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.

$10 Million 'Eat Me' Award: California Stem Cell Agency to Firm Called Forty Seven

The California stem cell agency is set this week to award $10 million to a Menlo Park firm to help finance a clinical trial for a therapy for colon cancer, which is the second leading cause of cancer death in this country.

The cash will go to Forty Seven, Inc., an enterprise using an immune system, "eat me" technology developed at Stanford University by stem cell scientist Irv Weissman. The firm is adding $6.8 million of its own cash to the project. Weissman has received $30 million over the years from the state agency.

The application to help with an early stage clinical trial was unanimously approved by the agency's scientific reviewers during a closed-door meeting last month. The full board will ratify the action at its telephonic meeting this Thursday. 

The agency, formally known as the California Institute for Regenerative Medicine(CIRM), has almost never overturned a positive decision by its reviewers.

The $3 billion agency does not release the names of successful applicants prior to board action. Forty Seven was identified through the use of public records.

According to a federal Web site,

"This trial will evaluate Hu5F9-G4 in combination with cetuximab. Hu5F9-G4 is a monoclonal antibody which is designed to block a protein called CD47, which is widely expressed on human cancer cells. Blocking CD47 with Hu5F9-G4 may enable the body's immune system to find and destroy the cancer cells. Cetuximab is a monoclonal antibody drug that is used for treatment of certain types of colorectal cancer as well as head and neck cancer."

The idea is to override a tumor's "don't-eat-me" signal and instead trigger the body's "eat-me" response.

California's scientific reviewers expressed high praise for the project. However, they also said,

"The design of the trial itself is fine, but the decision-making process is sub-optimal. It is critical to include clear go/no go criteria for the second phase of the trial and for the data to be evaluated by an independent, objective third party for a decision as it is unclear what toxicities are expected given the proposed new mechanism of action and use of a combination therapy." 

Forty Seven announced last February that it is backed by $75 million from a variety of partners including Google. Others in the venture capital group are Lightspeed Venture Partners, Sutter Hill Ventures (the two leaders on the financing) and Clarus Ventures.

In August, Karen Tkach wrote in BioCentury:

"With companies lining up to block CD47 for cancer, the cell surface protein is emerging as one of the top new targets in oncology. But the list of suitors could be about to get a lot longer as the target could have uses in a much broader range of indications, according to two studies from Stanford University that extend its prospects to cardiovascular disease and transplant biology, and hint at roles in several more diseases."

According to the clinical trial information on a federal Web site, Forty Seven will have clinical trial locations in Grand Rapids, Mich.; San Antonio, Texas, and Nashville, Tenn.  The California stem cell agency is limited to spending its award for work done in California. 

The federal information has conflicting indications on whether patients are currently being recruited for enrollment in the trial.

(In response to a query following publication of this item, Mark Chao, a co-founder and medical

Mark Chao, Stanford photo

director of Forty Seven and co-PI on the trial, said,

"We have been excited about the positive reviews by the CIRM committee and hope to hear good news on Thursday. Thank you for sending this article. With regards to initiating California clinical sites on the trial, this is a very big point of emphasis for us, in particular with CIRM’s mission and are currently working to activate two sites in California (Stanford University and UCLA) for the trial. One of our goals are to bring this therapy to patients within California and have designed our trials with this in mind. Please let us know if there are any further questions we can address. We look forward to a long relationship with CIRM.")

The chair of the study is Chris Takimoto of Forty Seven. The CIRM application number is CLIN2 -09577.

Stanford Pulls Its $10.9 Million Alpha Stem Cell Clinic Application

Stanford University has withdrawn its $10.9 million request to the California stem cell agency to create an Alpha stem cell clinic on its campus, along with a complaint that an illegal conflict of interest was involved in reviewing the proposal.

No further details about the alleged conflict were disclosed by the stem cell agency, which cloaks such matters in secrecy.

The Stanford application last October came before the board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. It was pulled from the agenda without a vote shortly before it was to be considered because of the late allegation of a conflict.

The application was to have come again before the CIRM board yesterday but again was removed. Kevin McCormack, senior director for communications, said that both the proposal and the complaint had been withdrawn by the applicant.

