Nature 511 Stem Cell Controversy NOT to be confused with The Nobel Prize in Physiology or Medicine 2012 Sir John B. Gurdon, Shinya Yamanaka

Press Release

2012-10-08

The Nobel Assembly at Karolinska Institutet has today decided to award

The Nobel Prize in Physiology or Medicine 2012

jointly to

John B. Gurdon and Shinya Yamanaka

for the discovery that mature cells can be reprogrammed 
to become pluripotent

Summary

The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body. Their findings have revolutionised our understanding of how cells and organisms develop.

John B. Gurdon discovered in 1962 that the specialisation of cells is reversible. In a classic experiment, he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.

Shinya Yamanaka discovered more than 40 years later, in 2006, how intact mature cells in mice could be reprogrammed to become immature stem cells. Surprisingly, by introducing only a few genes, he could reprogram mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body.

These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.

Life – a journey towards increasing specialisation

All of us developed from fertilized egg cells. During the first days after conception, the embryo consists of immature cells, each of which is capable of developing into all the cell types that form the adult organism. Such cells are called pluripotent stem cells. With further development of the embryo, these cells give rise to nerve cells, muscle cells, liver cells and all other cell types - each of them specialised to carry out a specific task in the adult body. This journey from immature to specialised cell was previously considered to be unidirectional. It was thought that the cell changes in such a way during maturation that it would no longer be possible for it to return to an immature, pluripotent stage.

Frogs jump backwards in development

John B. Gurdon challenged the dogma that the specialised cell is irreversibly committed to its fate. He hypothesised that its genome might still contain all the information needed to drive its development into all the different cell types of an organism. In 1962, he tested this hypothesis by replacing the cell nucleus of a frog's egg cell with a nucleus from a mature, specialised cell derived from the intestine of a tadpole. The egg developed into a fully functional, cloned tadpole and subsequent repeats of the experiment yielded adult frogs. The nucleus of the mature cell had not lost its capacity to drive development to a fully functional organism.

Gurdon's landmark discovery was initially met with scepticism but became accepted when it had been confirmed by other scientists. It initiated intense research and the technique was further developed, leading eventually to the cloning of mammals. Gurdon's research taught us that the nucleus of a mature, specialized cell can be returned to an immature, pluripotent state. But his experiment involved the removal of cell nuclei with pipettes followed by their introduction into other cells. Would it ever be possible to turn an intact cell back into a pluripotent stem cell?

A roundtrip journey – mature cells return to a stem cell state

Shinya Yamanaka was able to answer this question in a scientific breakthrough more than 40 years after
Gurdon´s discovery. His research concerned embryonal stem cells, i.e. pluripotent stem cells that are isolated from the embryo and cultured in the laboratory. Such stem cells were initially isolated from mice by Martin Evans (Nobel Prize 2007) and Yamanaka tried to find the genes that kept them immature. When several of these genes had been identified, he tested whether any of them could reprogram mature cells to become pluripotent stem cells.

Yamanaka and his co-workers introduced these genes, in different combinations, into mature cells from connective tissue, fibroblasts, and examined the results under the microscope. They finally found a combination that worked, and the recipe was surprisingly simple. By introducing four genes together, they could reprogram their fibroblasts into immature stem cells! 

The resulting induced pluripotent stem cells (iPS cells) could develop into mature cell types such as fibroblasts, nerve cells and gut cells. The discovery that intact, mature cells could be reprogrammed into pluripotent stem cells was published in 2006 and was immediately considered a major breakthrough.

From surprising discovery to medical use

The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.

Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.

For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.

 

Sir John B. Gurdon was born in 1933 in Dippenhall, UK. He received his Doctorate from the University of Oxford in 1960 and was a postdoctoral fellow at California Institute of Technology. He joined Cambridge University, UK, in 1972 and has served as Professor of Cell Biology and Master of Magdalene College. Gurdon is currently at the Gurdon Institute in Cambridge.

