Saturday, February 06, 2016

Big Money and Big Science: The Battle Over CRISPR

CRISPR: It’s simply a billion dollar matter of learning more or earning more. At least that’s the view of a Pulitzer Prize-winning columnist at the Los Angeles Times.

“A case of big money shaping science” said the headline on Michael Hiltzik’s piece on the website of California’s largest circulation newspaper. He said the tussle over the patent may be the 21st century’s “era-defining patent fight.”

Hiltzik wrote:
“The contestants are the University of California and the Broad Institute, a Harvard- and MIT-affiliated research foundation endowed by Los Angeles billionaire Eli Broad. At stake are the rights to a breakthrough gene-editing technology known as CRISPR — and more precisely, to billions of dollars in royalties and license fees likely to flow to whichever claimant prevails before the U.S. Patent and Trademark Office (and in the almost inevitable appeals in court).”

CRISPR is a new technique that allows relatively easy editing of human genes. Its potential use, with the possibility of permanent changes in the human race, has triggered an international hooha. Many leading scientists are calling for a moratorium until all the ramifications are fully explored.

The $3 billion California stem cell agency last Thursday held a day-long conference on the issue and announced it would hold a series of hearings into the matter, raising the likelihood of changes in research standards for California stem cell researchers.

The patent dispute, replete with the use of what Hiltzik notes are “outdated legal standards,” involves who was first with CRISPR -- Jennifer Doudna of UC Berkeley or Feng Zhang from Broad.

Both researchers say the patent fight is a distraction. But Hiltzik also wrote,

“Other scientists see the battle as a distasteful example of the influence of big money — and the race for Nobel credit — on basic research. ‘Having prizes and patents involved has transformed what should be one of the greatest success stories for basic research into this nasty, catty fight in which people are behaving poorly,’ says Berkeley biologist Michael Eisen, a colleague of Doudna's and the head of a lab that stands to gain resources if UC wins the patent fight.

“He added on his blog: ‘Neither Berkeley nor MIT should have patents on CRISPR, since it is a disservice to science and the public for academic scientists to ever claim intellectual property in their work.’ Indeed, neither the Doudna nor Zhang teams were the first to identify CRISPR or to use it; the history dates back as far as 1987 and involves researchers in Japan, Spain, Chicago, Quebec and other places’”

Hiltzik, author of the well-received book, "Big Science," said the real question involving CRISPR is whether "the future of the technology will be guided by the need to learn more or the opportunity to earn more."

Hiltzik’s column illuminated the enormous financial imperatives involved in the use of the CRISPR, which are publicly largely a side issue at sessions involving such agencies as California’s stem cell research effort and some international groups. However, the National Academy of Sciences is holding a session next Wednesday that includes a panel devoted to the CRISPR industry. Alta Charo, chair of the academy meeting, told the stem cell agency last week that she hopes that the scope of the market and its financial implications will be explored in more detail at the session, which will be webcast live.

Charo said she hopes for recommendations from her group by the end of the year concerning genetic modification of human embryos. The stem cell agency appears to be moving at the same sort of speed. All of which is a good thing since the lure of huge revenues will certainly stimulate even faster action by profit-hungry companies.
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Friday, February 05, 2016

California's Stem Cell Agency to Tackle Host of Touchy Issues on Human Genetic Changes

California's stem cell agency yesterday embarked on what is likely to be an exhaustive review of genetic alteration of human embryos with likely recommendations for changes in the $3 billion research effort.

The 11-year-old agency plans to examine a host of issues ranging from inadvertent, inheritable changes in the human race to informed consent on the part of patients.  The move emerged from a day-long review of the far-reaching subject at a meeting yesterday of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

Responding to a request from the California Stem Cell Report, Kevin McCormack, senior director for communications for CIRM, laid out the scope of the agency's future steps and gave his impressions of the session, which suffered from audio quality issues in its audiocast. (See here and here.)

