USC vs. UC San Diego: Unprecedented $50 Million Settlement in Academic Recruiting War

The University of Southern California in Los Angeles is coughing up $50 million and publicly apologizing for its tactics in recruiting a star Alzheimer's resarcher from UC San Diego, it was reported Thursday.

The Los Angeles Times story about the unprecedented settlement described the case as an "ugly academic war." It had the potential of bringing $340 million in research grants to USC.  

The move settled a $185 million lawsuit that at one point involved two directors of the $3 billion California stem cell agency, along with researcher Paul Aisen.

The Times story said the "unprecedented litigation in which UC accused its private rival of repeatedly stealing away top scientists and their lucrative research grants with 'predatory' practices and a 'law-of-the-jungle mind-set.'"

Aisen was a neurology professor at UC San Diego. He and his lab staff left the La Jolla school in 2015. The Times reported that the departures were secretly orchestrated by top administrators at USC.

The Times story, written by Harriet Ryan and Teresa Watanabe with additional reporting by Bradley Fikes, said,

"The self-described 'quarterback' of Aisen’s recruitment was then dean of USC’s Keck School of Medicine Carmen Puliafito, subsequently revealed to have been using drugs and partying with criminals during the time he was courting the scientist."

At the time, Puliafito and David Brenner, dean of the UC San Diego medical school, were both members of the governing board of the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known. Aisen, however, has not received funding from CIRM, which has financed $56.5 million in other Alzheimer's research. 

According to the Times, the apology said that the recruitment tactics "did not align with the standards of ethics and integrity which USC expects of all its faculty, administrators and staff."

The Times story continued,

"UCSD Chancellor Pradeep Khosla welcomed the settlement and said he was open to working with USC in the future.
"'For California and the country, it’s good that two great research universities can work on the Alzheimer’s problem,' he said in an interview. 'I look forward to a constructive collaboration in the future in solving other societal problems.'
"It is not unusual for professors to move to other institutions, but it is often a collegial process in which the universities work together to transfer grants and research."

The Aisen case was not the first instance of USC researcher poaching. The Times wrote,

"In 2013, Puliafito lured two well-funded brain researchers from UCLA, outraging the state university, which complained to government regulators. USC agreed to pay UCLA more than $2 million in a confidential settlement."

Head of NIH Troubled by Flagrant Violations of Law Requiring Public Disclosure of Research Results

The headline read “Failure to Report: Law Ignored, Patients at Risk.” The story this week began,

"Stanford University, Memorial Sloan Kettering Cancer Center, and other prestigious medical research institutions have flagrantly violated a federal law requiring public reporting of study results, depriving patients and doctors of complete data to gauge the safety and benefits of treatments, a STAT investigation has found.

"The violations have left gaping holes in a federal database used by millions of patients, their relatives, and medical professionals, often to compare the effectiveness and side effects of treatments for deadly diseases such as advanced breast cancer

"The worst offenders included four of the top 10 recipients of federal medical research funding from the National Institutes of Health: Stanford, the University of Pennsylvania, the University of Pittsburgh, and the University of California, San Diego. All disclosed research results late or not at all at least 95 percent of the time since reporting became mandatory in 2008."

Francis Collins, head of the NIH, said he finds the failure to report "very troubling."

The story was written by Charles Piller, West Coast editor of STAT, which is a new online news operation dealing with the life sciences. It was started by the owner of the Boston Globe. The STAT web site says it reports "from the frontiers of health and medicine."

California Stem Cell Agency and the Revolving Door: A Need for More Safeguards

The revolving door and related conflict of interest issues remain open at the $3 billion California stem cell agency despite the pledge by its new president, Randy Mills, to refrain from taking a job with a recipient of the agency’s largess for at least a year after he leaves.  

Mills’ action last week came in response to the controversial appointment of the agency’s previous president, Alan Trounson, to the board of StemCells, Inc.(SCI),  just seven days after he left the agency.  The firm was awarded $19.3 million while Trounson was its top executive.  Last year, members of the SCI board received as much as $99,000 in stock and cash. 

Mills’ move applied only to himself and excluded other members of the agency’s staff. He said they should not be denied the ability to seek employment with businesses or research organizations that the agency has funded.

John M. Simpson of Consumer Watchdog of Santa Monica, Ca., said, 

"The high profile Trounson Affair  focuses attention on CIRM’s potential revolving door problem that the agency needs to deal with.  Randy Mills' pledge not to take a job with a company funded by the agency for at least a year after leaving is a good step.  There  should be such a formal policy covering all employees. “Serious thought should also be given to the implications of employees leaving for jobs with non-profit entities that CIRM has funded and what safeguards are necessary.”

State laws do exist to deal with revolving door situations, but some consider them weak. (See here for an explanation of the laws.) Trounson’s appointment is an example of the circumscribed nature of the laws. Mills said the agency's “severely” limited investigation into the appointment did not show any illegal activities. Simpson said a more rigorous, independent investigation was needed. 

Mills’ move did send a clear message about his own views on some ethical matters and set a tone that should be helpful at the agency. Some employees might also view it as an example to emulate.

Playing a role in the revolving door concerns is the financial future of the agency. It is facing its effective financial demise in 2017 when funds for new awards are scheduled to run out, according to longstanding calculations by the agency itself. Last week Mills cast that financial picture in a more optimistic light. (The California Stem Cell Report will have more on his analysis in the next few days.)

Nonetheless, as the money runs out and there is no assured refinancing in sight, some employees are naturally going to be considering other employment. Three employees have departed or announced they are leaving since Mills was named. The move of Natalie DeWitt, who was a top aide to Trounson, was already reported by the California Stem Cell Report. DeWitt went to work for researchers at Stanford who have received about $5 million from the stem cell agency.