Shinya Yamanaka was born in Osaka, Japan in 1962. He obtained his MD in 1987 at Kobe University and trained as an orthopaedic surgeon before switching to basic research. Yamanaka received his PhD at Osaka City University in 1993, after which he worked at the Gladstone Institutes in San Francisco, USA and Nara Institute of Science and Technology in Japan. Yamanaka is currently Professor at Kyoto University, where he directs its Center for iPS Research and Application. He is also a senior investigator at the Gladstone Institutes.

Key publications:

Gurdon, J.B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology 10:622-640.

Takahashi, K., Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.

 Link: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html

Scientist who created STAP stem cells says studies should be withdrawn

This controversy has been brewing for more than 5 months, judging by this article from March 11, 2014.  Almost from the time they were first published in the January issue of the journal Nature.

Teruhiko Wakayama, right, who worked on two high-profile studies of STAP stem cells, now says the reports should be withdrawn. Haruko Obokata, left, who led both studies, has not addressed the controversy. (AFP/Getty Images)

Scientist who created STAP stem cells says studies should be withdrawn

by KAREN KAPLAN

 March 11, 2014

A number of scientists have been grumbling for weeks about a pair of breakthrough stem cell studies that seemed too good to be true. 

Now one of the senior researchers who worked on the papers agrees that they may be right.

The studies, which were published in January by the journal Nature, described a surprisingly simple method of transforming mature cells into pluripotent stem cells capable of regenerating any type of tissue in the body. 

The key was to stress them out by soaking them in an acid bath for 30 minutes, prompting genetic changes that made the cells more flexible. 

The researchers dubbed their technique “stimulus triggered acquisition of pluripotency,” or STAP.

But Teruhiko Wakayama, a senior author of one of the papers and coauthor on the other, said he had lost confidence in the studies and was "no longer sure the STAP cells were actually created,” according to NHK.
Wakayama, a professor at the University of Yamanashi in Kofu, Japan, told Japanese media Monday that he had asked his collaborators to withdraw the studies until the results could be verified by independent scientists. He added that “he is ready to provide cell samples and detailed data” to anyone who is willing to try, NHK reported.

Wakayama also echoed concerns raised by others that some of the images used in the Nature papers may have been published previously. According to Japan News, an English-language website from Yomiuri Shimbun, Wakayama said the images “look almost identical” to images that appear in the PhD thesis of Haruko Obokata, the lead author of both Nature studies. 

Haruko Obokata

Her thesis was about pluripotent stem cells in humans, but the cells in the Nature STAP paper were supposedly from mice.

Anonymous posters to a website called PubPeer have flagged several images in the Nature papers that they say look suspiciously like pictures in a 2011 study led by Obokata. That study, published in the journal Tissue Engineering, purports to show that cells removed from various tissues of adult mice could be coaxed to grow into other kinds of cells.

Duplicated images are not the only problem skeptics have flagged. A Japanese blog post has noted striking similarities in the words used to describe some of the methods used in one of the Nature papers and the words in a 2005 paper published in a journal called In Vitro Cellular & Developmental Biology – Animal. In the blog post, the overlapping language is highlighted in red.

“There sure seems to be a lot of overlap in text in the two papers,” Paul Knoepfler, a stem cell researcher at UC Davis, wrote on his blog.

“I’ve heard people react to this by saying 'no big deal, it’s just a methods section,' while I’ve heard others say 'this is misconduct,'” Knoepfler added. “I’m sure many people fall somewhere in the middle.”

Knoepfler has been blogging about the STAP research since the day the studies were published on Nature’s website, January 29, 2014. 

Right away, something about them seemed odd.

“After a relatively quick read, no particular red flags jump out at me from the STAP cell paper,” he wrote on his blog. “It just seems too good and too simple of a method to be true, but the data would suggest so far at least that this team is onto something really important.”

As the days and weeks passed, Knoepfler’s suspicions grew. 

He has posted polls asking readers to weigh in on whether they think STAP cells are “real.”  He has also asked fellow researchers who are trying to make STAP cells in their own labs to share their results. So far, none have succeeded.

