Update on California's $72 Million Bet on a Diabetes Cure: Gene Editing Holds Promise

Viacyte video

A San Diego stem cell firm fueled by $72 million from the state of California this week announced an "important step" in its search for a diabetes cure in collaboration with a Massachusetts gene-editing enterprise.

The California business is ViaCyte, Inc., a privately held company that has received more funding from the California stem cell agency than any other business. 

It ranks 9th on the list of all recipients of cash from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. The ranking places it ahead of such highly regarded research institutions as Salk in La Jolla and Gladstone in San Francisco.

The East Coast firm is CRISPR Therapeutics, AG, a publicly traded firm that aims at "developing transformative gene-based medicines for serious human diseases."

CRISPR and Viacyte announced on Tuesday that their research is now showing that ViaCyte's "CyT49 pluripotent stem cell line, which has been shown to be amenable to efficient scaling and differentiation, can be successfully edited with CRISPR. The CyT49 pluripotent stem cell line is currently being used to generate islet progenitors for clinical trials."

Paul Laikind, CEO of ViaCyte, said in a news release that the latest news brings the firms "potentially one step closer to a transformational therapy for patients with insulin-requiring diabetes through the development of an immune-evasive gene-edited version of our technology."

Laikind described the gene editing result as "an important step" in achieving "yet another first, the development of an immune-evasive cell replacement therapy as a potential cure for type one diabetes."

In 2017, CIRM gave ViaCyte $1.4 million for work on the CyT49 line. Maria Millan, president of CIRM, said at the time,

“Development of an immune-evasive cell therapy would increase the chances of engraftment and durable effect of a cell replacement therapy for diabetes."

Investors were not energized by the CRISPR/ViaCyte announcement. CRISPR's stock price closed at $49.40 today, down from a $49.67 close on Monday, the day prior to the announcement. The 52-week high for the firm is $53.97. The low is $22.22. 

CRISPR and ViaCyte announced their $15 million collaboration a year ago. Here is a 2018 overview of Viacyte by Bradley Fikes of the San Diego Union Tribune.  

Stanford Exonerates Researchers Who Had Ties to Scientist in Gene-edited Babies Experiment

Stanford University this afternoon cleared three professors of any wrongdoing in connection with their ties to a Chinese scientist who said his research had led to the world's first gene-edited babies.

Pam Belluck of the New York Times broke the story after obtaining a letter that cleared scientist Stephen Quake in connection with the research, which stirred a global controversy. 

Belluck wrote,

“'In evaluating evidence and witness statements, we found that Quake observed proper scientific protocol,' said a letter from the university to Dr. Quake, obtained by The New York Times on Tuesday.

"Referring to the Chinese scientist, He Jiankui, by his nickname, JK, the letter said that Stanford’s investigators concluded that Dr. Quake did not 'directly participate in any way in JK’s research, including in the conception or performance of the work.'

"In fact, the letter said, Dr. Quake discouraged Dr. He from pursuing the project and urged him to follow proper scientific practices after he insisted on going ahead."

The Times ran a front page story on Sunday focusing on Quake's email communications with He. Belluck wrote today,

"On Tuesday, Dr. Quake, who turned 50 this week, said: 'I’m pleased this inquiry is over and its conclusion is consistent with what I knew to be true: that I had urged Dr. He not to pursue this path and when it became clear he wouldn’t listen to me, to adhere to high scientific and ethical standards in his research.'"

Quake is involved in a $40 million program financed by the $3 billion California stem cell agency. 

The other two researchers are Matthew Porteus, a genetics researcher, and William Hurlbut, an ethicist.

As of this afternoon, the Times story on Sunday had generated 329 comments in the Times from readers, covering the full gamut of reaction.

One reader, only identified as JHP, had only this to say,

"For such an intelligent and accomplished person, Dr. Quake comes across as breathtakingly obtuse."

The Times said 134 readers "recommended" the remark.

Another reader, Robert Speth of Fort Lauderdale, said,

"Dr. Quake’s actions appear to be that of a dedicated mentor who encourages their students to be successful, but to do so while conducting themselves in an ethical manner. While the investigation by Stanford is warranted, from the information presented in this article, I cannot see even a hint of misconduct by Dr. Quake."

The Times said 175 readers "recommended" the remark.

The Times also makes its own judgment about comments and labels some as a "Times Pick," It also has a category called "Reader Picks" in addition to "All." The Times moderates its comments for civility.

The reader comments can be found by going to the story and clicking on a small box to the right of the reporter's byline.

The NY Times Details Stanford Scientist's Communications in the Gene-Edited Babies Controversy

The New York Times this morning carried a front page story dealing with Stanford University, scientist Stephen Quake and gene-edited babies in China. 

Stephen Quake
Chan Zuckerberg Biohub photo

The story appears to the first time that Quake, who is the Lee Otterson professor of bioengineering and professor of applied physics at Stanford as well as co-president of the Chan Zuckerberg Biohub, has spoken at length publicly about his role in the matter of the Chinese children, who are the first gene-edited babies to be born. 

Their announcement last fall created an international brouhaha about the ethics and science of the work by He Jiankui, who once worked in Quake's Stanford lab. 

Times reporter Pam Belluck began her story like this

"'Success!' read the subject line of the email. The text, in imperfect English, began: “Good News! The women is pregnant, the genome editing success!' 
"The sender was He Jiankui, an ambitious, young Chinese scientist. The recipient was his former academic adviser, Stephen Quake, a star Stanford bioengineer and inventor. 
"'Wow, that’s quite an achievement!' Dr. Quake wrote back. 'Hopefully she will carry to term...'"

Stanford is investigating Quake's ties and communication with He. The Times reported that the school has received a complaint from the president of He's Chinese university, alleging that Quake “violated the internationally recognized academic ethics and codes of conduct, and must be condemned.”

In the Times article, Quake, who is participating in a $40 million genomics program backed by the $3 billion California stem cell agency, denied the allegations. Quake said his interactions with He have been misinterpreted. 

The Times wrote, 

"'I had nothing to do with this, and I wasn’t involved,' Dr. Quake said. 'I hold myself to high ethical standards.'

"Dr. Quake showed The Times what he said were the last few years of his email communication with Dr. He. The correspondence provides a revealing window into the informal way researchers navigate a fast-moving, ethically controversial field."

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.”

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."

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.”