Elona Baum, general counsel and vice president for business development , this month left her $298,000-a-year job to take a position at Coherus Biosciences of Redwood City. The company yesterday refused to disclose her job title or whether she had already started work. Kevin McCormack, senior director for public communication for the agency, said he did not know her job title. He said the company “has no funding from us or any other business with us.”

The Coherus Web site says the company was founded in 2010 and is “the leading biologics platform company developing biosimilar(generic) therapeutics for global markets.”

The third employee scheduled to leave is Celeste Heidler, financial services officer. McCormack said she is retiring. The agency has posted an opening for her position.

McCormack said it has not been determined whether Baum’s position will be filled.  In addition to legal matters, she played an important role in relations with the biotech and stem cell industry.

Consumer Watchdog’s Simpson said more needs to be done to clear the air concerning the Trounson appointment.

In response to a query, he said,

“There must also be a deeper probe into Trounson’s relationship with StemCells Inc, and it its executives and directors.  Margaret Prinzing’s report, a small step in the right direction, only looked back as far as May 1.  Trounson’s relationship with StemCells Inc. since at least the beginning of 2012 should be examined and the investigation should be conducted by an entity not as closely tied to the agency as the Remcho, Johansen & Purcell firm.  I think the Citizens Financial Accountability Oversight Committee, chaired by the state controller would do a good job."

The committee is the only state entity charged with oversight of the stem cell agency. The governor and legislature have no legal ability to control its operations since it was created by a ballot initiative that specifically spelled out that they had no role.

Watchdog Says Trounson-StemCells, Inc., Connection Casts 'Shadow' Over California Stem Cell Agency

The San Francisco Chronicle today carried a story on the appointment of Alan Trounson, former president of the $3 billion California stem cell agency, to the board of  StemCells, Inc., which has received $19.4 million from the research program.

Trounson’s appointment came only seven days after he left state employment. Last year, members of the firm's board received as much as $99,800 in cash and company stock, as reported by the California Stem Cell Report yesterday.

Chronicle reporter Stephanie Lee today wrote that the agency's funding was "pivotal" for StemCells, Inc. On Saturday, in an overview of the stem cell agency, she quoted Martin McGlynn, CEO of the publicly traded company, as saying,

 “We would not have been able undertake another program, and certainly one as challenging and as risky as Alzheimer’s, were it not for the fact that (the agency) was willing to provide funding for us.”

Lee also quoted John Simpson of Consumer Watchdog of Santa Monica, Ca., a longtime observer of the agency, on the matter. Simpson said that Trounson’s joining of the board “calls into question not only his ethics, but unfortunately casts a shadow over CIRM and its award process as well.”

Simpson continued,

“Whether it’s true or not, this has every appearance of being a payback for the money CIRM paid out to Irv Weissman (an eminent Stanford researcher and founder of StemCells, Inc.) and Stanford University. StemCells Inc. and Stanford have received more than $300 million from CIRM — more than any other researchers.”

Simpson said that Trounson should have waited two years before joining a company that had received funds from the stem cell agency.

Lee said that StemCells, Inc., filed a document with the federal Security and Exchange Commission that said said,

 “There was no arrangement or understanding between the Company and Dr. Trounson pursuant to which he was selected as a director of the Company.”

Lee said the Newark, Ca., company declined to comment. The California Stem Cell Report yesterday asked StemCells, Inc., Weissman and Trounson for comment as well as the stem cell agency.  Their remarks will be carried verbatim when they are received.

Ron Leuty of the San Francisco Business Times also wrote a piece on the matter yesterday.

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

Art Caplan on Fake Stem Cell Research: 'Off-the-Rails Syndrome?'

One of the more prominent bioethicists in the nation, Art Caplan, is asking,

“Why so Much Fake, Unduplicable Stem Cell Research?”

Caplan weighed in on Medscape.com today, citing the STAP flap involving Japanese and American researchers as well as a scandal involving a false but widely accepted – for a time -- claim that a Korean scientist had cloned human embryos.

Caplan said,

“Stem cell research seems again and again to go off the rails when it comes to the ethics of research.”

He continued,

“I think there are a couple of reasons why this particular area has gotten itself in so much hot water. One is that there is a relative shortage of funding. Because of the controversial nature of cloning -- getting stem cells from human embryos -- some avenues of funding have dried up, and it puts pressure on people to come up with other ways to try to make human stem cells. With less funding, there is more pressure. Sometimes people cut corners. I think that can lead to trouble.

“Another problem in the stem cell field is that if you can come up with a way to produce human stem cells without sacrificing or cloning embryos from humans, you are going to find yourself being a hero to the world. That is what happened in Japan.”

Caplan said,

“There is a lesson here: Until somebody replicates and until somebody can show that they can also do what has been alleged, there isn't a breakthrough. There is only confirmation and then breakthroughs. I think we have to be a lot more careful -- both in science and in media coverage -- before we start saying, 'Aha -- here is a single study, a single report, a presentation. Now we have shown that something can be done.'”

Caplan said,

“Another major problem in the stem cell field is that the number of people doing research in this area has shrunk. It is obviously of keen interest to come up with regenerative medicine solutions to all kinds of healthcare problems. I think a lot of post-docs and graduate students are saying, "I am not sure that I want to set my career track into a field that is sometimes controversial and where funding may be dipping." That may mean that there are fewer people to watch one another. It is not a big field, so maybe part of the reason that it keeps getting in trouble is less ability to do peer review.”