McCormack said the issues were "too many and too complex" to produce recommendations immediately. He said,
"In the end it was decided that the most productive use of the day was not to limit the discussion at the workshop but to get those present to highlight the issues and questions that were most important and leave it to the (research standard group) to then work through those and develop a series of recommendations that would eventually be presented to the (agency's governing) board."
Matters to be addressed include the following, McCormack said, 
  • Possible changes in language used in getting informed consent from donors in light of the ability of Crispr to make relatively easy changes in human changes. Crispr is a new technique that has brought the whole question to international attention. 
  • Use of Crispr on previously donated materials/samples where general consent was given without knowing that these technologies could be available 
  • Genetic modification of mitochrondial DNA as well as genetic DNA. 
  • The possibility that somatic cell gene editing may lead to inadvertent germ line editing 
  • Engaging patient advocates and other community groups such as the social justice and equity movements for their views. McCormack said, "After all, we are a taxpayer-created and funded organization so we clearly have some responsibility to the wider California community and not just to researchers and patients." 
  • Financing the use of Crispr and other technologies that can modify the human embryo provided those embryos are not going to be implanted in a human uterus. 
Here is the full text of McCormack's summary, which we suspect is going to be turned into an item for the agency's own stem cell blog, The Stem Cellar.
"The meeting began with the hope that it would produce a strong, robust discussion of the issues surrounding the use of CRISPR to edit human embryos and to result in a series of recommendations that the Standards Working Group (SWG) could then forward to the CIRM Board on whether any changes needed to be made to our existing rules and regulations about funding such research.
"It turned out to be a thoroughly fascinating day with some thought-provoking presentations and equally thought provoking questions from the audience, from scientists, social researchers and members of the public.

"It quickly became clear that the discussion was going to be even more robust than we imagined and the issues raised were too many and too complex for us to hope reaching any conclusions or producing any recommendations in one day.

"In the end it was decided that the most productive use of the day was not to limit the discussion at the workshop but to get those present to highlight the issues and questions that were most important and leave it to the SWG to then work through those and develop a series of recommendations that would eventually be presented to the Board.
"The questions to be answered included but are not limited to:
"1) Do we need to reconsider the language used in getting informed consent from donors in light of the ability of CRISPR and other technologies to do things that we previously couldn’t easily do.

"2) Can we use CRISPR on previously donated materials/samples where general consent was given without knowing that these technologies could be available or can we only use it on biomaterials to be collected going forward.

"3) Clarify whether the language we use about genetic modification should also include mitochrondial DNA as well as genetic DNA.

"4) The possibility that somatic cell gene editing may lead to inadvertent germ line editing
"5) How do we engage with patient advocates and other community groups such as the social justice and equity movements to get their input on these topics – do we need to do more outreach and education among the public or specific groups and try to get more input from them (after all we are a taxpayer created and funded organization so we clearly have some responsibility to the wider California community and not just to researchers and patients)

"6) As CIRM already funds human embryo research should we consider funding the use of CRISPR and other technologies that can modify the human embryo provided those embryos are not going to be implanted in a human uterus.

"This was a really detailed dive into a subject that is clearly getting a lot of scientific attention around the world and is no longer an abstract idea but is rapidly becoming a scientific reality. The next step is for a subgroup of the SWG to put together the key issues at stake here and place them in a framework for another discussion with the full SWG at some point in the future.

"Once the SWG has reached consensus their recommendations will then go to the CIRM Board for its consideration. 
"I hope this captures the flavor and essence of what happened today. It really was a fascinating discussion and the issues raised, and their complexity, highlighted why so many different groups around the world are wrestling with the potential, and pitfalls, of this new technology."
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Thursday, February 04, 2016

Coverage Concluded on California Human Genetic Modification Conference

The California Stem Cell Report is concluding its live coverage of today's California conference on human genetic modification of human embryos. The quality of the stem cell agency's audiocast is so poor that it is impossible to compile an accurate account of what the speakers have to say.

We hope to bring readers more information on the impact of the proceedings on California stem cell research when written accounts of the meeting become available. Sphere: Related Content

California Stem Cell Agency Not Now Financing Genetic Modification of Human Embryos

The $3 billion California stem cell agency is not currently backing research that involves genetic modification of human embryos, but its standards appear to allow that possibility. 

The agency discussed its research rules at its conference today on the controversial subject. One of the slides presented by the agency said that its research standards group's intent under current regulation was "to allow for in-vitro use of human embryos for research while prohibiting reproductive use."