McCormack did not disclose the identities of the reviewers in the Alpha round nor the identity of the applicant, which the agency keeps secret. But the California Stem Cell Report has learned that it was Stanford.

The proposal received a low score, 64 or below, from the agency’s blue-ribbon reviewers, all of whom come from out-of-state, and was not recommended for funding. It was a rare loss for the Palo Alto institution, which has been the most successful in the state in winning money from CIRM. It has collected $298.3 million in 90 grants. The figure far surpasses the No. 2 institution, UCLA, which chalked up $215.3 million in 75 grants.

The winners in the $34 million round were the City of Hope in Duarte, UC San Diego and UCLA-UC Irvine. All of the institutions involved have representatives on the CIRM governing board. They are not allowed to vote on applications from their institutions.

In addition to Stanford, the other losing applicants in the round were UC Davis and UC San Francisco. 

See below for a CIRM list of the conflicts of interest in the round involving various directors.

   Conflict List -- Alpha Stem Cell Clinics -- Directors of California Stem Cell Agency

The Trounson Affair and its Financial Fallout

 StemCells, Inc., the California business founded by Stanford scientist Irv Weismann, seems almost certainly to have done a serious financial disservice to itself and its shareholders.

Alan Trounson
San Francisco Business Times photo

One week ago today, the publicly traded Newark, Ca., firm cast a dark shadow over its dealings with a $19-million benefactor, the California stem cell agency. The issue arose when the company appointed the former president of the research effort, Alan Trounson, to its board of directors, only seven days after the Trounson left the agency's employment.

Trounson earned $490,008 annually at the agency. Last year, directors of StemCells, Inc., received up to $99,800 each for their part-time efforts.

The Trounson announcement caught the agency by surprise, as it pointedly noted last week in a statement. Randy Mills, the agency's new president, expressed concern about a possible conflict of interest and ordered a “full review” of activities involving StemCells, Inc. Staffers and board members were banned from communicating with Trounson regarding StemCells, Inc.

Like most small biotech firms, StemCells, Inc., is in perennial need of cash. The firm has no products that generate significant income. Rather, it is in an almost constant fund-raising mode, either by selling stock, borrowing or securing awards, such as the $19.4 million “forgivable loan” from the $3 billion stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM). The award is basically a grant because it does not have to be repaid unless a product derived from the research reaches certain income thresholds.

But now StemCells, Inc., has damaged its relationship, probably irreparably, with the agency. The firm's chances of securing additional funding have to be rated nearly non-existent.  Putting aside purely business issues for the moment, the primary question for the agency now is whether it can trust StemCells, Inc. The company could not bring itself to notify – in advance – an enterprise with which it has a $19-million relationship about an event of importance to that enterprise. CIRM is likely to be wondering whether StemCells, Inc., can now be trusted to be forthright about other matters, such as results of its research or difficult problems that it faces in reaching the benchmarks laid out in its agreement with the agency.

Even prior to the Trounson announcement, StemCells, Inc., had a checkered history with the agency. The $19.4 million award  for Alzheimer’s research was rejected twice by CIRM’s prestigious reviewers. The 29-member CIRM board approved it on only a 7-5 vote in 2012 after heavy lobbying by the agency’s first chairman, Robert Klein. It was the first case of such public lobbying by Klein after he left the board.

It was also the first time the board had approved an application rejected twice by its reviewers. Almost universally, the board goes along with negative recommendations from its reviewers, saying it does not have enough information to override their decisions.

Pulitzer Prize-winning business columnist Michael Hiltzik of the Los Angeles Times later said the award was “redolent of cronyism.”

Approval of the award came during a grant round in 2012 that also saw StemCells, Inc., receive  another big award from the CIRM board -- $20 million. But that research received a high score from reviewers and was recommended by them.  Both awards required equal matching funds from the StemCells, Inc. – a total of about $40 million from a business that at the time was burning through $5 million a quarter and had only $10.4 million in liquid assets.   The financial capabilities of the firm were not discussed in public by the CIRM board. 

After eight months of negotiations with CIRM, the firm decided to take only the money for the project twice rejected by reviewers,  CIRM had no choice about whether it could fund the higher rated project, which is now in a clinical trial. That development came as the agency was urgently pushing to participate in clinical trials that would fulfill the promises to voters who created the agency in 2004 and help boost its drive for financing beyond 2017, when money for new awards runs out.