Our thoughts: There is no doubt some spectacular fraud has surfaced in stem cell research. But the problem of replication within stem cell research may not be entirely out of line with problems elsewhere in science. Los Angeles Times columnist Michael Hiltzik wrote last fall about a study by Amgen that examined 53 “landmark papers” in cancer research and blood biology. Only five could be proved valid, a shocking result, according to Amgen. Similar results were turned up by Bayer in Germany, Hiltzik said.

Additionally, as Caplan notes, the stem cell community is small and the hype is grand. With stupendous expectations come the likelihood that every missed shot – fraudulent or not – becomes an equally stupendous failure that is colored by suspicions of scientific misdeeds. Plus there are truly bogus practitioners at work, charging desperate people large sums for untested and potentially harmful treatments.

The mavens of science, those who control the medical schools and set the standards, may have some responsibility for some of the problems with replication. Writing May 8 on the blog of the Global Biological Standards Institute, scientist Beth Schachter touched on this in a post headlined, 

“What are science trainees learning about reproducibility?”

She asked one Ph.D. student at UC San Francisco what sort of training are he and his fellow students receiving on reproducibility and standards. The response?

“None.”

'Immortal' Stem Cells and Informed Consent in California

The California stem cell agency is looking for some help in connection with a $32 million stem cell banking program to be sure that people who donate tissue understand that their cells will be transformed and made “immortal.”

The agency has issued a $150,000 request for proposals (RFP) for a 12-month study dealing with informed consent matters in the banking effort. The agency's RFP said it is “a unique program because it involves the creation of 9,000 iPS cell lines, from 3,000 individuals” that could increase to 5,000.

The RFP requests a report that will provide “in-depth analysis of donors' current understanding with respect to the informed consent process” and “recommendations for education materials that may improve program performance over time.”

Issues dealing with informed consent and research were highlighted a few years ago in a book, "The Immortal Life of Henrietta Lacks," that was on the New York Times hardcover bestseller list for more than 40 weeks. 

The California stem cell agency's RFP said,

“Unique aspects of the tissue collection for disease modeling awards that is critical for donors to understand include that researchers intend to:
“• Test donors blood and skin samples for infectious disease
“• Transform donor cells and make them into immortal iPSC lines
“• Record the genetic sequence of donor their cells
“• Distribute donor cells and associated medical and genetic information widely
“• Use cells and associated information to develop commercial medical products with no financial compensation to donors.
“In addition, minors and/or individuals with cognitive impairments will be recruited for this research and consent may be obtained from their legal guardian."

The proposed California study is linked to a $4 million segment of its $32 million stem cell banking effort approved in March of 2013. Former CIRM President Alan Trounson said at the time,

“This initiative will provide scientists with access to multiple cell lines that should have much of the genetic variations that represent the variety within any human disease such as Alzheimer’s, heart disease, lung fibrosis and autism.”

The deadline for applications is June 1. Here is a link to a 2010 CIRM report on issues involved in the stem cell banking program, which was only a proposal at the time.

Bonilla: Veto of Pay-for-Eggs Bill Shows Troubling Mindset

A Democratic state legislator today assailed Democratic Gov. Jerry Brown's “mindset” as “particularly troubling” in his veto of legislation that would have allowed women to sell their eggs for scientific research.

The statement came from Assemblywoman Susan Bonilla, D-Concord, in response to Brown's action on her fertility-industry sponsored bill, AB926, which would have removed a ban on compensation for women who provide eggs for research.

Susan Bonilla
Photo from California Legislature

Brown cited health risks and other issues and said in his veto message,

“Not everything in life is for sale nor should it be.”

Alex Matthews, writing on Capitol Weekly, quoted Bonilla as saying,

“It (the governor's veto) shows a glaring inconsistency...The veto statement was very overreaching in the fact that it was making very broad statements about what women should be able to do, and while it's not legislation it certainly goes to a mindset that the governor has that I find particularly troubling.”

Bonilla continued,

“Market-driven compensation of donors by donor agencies and prospective parents continues unchecked.”

In a statement on her website, Bonilla said the governor's veto “is a regressive action that denies thousands of women the prospect of medical fertility breakthroughs.” She said,

“Many women...will be denied hope and the possibility of giving birth to a child because research on their behalf has been halted in California.”

Bonilla has argued that women involved in egg-related research, such as that involving stem cells, should be compensated, just as men are for their sperm. Women who provide eggs for fertility purposes can be legally compensated up to any amount. The current market runs about $10,000 or so per egg cycle but can be much higher.

Bonilla's measure would not have affected a ban on compensation involving research funded by the $3 billion California stem cell agency. It would have taken a 70 percent vote of each house to alter that restriction, compared to a simple majority for Bonilla's bill. The super, super-majority requirement was written into state law by Proposition 71, the measure that created the stem cell agency.

Bonilla did not indicate whether she would attempt to override the governor's veto, which would require a 2/3 vote of each house.

One of the opponents of the bill, the Center for Genetics and Society in Berkeley, called the veto a “welcome development.”

Diane Tober, associate executive director of the center, said,

“It would be unconscionable to expand the commercial market in women’s eggs without obtaining significantly more information about the risks of retrieving them.” 

Here are links to other stories today on the veto of the bill: Los Angeles Times, Sacramento Bee, an additional story from late yesterday on Capitol Weekly, TheAssociated Press and National Review.

California Stem Cell Agency on Lacks: Informed Consent Cannot Remove All Questions

(Photo and caption from the stem cell agency blog item this morning.)

The $3 billion California stem cell agency today weighed in on the Henrietta Lacks-NIH arrangement restricting the use of her cell lines in research.

