operated in obscurity and anonymity. They weren’t accustomed to ANY press attention, let alone being the subject of negative stories.

“They’d suffered significant self-inflicted damage as well, mostly because of unrealistic schedule pronouncements about when the first grants would be made, when BANs (bond anticipation notes) would be sold and bonds issued, etc., along with violations of public meeting and records requirements. 
“I loved the science and the scientists. I loved helping boost their confidence when dealing with reporters. I loved working with my counterparts at the recipient institutions. We were so strapped for resources that leveraging their capabilities and relationships was essential in getting our story out (and turning around our poor public image), and they were more than generous with their time and support.

“The many controversies that have plagued CIRM embroiled the board, not the staff with just one exception that I can remember: (Former CIRM President Alan) Trounson joining the board of a recipient company. Governance has always been CIRM’s Achilles heel. The board is ridiculously large and riddled with difficult-to-manage conflicts of interest. With so many members, it’s an easy temptation for individuals to assume others will attend meetings in sufficient numbers that there will be a quorum, or that others will provide leadership to deal with the agency’s ailments. But I’ve beaten that drum to death…

“It was a noble experiment. No state had ever funded biomedical research at that level. No government had ever used debt-financing to fund science. There’s no question that they moved the ball down the field, though the goal they set – clinical therapies – remains some distance away. California also has some magnificent new facilities and a large coterie of new talent, thanks to the taxpayers’ largess.

“When the bond funds are exhausted, it’s hard for me to see CIRM going forward with much (if any) public money. There just doesn’t seem an appetite in the Legislature for a significant appropriation or authorization. They may be able to raise private funds, though it may come with an insistence on governance reform. Time will tell.”

A CIRM Performance Perspective from Chief Staff Person on Oversight Panel

Here are comments from Ruth Holton-Hodson, who was the chief staff person on the only state body charged with overseeing the California stem cell agency, on the 10th anniversary of the program.

She worked for State Controller John Chiang, who is the chairman of the Citizens Financial Accountability and Oversight Committee. The committee was created by Proposition 71, which also removed the agency from normal budget oversight by the governor and legislature and ensured an unfettered flow of funds to the agency.

Holton-Hodson was asked for her comments for possible use in an article that appeared today in The Sacramento Bee. It was written by David Jensen, publisher of this blog. Because of space limitations, her remarks did not appear in the article. 

Chiang was elected state treasurer this fall. Holton-Hodson left her post prior to the election to travel and seek new opportunities.

Here is what she had to say via email:
"Proposition 71 exemplifies the problem of allowing individuals, if they have enough resources, to put an initiative on the ballot.  (The problems include) the built-in conflicts of interest of the governing board and the fact that the chair and the vice chair also play staff roles -- completely contrary to good governance practices.  In this case, (Robert) Klein (the first chairman of the CIRM board and who oversaw the drafting of the ballot initiative) wanted to lead the agency so he built the role he wanted.  
"Most voters don't read the fine print; for many the vote was a way to stand up to President Bush.  Probably most importantly, the allocation of huge sums for such a discrete project without any consideration of the opportunity costs (is an issue). Three billion dollars, which was really $6 billion, is a sum that should require vigorous debate as to whether that's the best way to spend taxpayer dollars,  Voters weren't presented a choice between stem cells and other critical issues, so I suspect most voters didn't think about whether that was the best expenditure of funds.  The legislative process, as frustrating as it is, involves a representative body that asks questions, determines the policy that is most acceptable and how or whether it is paid for.
"Klein, as the founder, leader, wanted to run the agency the way he saw fit. That’s fine in the private sector, but these are public dollars. There are rules and norms that must be followed, conflict of interest and transparency being a primary ones.  Klein and frankly the board were completely insensitive to what is an appropriate public sector  salary. They set the salaries based on what academics running large institutions make. Of course, this went back to language in the initiative.  CIRM, however, is hardly a large institution. 
 "Has the agency fulfilled the promise of the campaign of 2004, which left the impression with voters that stem cell cures were right around the corner? The promise of the campaign, as with any campaign, was caught up in the hyperbole needed to get votes.  Completely unrealistic,  and now they've set themselves up for public disappointment and disillusionment.  They promised but weren't able to deliver.
"If the major goal of Proposition 71 was to improve the health of Californians, was spending $6 billion of taxpayer dollars (including bond interest) on stem cell research the best way to do it? If the voters were asked if this was the best way to improve the health of Californians, I suspect they would say no.  Can you imagine what we could have done channeling that much money into the community clinic system, but there isn't a wealthy individual that wants to propose that we have a first class health care clinic in every community.
"Regarding the future of the agency, is it realistic to expect California to continue to invest billions more in the agency and stem cell research? Given both the changed politics around stem cells and the terrible budget years California has just gone through, I would be very surprised if the voters were to approve another initiative." 