These concerns and others prompted the RIKEN Center for Developmental Biology, where Obokata works, to launch an investigation into the matter in mid-February. That inquiry is still ongoing, with the research institution considering whether to withdraw the STAP studies, Japan News reported Tuesday.

Nature, the London-based journal that published the STAP papers, also began investigating the studies around the same time. The journal has declined to elaborate until its review is complete.

In the meantime, Obokata and two of her RIKEN colleagues published a more detailed explanation of their research methods on Nature’s Protocol Exchange website to address some of the questions that have been raised.

In late February, Wakayama told Knoepfler he was not surprised that other research groups hadn’t been able to make STAP stem cells yet. (Even he’s had trouble reproducing the study results since he left RIKEN and set up his new lab at the University of Yamanashi.)

“It is going to take time to reproduce the new technique,” Wakayama said in a Q&A posted on Knoepfler’s blog. “For example, the first cloned animal, Dolly, was not reproduced for one and half years after it was published. Human cloned ES cell paper[published in May 2013] has still not yet been reproduced. Therefore, please wait at least one year. I believe that during this period someone or myself will success to reproduce it.”

That optimism may be gone now. At Monday’s news conference, Japan News quoted Wakayama as saying, "I’m no longer sure that the articles are correct.”
Obokata, who became a national celebrity in Japan after the papers were published, has not addressed the controversy. But one of her coauthors, Dr. Charles Vacanti of Brigham and Women’s Hospital and Harvard Medical School in Boston, told the Boston Globe he still believes the STAP findings are sound.

“I think there were some simple, perhaps sloppy mistakes that I thought were honest mistakes,” said Vacanti, whose name is on both Nature papers and was also the senior author of the 2011 report in Tissue Engineering. “I don’t have any information that would make me change my opinion of what I said before.”

Harvard Medical School is looking into the matter as well, according to Japan News.

Link: http://www.latimes.com/science/sciencenow/la-sci-sn-stap-stem-cell-study-nature-controversy-wakayama-20140311-story.html#page=1

Nature 'critical errors' stem cell studies LA..

This image purported to show that STAP stem cells grew into every type of cell in the body of this developing mouse. Two studies describing the research were retracted Wednesday by the journal Nature. (Haruko Obokata)

KAREN KAPLAN  contact the reporter


Nature STAP stem cell studies retracted after more errors found


Discovery of "several critical errors" leads Nature to retract two controversial stem cell studies
Papers on STAP stem cells raised eyebrows among researchers shortly after they were published
One of the study authors says he is "deeply ashamed" of the mistakes made in STAP stem cell research

Following months of controversy, editors at the scientific journal Nature have retracted two high-profile studies that purported to demonstrate a quick and simple way of making flexible stem cells without destroying embryos or tinkering with DNA.

“Several critical errors have been found in our Article and Letter,” Nature wrote in a retraction statement issued Wednesday. “We apologize for the mistakes.”
------------

Haruko Obokata bows in apology at the beginning of a news conference addressing the STAP cell controversy. 
(JIJI PRESS/AFP/Getty Images)

FOR THE RECORD:
Stem cells:  An article in the July 3 Section A about two controversial stem cell studies that were retracted. had stated that the decision was made by editors at the journal Nature.
The retraction decision was made by the authors of the studies. 

Additionally, the comments in the retraction statement should have been attributed to the authors of the studies, not to the journal editors.
------------

The two reports described a new way of reprogramming blood cells so that they would revert to a developmentally primitive state and be capable of growing into any type of cell.

Researchers from Japan and the United States said they accomplished this feat by soaking the cells in an acid bath for 30 minutes and then spinning them in a centrifuge for 5 minutes.

The resulting stem cells – dubbed stimulus triggered acquisition of pluripotency, or STAP – had the hallmarks of embryonic stem cells. When the researchers injected them into developing mice, the STAP stem cells grew into heart, bone and brain cells, among others, the research team reported in January.