Writing on the agency's blog, Geoff Lomax, the agency's senior officer for its standards group, noted that the DNA sequence of her cell line was published without the knowledge of her descendants. Lomax said,

“The family was understandably upset by the lack of consultation and in response the research team removed the genome data from public access.”

Lomax continued,

“CIRM has benefited from these efforts. We are currently supporting an initiative to collect tissue samples from thousands of people with a range of incurable diseases and create reprogrammed iPS cells from those tissues (here's more about that initiative). These cells will be a resource for scientists worldwide working to understand and treat diseases. Part of this initiative includes a consent process to make sure people who donate fully understand how their cells will be used. (This process is formally called informed consent.) 

“The informed consent process includes a form that identifies the purposes of the research and describes the way cells will be used. We are also developing education materials that will help potential donors quickly and easily understand the basic aspects of research that will be conducted with those cells. The end result of this collaboration with our grantees will be a process that is truly informative to donors.

“The informed consent process can’t entirely eliminate all future questions on the part of the donor, but it does ensure that donors have a chance to understand how their cells will be used and what information will be made public—something Henrietta Lacks and her family never had.”  

Skloots, Collins and More on Henrietta Lacks' Cell Line Deal

More details about the unprecedented arrangement involving Henrietta Lacks' cell line emerged today in a wide range of publications, including a Nature journal piece that said it was not a precedent.

The article was co-authored by Francis Collins, head of the NIH, and Kathy Hudson, deputy director for science, outreach and policy at the NIH.

“It is important to note, however, that we are responding to an extraordinary situation here, not setting a precedent for research with previously stored, de-identified specimens. The approach we have developed through working with the Lacks family is unique because HeLa cells were taken and used without consent, and gave rise to the most widely used human cell line in the world, and because the family members are known by name to millions of people.”

The restrictions on use of the cell lines came about after a flap erupted about their recent use without the knowledge of her descendants. (The California Stem Cell Report carried a commentary on it yesterday.) Rebecca Skloots, author of the best-seller, “The Immortal Life of Henrietta Lacks,” wrote about the controversy in a March 23 op-ed piece in the New York Times. She said,

In the article, Skloots said,

“Imagine if someone secretly sent samples of your DNA to one of many companies that promise to tell you what your genes say about you. That report would list the good news (you’ll probably live to be 100) and the not-so-good news (you’ll most likely develop Alzheimer’s, bipolar disorder and maybe alcoholism). Now imagine they posted your genetic information online, with your name on it. Some people may not mind. But I assure you, many do: genetic information can be stigmatizing, and while it’s illegal for employers or health insurance providers to discriminate based on that information, this is not true for life insurance, disability coverage or long-term care.

“'That is private family information,” said Jeri Lacks-Whye, Lacks’s granddaughter. “It shouldn’t have been published without our consent.'”

Nature also carried a Q&A with Collins in which he said,

“This has wrapped in it science, scientific history, ethical concerns, the bringing together of people of very different cultures, a family with all the complications that families have.”

In the Wall Street Journal this morning, Ron Winslow described the arrangement with the NIH like this.

“Under the pact, two descendants of Ms. Lacks will serve on a six-member panel with scientists to review proposals from researchers seeking to sequence the DNA of cell lines derived from her tumor or to use DNA profiles of such cells in their research. That gives family members a highly unusual voice in who gets access to personal health information.

Terms call for controlled access to the genomic data and credit to the Lacks family in papers and scientific presentations based on the research done with the DNA data.”

In an interview in The Scientist, Skloots, who was involved in the Lacks-NIH negotiations, said the Lacks family asked for her participation.

“The only reason I was involved in this is because scientists did this without the family’s consent and then it got all of this press coverage, and no one asked the question, 'Did the family give consent?' So I sort of waded back in.”

She continued, 

“That OpEd that I wrote was the first time I’d ever publicly expressed an opinion, which was, 'Really?!? Are we going to continue to not ask the Lacks family questions?' I was kind of shocked in a sense that nobody thought to raise that issue.”

The Henrietta Lacks Story and Eggs, Money and Motherhood

The legacy of Henrietta Lacks popped up again today in a piece in the New York Times that should resonate among stem cell researchers and within the stem cell industry.

It even has a current hook involving California legislation to permit women to sell their eggs for the purposes of scientific research – a bill that is now on the desk of Gov. Jerry Brown.

The issues in the Lacks saga involve ownership of human cells, trafficking in them and informed consent, all of which surface in one form or another in the state legislation.

But first a refresher on Henrietta Lacks. She was an African-American woman who died in 1951 of cervical cancer at the age of 31. Shortly before her death, physicians removed some of her tumor cells, and, as recounted in today's NYTimes article by Carl Zimmer,

“They later discovered that the cells could thrive in a lab, a feat no human cells had achieved before.

"Soon the cells — nicknamed HeLa cells — were being shipped from Baltimore around the world. In the 62 years since — twice as long as Ms. Lacks’s own brief life — her cells have been the subject of more than 74,000 studies, many of which have yielded profound insights into cell biology, vaccines, in vitro fertilization and cancer.”

But Lacks never consented to her cells' being studied, a situation not uncommon at the time, nor did her family know about the situation until 1973. The complete story was chronicled in 2010 in a best-selling book, “The Immortal Life of Henrietta Lacks," by Rebecca Skloot.

Zimmer noted in today's article,

“For 62 years, (Lacks') family has been left out of the decision-making about that research. Now, over the past four months, the National Institutes of Health has come to an agreement with the Lacks family to grant them control over how Henrietta Lacks’s genome is used.”

