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

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

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

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

Peterson described how businesses are embracing CRISPR,

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

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

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

Peterson continued,

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

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

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

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

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

A Nobel Laureate's 'Unsettling Note' From California's Human Gene Editing Conference

The Center for Genetics and Society, which has been monitoring human gene editing for the past few years, weighed in this week on the possibility that the state of California will beef up its role in financing research involving the sometimes controversial process.

The Berkeley-based center has taken cautionary approach to the field. The article this week on the center’s blog by Marcy Darnovsky, executive director of the group, continued in that vein.

Darnovsky attended the session last week during which the $3 billion California stem cell agency decided to embark on a thorough examination of the topic with the possibility of moving forward on gene editing of human embryos, a field that the federal government does not fund.

Darnovsky provided a summary of the session and cited “an unsettling (if unsurprising) note” from David Baltimore. He is a Nobel Laureate, former president of Caltech and a former member of the governing board of the California Institute for Regenerative Medicine(CIRM), as the stem cell agency is formally known. Baltimore also has been active in sounding go-slow recommendations on human embryo modification.

The concluding paragraph in Darnovsky piece said, however,

“Finally, an unsettling (if unsurprising) note about David Baltimore, who has played an influential role in the current controversy about germline gene editing and who chaired the organizing committee for last December’s International Summit. In previous comments about human gene editing, Baltimore has talked about responsible science; at the CIRM meeting, he came out explicitly in support of human germline modification. In his invited presentation, he said – as if this were a matter of scientific fact – that the desire for biologically related children is genetically hard-wired. He acknowledged that people at risk of transmitting genetic disease can already almost always have unaffected children in a variety of ways, and that therefore germline gene editing would at best benefit very few. But, he continued, ‘there are circumstances where it is the only opportunity for doing what a patient wants....To me, that’s sufficient reason to bring it to clinical use.’"

Darnovsky’s article also discussed testimony by Charis Thompson of UC Berkeley, who raised a number of policy issues.

Darnovsky wrote that they included “reminders that CIRM is mandated to serve not only patients with unmet medical needs, but also the taxpayers and voters of California; that disability justice experts as well as patient advocates should be consulted about gene editing directions; that CIRM should ensure that the work it funds does not exacerbate health disparities; and that if evidence of health disparities or eugenic trends emerges,’real consequences’ must ensue. She concluded by saying that ‘It is not `anti-science’ to note that historically, slopes are indeed slippery,” and that “California deserves – and can have – both the best science and the best ethics.’”

Darnovsky additionally reported on comments by Jeff Sheehy, a member of the CIRM board. She wrote that Sheehy was concerned that the agency might “have little recourse if grantees used other funds to initiate a pregnancy. ‘Where does our reach start and end?,’ he asked. ‘Does it start at the purpose of the proposed research? Do we just say you can’t implant?’ Sheehy suggested that if CIRM approves any grants for research that would produce modified human embryos, it include as a contractual requirement that those embryos cannot be used to initiate a pregnancy, whatever the funding source for that final (and trivial) step.”

CRISPR Roundup: Weapons of Mass Destruction to Gene Spills

The technique called CRISPR and gene editing are making the news again this week, as they are likely to do for quite some time. So here is a quick roundup of stories and links for further examination.

Probably the most provocative story was the addition of gene editing by the nation’s top intelligence chief to a list of threats posed by weapons of mass destruction. Antonio Regalado wrote about the declaration in the MIT Technology Review but said specifics were not cited. Regadalo noted, however, that “scientists have previously speculated about whether CRISPR could be used to make ‘killer mosquitoes,’ plagues that wipe out staple crops or even a virus that snips at people’s DNA.”

Out here in California, the state's stem cell agency wrote about its gene editing review on its blog, The Stem Cellar. Kevin McCormack, senior director of communications, offered this quote from one agency governing board member, Jeff Sheehy:

“Do we need to think about the rights of the embryo donor? If they have a severe inheritable disease and the embryo they donated for research has been edited, with CRISPR or other tools, to remove that potential do they have a right to know about that or even access to that technology for their own use?”