Scientists in the field of regenerative medicine were giddy at the prospect of using the cells to grow new insulin-producing cells for people with Type 1 diabetes or central nervous system cells for people with spinal cord injuries, to name a few examples. Since these replacement tissues would be generated from a patient’s own cells, researchers believed they would not prompt the immune system to attack, eliminating the need for patients to take immune-suppressing drugs.

But it didn’t take long for some researchers to suspect that STAP stem cells were too good to be true. Critiques posted online gained more currency when labs began reporting that they weren’t able to replicate the experiments. Then one of the senior researchers who worked on both of the studies called for the papers to be withdrawn until the results could be independently verified.

In April, the Japanese research institute where most of the work was conducted accused study leader Haruko Obokata of intentional misconduct.

Investigators at RIKEN said Obokata had manipulated two images of DNA fragments to make the results of her experiments look better than they really were. They also found that data were handled inappropriately and that two of the images in the study were duplicates.

Investigators at Nature cited five additional errors that were not included in the RIKEN investigation. Figures and images in the studies were improperly labeled, and one of the images was digitally enhanced, according to the retraction statement. They also identified “inexplicable discrepancies” in the cells of mice that were injected with STAP stem cells.

“These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real,” Nature wrote in its retraction. “Ongoing studies are investigating this phenomenon afresh, but given the extensive nature of the errors currently found, we consider it appropriate to retract both papers.”

All of the researchers who contributed to both papers have agreed with Nature’s decision to retract them, according to an editorial published by the journal.

Obokata, who shot to fame in Japan after the studies were published, has not commented on the retraction. In April, she held a tearful news conference apologizing for what she described as careless mistakes. But she also struck a defiant tone, insisting that STAP stem cells were real and that she had created them “more than 200 times.”

Two of her colleagues at RIKEN have issued apologies for their roles in the troubled studies.

“As a researcher, I am deeply ashamed of the fact that two papers of which I was an author were found to contain multiple errors,” Yoshiki Sasai, a deputy director at the RIKEN Center for Developmental Biology, said in a statement. “I apologize wholeheartedly for the confusion and disappointment that this situation has caused.”

RIKEN said it had removed articles on its own website promoting the results of the STAP stem cell studies.

Dr. Charles Vacanti, a senior author of one of the studies and co-author on another, said he agreed that the papers should be retracted because the errors they contain undermine their credibility.

But Vacanti, a tissue engineering researcher at Brigham and Women’s Hospital in Boston who came up with the idea behind STAP stem cells with his brother, Dr. Martin Vacanti, held out hope that the studies would be verified by other research groups.

“There has been no information that cast doubt on the existence of the stimulus-triggered acquisition of pluripotency (STAP) cell phenomenon itself,” he said in a statement.

Sasai did not share that optimism, saying “there is no longer any experimental basis” to back up the idea that cells can be reprogrammed by exposing them to acid and other environmental stresses.


“It has become increasingly difficult to call the STAP phenomenon even a promising hypothesis,” Sasai said.

Paul Knoepfler, a stem cell scientist at UC Davis who was among the first to question the legitimacy of the STAP studies, said it was time for researchers to “move on from this mess,” as he put it in a blog post. He credited social media for enabling stem cell experts to get to the bottom of the controversy so quickly, thus expediting Nature’s retraction by more than a year.

“Why does this matter?” Knoepfler wrote. “Millions of dollars in scarce research funds would have been wasted along with potential damage to many young scientists’ careers who might have been directed to work on STAP in labs around the world potentially for years.”


Nature, too, used the occasion to reflect on the peer-review process that scientists have long used to vet and share scientific findings. In particular, the journal wondered whether it should should have caught the mistakes that skeptics flagged shortly after the studies were published.

In their editorial, the Nature editors exonerated the independent scientists who assessed the studies when they were submitted for publication. The editors also noted that they had checked to make sure that the STAP results “had been independently replicated” by the scientists who collaborated on the papers.


