Position of the California Stem Cell Agency on Gene-Edited Babies? No Go.

California's $3 billion stem cell agency may be on the leading edge of regenerative medical research, but it is clearly opposed to the type of work that has led to the international flap over the gene-edited babies in China. 

Its regulations have long barred that sort of experimentation. In 2016, the agency, known formally as the California Institute for Regenerative Medicine (CIRM), convened an international conference to discuss the issues involved.

The session in Los Angeles went on for hours, generating a 223-page transcript touching on the difficulty of regulating gene editing, among a host of other difficult issues. 

One patient advocate in the audience, Adrienne Bell Cors Shapiro, noted that it is nearly impossible to control all that might happen. She said,  

"People are messy. And if you develop this technology, somebody is going to find a way to use it."

Last week the MIT Technology Review published an article about a Stanford University investigation into what two of its researchers knew about the Chinese research. The scientists also have received CIRM funds for research unrelated to the Chinese work. 

Asked for a comment, a spokeswoman for the state stem cell agency said in an email:

"CIRM’s regulations prohibit nuclear genome editing for reproductive purposes. In February 2016, CIRM convened the Scientific and Medical Accountability Standards Working Group (SWG) for a workshop on Human Gene Editing. The SWG subsequently recommended that no changes be made to CIRM’s existing prohibition on nuclear genome editing for reproductive purposes."

In 2016, Hank Greely, a law professor at Stanford who deals with bioethical issues, told the gene editing conference:

"CIRM is in the human embryo experimentation world. It funds research as long as the embryos are not implanted. It funds it with special protections and special review considerations and special informed consent considerations. I don't think CRISPR-cas9 changes that."

The controversial research in China triggered a global uproar in the scientific community. The leading stem cell research organization, the International Society for Stem Cell Research, issued a statement opposing such experimentation. 

He Jiankui, the Chinese scientist who performed the experiment, has lost his job in that country, according to news reports, and may be facing criminal charges. His work has not been confirmed by an independent review. 

Stanford Probe into Researchers Linked to Gene-edited Babies in China

Stanford University is looking into the involvement of several researchers in connection with the Chinese, gene-edited babies, the MIT Technology Review reported today.

The article by Antonio Regalado said,

"Officials at Stanford University have opened an investigation into what several high-profile faculty members knew about a Chinese effort to create gene-edited babies led by a onetime researcher at the California school, He Jiankui. 

"The investigation, according to people familiar with it, aims to understand what liabilities or risks Stanford may have in connection with the controversial medical experiment, which led last year to the birth of two girls whose genomes had been altered with a molecular tool called CRISPR to render them immune to HIV."

Regalado reported, 

"Stanford launched the investigation following media reports that three of its faculty—more than at any other institution—were aware of He’s plans to create the gene-edited children. They are William Hurlbut, a medical ethicist and theologian who interacted extensively with He over many months; gene-editing specialist Matthew Porteus; and Stephen Quake, a biophysicist who holds a powerful role as co-president of the $600 million Chan Zuckerberg Biohub, as well as being He’s former postdoc advisor."

Porteus has received $7.7 million from the California stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM). He Jiankui worked from 2010 to 2012 in Quake's lab. Quake is participating in a $40 million genomics program backed by the $3 billion stem cell agency.

Quake has declined comment in the past on his connections to He. Porteus told STAT in December that he had "strongly rebuked" the controversial researcher for what Porteus said was "reckless" work.  Hurlbut has said he had a number of conversations with He and advised him on the moral implications of the work.

Regalado wrote,

"University-led investigations are typically private, toothless affairs with few consequences for important faculty, especially those who pull in millions in grants. The question of research involving human subjects is a critical one, however, in part because serious violations can endanger a university’s federal research grants." 

A Deep Probe by STAT into the Man Behind the CRISPR Babies

Want to know more about the researcher who spawned what are now known as the CRISPR babies? 

STAT published a cracker jack of a piece this morning about He Jiankui, including details about his life and his pathway into the gene editing game.

STAT promoted the article this morning in a newsletter with this squib:

"Every superhero, and antagonist, has his own origin story. He Jiankui, the scientist who stunned the world with a claim that he had already gene-edited two baby girls, has one too." 