Charles Piller of STAT caught up with the state stem cell agency’s examination of gene editing with a national overview. An excerpt:

“Among state agencies that support stem cell research — including in Texas, Connecticut, New York, and Maryland — only California’s has publicly contemplated human embryo gene editing. The Cancer Prevention and Research Institute of Texas and Bioinnovation Connecticut have not yet considered funding such experiments, their spokespersons said. The Maryland Stem Cell Research Fund has taken no position on this issue, and New York officials could not be reached for comment.”

Paul Knoepfler, a stem cell researcher at UC Davis, wrote on his blog about how CRISPR has

“...set the table for some novel kinds of technological problems for which we aren’t at all prepared including one that I call the ‘gene spill.’ ...We should be very concerned about the possibility that a self-propagating genetic modification could end up out in the real world via a technology called ‘gene drive’ in such a way that it spins out of control. That would be a gene spill.”

Ben Fidler of Exconomy had a piece this morning on the business side of CRISPR based on a conference in Boston. An excerpt:

“The big scare with CRISPR is off-target cuts; that the molecular scissors snip the wrong part of a person’s DNA and cause unintended effects. (Intellia Therapeutics CEO Nessan) Bermingham called this a 'very important question' but said CRISPR technology has come a long way.”

"All In' -- Good News for California's $56 Million Investment in Search for Diabetes Cure

A $56 million bet by the state of California on a diabetes cure is showing additional promise that it will ultimately pay off.

The latest indication came last week when Big Pharma’s Johnson & Johnson went “all in” on ViaCyte, Inc., which has received $56 million from the California stem cell agency during the last 11 years, surpassing the amount that UC Berkeley has been awarded during the same period.

J&J has already pumped $20 million into the San Diego firm, which is conducting a clinical trial for a virtual cure for type 1 diabetes. The effort is showing promising results, according to the stem cell agency.

Last week, in a sign that ViaCyte has was moving along nicely,  J&J turned over its Janssen BetaLogics group to ViaCyte.

BetaLogics was a competitor to ViaCyte and a hedging ploy by J&J.  Business columnist John Carroll of Fierce Biotech described the merger of the two as a major commitment by Johnson. He wrote: 

“J&J goes all in with ViaCyte.”

Carroll reported,

"'We needed to hedge our bet to make sure that we would be the leaders in this space,' says Diego Miralles, J&J's global head of innovation in San Diego. ‘It's clear that ViaCyte has pulled ahead.’”

Randy Mills, president of the $3 billion stem cell agency, said in a news release that “the latest clinical data from ViaCyte are very encouraging and a clear sign of progress.”

The company has been working for years on its product, which is based on human embryonic stem cells. The treatment involves insertion of a tiny device beneath the skin of a patient to produce  insulin when needed.

Linda Johnson of The Associated Press wrote,

"'This one is potentially the real deal,' said Dr. Tom Donner, director of the diabetes center at Johns Hopkins University School of Medicine. 'It's like making a new pancreas that makes all the hormones' needed to control blood sugar.

"Donner, who is not involved in the research, said if the device gives patients normal insulin levels, 'it's going to prevent millions of diabetics from getting dangerous complications.'"

Paul Knoepfler, a stem cell researcher at UC Davis, wrote on his blog that the J&J move was “great news” for ViaCyte. He said the folding of BetaLogics and recent results from the phase one clinical trial “solidify ViaCyte’s leadership.” Knoepfler also is not involved with the ViaCyte research.

Before the therapy can be marketed widely, it must clear both a phase two and phase three trial, which could take a few years.

Big Money and Big Science: The Battle Over CRISPR

CRISPR: It’s simply a billion dollar matter of learning more or earning more. At least that’s the view of a Pulitzer Prize-winning columnist at the Los Angeles Times.