The particulars involving her genome are in Zimmer's story. But the article implicitly raises anew questions that make many scientists uncomfortable. Often they contend that the situation involving Lacks could not occur today because of higher ethical standards. Standards ARE higher today. But problems continue to arise in the scientific community, including the sale a few years ago of willed body parts at UCLA for $1.5 million to private medical companies.

Development of products based on human stem cells promises even greater rewards, with billion-dollar blockbuster therapies not out of the range of possibilities. Profit and the desire to record a stunning research triumph are powerful motivators. They can lead to short cuts and dubious practices, such as seen in the Korean stem cell scandals of 2006.

So we come to whether women who donate their eggs for stem cell research can give truly informed consent when they surrender all rights to whatever products may result from parts of their bodies, as is common on such consent agreements. Or for that matter, what about the men who give up adult cells for reprogramming to a pluripotent state? Can they really understand the likelihood of a billion dollar product being generated with the help of their contribution? On the other hand, can the donors also truly understand that they are probably more likely to be struck by lightning than have their body parts result in a medical blockbuster?

These considerations may seem insignificant to some in science. But to grasp their full implications, one only has to read a few of the nearly 200 reader comments today on Zimmer's article today. Here is a sample.

From Frank Spencer-Molloy in Connecticut:

“(T)the Lacks family was robbed. Scores of companies profited to the tune of tens of millions of dollars from products they made derived from Henrietta Lacks' cancerous cells. Maybe this will provide some impetus to a wider consideration of the rights patients are entitled to when their tissues are cloned and disseminated to other researchers and ultimately put to use in profit-making ventures.”

From Robbie in New York City:

“At the very least, this family needs to be financially compensated for the anguish of their discovery and for the time and energy they've put into pursuing their rights. In my opinion, they also deserve a portion of any commercial gain that's been made using the HeLa cells. It is only through having to give away money that the powerful learn manners.”

From Julia Himmel in New York City:

“It is absolutely true that scientists have had a blind spot when it came to the human element of the HeLa cells.”

The pay-for-eggs legislation (AB926) now before Gov. Brown requires informed consent from those who provide eggs. Opponents of the measure, however, argue that truly informed consent from some women could be actually impossible because of economic pressures felt by the women. Writing in The Sacramento Bee last month, Diane Tober and Nancy Scheper-Hughes said,

“Allowing a market in eggs for research would reach beyond the current pool to target women who may be motivated by dire need. How many low-income women might consider selling their eggs, multiple times, to feed their children or pay the rent?”

Even the fertility industry group sponsoring the legislation acknowledges that informed consent can be problematic. A 2012 news release from the American Society for Reproductive Medicine said, 

“Prospective egg donors must assimilate a great deal of information in the informed consent process, yet it remains difficult to determine the extent of their actual understanding of egg donation and its potential risks.”

The story of the treatment of Henrietta Lacks and her descendants is a poor commentary on science and medicine. Yet it resonates with the public, which is keenly sensitive to scientific and medical abuses, even in situations that did not appear to be abuses at the time.

Stem cell research already is burdened by its own particular moral and religious baggage. With commercialization of new, pluripotent stem cell therapies coming ever closer, the last thing the field needs is contemporary version of the Lacks affair. It would behoove researchers and the stem cell industry to walk with more than normal care as they manipulate products that are tied inextricably to visions of both motherhood and money.  

California Legislation, Human Egg Sales and Profits

California legislation to allow women to be paid for their eggs for scientific research is sailing toward final passage literally swaddled in motherhood and apple pie arguments. Missing from the debate is a key reason behind the bill – building profits for what some call the “baby business.”

The legislation is touted as providing equal treatment for women, permitting them to be paid for supplying eggs for stem cell and other research, much as men are paid for sperm. It also would put women who sell their eggs for research on an equal economic footing with women who sell their eggs for fertility treatments, which is currently permitted under state law. Payments to those women range from an average of $9,000 to as much as $50,000, according to a legislative analysis of the bill.

 Assemblywoman Susan Bonillla, D-Concord, author of the bill(AB926), says,

“It is time to let women, just as any other research subject, make an informed decision as to participation, and justly compensate them for doing so.”

She also says that the ban on payments has had serious impact on fertility research. In a legislative bill analysis, she says,

“It has led to a de facto prohibition on women’s reproductive research in California, adversely impacting the same women that the ban intended to protect. With few oocytes donated, fertility research and fertility preservation research has been at a standstill. This greatly affects women suffering from fertility issues and women facing cancer who would like to preserve their oocytes.”

Bonilla is carrying the measure on behalf of an industry group, the American Society for Reproductive Medicine of Alabama. The fertility or baby business, which is largely unregulated, brings in about $5 billion annually in the United States from something like 500 clinics. It has grown rapidly over the last couple of decades, but is likely heading for a soft spot.

Little public information is available on the Internet discussing the industry's economic challenges. However, demographic studies show that the size of the key market for fertility services is stagnating. A 2012 report by the federal government projects that the number of women in the 35 to 44 age group, prime consumers of fertility services, is likely to grow only 0.5 percent from 2010 to 2020. And since that forecast was made, the Census Bureau has downgraded its projections for total population growth.

Bonilla's legislation effectively adds a new, potential revenue stream for the industry. Fertility clinics would be able to buy the eggs and then resell them to researchers, adding premiums for eggs from women with special characteristics. The bill would also add a tool for bringing down the cost of fertility treatments, which can run as much as $12,000 to $17,000 a round or more and require several rounds, according to the NIH. Clinics could discount those prices for some women, bringing in new customers, if they agree to authorize the use of excess eggs for scientific research.

None of this appears necessarily pernicious. What is pernicious is the absence of discussion of the economics of the legislation. Without a full understanding of all that is at stake, including economic issues and motivations, legislators, the governor and the public are hard-pressed to make good decisions about a significant change in California law.