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

More generally, the problems with duplicated figures and images may be “impossible for journals to police routinely without disproportionate editorial effort,” the editorial said. Though it’s easier to spot manipulated images, “our approach to policing it was never to do more than to check a small proportion of accepted papers. We are now reviewing our practices to increase such checking greatly.”





Follow me on Twitter @LATkarenkaplan for more news and discoveries from the world of science and medicine. Copyright © 2014, Los Angeles Times


Link: http://www.latimes.com/science/sciencenow/la-sci-sn-walking-parkinsons-disease-20140702-story.html

DENIED REPORT: Bidirectional developmental potential in reprogrammed cells with acquired pluripotency

Editor's summary: 

The fates of the somatic cells that form the bulk of the mammalian body are thought to be largely determined by the time the cellular differentiation processes of development have been completed.

Reprogramming in response to environmental stress has been observed in plants but not so far in mammalian cells.

Now two manuscripts by Haruko Obokata and colleagues describe an unexpected reprogramming phenomenon, which the authors call stimulus-triggered acquisition of pluripotency (STAP). In STAP, mouse somatic cells such as CD45+ haematopoietic cells are reprogrammed to pluripotency by transient exposure to low pH. Extensive analysis of the molecular features and developmental potential of STAP cells suggests that they represent a unique state of pluripotency — and provide an alternative source of pluripotent cells to the use of transcription factors, as has become routine for induced pluripotent stem cell production.




Link: http://www.nature.com/nature/journal/v505/n7485/full/nature12969.html

Retraction: Stimulus-triggered fate conversion of somatic cells into pluripotency

NATURE | RETRACTION

Haruko Obokata,
Teruhiko Wakayama,
Yoshiki Sasai,
Koji Kojima,
Martin P. Vacanti,
Hitoshi Niwa,
Masayuki Yamato
and Charles A. Vacanti

Nature 511, 112 (03 July 2014) doi:10.1038/nature13598Published online 02 July 2014

Retraction: 
Stimulus-triggered fate conversion of somatic cells into pluripotency

Subject terms:

• Reprogramming

Nature 505, 641–647 (2014); doi:10.1038/nature12968

Several critical errors have been found in our Article and Letter (http://dx.doi.org/10.1038/nature12969), which led to an in-depth investigation by the RIKEN Institute. 

The RIKEN investigation committee has categorized some of the errors as misconduct (see Supplementary Data 1 and Supplementary Data 2). Additional errors identified by the authors that are not discussed in RIKEN’s report are listed below.

(1) Figure 1a and b in the Letter both show embryos generated from STAP cells, not a comparison of ES- and STAP-derived chimaeric embryos, as indicated in the legend.

(2) Extended Data Fig. 7d in the Article and Extended Data Fig. 1a in the Letter are different images of the same embryo and not, as indicated in the legends, a diploid chimaera embryo and tetraploid chimaera embryo.

(3) There is an erroneous description in Fig. 1a in the Letter. The right panel of Fig. 1a is not a ‘long exposure’ image at the camera level but a digitally enhanced one.

(4) In Fig. 4b of the Letter, STAP cell and ES cell are wrongly labelled in a reverse manner.

(5) In the Article, one group of STAP stem cells (STAP-SCs) was reported as being derived from STAP cells induced from spleens of F1 hybrids from the cross of mouse lines carrying identical cag-gfp insertions in chromosome 18 in the background of 129/Sv and B6, respectively, and that they were maintained in the Wakayama laboratory. 

However, further analysis of the eight STAP-SC lines indicates that, while sharing the same 129×B6 F1 genetic background, they have a different GFP insertion site. 

Furthermore, while the mice used for STAP cell induction are homozygous for the GFP transgene, the STAP-SCs are heterozygous. 

The GFP transgene insertion site matches that of the mice and ES cells kept in the Wakayama laboratory. 

Thus, there are inexplicable discrepancies in genetic background and transgene insertion sites between the donor mice and the reported STAP-SCs.

We apologize for the mistakes included in the Article and Letter. 

These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real. 

Ongoing studies are investigating this phenomenon afresh, but given the extensive nature of the errors currently found, we consider it appropriate to retract both papers.