“A case of big money shaping science” said the headline on Michael Hiltzik’s piece on the website of California’s largest circulation newspaper. He said the tussle over the patent may be the 21st century’s “era-defining patent fight.”

Hiltzik wrote:

“The contestants are the University of California and the Broad Institute, a Harvard- and MIT-affiliated research foundation endowed by Los Angeles billionaire Eli Broad. At stake are the rights to a breakthrough gene-editing technology known as CRISPR — and more precisely, to billions of dollars in royalties and license fees likely to flow to whichever claimant prevails before the U.S. Patent and Trademark Office (and in the almost inevitable appeals in court).”

CRISPR is a new technique that allows relatively easy editing of human genes. Its potential use, with the possibility of permanent changes in the human race, has triggered an international hooha. Many leading scientists are calling for a moratorium until all the ramifications are fully explored.

The $3 billion California stem cell agency last Thursday held a day-long conference on the issue and announced it would hold a series of hearings into the matter, raising the likelihood of changes in research standards for California stem cell researchers.

The patent dispute, replete with the use of what Hiltzik notes are “outdated legal standards,” involves who was first with CRISPR -- Jennifer Doudna of UC Berkeley or Feng Zhang from Broad.

Both researchers say the patent fight is a distraction. But Hiltzik also wrote,

“Other scientists see the battle as a distasteful example of the influence of big money — and the race for Nobel credit — on basic research. ‘Having prizes and patents involved has transformed what should be one of the greatest success stories for basic research into this nasty, catty fight in which people are behaving poorly,’ says Berkeley biologist Michael Eisen, a colleague of Doudna's and the head of a lab that stands to gain resources if UC wins the patent fight.

“He added on his blog: ‘Neither Berkeley nor MIT should have patents on CRISPR, since it is a disservice to science and the public for academic scientists to ever claim intellectual property in their work.’ Indeed, neither the Doudna nor Zhang teams were the first to identify CRISPR or to use it; the history dates back as far as 1987 and involves researchers in Japan, Spain, Chicago, Quebec and other places’”

Hiltzik, author of the well-received book, "Big Science," said the real question involving CRISPR is whether "the future of the technology will be guided by the need to learn more or the opportunity to earn more."

Hiltzik’s column illuminated the enormous financial imperatives involved in the use of the CRISPR, which are publicly largely a side issue at sessions involving such agencies as California’s stem cell research effort and some international groups. However, the National Academy of Sciences is holding a session next Wednesday that includes a panel devoted to the CRISPR industry. Alta Charo, chair of the academy meeting, told the stem cell agency last week that she hopes that the scope of the market and its financial implications will be explored in more detail at the session, which will be webcast live.

Charo said she hopes for recommendations from her group by the end of the year concerning genetic modification of human embryos. The stem cell agency appears to be moving at the same sort of speed. All of which is a good thing since the lure of huge revenues will certainly stimulate even faster action by profit-hungry companies.

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

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

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

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

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

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

Matters to be addressed include the following, McCormack said, 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Coverage Concluded on California Human Genetic Modification Conference

The California Stem Cell Report is concluding its live coverage of today's California conference on human genetic modification of human embryos. The quality of the stem cell agency's audiocast is so poor that it is impossible to compile an accurate account of what the speakers have to say.

We hope to bring readers more information on the impact of the proceedings on California stem cell research when written accounts of the meeting become available.

California Stem Cell Agency Not Now Financing Genetic Modification of Human Embryos

The $3 billion California stem cell agency is not currently backing research that involves genetic modification of human embryos, but its standards appear to allow that possibility. 

The agency discussed its research rules at its conference today on the controversial subject. One of the slides presented by the agency said that its research standards group's intent under current regulation was "to allow for in-vitro use of human embryos for research while prohibiting reproductive use."

Earlier this week, the California Stem Cell Report queried the agency about the extent of  human genetic modification in research financed by the agency. Kevin McCormack, senior director of communications for the agency, replied, 

"As for the number of awards involving human genetic modification that’s a large number, five of our clinical trials in HIV/AIDS and our work with Sickle Cell Anemia and Chronic Granulatomous use human genetic modification techniques and many other preclinical/translational research projects do as well. 