Opponents of the legislation have raised serious questions about the treatment of women by fertility clinics, noting that the bill would turn egg providers into “vendors” – not patients of the clinics. The Center for Genetics and Society in Berkeley has captured the arguments in opposition including testimony before a Senate committee hearing early in June.

Jennifer Schneider, a physician who lost a 31-year-old daughter to cancer seven years after the younger woman sold her eggs three times, told lawmakers,

“Unlike infertile women who are considered patients, egg donors are treated as vendors( (her italics). When they walk out of the IVF clinic, no one keeps track of them.  My daughter’s death was not reported. The long-term risks of egg donation are unknown."

Sindy Wei, a former egg provider and now a physician with a Ph.D. in biology, testified that she wound up in an intensive care unit after 60 eggs were extracted from her in 2001. She said,

“I fear that cases like mine are buried deep by fertility centers concerned about their image. An industry thriving on profits and reputation has little incentive to report adverse events, or protect the health and medical rights of donors.”

Where is the $3 billion California stem cell agency on all this? The agency has not taken a position on the bill nor have any major research organizations. The measure does not change the law affecting agency-funded research, which bans the use of compensation for eggs in its research. Enactment of the law, however, would create a two-tier stem cell research standard in California, one for scientists not constrained by the payment ban and another for those who could use the full range of research tools. Some stem cell researchers may well think that they have become disadvantaged as a result.

(Editor's note: An earlier version of this article said the IVF business generated $4 billion in revenues annually. More recent estimates place it at $5 billion.)

Klein, StemCells, Inc., and $31,000 in Consulting Fees for Torres

The Robert Klein-StemCells, Inc., affair has taken another turn with the disclosure that a vice chairman of the California stem cell agency was paid at least $31,000 over a two-year period by Klein and also voted on behalf of Klein's effort to win approval of a $20 million award for StemCells, Inc.

Art Torres received what he reported were consulting fees during 2011 and 2012 from firms controlled by Klein, former chairman of the agency. In 2012, Torres backed Klein's efforts to override grant reviewers' rejection of the $20 million application from the Newark, Ca., publicly traded firm.

Art Torres, center, with Bob Klein, left, at Klein's last meeting in
2011 as chairman of the California stem cell agency.
 Incoming chairman Jonathan Thomas is at right. 

The 29-member board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, narrowly voted 7-5 last September for the award. It was the first time that the board has approved an application rejected twice by its scientific reviewers. It was also the first time that Klein has lobbied the board on behalf of a specific application since stepping down in June 2011. He was elected chairman in 2005 as the agency was just beginning its work and is an iconic figure to many in the California stem cell community.

Asked for comment last week by the California Stem Cell Report, Torres said,

"My decision to support an award to StemCells, Inc. to explore the use of neural stem cell transplantation to treat Alzheimer's disease was based on the merits of the application and the hope it offers to patients who suffer from Alzheimer's, a disease that affects millions, including Bob Klein's late mother. I have no financial interest in StemCells, Inc. nor does Bob Klein, and my decision to support the award has no connection whatsoever to the work I do with Bob Klein."

Kevin McCormack, senior director for public communications at CIRM, said that Torres' statement would be the only comment on the matter from the agency.

Klein did not respond to questions, declaring that personal issues were occupying his time.

The California Stem Cell Report's questions to all three dealt with the propriety of Torres' employment by both CIRM and Klein while Klein was asking the board to award a business $20 million. The governing board has a code of conduct that declares members should “maintain the highest standards of integrity and professionalism.” However, it does not speak to questions of appropriate employment by CIRM directors outside of the agency.

In January 2012, Torres authored a document discussing CIRM's conflict of interest rules. He said they are intended “to eliminate even the appearance of impropriety.” He also referred to CIRM's policy on “incompatible activities” for employees. It deals with activities that could “discredit” the agency or that are “inimical” to it. However, it does not specifically deal with the type of situation involving Torres and Klein, who is a real estate investment banker and attorney. The policy additionally does not address cases where a governing board member is also an employee of the agency.

Torres' economic disclosure statements, which are required by state law, contain only broad ranges for compensation, and the amount could be significantly higher than $31,000. Torres reported that in 2011 he was paid between $10,001 and $100,000 by both Klein Financial Corp. and K CP Cal, which share the same address as Klein's offices in Palo Alto. In 2012, Torres reported receiving between $10,001 and $100,000 from K CP Cal and between $1,001 and $10,000 from Klein Ventures LLC, which also has the same address.

Torres reported that the payments were consulting fees and that the firms dealt with real estate. He did not respond to requests for more details.

Torres earns $225,000 a year in his part-time role as one of two vice chairmen for the agency. Under the arrangement, he works four days a week.

Torres was chairman of the state Democratic Party and a longtime state legislator. He was nominated for vice chairman in 2009 by state Treasurer Bill Lockyer, among others.

Last week, another financial arrangement involving Klein surfaced in connection with the StemCells, Inc., application. Klein gave the agency $21,000 last May,two months before he pitched the board on the StemCells, Inc.,application. The donation was not reported to the board prior to Klein's appearances before the panel. The agency's regulations require such gifts to be reported to the board but do not specify a time frame. Following inquiries from the California Stem Cell Report, the agency said it would report the donation at the agency board meeting next week.

Klein's donation financed a trip by six CIRM science officers to Japan for an international stem cell conference. The agency directed the officers to give special access to Klein. Two of the officers were heavily involved in the grant round that included the StemCells, Inc., application, which scientific reviewers scored at 61 on a scale of 100.

