Stem cell good news briefs: TiGenix, Asterias, CIRM, Awards, & More

TiGenixThere’s a growing stream of stem cell good news of late.

Stem cell biotech, TiGenix, reported encouraging Phase 3 allogeneic results on stem cells. A big milestone. I can’t wait to see the actual data. Its product, Cx601, has so far been safe and effective for perianal fistulas in Crohn’s disease. See more from Alexey on this.

CIRM has funded the largest public stem cell bank in the world. Want to make a withdrawal?CIRM 2.0

Asterias reported some great news. It’s AST OPC-1 product showed some signs of encouraging efficacy in the first three patients treated. They are hoping to expand the trial.

Asterias BioTimeIn about two weeks on September 16th, the first winner of the new Ogawa-Yamanaka Stem Cell Prize will be announced at Gladstone Institutes. This should be a very exciting event honoring a top stem cell translational innovator in the area of cellular reprogramming, who will also received a cash prize of $150,000. According to the organizers, “The Prize was established through a generous gift from Hiro Ogawa to honor the memory of Betty Ogawa, who passed away in May 2014. It continues the philanthropic legacy she shared with her husband of 46 years.” The prize also recognizes Shinya Yamanaka too of course.

Any guesses on who will win? Let us know in the comments. Any kind of recognition of achievement and innovation in stem cells is wonderful.

On that note, I’m also starting to think about candidates for my own stem cell prize, the annual Stem Cell Person of the Year Award. It’s not to the same scale with a $2,000 prize, but I fund it out of my own pocket. The focus is different too. My award goes to the person who has had the single strongest, most innovative impact in the stem cell world for a given year and has taken risks either scientifically or in the area of advocacy. I’m looking for outside-the-box thinkers and doers.

Past winners have included super patient advocate Roman Reed, scientist and politician Elena Cattaneo (who went on to win the ISSCR Public Service Award), and this past year, pioneering stem cell translational scientist Masayo Takahashi. Dr. Takahashi might be a good bet to win the Ogawa-Yamanaka Prize this year.

Who should be nominated this year for the 2015 Stem Cell Person of the Year Award?

It’s not too soon to let me know your thoughts even though nominations don’t officially open quite yet. Last year we had more than two-dozen amazing nominees. The process includes an Internet vote to choose finalists and then I pick the winner from those, sometimes consulting privately with global stem cell scholars.

Getting to know @PubPeer founders including neuroscientist Brandon Stell

For the past few years post-publication peer review (PPPR) has grown in influence and one particular website, PubPeer, has become the primary go-to place specifically for blunt PPPR. The kind that happens in journal clubs in labs across the world. Comments on PubPeer have led to numerous serious corrections and retractions of flawed articles. I’m most familiar with its role in the STAP cell case.

Both the founders of and most of the commenters on PubPeer have remained anonymous.Brandon Stell

That is until today.

The founders of PubPeer have publicly identified themselves in a blog post and formed a new non-profit organization, The PubPeer Foundation.

PubPeer founders include Brandon Stell, George Smith and Richard Smith. Also with the founders on the PubPeer Foundation Board of Directors will be Boris Barbour and Gabor Brasnjo.

Who are these guys?

RetractionWatch (big HT to them) has an interesting interview with PubPeer founder Stell. I highly recommend reading it. Jennifer Couzin-Frankel over at Science also has a nice piece on this development.

Stell is a neuroscientist and Co-Team Leader at the Brain Physiology Lab in Paris, the source of his picture above.

I was trying to learn more about the other two founders, George Smith and Richard Smith. From Couzin-Frankel’s piece it appears that the brothers want to remain relatively out of the limelight, and their very common names may very well aid them in that. Couzin-Frankel does write that Richard was a grad student who briefly worked in Stell’s lab and George is a web developer.

As to the Foundation, RetractionWatch has a helpful quote from Stell on looking ahead:

What role do you hope PubPeer plays moving forward? What plans do you have for the Foundation?

We hope that the PubPeer Foundation will provide us with more opportunities to develop the site in ways that will help grow the community of post-publication peer reviewers and further encourage quality science. As more of us scientists become accustomed to commenting on papers, and as that becomes more of a part of the overall scientific process, I think we’ll be able to finally up-end the backwards reward structure that is currently in place in science.  Hopefully we can get to a point where the data are much more important to a scientist’s career than the journal that published them.