Author information

Supplementary information

PDF files

1. Supplementary Data 1 (185 KB)

   This file contains a report by the Research Paper Investigative Committee of RIKEN titled ‘Report on STAP Cell Research Paper Investigation’. RIKEN President Ryoji Noyori received and assented on this report on 31 March 2014; the report was published by RIKEN on 1 April 2014. The report is re-published with permission from RIKEN.

2. Supplementary Data 2 (92 KB)

   This file contains a report by the Research Paper Investigative Committee of RIKEN titled ‘Report on Review of Appeal of STAP Cell Research Paper Investigation Results’. RIKEN President Ryoji Noyori received and assented on this report on 7 May 2014; the report was published by RIKEN on 8 May 2014. The report is re-published with permission from RIKEN. This is a translation prepared by RIKEN of a report originally submitted in Japanese and is for information purposes only. The original Japanese document is the only official document and is to be referred to in the event of questions concerning this translation.

 Link: http://www.nature.com/nature/journal/v511/n7507/full/nature13598.html

Electrifying stem cell finding retracted

YOON S. BYUN/GLOBE STAFF

Dr. Charles Vacanti of Brigham and Women’s Hospital in Boston is the senior author of one paper and a coauthor of the second.


Electrifying stem cell finding retracted

By Carolyn Y. Johnson | GLOBE STAFF JULY 02, 2014


A bombshell stem cell discovery by Boston and Japanese scientists was withdrawn Wednesday from the journal that published the work — amid allegations of fraud and a tide of incredulity from outside scientists.

It is one of the highest-profile retractions of the last decade, and several stem-cell researchers said they are now convinced that the stunningly simple method for producing stem cells, reported in two papers in January, won’t work.

The journal Nature published a retraction notice Wednesday from the authors, including the Harvard and Brigham and Women’s Hospital scientist who originated the idea and oversaw part of the work.

Nature cited the results of a Japanese investigation that found evidence of scientific misconduct and listed five additional errors they had identified, including misrepresented or mislabeled images and “inexplicable discrepancies” that raise questions about how the cells were created.

“Ongoing studies are investigating this phenomenon afresh, but given the extensive nature of the errors currently found, we consider it appropriate to retract both papers,” the retraction notice states.

The authors apologized for the mistakes in the articles, writing, “These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the . . . phenomenon is real.”

Rudolf Jaenisch, a stem cell biologist at the Massachusetts Institute of Technology who was not involved in the research, said experiments in his laboratory quickly convinced him the technique does not work. “It’s fine to have it finally settled,” he said. “Many people wasted their money and their time and their resources on repeating this.”

He added that Harvard should be more forthcoming as evidence mounts of errors, image misrepresentation, and possible fabrication. “I think the silence of the Brigham, of Harvard, was deafening,” Jaenisch said. “I find this just really not good and a bit problematic. . . . There are so many great stem cell biologists at Harvard, and I think they are embarrassed by it.”

In the January papers, the researchers claimed they had created powerful stem cells, capable of becoming any organ or tissue in the body, simply by dipping white blood cells from young mice in an acid bath. 

The result generated enormous excitement because it pointed to an easy and fast technique for creating stem cells, which are seen as potential therapies for diseases ranging from type 1 diabetes to heart failure.

But almost immediately, other scientists began questioning aspects of the work. Key authors of the papers publicly called for them to be withdrawn, especially after an investigation by the RIKEN Institute, a Japanese research center, found evidence of fraud by one of its scientists, Haruko Obokata, who led the work.

The official decision to withdraw the research depended on the agreement of all 14 of the scientists who contributed.

Dr. Charles Vacanti of the Brigham and Harvard Medical School, the senior author of one paper and a coauthor of the second, had not publicly said he agreed to withdraw the findings until now.

Vacanti, chairman of the Brigham anesthesiology department, said in a statement that he still believed the concept would be proven right, but felt that problems with the paper “impair the credibility of the manuscript as a whole.”