"I think what’s more important is that right now none of our awards involve the genetic modification of human embryos, and that’s obviously the goal of the workshop to see if this is something we should fund and under what circumstances and with what controls in place." 

Today's presentation also said that stem cell agency "rules on clinical use of gametes and embryo are consistent with the statement from the International Summit on Human Gene Editing and the Draft ISSCR Guidelines."

Here are the presentation slides from the agency.

Genetic Modification Human Embryos -- California Stem Cell Agency Regulations

California Crispr Conference -- Presentation Slides

Here are presentation slides from some of the speakers at the California stem cell agency conference today on genetic modification of human embryos. They include Jonathan Kimmelman, Alta Charo and Amander Clark.

  Genetic Modfication Human Embryos -- Presenter Slides CIRM Crispr Conference 2-4-16

California Crispr Conference Has Begun but Audio Feed is Less Than Adequate

The audiocast from the California Crispr conference remains garbled although the session appears to be well underway. We expect to post some slides from the presentations shortly which CIRM has emailed to the California Stem Cell Report.

Waiting for the California Crispr Conference

The California stem cell agency is testing the ATT audiocast line to its conference this morning on the genetic modification of human embryos. We believe the conference has not yet started with its presentations.

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

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

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

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

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

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

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

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

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

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

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

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

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

Her statement said, 

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

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

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

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

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

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

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

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

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

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

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

Juan Carlos Izpisua Belmonte
Salk photo

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

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

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

Amander Clark, UCLA photo

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

Jacob Corn, UC Berkeley photo

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

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

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

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

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

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

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

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

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

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

David Baltimore, Pasadena Now photo

 conclave in December, Baltimore said,

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

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

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

Charis Thompson, UC Santa Cruz photo

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

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

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

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

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

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

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

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

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

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

A Book Review: Stem Cell Battles in California, a Pioneer's Perspective

(Editor's note: The following book review was offered by Raymond Barglow of Berkeley, who describes himself as a veteran of the Proposition 71 ballot campaign of 2004.) 

By Raymond Barglow

Don Reed's new book "Stem Cell Battles: Proposition 71 and Beyond" (available at Amazon) gives us an insider's perspective on the historical whirlwind that today is driving forward medical research in California and elsewhere. The author, who has been called the "Grandfather of Stem Cell Research Advocacy" for his longstanding commitment to this cause, is intimately familiar with the community of scientists, politicians, and patient activists who first came together over a decade ago to advocate stem cell research. Their signature achievement has been passage of Proposition 71 in California, which established financing for the research to the tune of three billion dollars. Largely as a result of their effort, we stand today at the threshold of medical breakthroughs that will save millions of lives.

As Reed explains, the stem cell research mission is advanced out not only in laboratories but also in the centers of political power. The research requires funding and has to withstand attack from

Don Reed on right, left is Bob Klein, former
 chairman of the stem cell agency,  and center is
Arnold Schwarzenegger, former governor of California

religious fanaticism that aims to shut it down. Standing staunchly against publicly funded embryonic stem cell research have been not only anti-government conservatives but also fundamentalist religious organizations and Catholic officialdom.

Claiming that the very earliest embryo, consisting of a few hundred cells and so small that it is invisible to the naked eye, has a sacred "right to life," opponents of embryonic stem cell research have organized to defeat funding in federal and state legislatures and have sued in court to make the research illegal. This has been and continues to be a hard-fought battle, with neither side clearly prevailing to date.

In the 1980s and '90s, AIDS activism united patient advocates with doctors and scientists to push forward the search for cures. Less well known is the stem cell research movement whose equally challenging path forward Reed chronicles for us. Although the story that he tells begins in California, many milestones have also been achieved in other states and abroad. Researchers in Canada, China, Singapore, Brazil, Japan and many other countries form a worldwide community to advance the search for deeper understanding of diseases and the invention of effective stem cell treatments to cure them. In a world torn apart by narrow interests and violent antagonisms, we have much to learn from the example of impassioned cooperation that the worldwide stem cell research community has set.

