STAP Voted as the Stem Cell Story of the Year for 2014

Stem Cell Story of 2014When I asked the readers of this blog what they felt was the biggest stem cell story of 2014 in a poll, they overwhelmingly picked the STAP cell scandal.

For background on STAP you can toggle through the many STAP cell pieces on this blog here, see a STAP timeline, and a STAP image gallery.

Basically, STAP was a bogus scientific claim about a supposedly simple reprogramming method to make powerful stem cells induced by cellular stress.

Despite many flaws in this STAP research and the fact that it seemed way too good to be true, STAP was published in two Nature papers that came out toward the end of January 2014 that are now retracted.

The STAP mess was the product of many things going wrong, almost a perfect storm of research missteps and some have said even misconduct as well as arguably puzzling editorial decision making at one of the most prestigious journals in the world, Nature. Discussion of STAP pointed to more specific, serious problems. Image and data reuse. Plagiarism. Hype. Rush to publish. Unhealthy competition. Gift authorship. And more.

At some point we need to move on from STAP and thankfully that is happening, but there is still more to discuss before we can really fully move on and focus more squarely on the positive stuff. For example, a few puzzles remain about STAP such as where the supposed STAP cells really came from and also how Nature ended up publishing the STAP work when the scientific reviewers that Nature itself enlisted to review the submitted manuscripts skewered them.

The younger generations of scientists in the stem cell field are also watching how the field handles STAP and other events that invoke similar problems too. What lessons will they and the public take home from all of this? There are so many very real, wonderfully positive developments ongoing in the stem cell and regenerative medicine fields that I would rather be discussing instead of STAP, but we have to be careful. The risk that STAP-like events pose to our field comes in the form of a possible harmful narrative of the stem cell field fundamentally losing the public trust.

The 12 months of stem cell blog mass

12 days of ChristmasInspired by DrugMonkeyBlog, I have gone through and listed the first ipscell.com blog posts of each of the 12 months of 2014. It makes for a surprising summary of the year. Think of it as the 12 months of stem cell blog mass (12 days of Christmas image from Wikipedia).

Just for fun, I’ve included both the blog post title and the first sentence of each post.

2014

Jan: Stem Cell Outreach Success in Spanish: ¿Qué son las células madre? I’ve been working on a stem cell outreach program for education (SCOPE) the last couple years.

Feb: Interview with Charles Vacanti on STAP Cells: Link to Spore Stem Cells & More. The recent publication of two Nature papers on acid treatment produced stem cells (so-called STAP stem cells) has been a blockbuster story in the stem cell field and has grabbed major global media attention as well. 

Mar: Latest STAP stem cell whispers: glimmers of hope or mirages? I’ve heard several reports now that labs can sometimes see some kind of either Oct4-GFP reporter activity or pluripotency gene expression in acid treated cells, but the scientists do not seem particularly encouraged.

April: RIKEN Report Is Virtual Acid Bath of Criticism for Obokata: What’s Next? RIKEN Institute in Japan has formally announced the complete findings of its investigation into the STAP cell research and Nature papers.

May: Welcome CIRM 2.0 and President Mills. The future is now.

June: Human skin stolen from regen med firm? The AP reports that one Gary Dudek of Pennsylvania is facing criminal charges for allegedly stealing more than $350,000 worth of human skin from a Massachusetts regenerative medicine company that was his former employer.

July: The Measures Size Up Stem Cells. Last week I visited NIST, the National Institute for Standards and Technologies in Gaithersburg, Maryland as a member of a review panel.

Aug: STAP cell scandal image galleryWant to go the links associated with specific images? 

Sep: Given a do-over, would you still go to grad school again? Take Our Polls. Science is a wonderful field to be in, but there are many challenges too and in some ways things have gotten more complicated and difficult.

Oct: Home stretch on October deadline NIH grant & I’m…(fill in the blank). Grant deadlines are no picnic.

Nov: Open letter to UK Parliament: avoid historic mistake on rushing human genetic modification. Dear UK Parliament and Science and Technology Committee,

Dec: New Interview with FDA on Key Stem Cell Regulatory Issues & Its Own Research. It’s been a seemingly rather quiet year on the regulatory front in the US when it comes to direct-to-consumer stem cell interventions even as the number of dubious stem cell clinics continues to skyrocket.

Diverse Stem Cell Person of the Year 2014 Award Finalists

Stem Cell Award Poll 2014With more than 4,142 votes cast, the readers of this blog have chosen the top 12 finalists for the Stem Cell Person of the Year Award for 2014 from the 27 nominees.

You can see the final vote tallies at left. The votes came from more than 50 countries with some interesting geographic patterns (I may do a post on that as a follow up).

I’ve pasted the brief bios of the twelve finalists below at the end of this post.

Now comes the tough task for me to pick a single winner from this amazing group. I will announce the Stem Cell Person of the Year 2014 within 1-2 weeks.

The finalists are a diverse group. They include scientists from academia and industry, patient advocates, a blogger, and the Pope. We have six male and six female finalists who live all around the world including in the US, Japan, Sweden, Canada, and Vatican City.

I’m happy to see both some familiar faces from nominees and finalists from past years and new ones too.

