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." 

Roman Reed Act: $5 Million Proposed for More Research into Spinal Cord Injury

Roman Reed discusses stem cell research in 2017

Legislation to provide $5 million for stem cell and other research involving spinal cord injury has been introduced in the California state legislature and is expected to be heard soon in a key committee.

Assemblyman Kevin Mullin, D-San Mateo, introduced the measure that would re-fund the Roman Reed Spinal Cord Injury Research Act. 

Mullin, chair of the Assembly Select Committee on Biotechnology,  said in a news release 

“Sadly, efforts to continue this funding stream that expired in 2011 have failed and critical research in this area has suffered. The absence of state funds has limited the programs ability to attract private investment, limiting the work being done.” 

The news release continued, 

"The Roman Reed Spinal Cord Injury Research Act was originally established in 2000 and was subsequently renewed in 2004. The program, based at the University of California Irvine has continued its work, but on a smaller scale. According to the Reeve-Irvine Research Center, the earlier allocations of approximately $15 million in state funding allowed the program to leverage over $80 million in new grants benefitting virtually all California spinal cord scientists."

The legislation is named after Roman Reed, who suffered a paralyzing spinal cord injury in 1994. He and his father, Don, have been longtime backers of the $3 billion California stem cell agency.  Roman Reed came up with the first slogan of the agency, formally known as the California Institute for Regenerative Medicine (CIRM): "Turning stem cells into cures."

A comment by Don Reed wound up as the title of CIRM's  2018 annual report: "Something better than hope." The senior Reed lobbied the legislature for several years to create the act that ultimately provided the funding for the spinal cord research.

The bill is slated to come before the Assembly Health Committee for its first hearing, perhaps as early as this month. 

A Stem Cell Media Story: The Case of the Missing Mention

Storks and stem cell blessings

California's $3 billion stem cell agency, which is fighting to demonstrate its value proposition, this week received what could be considered some favorable attention in the prestigious journal Nature.

The catch is that the 14-year-old research program was not mentioned by name by Nature.

The question is: How does that work and why it is important?

First things first: It is important because the agency, known formally as the California Institute for Regenerative Medicine (CIRM), is hoping that the voters will bless it with another $5 billion come the November 2020 election.

The agency expects to run out of money for new awards this year and is also trying to raise privately more than $200 million to tide it over until the 2020 election. In both cases, it needs clear successes that demonstrate that it has earned its keep and will do even better in the future. 

Unproven Therapies in Japan

The not-so-odd case from Nature involves an editorial that cited a CIRM-funded clinical trial.  Nature praised it as something to be emulated in Japan as an example of good ethics and good science. 

Nature's editorial zeroed in on how Japan has embarked on "a worrisome approach." The headlines said,  "Japan should put the brakes on stem cell sales. Unproven therapies should not be marketed to patients."

Instead, Nature declared that Japan should focus on the approach taken by Asterias Biotherapeutics, Inc., of Menlo Park, Ca., which arguably owes its existence largely to CIRM. (See here, here and here.)  Nature wrote, 

"Last week, a Californian company called Asterias Biotherapeutics released promising results from a 12-month first phase clinical trial, in which embryonic stem cells are converted into oligodendrocytes — cells of the central nervous system that support neurons and can stimulate their growth — and then injected into the backs of people with a spinal-cord injury. The data show that injected cells do stick around at the injury site, and that most patients (21 out of 22) showed improved movement. 

"But these are still early-stage results. It is not clear yet whether the improvements are the result of the cells, or whether something else, such as the body’s own regenerative capacity, was at work. To find out, the company wants permission to move forward with a randomized, controlled phase II clinical trial. That’s the right way to do things: stepping carefully, slowly and rigorously forward."

It's Not the Stork

The problem for the stem cell agency, of course, is that Nature did not identify CIRM as a player in the Asterias effort, although the agency has pumped more than $20 million into the research. The case of the missing mention is not an unfamiliar situation for the agency, which is often not noticed in news and press releases about the scientific accomplishments that it has backed with tens of millions of dollars. 

Of course, CIRM cannot take full credit for the Asterias work. And federal regulators have rules for clinical trials. But CIRM put up the cash for the research after Asterias' predecessor bailed out.  The agency also partners closely with its grantees and has a clear set of pioneering research standards that it worked out more than a decade ago. 

Obviously, CIRM would have been only a brief note, perhaps only a phrase in the Nature editorial if it had decided to include a mention. But these things add up and are needed by CIRM as it tries to tell California voters that it has been worth $3 billion. Their absence can amount ultimately to a substantial negative. 

One does not have to support more cash for CIRM to recognize that California voters need the full array of information about the agency to make an informed decision in 2020. Currently, however, the traditions and practices of scientific journalism regularly omit significant financial information.

When one reads about scientific advances in the mainstream media as well as journals, it seems as if the research magically materializes without a critical insemination of cash -- much like a baby being brought by the stork.

Perhaps it is time for CIRM, other research funding agencies and patient advocates to have a facts-of-life "talk" with the scientific press about the reality of what it takes to give birth to prodigious medical advances.

(Editor's note: Here is a related item by UC Davis stem cell research Paul Knoepfler on the Japanese program.)

California Stem Cell Agency Approves Assault on "Terrorizing" Affliction: Huntington's Disease

Frances Saldana, at a stem cell agency meeting last year, spoke emotionally about the loss of her three children to Huntington's disease. 

Directors of the California stem cell agency this morning approved $18 million in clinical stage research awards, including a "high risk" plan to tackle a degenerative brain disease for which there is no treatment.