Earlier this week, the California Stem Cell Report queried the agency about the extent of  human genetic modification in research financed by the agency. Kevin McCormack, senior director of communications for the agency, replied, 
"As for the number of awards involving human genetic modification that’s a large number, five of our clinical trials in HIV/AIDS and our work with Sickle Cell Anemia and Chronic Granulatomous use human genetic modification techniques and many other preclinical/translational research projects do as well. 
"I think what’s more important is that right now none of our awards involve the genetic modification of human embryos, and that’s obviously the goal of the workshop to see if this is something we should fund and under what circumstances and with what controls in place." 
Today's presentation also said that stem cell agency "rules on clinical use of gametes and embryo are consistent with the statement from the International Summit on Human Gene Editing and the Draft ISSCR Guidelines."

Here are the presentation slides from the agency.
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California Crispr Conference -- Presentation Slides

Here are presentation slides from some of the speakers at the California stem cell agency conference today on genetic modification of human embryos. They include Jonathan Kimmelman, Alta Charo and Amander Clark.
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California Crispr Conference Has Begun but Audio Feed is Less Than Adequate

The audiocast from the California Crispr conference remains garbled although the session appears to be well underway. We expect to post some slides from the presentations shortly which CIRM has emailed to the California Stem Cell Report. Sphere: Related Content

Waiting for the California Crispr Conference

The California stem cell agency is testing the ATT audiocast line to its conference this morning on the genetic modification of human embryos. We believe the conference has not yet started with its presentations. Sphere: Related Content

Monday, February 01, 2016

World's First Approval of Genetic Changes in Human Embryo; California Eyes the Issue Thursday

The Guardian newspaper in England did not back away from the big science story today. Its article by Haroon Siddique said flatly in the first paragraph,
“Britain’s first genetically modified human embryos could be created within months….”
Siddique's piece dealt with the approval today by the key regulatory body in the United Kingdom for genetic changes in human embryos, a topic of international controversy and concern but with a special connection to California.

The news came as the state’s $3 billion stem cell agency plans a full-day examination Thursday of the issue and its implication for research in the Golden State. Of particular concern is a gene editing tool called Crispr that makes it much easier to alter genes and raises the possibility of permanent changes in the genetic make-up of the human race.

The journal Nature said the UK action was “the world's first endorsement of such research by a national regulatory authority.”

Kevin McCormack, spokesman for the California stem cell agency, told the California Stem Cell Report that the move demonstrated the timeliness of this week’s conference, which could lead to changes in California stem cell research standards.

Eminent scientists internationally have called for a go-slow approach until the issues are examined more closely. Leading that effort is David Baltimore, a Nobel Prize winner and a former member of the state stem cell agency board. He is scheduled to speak at Thursday’s session.

Baltimore was interviewed today by Nicholas Wade for a piece in the New York Times. Wade wrote that Baltimore “said the proposed experiment appeared to be consistent with the principles laid out by the (scientific) academies.
“Many such experiments are impossible for government-funded researchers in the United States because of the congressional ban (on destruction of embryos in federal research), but ‘luckily, private and state funding sources are available to carry forward such work,’ Dr. Baltimore said.”
The research in the UK is expected to be conducted with embryos donated via an IVF process. The UK rules restrict the length of the experiment to 14 days. None of the embryos will be transplanted to a womb, according to the rules.

In California, the Center for Genetics and Society in Berkeley issued a news release raising questions about the UK action. Marcy Darnovsky, executive director of the center, asked,
“Is today's decision part of a strategy to overturn the widespread agreement that puts genetically modified humans off limits?”
Her statement said, 
“The designer-baby question is a social and political question more than a technical one, and we are at a tipping-point moment on it. Now is the time to ensure that gene editing is not used to create GM babies, and that we stay off the high-tech road to new forms of inequality, and to a consumer-driven form of eugenics.”
Stem cell researcher Paul Knoepfler of UC Davis, author of “GMO Sapiens: The Life-Changing Science of Designer Babies,” wrote on his blog,
“It’s frustrating for us biologists that we still know more about the development of other animals (e.g. mice or fruit flies) than that of our own species. Crispr could change that and I believe it could do it in a big way. So with the appropriate oversight, bioethics training, and transparency, I could support this Crispr work in the UK. I need time to read up on what exactly they have planned….”
Thursday’s conference in Los Angeles will be audiocast live via an 800 number. It is also a public meeting at which anyone can make comments. Directions for the audiocast and the specific location are on the meeting agenda. The California Stem Cell Report will be providing live coverage of the day’s discussions.
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Sunday, January 31, 2016