“In science, the integrity of data is the foundation for credible findings. I am deeply saddened by all that has transpired, and after thoughtful consideration of the errors presented in the RIKEN report and other concerns that have been raised, I have agreed to retract the papers,” Vacanti wrote.

Although much of the research was based in Japan, Vacanti and his brother, Martin, began working on the idea more than a decade ago at the University of Massachusetts Medical School. In an e-mail interview with the Globe earlier this year, Vacanti said he and another scientist in his laboratory worked closely with Obokata, when she was a researcher in his Brigham laboratory, “to develop, design, review, and discuss the results of many of the experiments” in one of the withdrawn papers. Vacanti has not been implicated in the fraud allegations made by the Japanese investigators.

It is not clear whether the Brigham or Harvard Medical School is investigating the research to assess whether any of the problems that have been found in Japan occurred while Obokata worked here. Both institutions have a policy to not confirm or deny the existence of such reviews.

In an editorial accompanying the retraction notice, Nature said the critical errors that undermined the evidence in the papers were found during the Japanese investigation.

“Figures that were described as representing different cells and different embryos were in fact describing the same cells and the same embryos,” Nature editors wrote. “All co-authors of both papers have finally concluded that they cannot stand behind the papers, and have decided to retract them.”

For many outside scientists, the retraction will bring closure to a high-profile drama that has played out in packed press conferences in Japan, anonymous attacks on blogs, and within laboratories where scientists have so far unsuccessfully tried to repeat the technique, called stimulus-triggered acquisition of pluripotency, or STAP.

For a scientific finding to be accepted as true, it must be repeated by other laboratories. That hasn’t happened yet, and the retraction means that the finding itself no longer exists.

Japanese media recently reported that RIKEN, where many of the authors work, planned to allow Obokata to repeat the experiment for five months — despite the institute’s finding that she committed scientific misconduct. Obokata will work under close supervision, including video surveillance.

“The suspicions surrounding the STAP cell papers have not been decisive (in denying the existence of STAP cells). We’d like to determine whether STAP cells really exist or not through experiments at the hands of Obokata herself,” Masatoshi Takeichi, director at the RIKEN Center for Developmental Biology, told the Japanese newspaper Mainichi Shimbun.

In his statement, Vacanti said he was heartened by news that efforts would be made to repeat the technique. Vacanti has also been trying to replicate the technique in his own laboratory, but an update on those efforts was not available.

A statement from the Brigham said Vacanti had found the last six months a frustrating ordeal.

“He firmly believes in the STAP cell phenomenon and is devastated by all that has transpired. At this time, he feels that it is not productive to rehash what has transpired and is instead focused on his research and his efforts to replicate the STAP cell findings,” the statement said.

One of Vacanti’s coauthors, however, said he now doubts that the method works.

“With the retraction of the papers, there is no longer any experimental basis to support the consistency of the STAP phenomenon, and considering the discrepancies that have been pointed out recently . . . it has become increasingly difficult to call the STAP phenomenon even a promising hypothesis,” Yoshiki Sasai, a scientist at the RIKEN Center for Developmental Biology, wrote in a statement.

Dr. Leonard Zon, a Harvard scientist and director of the stem cell biology program at Boston Children’s Hospital, said that the topic has dominated discussions in the field and the retraction should seal the fate of the finding.

“I don’t think there’s any shred of hope for these cells,” Zon said. “I really feel that there have been a lot of people trying different techniques, modified techniques, and I can’t find anybody who can reproduce it.”

The episode is already having an effect on stem cell research, Zon said. At the meeting of the International Society for Stem Cell Research last month, there was a mentoring session for junior scientists focused on scientific integrity and best practices for collecting and publishing evidence.



Related coverage:

• Fraud alleged in findings on stem cells

• Scientists discover a new, simpler way to make stem cells

• Evan Horowitz: Studies show many studies are false

• Nature’s retraction notice



Carolyn Y. Johnson can be reached at cjohnson@ globe.com. Follow her on Twitter @carolynyjohnson.