The lengthy article was written by Sharon Begley and Andrew Joseph and covers He's path from physics to biology. They quoted UC Berkeley scientist Jennifer Doudna as saying, 

“His demeanor was an odd combination of hubris and naivete. He was very confident in his work, and not totally understanding what an explosion he had caused.

The STAT piece is based on extensive reporting. Its authors wrote,

"With details reported for the first time, it describes the many times He met with and spoke before some of the world’s leading genome-editing experts, the low opinion they had of his research, and the hints he dropped about his grandiose aspirations. It is based on interviews in Hong Kong and with experts on four continents, with scientists and others who have crossed paths with He, as well as on documents and published accounts. He did not reply to requests for an interview."

The article's final paragraph ends like this:

"Even those who condemn his experiment doubt it will be more than a speed bump on the road to editing of embryos to prevent severe inherited diseases. 'We have to acknowledge there is interest in using [CRISPR] clinically,' Doudna said. To those calling for a moratorium or an outright ban on such research, she has one response: 'It’s too late.'"

The Genetically Altered Babies Story: More Information Surfaces on Researcher's California Links

More details are emerging this week concerning the California connections of the man behind what are being described as the world's first gene-edited babies. 

The scientist is He Jiankui, who spent two years in a lab at Stanford University, according to the lab's web site.

Lisa Krieger of the San Jose Mercury News has produced a roundup of the information about the researcher's activities in the Golden State. They include the connections with Stephen Quake of Stanford, who heads the lab where He Jiankui worked from 2010 to 2012.

She reported that Quake is declining any comment on He Jiankui.

Also mentioned in Krieger's piece are Mark Dewitt of UC Berkeley, William Hurlburt of Stanford and Jennifer Doudna, also of Berkeley.

Another useful piece exploring He Jiankui's training was produced by Sharon Begley, Andrew Joseph and Rebecca Robbins at STAT. The article takes a broad look at the researcher's training and background.

One cautionary note: The "facts" in this ongoing tale sometimes seem in conflict and sometimes murky. UC Davis' Paul Knoepfler raised the matter on his blog yesterday in an item headlined, 

"Trying to connect the dots on CRISPR baby story paints a dark, cloudy picture."

Even determining the number of years He Jiankui worked at Stanford is in question. Quake's lab clearly reports two years. STAT reports that it was "about a year" without identifying a source. A relatively minor point, but if that can't be nailed down, what else is missing? As Knoepfler wrote, much murkiness exists in the morass of stories and commentary that has emerged this week.

The caveat for those who follow this matter? As the old adage goes,

"Even if your mother says it's true, check it out."

The California Stem Cell Agency Speaks Out on Raelians and New Types of Human Beings

The California stem cell agency this morning is asking us all whether we remember the Raelians?

The agency, however, is not offering a $64,000 prize for the answer. No quiz show contest at the Oakland headquarters of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Instead the Raelian recollection is the lead-in to a cautionary note about the reports out of China that a researcher, who once worked at Stanford, has genetically altered two babies in embryo. The news has triggered an international flap about the ethics involved along with warnings about gene editing that results in "new kinds of human beings."

Writing on the agency's blog, Kevin McCormack, senior director for CIRM communications, said,

"Remember the Raelians? Probably not. But way back in 2002 the group, some described them as a cult, claimed it had created the world’s first cloned baby. The news made headlines all around the world raising fears we were stepping into uncharted scientific territory. Several weeks later the scientist brought in by the Raelians to verify their claims called it an 'elaborate hoax.'"

McCormack cautioned that ultimately the news out of China could amount to the same sort of thing. 

He noted the use of the CRISPR gene editing technique which has made it much easier to dip into the genetic process. McCormack wrote,

"CRISPR has been making headlines all of its own in the last few years as a fast, cheap and efficient way of editing genes. CIRM supports research using CRISPR for problems such as sickle cell disease. The difference being that our research works with adults so any changes in their genes are just for them. Those changes are not passed on to future generations.

"The work making headlines around the world used CRISPR on embryos, meaning a child born from one of those embryos would pass those changes on to future generations. In effect, creating a new kind of human being."

McCormack picked up a sample of reaction around the world, including a comment from Stanford bioethicist Hank Greely on CNBC. Greeley said that that if the report is accurate, the research is "criminally reckless, and I unequivocally condemn the experiment.”

McCormack concluded,

"Our best hope right now is that this is just a repeat of the Raelians. Our worst fear, is that it’s not."