Action on the proposal to create a therapy for the genetic disorder, Huntington's disease, came after a woman who lost all of her three children to the affliction said it has "terrorized my family for generations."

Frances Saldana of Fountain Valley, Ca., wept as she pleaded for approval of the $6 million effort to treat the disease that  lingers in her family. 

Another patient advocate, Bill Waddington, whose mother died from the affliction, told the agency in a letter, 

"Huntington’s disease isn’t just death.  It’s complete and utter devastation to families."

Maria Millan, president of the stem cell agency, said later in a news release that children born to parents with Huntington's have a 50/50 chance of getting the disease.

Huntington's affects 30,000 persons with another 200,000 at risk. It  progresses slowly. Symptoms are unrelenting and include inability to control movement and declining cognition leading to dementia, according to experts. Affected persons usually die within 15 to 20 years after diagnosis,. 

The applicant for state stem cell funding, Leslie Thompson of UC Irvine, told the board in a letter,

Leslie Thompson
UC Irvine photo

"Given the relatively slow progression of HD, care-giving stretches over 10 years or more after the patient loses independence. Patients become completely dependent on family and caregivers, who in turn have an emotional and debilitating economic burden managing the physical, cognitive and psychiatric manifestations of the disease.  

"HD can lead to catastrophic events such as homelessness, prolonged hospitalization awaiting placement, or long-term psychiatric placement. The length and severity of the disease has a profound financial and emotional impact on families and health systems. The direct medical costs and costs of disability and care giving for each patient are substantial and pass from one generation to the next."

Members of the governing board of the agency, formally known as the California Institute for Regenerative Medicine (CIRM), discussed the application at some length because of a split involving the application reviewers. The summary of comments by reviewers said,

"Reviewers disagreed on whether the treatment offers a significant value to the patients and caregivers. Some reviewers thought the immunosuppression and surgical risk that is required for this cell therapy may outweigh any potential therapeutic benefits given that there are other less invasive treatment options being tested. Others thought that despite the stated risks, any potential treatment for slowing down disease progression is worth pursuing as current alternative therapeutic approaches are still many years away from commercial use."

Last month, the agency's reviewers, meeting behind closed doors, approved the award on an 8-1-5 vote with five against funding, eight for funding and one saying the application needs improvement and could be resubmitted. The latest application was, in fact, a resubmission after changes were made to deal with reviewers' concerns.  The summary of the latest version described the effort as "high risk."

In one of the six letters of support for Thompson's research, Michael West, CEO of AgeX Therapeutics, Inc., of Alameda, Ca., said the work could have application in treatment of other neurodegenerative diseases such as Alzheimers and Parkinson's.

Six is a relatively high number of letters for the board to receive on an application.  Advocates dealing with Huntington's have been active in the past, appearing before the CIRM board on a number of occasions.

The second award today went to Everett Meyer of Stanford and totalled $12 million. It involves a clinical trial for renal failure. 

Here are links to review summaries for each application considered today, the principal investigator, institution and other information. 

Application number, CLIN1-10953; amount, $6.0 million; title, "An hESC-derived hNSC Therapeutic for Huntington’s Disease;" principal investigator, Leslie Thompson; institution, UC Irvine; review summary; letters of support, letter to the board CLIN1-10953, letter to the board #2 CLIN1-10953,​ letter to the board #3 CLIN1-10953, letter to the board #4 CLIN1-10953, letter to the board #5 CLIN1-10953, letter to the board #6 CLIN1-10953, letter to the board CLIN2-11431, other CIRM funding for the PI, $12 million.

Application number, CLIN2-11400; amount, $12.0 million; title, "Induction of Tolerance by Combinatorial Therapy w/ Donor Stem Cells and Expanded Recipient Treg cells in HLA-mismatched Kidney Transplant Recipients;" principal investigator, Everett Meyer; institution, Stanford; review summary; letters of support, none; other CIRM funding for the PI, none.

Action on the following application was put off until Feb. 21 to provide time to answer financial questions raised by board members today: 
Application number, CLIN2-11431; amount, $6.0 million; title, "A monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants;" principal investigator, Judith Shizuru; institution, Stanford; review summary; one letter of support; other CIRM funding for the PI, $20.4 million.

California Stem Cell Agency to Award $24 Million for Three Clinical Trials

If all goes according to plan, in just three days the California stem cell agency will be down to its last $69 million for clinical trials.

Directors are set to give away $24 million on Wednesday for three clinical trial programs as the agency runs out of cash this year for new awards. The agency started with $3 billion 14 years ago. It has allotted $144 million for research awards this year.

The agency, known formally as the California Institute for Regenerative Medicine (CIRM), is attempting to raise privately more than $200 million this year. It is also hoping that voters will approve $5 billion more in funding in the November 2020 election. 

Applications coming before directors this week involve $6 million for Huntington's disease, $6 million for immunodeficiency studies and $12 million for renal failure research. 

The agency withholds the names of researchers and institutions involved until directors act publicly.  The agency's reviewers earlier approved the applications during a closed door session. The agency board almost never overturns the decision of its reviewers. 

The public can participate in the teleconference meeting via the Internet. Instructions can be found on the meeting agenda along with summaries of the reviewers comments on the applications.

CIRM was created by California voters in 2004 and provided with $3 billion in bond funding. No other significant source of income was provided under the ballot initiative.

Correction: An earlier version of this item that was up briefly incorrectly described the $69 million as all that remained for all awards this year.