Electrifying stem cell finding retracted

Amid allegations of fraud, a bombshell stem cell discovery using an acid bath was withdrawn by the journal that published the work.

Related
4/2: Fraud alleged in findings
1/29: New way to make stem cells
Horowitz: The problem with studies
Nature’s retraction notice


Link: http://www.bostonglobe.com/news/science/2014/07/02/controversial-stem-cell-creation-method-retracted/NiScjZhcPcaopw7ziGvWaN/story.html

Flower duet - Anna Netrebko & Elina Garanca (Lakmé de Delibes)

Uploaded on Oct 23, 2010

Lakmé, Flower duet (Duetto) by Léo Delibes : Viens, Mallika... Dôme épais le jasmin.
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Anna Netrebko (soprano).
Elina Garanca (mezzo-soprano).
Baden-Baden Opera Gala 2007.
Duo des fleurs.

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  Music

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Aria from Diva - Wilhelmenia Wiggins Fernandez

Uploaded on Dec 17, 2008

Fernandez sings the aria "Ebben? Ne andrò lontana", from Act I of Catalani's opera "La Wally." The piece is a haunting reverie on the theme of traveling alone and far from home. Catalani died in 1893 of consumption at the age of 39, only a year after the triumphant premiere of "La Wally" at La Scala.

This performance plays a prominent role in the 1981 French romantic thriller, "Diva" - and is an excerpt from the DVD. Roger Ebert, film critic for the Chicago Sun Times, rates the movie 5 stars out of 5.

This was one of the most frequently "favorited" videos on BestArts.

The opera, based on a German novel, has a libretto by the young Luigi Illica, who went on to collaborate on the texts for "La Boheme," "Tosca" and "Madama Butterfly." It tells of a wild, headstrong Swiss mountain girl who loves one local huntsman and is loved by another. Eventually she wins her true love, the pair embraces high in the Alps, an avalanche entombs the hero and she leaps after him to her snowy death.

The libretto for the opera is available (in Italian) athttp://www.karadar.com/Librettos/cata...

A plot summary of the opera is available in English athttp://www.spikesworld.spike-jamie.co...

Browse our website at http://www.theBestArts.com for more great dance, music and musical theatre performances!

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Link:http://youtu.be/2hsmoo97CVA

Elīna Garanča - La Cenerentola - Rondò finale (Gioacchino Rossini)

Uploaded on Sep 13, 2011

Come Visit My Blog - https://philipcarusostory.wordpress.com/

For more beautiful videos, visithttp://www.youtube.com/user/PhilipCar...

THE OPERA GALA - Live from Baden-Baden (2007),
Anna Netrebko · Elina Garanca, Ramón Vargas, Ludovic Tézier
SWR Sinfonieorchester Baden-Baden und Freiburg ·
Conductor: Marco Armiliato

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Link:http://www.youtube.com/watch?v=sllhVK2_Gug&list=RDvF5BBoylCzQ&feature=share

Dein ist mein ganzes Herz (Domingo,Netrebko,Villazon)

Uploaded on Jun 17, 2008

"Three Superstars"
Live at the Waldbuhne

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  Music

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Link:http://www.youtube.com/watch?v=Pa58TdbRGJ4&list=RDvF5BBoylCzQ&feature=share

Flower duet - Anna Netrebko & Elina Garanca (Lakmé de Delibes)

Uploaded on Oct 23, 2010

Lakmé, Flower duet (Duetto) by Léo Delibes : Viens, Mallika... Dôme épais le jasmin.

http://www.agoravox.tv

http://www.agoravox.tv/auteur/juasugi

http://www.agoravox.tv/auteur/stupeur

http://www.agoravox.fr



Anna Netrebko (soprano).

Elina Garanca (mezzo-soprano).

Baden-Baden Opera Gala 2007.

Duo des fleurs.

• Category

  Music

• License

  Standard YouTube License

LINK:http://www.youtube.com/watch?v=Vf42IP__ipw&list=RDvF5BBoylCzQ&feature=share