In brief, Don Reed provides in this book an inside view of the stem cell research saga, and he's done so with wisdom, spirit, and a sense of humor that combine to make the book entertaining as well as profoundly illuminating.

Plug Pulled on Cancer Clinical Trial: Sudden End for $18 Million Push by California Stem Cell Agency

Caladrius stock price plummets -- Google graphic

California’s ambitious, $18 million effort to develop -- in relatively short order -- a stem cell therapy for a deadly form of skin cancer collapsed abruptly last week, apparently the victim of “excessively long development timelines.”

Caladrius Biosciences, Inc., the recipient of the California funding, terminated the late stage clinical trial, declaring that other treatments have outpaced its approach and that it is no longer “optimally leverage(d).”

The award last May marked a big advance for California’s $3 billion stem cell research program. It was the first phase three clinical trial for the agency, known formally as the California Institute for Regenerative Medicine(CIRM).  A phase three clinical trial is the last step needed before federal approval for widespread use of a treatment. The award came as the agency is entering what could be the last years of its life and is pushing hard to fulfill the promises of the 2004 ballot initiative campaign that led to its creation.

CIRM, which is based in Oakland, Ca., is scheduled to run out of cash for new awards in 2020. The agency expects to intensify its efforts this year at developing a plan to replace the state bonds that it has used since 2004.

The $18 million award to Caladrius was made last spring with considerable ballyhoo. Jonathan Thomas, chairman of the agency’s governing board, said at the time that the  treatment had “the greatest chance of success for the people of California that we have funded.”

After the Caladrius announcement, Randy Mills, president of the agency, said in a news release,

“Ultimately this program suffered from the excessively long development timelines common in cell therapy, a fact that further underscores the need for CIRM to work hard to create faster development pathways as called for in our new strategic plan.”

CIRM’s statement also said,

“Only $3 million of the $17.7 million awarded by our governing board had been distributed to Caladrius, which matched that money with $3 million of its own. CIRM will now make the unused $14.7 million portion available to other applicants for investment into projects that accelerate stem cell therapies to patients with unmet medical needs.”

In a document filed with the Securities and Exchange Commission, Caladrius, formerly known as NeoStem, said the end of the trial would lead to layoffs for about 40 employees in Irvine, Ca., the home of what once was California Stem Cell, Inc. That firm was acquired by Caladrius in 2014 for $124 million. It  was founded by Hans Kierstead of UC Irvine, who is senior vice president for research and chief science officer of Caladrius.

The company’s SEC filing said,

“The treatment paradigm in metastatic melanoma was transformed during the course of 2015 by the accelerating adoption of multiple immune checkpoint inhibitors used as monotherapy and in combination treatments. These new drugs have significantly improved outcomes in metastatic melanoma and therefore have altered the opportunity for a monotherapy such as CLBS20 in a landscape that is quickly converting to combination therapies. Therefore, we have concluded that, as designed, our current program in metastatic melanoma will not optimally leverage this asset..."

Cancellation of the phase three trial led to a sharp drop in Caladrius’ stock price. It closed at $1.08 on Jan. 6, the day prior to the announcement. Today, the stock closed at 65 cents. The 52 week high for the stock was $4.26 and the low 40 cents. The chair of Caladrius, Robin Smith, resigned on Dec. 23.

California’s stem cell agency is now participating in only one phase three trial, which is not yet recruiting patients. That effort involves a brain tumor program with ImmunoCellular of Calabasas, Ca. The agency is currently participating in a total of  15 clinical trials at various stages.

California Stem Cell Agency Alters Grant Rules to Hasten and Improve Basic, Translational Research

A key committee of the governing board of the $3 billion California stem cell agency this morning approved changes in its grant rules in an effort to speed basic and translational research and attract higher quality applications.