To form the PubPeer Foundation, the leaders could not remain anonymous. It seems like a good thing that the founders of PubPeer have identified themselves. They deserve a lot of credit for having had a transformative impact on how science corrects itself. They’ve also faced tough situations such as being sued by Fazlul Sarkar, a case that is still working its way through the legal system. Sarkar wants to know the identity of some anonymous PubPeer commenters. I predict that the PubPeer Foundation will now receive substantial financial support, which in part can be used to get legal assistance for possible future challenges.

PubPeer has grown quickly, now has a striking following with around 300,000 pageviews/month and contains 35,000 total comments.

ISSCR President Sean Morrison on challenges and future of stem cell field

Sean Morrison M.D.I recently chatted with Sean Morrison, current President of ISSCR, on his goals for the Society, where the stem cell field stands today, top challenges, and the future.

What are your goals for your tenure as President of ISSCR?

SM: ISSCR is the international voice for research in the scientific community. There’s been less effort though amongst policy makers and the general public. I want to expand the reach beyond just the scientists. ISSCR will be building its capacity to participate in stem cell policy issues worldwide and also it’s capacity to communicate with the public.

What’s the plan to make this happen?

SM: A range of things. Beefing up ISSCR communications programs. Blogging, twitter and other efforts.

What are the main challenges & opportunities that ISSCR faces now?

SM: ISSCR has had steady and remarkable growth. It has grown and its scope has grown too. Managing the growth is a challenge. Prioritizing future opportunities. How can we have the most impact for the membership? How can we grow that impact? The annual meeting continues to grow. International ISSCR symposia have grown. Publishing activities have expanded including with Cell Stem Cell and now Stem Cell Reports. We continue to expand those kinds of activities. There is a set of opportunities related to going beyond the science. Our mission is to improve human health through stem cells. We can’t do that solely by meetings and publishing. Those are critical core activities, but there’s more that we can do such as in industry. Reaching out to those stakeholders. Expanding the activities of the Global Advisory Council (philanthropists, Susan Lim, and Deepak), stem cell policy, and communication.

How can ISSCR bring in more industry people?

SM: I do think more involvement of industry is important. How best can we do that? I attended the Industry Committee meeting at ISSCR meeting in Stockholm, where we had that conversation. I really do hope that we can increase the attractiveness and value provided by the annual meeting to people in industry. We want people talking about exciting unpublished data. One difficulty comes up though in this regard: who from industry is willing to talk about unpublished data? Some people have shown up in the past and are not willing to talk about data. The program committee needs to address that.

What’s your view on the evolution of the IPSC subfield?

SM: I’m excited about stem cells generally. We need all kinds of stem cell research to move forward. Historically we’ve not been very good at predicting which cell type will work. I’m very excited about somatic stem cell research and pluripotent stem cells, both embryonic and IPSC. Look at the things going on at Shinya’s institute. They’ve been bold at diverse ways that they can have impact. With each year that goes by, the more plausible scenarios arise for possible therapies using pluripotent stem cells.

The pioneering IPSC trial in Japan was put on hold. How serious is that?

SM: If you’ve been culturing cells, some of the time there’s going to be mutations. The fact that they found the mutations says that the process that they have in place worked. It’s not uncommon in clinical trials for things to go on hold. It’s not unique to stem cell trials or IPSCs. I have every expectation that they’ll get that back on track. 

What are you most excited about with your own research?

SM: We’re doing a lot of work to characterize the HSC niche. We’ve now identified the cells that are sources of the key factors for stem cell maintenance. In many ways the hematopoietic system is a paradigm. This will allow us to understand at a single cell level how the niche works and look for novel growth factors. Each time we identify one of those it has the potential to provide new tools.

What do you see as the most important and exciting stem cell development or trend of 2015 so far?