Trounson recused himself from the 2012 public discussions of the StemCells, Inc., applications because of his relationship with Weissman, who is a member of the company's board and chairman of its scientific advisory panel. Last January, Trounson strongly backed a $40 million award to a Stanford-led consortium that also involved one of Weissman's top associates. 

Beyond CIRM, the Trounson affair will also raise questions for StemCells, Inc.,’s efforts at private financing. The firm will now have to answer difficult questions about the appointment as it seeks loans or stock sales. The appointment could also play a role in the possible sale of the firm’s research to a Big Pharma company. One of the hopes of small biotech companies is that they will be purchased by a larger enterprise that wants to acquire their research. That is a common way for early investors to reap their profits.  But those big companies do not want unnecessary baggage in the deal.

The stock price of StemCells, Inc., last Monday hit $2.31. It dropped to $2.05 by the end of the week. The price has ranged from $1.15 to $2.43 over the last 52 weeks.

The company lists five analysts that follow its activities. Last week one recommended a buy and the others rated the stock as“outperforming.” Two of the analysts’ companies have financial relations with StemCells, Inc. The others may as well but that could not be immediately determined.

On July 2, prior to the Trounson announcement, The Street.com, which is not listed by the company as an analyst, said,

“TheStreet Ratings team rates STEMCELLS INC as a Sell with a ratings score of D-. TheStreet Ratings Team has this to say about their recommendation:

"We rate STEMCELLS INC (STEM) a SELL. This is driven by a number of negative factors, which we believe should have a greater impact than any strengths, and could make it more difficult for investors to achieve positive results compared to most of the stocks we cover. The company's weaknesses can be seen in multiple areas, such as its deteriorating net income, disappointing return on equity and generally high debt management risk."

The California Stem Cell Report last Monday asked StemCells, Inc., and Trounson for comments on the controversy about his appointment. They will carried verbatim when they are received. 

A Nearly $1 Million Award, the California Stem Cell Agency and the Revolving Door

Directors of the California stem cell agency tomorrow are scheduled to deal once again with a $900,424 proposed award to a Stanford researcher who recently hired a top staffer from the state research effort.

The award would go to Helen Blau, one of the leaders of Baxter Laboratory at Stanford. On Monday, Natalie DeWitt, who was special projects officer for former CIRM President Alan Trounson, went to work for Baxter as director of research development.

The award first came up at the directors' meeting May 29. It was recommended for board approval by Trounson and unidentified CIRM staff.

During that meeting, CIRM Director Jeff Sheehy, who is also a member of the grant review group, said that a copy of the application and the scientific critique was not provided to him at the March 24 review session. The application was submitted by Blau in January.

Sheehy and another director said the review was flawed. Sheehy noted that the Blau proposal was not approved for funding by the agency's out-of-state scientific reviewers. He said that during the closed-door review session several negative comments were made about the proposal during oral discussion. The application received a scientific score of 73, two points below the cut-off for funding. CIRM staff said, however, the proposal had merit and should be funded.

Director Sherry Lansing said it was important for the board to be open and transparent and suggested that the application be sent back to the full review group for further consideration. The 29-member board did so on a 9-0 vote. Members not voting either had conflicts of interest or were not present.

At the time of the meeting, DeWitt's then future employment by Baxter was not widely known and was not mentioned during the discussion.

Asked for comment today by the California Stem Cell Report, DeWitt said in a telephone interview that she was not involved in any way with the application. She also said she has not been involved with any of Blau's applications to CIRM or those from Garry Nolan or Peter Jackson, the other two leaders of the Baxter lab. Blau has been awarded $2.8 million by CIRM and Nolan $1.3 million. He is also a leader on a $20 million CIRM grant.

In response to questions, CIRM spokesman Kevin McCormack today said in an email that DeWitt was not involved with the $900,424 application by Blau. He said DeWitt served notice May 19. DeWitt said that sometime in late April or May that she “let a few key people (at the agency) know” that she was looking for work elsewhere and “spoke with the (CIRM) lawyers.”