Genetically Altered Babies: A Bit of a California Connection

This You Tube video produced by He Jiankui had drawn 19,723 views at the time of this posting along with nearly 300 comments, pro and con.  The number of views jumped about 5,000 during one hour this morning.

The startling news about what is being described as the world's first gene-edited baby has a something of a California tie.

The scientist behind the work, He Jiankui, worked from 2010 to 2012 in the lab of Stephen Quake at Stanford University, who is participating in a $40 million genomics program backed by California's $3 billion stem cell agency.  

Like many other scientists, He Jiankui was trained in the United States, receiving his Ph.D. from Rice University. 

A statement on the web site of Direct Genomics, a company He Jiankui founded, said,

"He was working on genome sequencing research during his postdoc training in the lab of Stephen Quake at Department of Bioengineering, Stanford University. Dr. He has multidisciplinary research background, such as in physical theory of network evolution, influenza virus, immune repertoire sequencing, single cell genomics and bioinformatics."

Quake's lab is currently dealing with ultra high throughput DNA sequencing. On the lab's web site, a mission statement by Quake said,

"My work in single molecule biophysics led to the first demonstration of single molecule sequencing, and my research in this field has led me to become deeply involved in human genetics, immunology, and the development of new clinical diagnostics."

Quake has not yet responded to a query concerning He Jiankui's work at Stanford.

In the stem cell agency's genomics project, Quake is the lead on a project dealing with cell differentiation.

California's Center for Genetics and Society in Berkeley released a statement on the news about the gene editing. Executive Director Marcy Darnovsky, said, 

“If true, this amounts to unethical and reckless experimentation on human beings, and a grave abuse of human rights. We wish the best for the health of these babies, but strongly condemn the stunt that threatens their safety, and puts the rest of us at risk. Throwing open the door to a society of genetic haves and have-nots undermines our chances for a fair and just future.”

CRISPR, the Cancer Question and the California Stem Cell Agency: $13.5 Million Investment in Eight Projects

CRISPR was in the news this week, and it wasn't about how you like your French fries cooked.

CRISPR, for those of you who don't know already, is a relatively easy way to edit genes. The technique is used in at least eight research projects backed by the California stem cell agency, totalling about $13.5 million.

What made CRISPR generate the headlines was research -- as Business Insider reported -- that the "blockbuster gene-editing tool has been linked to cancer." The assessment was described as hype by some scientists.

Paul Knoepfler, the peripatetic stem cell blogger and researcher at UC Davis, explored the implications of the findings in an item earlier this week. He wrote,

"To say that CRISPR-Cas9 gene editing might 'cause cancer' seems premature to me so there probably were and are better ways for people to phrase the big-picture meaning of these new papers and others like them that may pop up in the future. However, to be clear safety is crucial, so this is an important development and risks of any potential therapy including gene editing-based approaches should be carefully weighed against potential benefits as trials are designed and then progress."

The California Stem Cell Report asked the agency, which monitors the research it funds, for a list of its projects involving CRISPR. Here is what the agency provided, including the disease focus, principal investigator and grant number.

• Sickle cell disease, $4.5 million, Childrens Hospital Oakland Research Institute, Mark Walters, TRAN1-09292
• Muscular dystrophy, $2.2 million, UCLA, April Pyle, DISC2-08824
• Vision loss, $232,200, UC San Diego, Karl Wahlin, DISC1-08683
• Neurological disorders, $1.9 million, Parkinson's Institute, Birgitt Schuele, DISC2-09610
• Blood disorders, immune disease, $984,228, Stanford, Rosa Bacchetta, DISC2-09526
• Blood disorders, $1.5 million, UCLA, Caroline Kuo, DISC2-10124
• Cystic Fibrosis, respiratory disorders, $2 million, Stanford, Matthew Porteus, DISC2-09637
• Blood Cancer, cancer, $235,800, UC Berkeley, Jacob Corn, DISC1-08776

The Smell of Money and Gene Editing of Human Embryos -- Not to Mention the Breakthrough Science

"Horror to be avoided," "superbabies" and "what it means to be human" -- Just some of the language that turned up today concerning the news about the first human embryo editing experiment in the United States. 

Publications ranging from Wired to the Financial Times all had pieces discussing the work led by Shoukhrat Mitalipov of the University of Oregon in collaboration with researchers from California's Salk Institute, China and Korea. A search on Google news this afternoon turned up more than 1,000 citations dealing with the work.