SM: We’re at an inflection point in terms of stem cell therapies moving into high-quality clinical trials. In 2008 when we were fighting the public policy battles about where the line should be drawn on ESC research. Also there were people making claims about difficult problems. I was skeptical at the time. I felt that a lot of the problems could be too biologically complicated for cell therapies to work. Yet the science has surged forward much more quickly. There’s really exciting preclinical data and actual clinical trials that are about to start or have started. Spinal cord. Macular degeneration. And others. Some people have spent 10-20 years trying to understand the biology. Parkinson’s with Lorenz Studer. Cell therapy for heart disease with Chuck Murry. It’s important for the general public to understand the timeframe and that some will fail. In the past some were just squirting cells into tissues…sort of like buying a lottery ticket. People now understand the biology better. Now we have a rational chance of success.

The debate that is shaping up for CIRM is also very important now. Stem cell research is already delivering and there’s opportunity looking ahead. More funding for CIRM makes sense and it would be a major setback to not do that, especially with declining federal funding. One thing that will distinguish the winning states from the losing states is who has the vision to keep the biomedical research enterprise going at the state level. The conversation changed with CIRM’s birth. It became, “How do we keep up with California?”

The spread of stem cell clinics selling non-FDA approved offerings in the US has accelerated. What should ISSCR and individual stem cell scientists be doing to address this growing problem?

SM: There’s a lot that you’ve done and we appreciate that. There’s also a lot that ISSCR has done. We have our A Closer Look website. ISSCR has spoken out more on this topic than any other topic relevant to the general public. Although stem cell research has enormous promise—and this is the most exciting time that we’ve ever had—unfortunately most people in the general public don’t understand how long it takes to go from the idea or proof of principle in a mouse to do it in humans. Sadly there are fraudulent people out there that are preying on patients. These are at best unproven and in many cases not even plausible therapies.

Where do you see the stem cell field in 5-10 years?

SM:  We should be excited, but I’m always wary of these kinds of predictions. If we look over the last 10 years there’s been a lot of twists in the plot. There’s been both good news and bad news. Some things have surged forward more quickly and some things that we are most excited about now weren’t on our radar screens then. We don’t really know where we’re going to be. But I’m very optimistic. The thing that we have to remember that we always forget, even when we identify an idea that works, it takes a lot of years to get that to a patient. Look how long it took for bone marrow transplant to develop. We now talk about bone marrow transplant as an example but it took 14 years. We should bear in mind that even if some of the things now in clinical trials are correct, it could take years to develop them in a safe and efficient way.

With CRISPR, is GMO also for Google?

Google is reportedly getting into the genetic modification business. It plans to use a sexy, new genetic technology called “gene drive”, which has both excited and unsettled scientists due to its great power to make GMOs in nature via reproductive chain reactions.

This move toward genetic modification is part of a larger trend of Google and now its parent company Alphabet branching out into biology. Alphabet has said that “G is for Google”, but there could be the letters “G-M-O” in there too.

GMO google

I’m not saying there’s anything wrong with GMOs. Some of my own research focuses on GMOs in the lab for genetic research on development and disease, but this move on gene drive technology is a new one for Google and into potentially risky territory.

What Google or at least one of its leaders Linus Upson seems to be contemplating is the use of powerful genetic modification experiments out in nature. It could be done, for example, via gene drive to target mosquitos that transmit malaria and save a lot of human lives. It’s a great idea in principle, but in practice because gene drive technology is so robust and self-propagating it could spiral out of control with huge, unintended consequences.

So what exactly is gene drive?

Gene drive can genetically modify an entire population into GMOs and do it millions of times faster than evolution changes DNA naturally. In principle, any sexually reproducing species can be subject to forced genetic modification with gene drive and the mutations produced would be heritable. The most talked about form of gene drive is powered by a gene editing technology called CRISPR-Cas9.

By analogy, gene drive is like a computer virus but for organisms and one that changes code (in this case DNA via mutations). By design gene drive is sexually transmitted to essentially all offspring. It’s a GMO chain reaction.

For more background, I blogged about gene drive earlier this month and potential concerns over gene drive were the focus of my recent interview with leading geneticist Harmit Malik.