Who would you pick as the one winner and why? Post in the comments.

Finalists Bios (including in bold quotes from nominators)

Chris Fasano. A principal investigator at the Neural Stem Cell Institute where he uses stem cells to study early nervous system development. “Chris stands out for his energy, enthusiasm, dedication to the field, creativity and accomplishments.”

Don C. Reed. Long-time stem cell research advocate who played a key role in the success of Prop 71 and the creation of CIRM. “A tireless stem cell advocate always there to make a positive difference.”

Janet Rossant. Professor, University of Toronto. Stem Cell Researcher and Past President, ISSCR. “She works tirelessly to create new opportunities and collaborations…globally respected for her work in early development and embryonic stem cells”

Judy Roberson. Long-time Huntington’s Disease patient advocate. “She makes concrete positive developments happen such as millions of dollars in research funding for HD.”

JuuichiJigen. Japanese blogger who investigates scientific misconduct and played a key role in revealing the STAP scandal. He was the first to investigate and bring to the public of problems with STAP papers. His investigations demonstrated the role of social media and post-publication peer review in rapid self-correction of science.”

Malin Parmar. Associate Professor, Developmental and Regenerative Neurobiology, Lund University. Top neural regeneration scientist. “Young, hard worker who is doing very well”.

Masayo Takahashi. Stem cell researcher leading the team that is doing the first ever clinical study based on human iPS cells. “Creative and courageous clinical stem cell researcher.”

Pope Francis. Leader of Worldwide Catholic Church. “Strong supporter of adult stem cell biotechs and research”.

Robert Lanza. CSO of Advanced Cell Technology, which has multiple ES cell-based clinical trials ongoing. “Visionary and practical so makes the impossible possible with stem cells”.

Susan Solomon. Co-Founder and CEO of The New York Stem Cell Foundation (NYSCF). Remarkably effective advocate for stem cell research. “Not many leaders have created their own research laboratories and raised $100 million plus. Seriously, what an accomplishment!”

Ted Harada. Leading stem cell research advocate and very effective ALS patient advocate. “An Energizer Bunny for the ALS community and stem cell advocate”

Tory Williams. Stem cell advocate and author of the 2014 book, Inevitable Collision. Co-Founder and Executive Director of the Alabama Institute of Medicine (AIM). “A true hero who inspires and makes real things happen like AIM”.

Yamanaka Interview on Clinical Use of Pluripotent Stem Cells

Dr. Shinya Yamanaka

Dr. Shinya Yamanaka.                                           Photo from CiRA, Kyoto University

I invited Nobel Laureate Shinya Yamanaka to do an interview on the future of clinical translation of induced pluripotent stem cells (iPSC).

He provides some intriguing new insights into the iPSC field and the broader stem cell arena.

PK: The Takahashi Team’s active Clinical Study using iPSCs to make RPEs to treat Macular Degeneration has generated a great deal of excitement. Can you please share your perspectives on the importance of this work and the team involved? 

SY: This is the first study to apply iPSC technology to human care. This is a very important study, because if it succeeds it will show that iPSCs can be safely used in humans and also their potential for cell transplantation treatment. We collaborated with Dr. Masayo Takahashi of RIKEN CDB by evaluating the safety of the iPSCs and iPSC-derived cells that were used for the cell transplantation. She is an excellent researcher, and I am not surprised that her team is the first to have succeeded in this transplant.

PK: Any cutting edge investigational clinical work such as this has some risks. Could you please comment on the potential risks in this iPSC trial? Are there some elements here such as preclinical data, the number of cells used, or the target tissue of the eye that lower risks?

SY: One of the major concerns is whether transplanted cells such as the RPE sheets will cause tumors. In our collaboration with Dr. Masayo Takahashi’s team, we evaluated the safety of iPSCs and iPSC-derived cells by genome and epigenome analysis. While we minimized the risk to a level acceptable for clinical trials, we really cannot confirm how the cells will respond until we actually do experiments with humans, which is why this project is so important. One advantage of treating age-related macular degeneration is that it is easy to detect any abnormalities in the eyes, which is why the disease is a good starting model for iPSC-based treatment.

PK: As the inventor of iPSCs did you imagine 7-8 years ago that a patient in a clinical study in 2014 would already have received an iPSC-based treatment? How was this rapid translation from bench to bedside possible?

SY: I was surprised that after the announcement of human iPSCs in 2007, Dr. Takahashi told me that she would bring iPSC to the bedside within five years. I thought it possible technically speaking, but doubted it could be done so soon, since we needed to improve the technology and get government approval. It took 7 years, which is remarkable considering the work required. Both the accomplishment and the speed at which it was achieved are testaments to Dr. Takahashi’s leadership and her strong team.

The rapid transition is because many bright and passionate people are in the iPSC field. The funding and infrastructure provided by the Japanese government is also a major factor, as these have encouraged excellent scientists to enter the field.

PK: We are also starting to hear more about Dr. Jun Takahashi’s Team’s important work towards using iPSCs to treat Parkinson’s Disease. Can you please tell us more about that?