The Back Story on Baylis and the Ethics of Geron's hESC Trial

Last week Canadian bioethicist Francoise Baylis raised ethical questions about Geron's abandonment of its hESC clinical trial in an article that, it turned out, has a bit of a history.

When we notified her that we had written about her piece and its implications for the California stem cell agency, Baylis replied with a thank you and said,

"As an aside, you might be interested to know that I sought to publish a version of this commentary as a letter to the editor in a peer reviewed stem cell science journal and received the following response: I and two experts 'found the overall tone and presentation of the letter inappropriately strong and confrontational. As a result, it does not seem appropriate for us to offer to consider it further.'

"In my view, this was an unfortunate editorial decision as I believe the stem cell science community needs to engage with this issue. Moreover, I know of responsible stem cell researchers who share my point of view. Beside which, I disagree with the characterization of the piece as confrontational ...

"Another posting of mine on The Mark News makes the same point, but in a more journalistic style."

In that piece, Baylis also wrote about Geron's position that the results with four clinical trial participants would "be a fair reflection of what would have happened if we had completed the study(with 10).” She said,

"I want to suggest, however, that this is an ethically problematic response to a situation that could have been anticipated, and thus avoided. Failure to name the problem in this way leaves future participants in safety studies of novel hESC interventions at risk of abandonment whenever a private biotech company decides to end a trial mid-stream for business reasons."

Our take? The California Stem Cell Report agrees that the decision by the unnamed journal was unfortunate, to put it mildly. Baylis' comments were neither inappropriate nor confrontational, but they did raise questions that could well make some persons uncomfortable. Nonetheless, the questions were the sort that the general public and patient advocates raise in one form or another in their dealings with the enterprises that develop therapies and drugs. Either the questions are addressed now or later -- when they may well have to be dealt with under much more difficult circumstances when things go awry.

California Stem Cell Agency and Geron: Ethical Issues with Sale of hESC Trial

A Canadian bioethicist is raising ethical questions about Geron's hESC trial that have implications for the attempt by the California stem cell agency to salvage the once-vaunted effort.

Writing yesterday on the Hastings Center Bioethics Forum, Francoise Baylis of Dalhousie University said,

"It is one thing to close a trial to further enrollment for scientific reasons, such as a problem with trial design, or for ethical reasons, such as an unanticipated serious risk of harm to participants. It is quite another matter to close a trial for business reasons, such as to improve profit margins."

Geron last month said it was ending the trial because of financial reasons and to pursue development of its cancer treatments. CIRM awarded Geron a $25 million loan just last May and was surprised by the Geron move. The $3 billion state research program is now attempting to find a buyer/partner for Geron's hESC business.

Baylis noted that Stephen Kelsey, chief medical officer of the Menlo Park, Ca., firm, has been quoted as saying that the results of Geron trial – now with five patients instead of the projected 10 – "will be a fair reflection of what would have happened if we had completed the study."

Baylis wrote,

"This statement is deeply problematic, however."

Baylis, a professor and the Canada Research Chair in the departments of philosophy and of obstetrics and gynecology at Dalhousie, continued,

"No clinical trial should involve too few or too many participants. It is important that the trial not be underpowered and thus unable to generate scientific knowledge. It is equally important than no more research participants than necessary be exposed to potential research risks. If only five participants were needed to generate the scientific knowledge, then why would Geron and the F.D.A. have agreed to expose additional persons to the potential harms of trial participation?

"On the other hand, if Kelsey’s statement is false, and the findings from five research participants will be underpowered, then they may have been exposed to the potential harms of trial participation without the potential for benefit in the form of scientific knowledge."

She concluded,

"In either case, the scenario forces us to consider what measures should be taken with respect to future trials funded in the private sector so that participants are not left stranded. Perhaps regulators and institutional review boards should critically examine whether a company has both the financial (and other) resources and the will to complete a trial under review before granting regulatory or ethics approval.  If there are doubts about this, then either the trial should not be approved, or there should be stringent disclosure requirements so that prospective research participants are aware of the possibility that research may stop mid-trial for financial reasons."

NIH and Exculpation

For those of you not fully informed of the tricky byways of stem cell science, the Boston Globe carried a nuanced editorial today that laid out the significance of an arcane “exculpatory” matter last week

Arcane, that is, to folks who do not fiddle with human embryonic stem cells.

The case involved possible use in federally funded research of embryos donated some years back. The feds said no because they were given under conditions that do not meet today's ethical tests, although the donations met the standards of the day, which actually was only a decade or two ago. The Globe called the NIH action a “major blow.”

You can read all about it here.

A Re-Look at Friday's Egg Meeting

The California stem cell agency has taken issue with the way we have framed this coming Friday's meeting dealing with human eggs.

It is not really about availability, cost and prices, says CIRM. But rather about stem cell lines and embryos created through IVF treatments and their possible use in CIRM-financed research.

Geoff Lomax, senior officer for the Standards Working Group, said,

"You have got this one completely wrong and framed the meeting in a sensational and inflammatory way which does a disservice to thoughtful policy deliberations."

Lomax prepared the briefing paper – called "Use of Embryos Created for Reproductive Purposes with Paid Gametes" – for use at the Standards meeting later this week.

When we read it, we took a broader perspective, one that concerned the general availability of eggs for research and the economics behind their apparent scarcity.

But first CIRM must deal with the information Lomax presents in his background material as well that which will be brought to the table by others.

He wrote:

"Nationally, the CIRM policy deviates from other jurisdictions that have developed policies to advance stem cell research. This deviation has raised concerns over the ability of CIRM researchers to utilize materials derived under other jurisdictional policies or the National Academies Guidelines."