Ben Kaplan of Prop. 71 Campaign on Performance of Stem Cell Agency

The following is the text of what Ben Kaplan, one of the persons featured in Proposition 71 TV ads in 2004, had to say about the California stem cell agency’s  performance over the last decade.

He commented for a piece written by David Jensen, the publisher of this blog. The article appeared in the Nov. 16, 2014, edition of The Sacramento Bee.

Kaplan and others queried were told that it was likely that their comments would be limited in the piece in The Bee because of the space limitations of the print media. They were also told that the full text of their comments would be carried on this Web site. In Kaplan’s case, his remarks were originally included but were trimmed to meet the space constraints as were others.

Those queried were given generally free rein but were told that the print article would address such questions as whether the work of the agency would be worth its $6 billion cost(including interest), whether it had fulfilled the expectations of voters in 2004 along with discussing the achievements and shortcomings of the agency.
Ben Kaplan
Prop. 71 photo

Here is what Kaplan, who lives in Palo Alto, had to say via email: 
“Having worked as a consultant for a biotechnology software startup, I have seen the challenges of developing new medical treatments up close.  Thus, I have a degree of understanding of what CIRM is facing.  While new therapies or cures have yet to emerge from CIRM-funded research, knowledge of stem cell function and disease processes has advanced dramatically.
 “However, CIRM could also more effectively communicate research advances to the general public, who remain largely uninformed about its progress, achievements and future goals.  Despite this communication gap, I believe the research the CIRM has conducted lays the groundwork for treatments that will hopefully be available in the near future.”

Patient Advocate Roman Reed on Stem Cell Agency Record

Roman Reed on right at stem cell agency news event. Former
California Gov. Arnold Schwarzenegger is on left and Don
Reed, Roman's father is in the center.
Associated Press photo

Roman Reed, the patient advocate who came up with the motto of the California stem cell agency, was asked for a brief comment for the 10th anniversary piece today in The Sacramento Bee that was was written by David Jensen, the publisher of this blog.

Here is the text of what Reed had to say via email: 
“The California Institute of Regenerative Medicine-CIRM can summed up in three words: Beacon of Hope. 
 “California’s Proposition 71 is the support, the foundation for the research that will one day give us the cures that we so desperately need. 
 “Today, there are nearly one dozen human clinical trials supported by CIRM!  (With another 40 diseases already planned for to go to trial in the pipeline.)
 “We Need CIRM. 
 “I am honored to have helped passed CIRM, Bob Klein's vision, California prop 71. This is a legacy that we leave to the People of California and the World. 
 “CIRM Is the World's greatest hope for Medical Cures!”

Wednesday, November 12, 2014

Venture Capitalist Kathy LaPorte Named to California Stem Cell Agency Board

The venture capital world has a “stunning lack of female decision-makers” but the $3 billion California stem cell agency has snagged one for its board of directors.

Kathy LaPorte
Nodality photo
She is Kathy LaPorte, who is a founding partner of New Leaf Venture Partners of San Mateo, Ca., and New York, which focuses on health care technology. LaPorte is chief business officer of Nodality, Inc., a biotech firm in South San Francisco, whose executive chairman is Michael Goldberg, who LaPorte replaces on the stem cell agency’s board.  And she is also a co-founder of Healthtech Capital of Los Altos Hills, Ca., an angel investor group.

The agency earlier this week announced her appointment to the board by California Treasurer Bill Lockyer, who leaves office this year.