SY: Prof. Jun Takahashi’s team at CiRA is working on cell therapy for Parkinson’s disease, aiming to transplant iPSC-derived dopaminergic neural progenitor cells into PD patients’ brains. Early results suggest this treatment can be effective, and his team has established the protocol for transplantation. They are now focusing on validating its safety using monkey models. We hope his work will soon reach the operating room within the next few years.

PK: What other clinical applications of iPSC technology are in the works and that might begin clinical studies in the next few years?

SY: There are two major clinical applications of iPSCs, namely regenerative medicine and drug discovery. CiRA has a number of researchers working on either or both. For regenerative medicine, Prof. Koji Eto at CiRA is working on generating platelets via iPSCs, and we expect this will also proceed to clinical research in a few years. Besides work at CiRA, a team at Keio University has a plan to conduct clinical research on patients with acute spinal cord injury in four to five years, while Osaka University and Keio University hope to transplant iPSC-derived cardiac myocytes into patients with heart diseases within a few years. CiRA is collaborating with these teams as well.

Regarding drug discovery, you may have heard recently of CiRA’s Prof. Noriyuki Tsumaki’s paper about statins effects on bone growth, which was published online in Nature last month.

PK: Some in the media are taking about a certain tension between clinical iPSC work in Japan and clinical iPSC work in the US. Do you believe such a tension exists and if so, why? What does it mean for the iPSC field overall?

SY: I am not sure what “tension” means. I understand that both competition and collaboration exist between the US and Japan.

PK: How do you view hESCs today? Are there hESC clinical trials or potential applications that are of particular interest? What is your view of the argument by some that hESC are no longer needed?

SY: Human ESC was a great discovery for regenerative medicine and also instrumental to the discovery of iPSC and the type of medical treatments we are aiming to apply iPSC. At the same time, the ethical issues that hESC possess mean that as iPSC technology improves, hESC will be less needed. Still, iPSC is a new technology, and its safety and efficacy still needs to be confirmed. In addition, there may be some therapies for which hESC are better than iPSC. Thus, I think basic and clinical research of hESC is also important and should be done in parallel with iPSC research.

PK: What excites you most about the stem cell/regenerative medicine field right now today?

SY: I am excited about the possible number of people treated with iPSCs. This field has great potential to provide treatments for currently incurable diseases. Hopefully, within 5 years, we will refer to Dr. Masayo Takahashi’s AMD work as just one of many patient studies using iPSCs.

PK: Where do you see the iPSC field and the broader stem cell field in say 5-10 years?

SY: It is pretty amazing how much it has changed in the past years, so predicting the next 5-10 years is very difficult. I certainly hope we will see more diseases being treated with iPSC and related technologies such as direct reprogramming. I also hope that iPSC will be used more widely and routinely in drug development.

PK: What advice would you give to young scientists today who are excited about a career in stem cells/regenerative medicine?

SY: Through biomedical research, you could help thousands of patients in the future. Stem cells provide unprecedented opportunities in stem cell therapy and drug development. Biology of stem cells itself is extremely interesting. I hope many young scientists will enter to this field.

“Magical” STAP papers were blistered by Nature’s own reviewers, but then accepted just months later

The reviews of a STAP paper submitted to and rejected by the journal Science in 2012 were posted at Retraction Watch yesterday. They filled in some gaps in the puzzle of the series of events that led to such flawed science being published in Nature in January 2014, but the reviews also raised more questions.

Today, more STAP paper reviews have surfaced.

ScienceInsider posted a piece with additional STAP paper reviews with these coming from Nature reviewers commenting on what would later become accepted and published by Nature only months later in seemingly only moderately revised form.

The Nature reviews (you can read them here on the Science website) are very critical of the STAP papers and raise a host of important, largely still unanswered questions about STAP.

STAP magic

My overall sense is that the three reviewers did a thorough and fair job of reviewing these STAP papers. It sure seems that none of the three reviewers were even remotely close to being comfortable with these papers being published in Nature. In each case it would seem that a major revision would have been necessary prior to even having a remote chance at publication. One of the reviewers summed up a STAP cell article as essentially reporting an unproven, “magical” approach (see screenshot above).

The ball is now firmly in Nature‘s court to facilitate a thorough understanding of the STAP situation. It seems reasonable to expect more from Nature than its one editorial that shrugged off any significant responsibility including this key portion:

“We have concluded that we and the referees could not have detected the problems that fatally undermined the papers. The referees’ rigorous reports quite rightly took on trust what was presented in the papers.”

Nature‘s own reviewers’ comments would seem to directly challenge this statement.

I’m not going to go through all of these criticisms and questions raised in these reviews of the originally submitted Nature STAP papers point-by-point, but the overall consensus was that these papers were seriously flawed. This fits well with the gestalt of the reviewer comments on the rejected STAP/SAC paper at Science.

If you look at the published STAP cell Nature papers and think about the details mentioned in these acidic reviews of the original forms of the same papers, there is a sense that not much fundamentally was improved in the papers during that intervening period of months.

The big question remains then: how did these STAP papers go from being rebuffed based on scathing reviews at Nature on April 4, 2013 to acceptance by the same journal on December 20, 2013 and publication about a month later?