Details of the science can be found in the journal Nature with a critique by UC Davis stem cell scientist Paul Knoepfler on his blog. He praised the research and said it "raises the stakes on future CRISPR use in humans." Elsewhere, the implications of the work also generated both heat and caution.

 The headline on a commentary in the Chicago Tribune said,

"Don't fear the rise of super babies. Worry about who will own genetic engineering technology."

The piece was written by bioethicist Arthur Caplan. He said,

"Freaking out over impending super babies and mutant humans with the powers of comic book characters is not what is needed....How close are they to making freakish super people using their technology? About as close as we are to traveling intergalactically using current rocket technology."

Caplan continued,

"We need to determine who should own the techniques for genetic engineering. Important patent fights are underway among the technology's inventors. That means people smell lots of money. And that means it is time to talk about who gets to own what and charge what, lest we reinvent the world of the $250,000 drug in this area of medicine."

Pam Belluck of the New York Times reported that the findings are "sure to renew ethical concerns that some might try to design babies with certain traits, like greater intelligence or athleticism."

She interviewed Hank Greely, director of Stanford's Center for Law and Biosciences. 

"'If you’re in one camp, it’s a horror to be avoided, and if you’re in the other camp, it’s desirable,' Dr. Greely said. 'That’s going to continue to be the fight, whether it’s a feature or a bug.'

"For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos."

Marcy Darnovsky, executive director of the Center for Genetics and Science in Berkeley, said in a news release,

"We have not yet engaged in processes that would promote the`broad societal consensus’ about human germline modification that the National Academies of Sciences and other prominent advocates of gene editing have recommended. Until that is achieved, we call on scientists around the world to refrain from research aimed at refining gene editing for use in human reproduction."

Bradley Fikes of the Union-Tribune in San Diego, a hotbed of biotech activity and the home of Salk, wrote that the study

"...brings to a head fundamental questions about what it means to be human, and whether changing the human genome would also change the human identity. And scientists — including those involved in the study — say it’s time for the public to speak up."

Given that this type of research is not funded by the United States government, just where the money came from is of interest. The Salk Institute had the answer. It said in a news release that the funding was provided by the "Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, and Shenzhen Municipal Government of China."

Some of the money "compensated" the women who provided the eggs, according to an article by Kelly Servick in the journal Science. Compensation, as opposed to expense reimbursement, is problematic in some areas of research. For example, it is banned in research that is funded by the $3 billion California stem cell agency.

The stem cell agency wrote about the research last week after the findings leaked out early. In February 2016, the agency convened a day-long session to examine issues involving gene editing. Last summer it issued new regulations that say that consent forms involving CIRM research must be modified to include a mention of genetic research. Added was the following phrase: "donated embryos [blastocysts], derived cells or cell products may be used in research involving genetic manipulation."

Regarding the future of the research, Mitalipov told the Financial Times that he wanted to perform regulated clinical trials at some point in the U.S. Unless something changes, he said that “unfortunately this technology will be shifted to an unregulated place."

CRISPR and Anti-HESC Updates from UC Davis Researcher

UC Davis stem cell scientist and blogger Paul Knoepfler has been busy this week, posting updates on CRISPR and two persons who have been behind the drive against the research use of human emrbryonic stem cells.

First, the information about the embryonic stem cell opponents, James Sherley and Theresa Deisher.

Sherley is running Asymmetrex, Inc., an adult stem cell firm in Boston. Knoepfler reported,

"I haven’t really seen Sherley out there in the public domain as an activist that much ever since the ES cell court ruling."

The negative ruling came in a federal court case challenging federal financing of human embryonic stem cell research.

Knoepfler cited a piece in Mother Jones magazine for his description of continuing activism on the part of Deisher. She was involved in the secretly recorded video tapes of Planned Parenthood officials. Among others, employees of Stem Express of Placerville, Ca., were also taped without their permission, and the California Department of Justice is investigating whether state laws were broken.

On the CRISPR front, Knoepfler has a series of links to good articles on the ongoing discussion involving the genetic modification technique. The debate continues unabated, although not in the mainstream media.

California's $3 billion stem cell agency held a daylong session on the matter some months ago. The agency is scheduled to take another look at it, but no date has been announced yet.

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.”

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

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.