California CRISPR: Three Golden State Researchers Slated to Explore Gene Editing Directions

Three California stem cell researchers are on tap this week to discuss current and future projects that could involve the state's $3 billion stem cell research agency, CRISPR concerns and the possibility of scientific missteps or worse.

The trio is scheduled to speak at a day-long conference Thursday in Los Angeles which has been convened by the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

The CRISPR technique allows relatively easy changes in genes, including alterations that could be inherited and become part of the human race.

The possibilities have stirred concern internationally, leading many blue-ribbon scientists to call for a moratorium on use of the technique in some cases.

CIRM has promised a full array of bioethicists and others for its conclave. Specifically scheduled to explore research directions in California are Jacob Corn, managing director and scientific director of the Innovative Genomics Initiative at UC Berkeley; Amander Clark, professor and vice chair of the Department of Molecular, Cell and Developmental Biology at UCLA, and Juan Carlos Izpisua Belmonte of the Salk Institute and former director of the Center for Regenerative Medicine in Barcelona.

Clark and Izpisua Belmonte are both recipients of awards from the California stem cell agency.
Juan Carlos Izpisua Belmonte
Salk photo

Izpisua Belmonte has received three CIRM grants totaling $6.6 million, one of which deals with vascular disease. He filed a progress report on the research that said, 

“During the course of this project we have been able to identify novel genetic elements and laboratory conditions facilitating the conversion of human skin cells to vessels comprising the vascular system. The generation of vessels in the laboratory may allow for the treatment of multiple human maladies including ischemic situations.”
Clark received a $1.2 million award from CIRM dealing with human embryonic stem cells. Her CIRM progress report said that the research resulted in development of 15 new hESC lines and will help improve understanding of Down Syndrome.
Amander Clark, UCLA photo

Corn is closely connected to Jennifer Doudna, who is executive director of Berkeley’s Innovative Genomics Initiative. Doudna developed the CRISPR technique at her lab at Berkeley. 

Jacob Corn, UC Berkeley photo
Last month, Corn provided a “translation” of the statement from the widely publicized international conference in December on human gene editing.

Corn wrote, at one point, that the document said “trans-generational gene editing could be very unfair, and might extend ‘rich get richer’ societal problems into our very genes, and trans-generational edits could change our own evolution more than societal influences, and it’s not clear that we actually want to or should do that.”

In addition to the public session in Los Angeles, Thursday's meeting will be available via an audiocast. Directions are on the agenda, but allow some time in advance for setting up your access.
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Wednesday, January 27, 2016

Human Genetic Alteration and Gold Mines: California's Stem Cell Agency Takes a Hard Look at Research Standards

The $3 billion California stem cell agency next Thursday will convene a day-long examination of human gene editing, a field that could be a “gold mine for biotechnology” and perhaps alter the human race permanently.

“Easy DNA Editing Will Remake the World. Buckle Up.” is the way Wired magazine put it in a headline on a lengthy overview article last July.

The piece by Amy Waxmen said that gene editing has “already reversed mutations that cause blindness, stopped cancer cells from multiplying, and made cells impervious to the virus that causes AIDS.”

The key focus is on CRISPR, which is a technique developed at UC Berkeley and which is involved in substantial amounts of the research funded by the California stem cell agency. CRISPR, according to one description, makes changing genes as easy as cutting and pasting changes in this article.

The session next week at Los Angeles International Airport is chock-a-block with big names in
scientific research and ethics, including David Baltimore, a Nobel Prize winner, former president of Caltech and a former member of the stem cell agency board. At an international CRISPR
David Baltimore, Pasadena Now photo
 conclave in December, Baltimore said,
“The overriding question is when, if ever, we will want to use gene editing to change human inheritance.”
The New York Times reported that the group called for what would be, “in effect,” a moratorium on making inheritable changes to the human genome.