DeWitt said her work at CIRM involved the $70 million Alpha Clinic proposal and the $40 million stem cell genomics award that went to a Stanford-led consortium. She said Baxter's Peter Jackson, who has some expertise in human genetic disease, is not involved in the genomics proposal. The CIRM contract on the award is yet to be signed.

DeWitt was mentioned yesterday in an article on the California Stem Cell Report dealing with “revolving door” issues involving government employees who go to work for enterprises that are linked to their former agency. The issues are likely to become of more concern to the stem cell agency in the next couple of years. The agency is scheduled to run out of money for new grants in 2017, and some employees are likely to be looking for work in the stem cell field in California, which only involves a small number of private and public enterprises.

CIRM employees are briefed on conflict-of-interest and revolving door issues, according to the agency. Its employee handbook also contains information on the subject along with a link to a state Fair Political Practices Commission document further explaining revolving door rules.

It says state officials are barred from taking part in decisions that directly relate to a prospective employer. The document says,

“The ban of influencing prospective employment prohibits any public official from making, participating in making, or influencing a governmental decision that directly relates to a prospective employer while negotiating or after reaching an employment arrangement.”

It continues,

 “The ban on influencing prospective employment is triggered by negotiating or having an arrangement regarding prospective employment. While submitting a résumé or an application to a prospective employer does not trigger the ban, the following contacts will trigger the ban:

• “An interview with an employer or his or her agent.

• “Discussing an offer of employment with an employer or his or her agent.

• “Accepting an offer of employment

In response to a question, McCormack said,

“Very few people, Natalie included, tell their employer that they are looking for work so I have no idea when she started looking.”

McCormack did not respond to a request for the names of the CIRM staff involved in making the recommendation to approve the $900,424 Blau award.

At tomorrow's teleconference meeting, the CIRM board is scheduled to act on a proposal to have the Blau application re-examined by a subset of the grant review group -- not the full group. Interested parties can either take part in the meeting or listen in from a number of sites in Northern and Southern California and elsewhere. Specific locations can be found on the agenda. 

Stem Cells and Revolving Doors: The California Experience

The phrase “revolving door” is not one that rolls off the tongues of most Americans. But it is shorthand for an issue that concerns both Elon Musk of Tesla and SpaceX fame as well as taxi drivers in New York City.

It is also a matter of importance to the $3 billion California Institute for Regenerative Medicine (CIRM) and other state agencies.

Natalie DeWitt
CIRM photo

The issue surfaced this week with the departure of a high level staffer at the San Francisco-based agency -- Natalie DeWitt, special projects officer for its former president, Alan Trounson. DeWitt's final day at the agency was last Friday. She began her new job on Monday at Baxter Laboratory at Stanford University.

Garry Nolan, Helen Blau, Peter Jackson
Baxter Laboratory photo

Baxter is run by Stanford scientists Helen Blau, Garry Nolan and Peter Jackson. Blau has received $2.8 million from the stem cell agency. Nolan has received $1.3 million. He is also a leader (co-PI) on a $20 million award in the agency's signature disease team effort.

No one is alleging that DeWitt or others have done anything wrong. She has a fulsome resume and a record of accomplishment.

Her departure from CIRM and employment at Baxter, nonetheless, does bring to the fore revolving door employment issues that now are a matter of greater concern for the agency than they were five years ago. The agency is scheduled to run out of funds for new awards in less than three years. Some of its employees are undoubtedly going to be looking for future employment in California's small, stem cell research community. It would be natural for agency employees to want to capitalize on their unique experience at CIRM. That is what gaining professional experience is all about.

But there are legal and ethical constraints. To prevent improper influence on governmental actions, the state of California has laws dealing with revolving door employment. Briefly summarized, state law says that certain former state employees and consultants can be banned from attempting to influence their former agency, either for one year or permanently. Current state officials also can be barred from taking part in decisions that directly relate to a prospective employer.

The California Stem Cell Report this week queried CIRM about its revolving door policies. Kevin McCormack, senior director of public communications, replied,

“These are issues that we are encouraged to be mindful of from the day we are hired to the day we leave. Once we accept the job we are given an 'employee handbook' (see below) which includes information about the state policy on what is appropriate behavior. As state employees, we have to periodically go through ethics training, and this covers what is and is not acceptable behavior in these instances. We are also encouraged to consult our in-house lawyers for guidance or to get advice from the state ethics agency on how the rules might apply to a particular situation.”