Based on Google’s investment in CRISPR genetic modification company Editas Medicine via Google Ventures and a report from The Information website, it would seem that gene drive is in the company’s future and there’s a seed there already in the present:

“Linus Upson, the man who helped build Google’s Chrome browser alongside new CEO Sundar Pichai, recently said he intended to start a biology project involving genetically engineered mosquitoes that would help wipe out other mosquitoes that carry illnesses like dengue fever and malaria”

Sounds wonderful, right? However, if gene drive went awry there might be almost nothing that we could do about it because it is self-propagating like a virus. Still gene drive is a seductive idea and this plan by Google seems consistent with the new Alphabet corporate path to change the world beyond computing at least in part via Google X, the research arm of Google:

“Whatever happens to the idea, it would seem to fit within the new corporate structure announced Monday by Larry Page, who wants to pursue world-changing ventures far beyond the Web business he’s occupied for nearly two decades. Alphabet’s mission is to incubate and help operate a variety of businesses, from hardware (Nest and a separate robotics division) and “smart” cities (Sidewalk Labs) to self-driving car technology and human biological improvement (Calico and the Google X life-sciences group). The formation of Alphabet, which will run these divisions separately from, but under the same umbrella, as Google, is expected to be completed in the fourth quarter.”

What should we make of Google and Alphabet’s expanding ventures into biology reportedly including now genetic modification and gene drive? I’m not sure, but I hope they realize how powerful and potentially dangerous gene drive may turn out to be.

Paolo Macchiarini cleared of misconduct, but some charges remain

There has been a great deal of excitement during the past several years over the regenerative medicine work of often-called “super surgeon” Dr. Paolo Macchiarini.

Paolo Macchiarini


Hei has done pioneering work. For instance, he created and transplanted bioengineered windpipes that were produced in part via stem cells. However, Macchiarini also faced allegations of multiple serious instances of misconduct from others at Karolinska Institute, where he was a visiting professor. These allegations included charges of deleting or falsifying patient data, and involve seven different publications.

The engineered windpipes were transplanted into three seriously ill patients, two of whom have died while the third has remained hospitalized ever since surgery. We cannot know for sure, but it is quite possible that without treatment all of the patients would have died.

The Karolinska Institute has investigated at least some of the charges and now reportedly has exonerated him. This is a particularly striking outcome because just a few months ago in May a separate, independent investigator (surgeon Dr. Bengt Gerdin) had concluded that the misconduct had in fact occurred. Macchiarini and others reportedly provided additional information to the institution that may have played an important role in the Karolinska decision.

The NYT reports that Macchiarini is not entirely out of the woods yet though as he faces other accusations:

“Dr. Hamsten said that other accusations against the surgeon, regarding whether he had obtained the necessary permits and ethical clearances for the work, were not included in the decision, and that a prosecutor was conducting a preliminary inquiry on those issues.”

In addition to these unresolved issues, the Karolinska wasn’t exactly thrilled with how some of the work had been by done by Macchiarini:

“But the report said that Dr. Macchiarini’s work “does not meet the university’s high quality standards in every respect,” and that it “could therefore be appropriate” for him to submit corrections to some of the published scientific papers that described his work.”

The NYT was able to reach him by email in Russia, where he is now working, for comment on the resolution of the misconduct charges:

“To have been falsely accused of such serious misconduct is every researcher’s nightmare,” he said. “I am very keen that this case prompts a discussion of how such events can be avoided in the future.”

The original investigator, Dr. Gerdin, apparently was not made privy to the new documents of the Karolinska investigation and hence couldn’t comment on the new decision, but he didn’t seem pleased with today’s outcome according to a piece in Science:

“Gerdin says he has not yet read the material submitted in response to his report. But he says the process was flawed, in that it allowed Macchiarini to pull “aces from his sleeve” after the external investigation was complete. That seriously undermined the impartiality of the investigation, he says. “It’s a meaningless process” to commission an independent external reviewer if the final decision is based on documents available only to Karolinska officials, he says.”

In past years, Macchiarini had faced charges in Italy as well, where he reportedly had been arrested (also see news piece in Italian) and related to this some of his work was retracted. I was not able to determine the outcome of the charges in Italy so far, but some have speculated that that was a case of an overzealous Italian prosecutor going after a famous surgeon.

It remains unclear what comes next for the super surgeon, but at least overall Macchiarini appears to have been cleared of the most serious allegations stemming from the Karolinska situation.