In addition to Baltimore, next week’s California conference is scheduled to hear from Alta Charo of the University of Wisconsin and a leading authority on bioethics; Hank Greely, a specialist in bioscience issues at Stanford law school; Jonathan Kimmelman, a bioethicist from Canada’s McGill University, and Charis Thompson, founding director of the Science,
Charis Thompson, UC Santa Cruz photo
Technology, and Society Center at UC Berkeley, along with a number of scientific researchers.

The agenda for the meeting states that the stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), “will continue to support groundbreaking stem cell treatments and technologies, including gamete and embryo research, from their inception to translation.”

“In light of recent science-policy initiatives,” said the CIRM document, the agency’s research standards group has been asked to examine the agency’s policies dealing with human gene editing.

“One objective of this review is to ensure CIRM research continues to be conducted under the highest medical and ethical standards,” the agency said.

An upshot from next week’s meetings could well be changes in what is permitted to be done by the hundreds of researchers who have funding from the stem cell agency. Beyond that, decisions by the Golden State agency are likely to influence other funding agencies and researchers globally.

CIRM already has alliances with a number of countries, including China, Spain, Israel and Poland. And the agency is closely watched by many from outside California.

Many of the stem cell agency’s meetings of much less import are available live on the Internet. The meeting agenda initially did not list such access. The California Stem Cell Report earlier this week queried the agency about audiocast or Internet access to the session.

Kevin McCormack, senior director of communications, replied late today, 
“When it comes to CIRM, transparent is the new black. Yes, we will be having an audio feed for the standards working group on Feb 4th. Details will be posted on the website shortly.”
The agenda also has links to several useful background pieces along with the names of other invited participants.
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Monday, January 25, 2016

A Book Review: Stem Cell Battles in California, a Pioneer's Perspective

(Editor's note: The following book review was offered by Raymond Barglow of Berkeley, who describes himself as a veteran of the Proposition 71 ballot campaign of 2004.) 

By Raymond Barglow

Don Reed's new book "Stem Cell Battles: Proposition 71 and Beyond" (available at Amazon) gives us an insider's perspective on the historical whirlwind that today is driving forward medical research in California and elsewhere. The author, who has been called the "Grandfather of Stem Cell Research Advocacy" for his longstanding commitment to this cause, is intimately familiar with the community of scientists, politicians, and patient activists who first came together over a decade ago to advocate stem cell research. Their signature achievement has been passage of Proposition 71 in California, which established financing for the research to the tune of three billion dollars. Largely as a result of their effort, we stand today at the threshold of medical breakthroughs that will save millions of lives.

As Reed explains, the stem cell research mission is advanced out not only in laboratories but also in the centers of political power. The research requires funding and has to withstand attack from
Don Reed on right, left is Bob Klein, former
 chairman of the stem cell agency,  and center is
Arnold Schwarzenegger, former governor of California
religious fanaticism that aims to shut it down. Standing staunchly against publicly funded embryonic stem cell research have been not only anti-government conservatives but also fundamentalist religious organizations and Catholic officialdom.

Claiming that the very earliest embryo, consisting of a few hundred cells and so small that it is invisible to the naked eye, has a sacred "right to life," opponents of embryonic stem cell research have organized to defeat funding in federal and state legislatures and have sued in court to make the research illegal. This has been and continues to be a hard-fought battle, with neither side clearly prevailing to date.

In the 1980s and '90s, AIDS activism united patient advocates with doctors and scientists to push forward the search for cures. Less well known is the stem cell research movement whose equally challenging path forward Reed chronicles for us. Although the story that he tells begins in California, many milestones have also been achieved in other states and abroad. Researchers in Canada, China, Singapore, Brazil, Japan and many other countries form a worldwide community to advance the search for deeper understanding of diseases and the invention of effective stem cell treatments to cure them. In a world torn apart by narrow interests and violent antagonisms, we have much to learn from the example of impassioned cooperation that the worldwide stem cell research community has set.

In brief, Don Reed provides in this book an inside view of the stem cell research saga, and he's done so with wisdom, spirit, and a sense of humor that combine to make the book entertaining as well as profoundly illuminating. Sphere: Related Content