The Science Subcommittee sent the changes to the full board on an 8-0 voice vote with no discussion and no public comment. The full board is expected to ratify the proposals at its Jan. 19 meeting.

The action came as the agency continued its new effort to provide more public access to important policy discussions and actions by the board's key committees. Today's meeting was accessible live on the Internet and by audiocast. For the past decade or so, only the meetings of the full board were available live on the Internet.

The new rules will cover hundreds of millions of dollars in awards for basic and translational research as well as educational training.  Hundreds of California researchers could be affected.

The proposals were based on earlier changes in clinical award rules. They are expected to strengthen the agency's ability to terminate research when milestones are not being met and establish a researcher's past performance on agency awards as a criteria for future funding. Also to be altered are rules about use of funds not spent during the award period.

The regulations are being enacted on an interim basis and will be subject to change as they wend their way through the official state regulation process.

Here is a staff memo on the rules and the full text of the agency's grant administration regulations. 

California Stem Cell Agency Opens Live Internet Access to Key Subcommittee Meetings for First Time in 12 Years

Highlights
Move Opens Door to More Public Participation
Major Policy Sessions to be Available
Tuesday Meeting Involves Hundreds of Millions in Grants

With no fanfare, California's $3 billion stem cell agency is making a significant step forward in openness and transparency regarding the dealings of its governing board, which operates outside of the control of the governor and legislature.

Next Tuesday’s meeting of the directors’ Science Subcommittee will be available live for the first time -- for all practical purposes -- on the Internet and as an audiocast, including access to presentations that are used at the meeting. The agency intends to allow public access for other directors' subcommittee meetings as well.

The move appears to be patterned after action by state Treasurer John Chiang, whose office holds many public meetings involving sometimes billions of dollars.  Last summer he added an audiocast feature to treasurer’s meetings.

A spokesman for the treasurer told the California Stem Cell Report last summer that Chiang wanted to enhance public access and to “increase public participation in and increase awareness of the many boards, commissions and authorities" that he chairs. The treasurer’s office said the cost was much less than $100 a session.

Tuesday’s stem cell audiocast follows procedures of the full board but never applied to other meetings of the California Institute for Regenerative Medicine, as the agency is formally known.

Last month, the stem cell agency attempted to provide an audiocast, which are also available for later listening, of a subcommittee meeting. However, the audiocast was not accessible for subsequent public use. The problem seemed to be a technical glitch because the agency said that it could be heard when CIRM staffers logged in.

Generally subcommittee meetings of the board rarely attract attendees from the public or the scientific community. However, major policy and scientific initiatives are discussed in more detail than at full board meetings. Suggestions for changes in proposals are more likely to be accepted in a subcommittee than at full board meetings, where proposals are ratified, usually without much discussion.

At next Tuesday’s meeting, for example, the Science Subcommittee is scheduled to act on new rules that will involve hundreds of millions of dollars in grants. Hundreds of California scientists engaged in basic and translational research as well as the progress of their efforts are likely to be affected. Educational training awards will also see new rules.

A memo to the subcommittee from Gabriel Thompson, director of grants management, said that the proposed rules are “designed to attract more high quality applications, reduce the cycle time from application to project start, accelerate progression of funded projects and provide for more efficient administration of the projects.”

One of the proposed changes appears to give the agency more power to pull the plug on research when it is not progressing satisfactorily by agency standards. The new rules would affect use of grant funds that are not spent by the end of the research. Past performance of grantees would also be established as a criteria for future funding.

Interested parties can find directions for logging into the Internet and audiocast on the meeting agenda. Some set-up may be required so it is best to check in advance the instructions on the agenda. 

The meeting will be based at the agency’s new headquarters in Oakland and is open to the public there. Teleconference locations where the public can speak to the committee as well as listen are available in Los Angeles and La Jolla. Addresses can be found on the agenda.