Revolving door problems are not new to either state or national government. They have long dogged such agencies as the Department of Defense. That's what Musk complained about via Twitter in a matter involving his space exploration firm, SpaceX. According to Bloomberg News, Musk tweeted last month about how competitors of his space company hired an Air Force official allegedly as part of a move to secure a chunk of a $68 billion Pentagon satellite project. And in New York City, questions also rose last month concerning the employment of a former top city taxi regulator by the noted ride-sharing company Uber, a competitor in the city's big taxi business.

DeWitt, who was paid $199,000 in 2013, worked for the stem cell agency from September 2011 until this month.  She played a key role in the $70 million Alpha Clinic proposal championed by Trounson. She was also deeply involved in the $40 million stem cell genomics award that went to a Stanford consortium last January following a controversial review process. She and Trounson co-authored an article in Nature Biotechnology promoting the genomics plan.

DeWitt, who has a Ph.D. in cell and molecular biology from the University of Wisconsin, was a senior editor at Nature from 2001 to 2010. Seven months after joining CIRM, she co-founded a firm called AccendoEditing. According to her Linked In profile, the firm works with clients to “to present scientific manuscripts and grants in a clear and engaging fashion.” It also “provides insights into the review process.”

DeWitt was one of the organizers of a conference last September at the University of Oxford dealing with cancer and stem cells. Her new bosses, Blau and Nolan, were scheduled speakers along with Stanford's noted stem cell scientist Irv Weissman.

At the Baxter Laboratory, DeWitt is its director of research development. Asked last Friday about leaving CIRM, she replied via email,

“The reason I'm moving on is simply that what I consider a fantastic opportunity presented itself to me.”

She has not responded to a query Monday about her views on the subject of revolving door issues.

  California Stem Cell Agency on Revolving Door Issues

Stanford Loses Star Stem Cell Researcher to Montana State University

Renee Reijo Pera, Stanford photo

The California stem cell community today chalked up its second departure of the month with the announcement that Renee Reijo Pera is leaving Stanford to join Montana State University.

The news about Reijo Pera, whose research is recognized internationally, comes only one week after Alan Trounson announced he was leaving his post as the president of the $3 billion California stem cell agency to return to Australia. 

Reijo Pera, 54, will become the new vice president for research, creativity and technology transfer at Montana State in Bozeman beginning Jan. 15. Currently director of Stanford's Center for Human Pluripotent Stem Cell Research and Education, Reijo Pera has won $24.4 million from the California stem cell agency in addition to her federally funded research.

She has been at Stanford since 2007 after leaving UC San Francisco. Prior to her 10 years at UC San Francisco, she was at MIT and the Whitehead Institute for Biomedical Research. (Her resume can be found here.)

Reporter Gale Schontzer of the Bozeman Daily Chronicle wrote anicely detailed story on Reijo Pera's appointment. Schonzter said that MSU research funding dropped 17 percent this year to $94 million, partly because of the loss of some researchers. She quoted a Montana spokesperson as saying that Reijo Pera “has amazing credentials that we think will continue to move our research forward.”

Schontzer reported that Reijo Pera's salary will be $200,000, “making her the third highest-paid administrator on the Bozeman campus.”

Reijo Pera also told the reporter that she “'absolutely loved' Stanford, but felt 'it's kind of time to do the next thing…. There is potential to do more at Montana State.'”

The news article also provided some interesting history on Reijo Pera. Schontzer said, 

“In high school, Reijo Pera said she had no interest in science or college. But after graduating and working as a car dealership bookkeeper, she wanted more. She enrolled at the University of Wisconsin-Superior to major in business. A class in human genetics for non-majors changed her life.”

Not mentioned in the Bozeman Chronicle story was a professional, Montana-Stanford linkage involving stem cell scientist Irv Weissman and Reijo Pera. In 2007, Weissman, director of the Stanford stem cell institute, hailed the hiring of Reijo Pera after playing a role in recruiting her.

Weissman has strong ties to Montana where he grew up and where he has a ranch.