The issue of the use of human eggs is freighted with emotional and political baggage, plenty of which will surface eventually. But meantime, Lomax is trying to lay the groundwork for a straightforward consideration of practical issues that need attention sooner rather than later.

San Diego Researchers Say No Shortage of Human Eggs

Jeff Sheehy, a member of the board of directors of the California stem cell agency, has brought to the human egg debate a new entry that appears to fly in the face of assertions that scientists cannot get enough eggs for their human embryonic stem cell research.

His comments and information come as the CIRM Standards Working Group plans to dig into the topic again this Friday during a public hearing in Los Angeles. The issue of egg availability, however, goes well beyond California, reaching out to such places as the United Kingdom, where discounted IVF services are being offered to generate eggs for research.

Sheehy, also a member of the Standards Working Group, pointed to work being done by Cascade LifeSciences in San Diego and others to show that the egg shortage concerns of CIRM President Alan Trounson and Harvard's Kevin Eggan may be overstated.

Sheehy's starting point is a letter for reconsideration of Cascade's rejected application for a CIRM grant. Cascade's letter, which can be found here on the California Stem Cell Report, stated that the firm was collaborating with David Smotrich of the La Jolla IVF clinic to obtain eggs. Cascade said that the clinic had a "list of young and healthy volunteers who desire to donate oocytes specifically for this SCNT project. All these donors were pre-tested and demonstrated a high oocyte production (20-25 oocytes per cycle) in response to homornal stimulation."

Last week Sheehy queried Ken Woolcott, who wrote the reconsideration request, about the availability of eggs, which Sheehy recalled as being 100 a year. Sheehy also asked whether they were obtained under circumstances that would make them available for use by CIRM grantees i.e. proper consent, no payment outside of CIRM policy, etc.

In response, Woolcott, Cascade's chief business officer, emailed Sheehy that he checked with Cascade's primary investigator, Dr. Sophia Khaldoyanidi, as well as Smotrich, head of the collaborating La Jolla IVF clinic. Woolcott replied,

"Dr. Smotrich confirmed that the oocyte donors are only reimbursed for their time and medical care expenses.   These donors are not IVF patients that receive discounts or are paid for their eggs.  They tend to be donors that desire to enhance medical research in the Stem Cell  area, are younger and have a track record of high oocyte quality and productivity. 

"I believe that this is consistent with the draft guidelines prepared by CIRM and is consistent with the law in California.    More importantly, any work in this area would be subject to IRB approval."

Sheehy said that Woolcott's information is "very important" if it "confirms that at least one investigator in California is able to obtain sufficient oocytes to conduct research within the confines of CIRM's ethical standards and the provisions of Prop. 71 and SB 1260(the law that deals with non-CIRM funded hESC research)."

But the devil may well be in the details. In this case, does the La Jolla clinic's definition of reimbursement for "time and medical care expenses" match that of CIRM's?

Consumer Watchdog Rethinks Stand on Klein's Private Contact with Grant Applicants

The man who probably has spent more time than any other independent observer physically watching the affairs of the California stem cell agency now believes that CIRM Chairman Robert Klein did not violate the agency's no-contact rule with grant applicants. We disagree.

It is a change of position for John M. Simpson, stem cell project director for Consumer Watchdog. Earlier he responded to questions from the California Stem Cell Report about Klein's actions, which you can read all about here, by saying there could have been a technical violation.


Simpson now says,

"Upon further reflection, I don't believe Bob Klein violated the Facilities Working Group bylaws when he played a role in negotiating discounts if applicants take all the CIRM money upfront.

"First, the applications were no longer before the Facilities Working Group. The group's work was done.

"Second, the discussions weren't focused on specific applications but on a discount rate that would apply to all equally if accepted.

"Not that it's relevant to whether there was a technical violation, it's also the case that everyone at the meeting -- including me - understood from the discussions that Klein would be involved in the negotiations."

However, the ban in the bylaws does not permit conditions. Drafted by CIRM's outside counsel, James Harrison, the single sentence states flatly:

"Members of the Facilities Working Group shall not communicate with an applicant about an application to CIRM."

The facilities group work is not really done until the CIRM board of directors act. The board has absolute authority over grant approval, as CIRM likes to point out. Directors could well send a recommendation back to a review group for reconsideration.

Another possibility: Sometimes, reviewers make a recommendation that basically says a grant should be funded if there is enough cash. Let's say a reviewer, following the review group action, decides that the applicant needs a little guidance to help bring about directors' approval. He or she could contact the applicant and give them suggestions on how to successfully approach the directors. Under Simpson's construct, that certainly would be permissible.

In this particular case, Klein's proposal to stretch CIRM funds was inventive and successful. But, in our view, he violated the bylaws to do it, although it seems at this point to have created no harm. Nobody is arguing he performed a dastardly deed.

However, bylaws are in place for a reason. If they are violated on relatively minor matters, what does that mean ultimately for CIRM's credibility and integrity.

Response from Grant Applicants on Klein Contact

In an earlier item concerning private contacts by Robert Klein, chairman of the California stem cell agency, with some of the applicants for $262 million in stem cell lab construction grants, we mentioned that we had queried some members of the CIRM board about whether they or their staff had been dealing with Klein on their applications. We also queried other applicants that do not have representation on the CIRM board.

CIRM has since acknowledged that Klein has been in contact with some applicants. The agency contends he has done nothing wrong despite a no-contact rule in the agency's bylaws. (See the "zeal" item below.)

However, for the record, we received responses from five institutions. Two shunted the query to other entities. Three addressed the question at least partially or completely. Of those, only one responded fully to the question of whether he or his staff had contact with Klein. That answer was no.