Kevin McCormack, senior director for communications for the agency, wrote on the agency’s blog, The Stem Cellar,  
“Laporte started out with dreams of being a doctor and, after getting a biology degree at Yale University, she applied to go to medical school at both Stanford and Harvard (she was accepted at both, which tells you something about her ability). But somewhere along the way she realized that being a doctor was not for her and so she started thinking about other directions. The one she ultimately chose was business.” 
A profile of her in the Silicon Valley Business Journal described her as ‘smart, thorough and solution-oriented, Ms. LaPorte has spent nearly her entire professional life in venture capital -- something of a rarity -- and is considered a quick study by those who have worked with her.’”
It was Fortune magazine that remarked last February on the “stunning” shortage of women in venture capital. In September, Business Week reported on a study involving venture capital companies and women. The magazine said,
“Only 15 percent of nearly 7,000 VC-backed companies analyzed had a woman executive. And a paltry 2.7 percent had a female chief executive, the research from Babson College shows.”
LaPorte was also on the board of Affymax, Inc., of Cupertino until 2013. She was there at the same time another stem cell board member, Anne-Marie Duliege, was head of research and development for the firm.  Duliege is currently executive vice president of ChemoCentryx, Inc., a publicly traded firm in Mountain View.

LaPorte also holds an MBA from Stanford. 

Monday, November 10, 2014

BS and Ebola, Hype and Stem Cells

Hyperbole surrounding both stem cells and Ebola research has surfaced recently with cautionary notes concerning the damage it can do to the reputation of researchers and science.

Just last week UC Davis stem cell scientist Paul Knoepfler took up the matter in a piece headlined “The Cheating Death Excitation.” Over on the Pacific Standard Web site, Michael White of the Washington University School of Medicine wrote an article titled “Why Scientists Make Promises They Can’t Keep.”

White’s entry point was a flap last month about whether more federal funding would have meant faster progress on an Ebola vaccine. The hooha started with a statement by Francis Collins, head of the National Institutes of Health, and included a retort by Michael Eisen of UC Berkeley that Collins’ comments were “complete BS.”

Subheads in White’s Oct. 31 piece summarized his view nicely,
“A research proposal that is totally upfront about the uncertainty of the scientific process and its potential benefits might never pass governmental muster.”
“We, scientists and society, need to be more honest about the uncertainty inherent in the scientific process and in any projection of society’s future needs.”
Out west in California, Knoepfler remarked Nov. 6 on his blog,
“Can stem cells help many people in the immediate future to escape death? Recent headlines on new stem cell-related clinical developments would make you think so and they go a step further to indicate that such miracles are just around the corner.”
He continued,
“In the last few weeks there’ve been an unusually large number of papers and newspaper headlines about stem cell clinical developments, and as much as I hate to say it as an advocate for the stem cell field, many of these cases have been hyped.
“The reporters, their headlines and in some cases even some of those involved in the research seemingly would like you to think that cures for all kinds of bad things are about to happen tomorrow.”
Knoepfler said stem cell technology will be important and it will lead to “humanity changing events…but we aren’t there yet.”
“It’ll probably take another decade or two to really get closer to being a reality. Raising expectations sky high right now with over-the-top claims and headlines is not helpful to progress.”
Our comment: In the case of the $3 billion California stem cell agency, it has been burdened by the hype of the 2004 ballot campaign that created it. Voters were led to believe that miracles were in the offing and only 10 years or less away. That perception has not served the agency or the people well. Nor does it enhance the credibility of stem cell researchers, who were largely silent in 2004 about the grindingly slow process of science and government regulation of new treatments. Yes, ballot campaigns do need to generate excitement and hope. They also have a propensity to degenerate into falsehoods, critical omissions and exaggeration. That is one good reason that expensive ballot campaigns ($35 million in the case of the stem cell agency) are not necessarily the best way to fund scientific research.

As Knoepfler said,
“The key is balance….get excited and talk about the cool stem cell work (but) temper your statements a bit and keep plugging away at the research.”

Tuesday, November 04, 2014

Researcher Takahashi Honored as Stem Cell Person of the Year

Riken photo

Masayo Takahashi, the scientist in Japan who is leading the first clinical trial involving reprogrammed adult stem cells, today was named the stem cell person of the year.

The announcement was made by Paul Knoepfler, the UC Davis stem cell researcher who sponsors the award and personally funds its $2,000 prize.

Knoepfler said,
“In an astonishing feat, Takahashi's team transplanted its first macular degeneration patient recently on September 12, only 7 years after human IPSCs (induced pluripotent stem cells) were first ever published.”
The development of IPS cells, which also originated in Japan, has been hailed because they remove the moral objections that some persons have concerning the use of human embryonic stem cells. Many scientists, however, continue to consider the human cells as the gold standard.

Takahashi is a physician-scientist and a faculty member and project leader at the Laboratory of Retinal Regeneration at the Center for Developmental Biology at RIKEN.

Last December, Takahashi said she was wary of the high economic expectations surrounding potential stem cell therapies. In an article in the Financial Times by Jonathan Soble, she said, 
“Start-up companies are already involved and the road to commercialization is there, but to assume that the concept of iPSCs and regenerative medicine will yield a lot of money is na├»ve. Only parts of the field will become industries. It’s dangerous to think that all of regenerative medicine will.”
Takahashi was introduced to the field of stem science in 1995 when she followed her husband to the Salk Institute in the San Diego area in California.

Soble wrote,
“Paradoxically, because she had chosen clinical research, academia’s mix of glass-ceiling sexism and disdain for applied science worked in her favor. ‘I could do what I wanted because I was a woman,’ she says. ‘I didn’t think about career advancement.’”
She said barriers to women in science have largely disappeared in Japan although the comment was made before the STAP scandal that involved Riken. A key figure in the STAP research was a woman scientist, and persons prejudiced against women in science may well to use it to justify their biases.

Takahashi did say last year that traditional cultural values remain a problem in Japan. She said,
“'Japanese women don’t want to stand out, they don’t want to be leaders. They don’t think, ‘I want to have my own lab and reach the top in my field.’ I certainly didn’t until Salk.’ But Dr. Takahashi believes things are changing, in part because of the growing number of role models such as herself. ‘Sometimes,’ she says, ‘I meet young women who tell me, ‘You’re cool.’”

Monday, November 03, 2014

WARF, Oatmeal and the Patenting of Life

The battle over the WARF patent on human embryonic stem cells caught the attention of the Los Angeles Times last week, which added some oatmeal and history to the tale.

Michael Hiltzik, a business columnist with the largest circulation newspaper in the Golden State, reported on the challenge by Consumer Watchdog of Santa Monica, Ca., Jeanne Loring, head of the stem cell program at Scripps, and the Public Patent Foundation of New York.

The trio on Friday asked the U.S. Supreme Court to intervene and affirm their right to sue(See here and here.).  Hiltzik said, 
“The group has challenged the patent on two grounds: first, that the work covered wasn't novel or original, and second, that the Supreme Court has ruled that a ‘product of nature’ can't be patented.   
“All this is happening, researchers say, because WARF (Wisconsin Alumni Research Foundation) made exceptionally broad claims for its patent rights and exercised them very aggressively. This is, in fact, WARF's business; the nonprofit foundation was formed in the 1920s to exploit a patent issued to a University of Wisconsin professor on fortifying food with vitamin D, which it promptly licensed to Quaker Oats. By 1930, the deal was producing $1,000 a day. WARF also owns the rights to the drug Warfarin, which is named after the foundation.”
Hiltzik continued,
“The foundation demanded steep licensing fees of $5,000 a year from academic researchers and as much as $400,000 from commercial firms, plus royalties from product sales. 
“Eventually this backfired. When San Diego researcher Jeanne Loring was confronted by a demand for $75,000 a year from her start-up company—‘that's a lot, when your entire budget is $75,000,’ she told me--she looked closely at the patents only to conclude that they should never have been issued. 
“The key to (Wisconsin researcher Jamie) Thomson's success, she contends, was that he was able to get his hands on human embryos at a time when other researchers could not; the techniques he used had been applied to embryos of other species and shown to be effective. ‘Had I or any other stem cell scientist been given human embryos and sufficient funding, we could have made the same accomplishment, because the science...was obvious at the time,’ Loring says in a court declaration.  
“WARF disagrees. Thomson's success, it says in its own legal filings, ‘was anything but routine....He identified the critical steps needed to generate and culture these cells....No prior art reference taught these insights.’"

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