Closing the Door on the STAP Episode


Last year, a group of Japanese researchers, led by scientists from the high-regarded RIKEN Center for Developmental Biology, reported a break-through in stem cell technology. Their so-called STAP or stimulus-triggered acquisition of pluripotency cells could be derived from mature, adult cells by exposing those cells to stressful conditions. Even though the papers that reported these advances were published in the prestigious journal Nature, immediately, people found problems in the papers that could not be easily resolved. Several laboratories tried to replicate the STAP results, with no success. The papers were eventually retracted and an internal investigation by the RIKEN Center also suggested that foul play might have been at work. Amidst all this, a question that hung in the air was this, “Was there something to the original discoveries but it was overstated?”

That question has now been definitely answered in the negative, thus closing the door for good on this whole sordid affair. Two papers were published on 23 September in the journal Nature, which was the same journal that published the original, ill-fated papers early last year that showed that STAP cells should be called NE (never existed) cells.

The original STAP papers were published in January 2014 by a team led by researchers at the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, in collaboration with scientists from Harvard Medical School in Boston, Massachusetts. These two papers claimed that embryonic-like stem cells could be produced by exposing adult body cells to stress, such as acidic conditions or physical pressure. These papers dubbed their technology “stimulus-triggered acquisition of pluripotency,” or STAP. Unfortunately, other scientists quickly discovered problems with data in the research. These problems then generated an investigation, and these papers were eventually retracted.

The paper retraction, however, did not answer the nagging questions as to whether or not the STAP procedure might have worked, and where the pluripotent stem cells labelled STAP in the RIKEN laboratory came from.

Such questions were addressed by seven teams in four countries who tried to replicate the procedure under various conditions (De Los Angeles, A. et al. Nature http://dx.doi.org/10.1038/nature15513 (2015). These teams collaborated to generate 133 attempts to produce STAP cells, and all of these attempts failed. One of these teams was led by researchers at Harvard Medical School who had worked with one of the original STAP co-authors. In this laboratory, cells were engineered to express a fluorescent protein when a gene related to pluripotency was expressed. When cells were exposed to stressful conditions, they did find some fluorescence, which suggested that pluripotency genes were expressed when cells were subjected to such conditions. However further testing showed this result to be an artifact since cells can naturally emit light; a phenomenon known as autofluorescence. Six other groups also observed autofluorescence in stressed cells, but no convincing evidence of STAP conversion.

A group of RIKEN researchers that did not include any authors of the original STAP papers analyzed the genomes of purported STAP cell lines that had be derived at the CDB. These scientists discovered multiple instances of contradictory data that probably resulted from contamination of purported STAP cells by other known cell types. The RIKEN group’s analyses showed that all remaining purported STAP stem cell lines, for example, were genetically identical to embryonic stem cell lines that already existed in the laboratory.

Additionally the “chimeric” mice that were reportedly produced by injecting STAP cells into the embryo of a developing mouse were found to have been produced by injecting pre-existing embryonic cell lines, rather than STAP cells, into the embryo. The production of chimeric mouse embryos is an experiment that definitively shows that particular cells are truly pluripotent.

Cell contamination also explains one of the most puzzling features of the original work, and that has to do with why the alleged STAP cells were reported to be capable of forming placental tissue, which is something that embryonic stem cells are not able to do (De Los Angeles, A. et al. Nature 525, 469–478 (2015)). These most recent analyses show that mixtures of trophoblast stem cells (which form the placenta in a developing embryo) were mixed with embryonic stem cells and that this mixture was used in the mouse chimeric experiments, leading to the production of mouse placental and embryonic tissue.

Stem-cell scientist Rudolf Jaenisch of the Massachusetts of Technology in Cambridge, who was part of the replication efforts, originally suggested in April 2014 to Nature’s news team that contamination was the reason for the results in the STAP papers. Unfortunately, he did not have evidence at the time for his hypothesis, but this most recent work has vindicated Jaenisch’s hypothesis.

A lingering question is how these embryonic stem cells and trophoblast stem cells came to replace purported STAP cells when the chimeric mouse experiments were performed. So-called cross-examination, which is the accidental contamination of one cell culture by another type of cell, is a well-known problem in cell culture experiments and biological research that depends on cultured cells. However, to properly explain the results in the original STAP papers, multiple independent contamination events must be invoked. “It is very difficult to reconcile the data with simple contamination or careless mislabeling,” says stem-cell scientist George Daley at Harvard Medical School. Unfortunately, requests for clarifying comments from corresponding authors of the original papers went unanswered.

In a review article published in Nature, Daley, Jaenisch argue that all new reports of new types of pluripotency should be subjected to rigorous “forensic” analysis that examines the genomes of the cells under consideration before publication. According to the authors, besides the failed STAP papers, “numerous groups are reporting ever more nuanced states of pluripotency.” In particular, the article focuses on genomic analyses, which are enabled by advances in sequencing technology, that will help evaluate such cell types.

Daley says that these experiments bring some well-desired closure to the STAP. He ended, however, with a warning to scientists who are looking for ways to reprogram cells to an embryonic-like state: “We will all be a tad more cautious in evaluating such claims.”

Embryonic Stem Cell Contamination Responsible for STAP Research Snafu


STAP or stimulus-triggered acquisition of pluripotency cells were allegedly derived from mature, adult cells by simply subjecting those cells to environmental stresses. These environmental stresses, such as low pH treatments and so on, were thought to cause cells to express genes that pushed them into an embryonic stem cell-like state. Researchers from the RIKEN institute reported these reports in the prestigious international journal Nature, and these advances were hailed as a stupendous advancement in stem cell biology.

However, as soon as stem cell scientists tried to repeat the results from these papers and failed, trouble started. Major laboratories had no success in recapitulating the results in the RIKEN institute papers, and, on-line post-publication reviews noticed some nagging problems in the published papers. RIKEN institute launched an investigation into the matter, and concluded that the lead researcher in these papers was guilty of scientific misconduct.

Now, new work as suggested that the whole thing was the result of contamination of the RIKEN group cells with embryonic stem cells. How that contamination occurred, however, remains unknown.

The RIKEN institute investigation was instigated by the institute and was carried out by a committee composed of seven outsiders. The committee analyzed DNA samples and laboratory records from two research teams who had participated in the STAP cell research. Those Nature papers have been retracted, but were once thought to provide a shortcut to producing pluripotent stem cells. The latest investigation suggests that the STAP findings resulted from contamination by embryonic stem cells. The investigation found signs of three separate embryonic stem cell lines, and they noted that it is difficult to imagine how contamination by three distinct lines could be accidental, but that they could also not be certain that it was intentional.

“We cannot, therefore, conclude that there was research misconduct in this instance,” the committee wrote. It did, however, find evidence that lead investigator Haruko Obokata, the lead author of the STAP papers, who formerly worked at the RIKEN Center for Developmental Biology in Kobe, Japan, had fabricated data for two figures in the original STAP publications.

Attempts to Recapitulate STAP Cells Fail


Japanese stem cell scientist Haruko Obokata was the first author of two papers that appeared in the journal Nature earlier this year that described the derivation of pluripotent stem cells from mature cells without the use of genetic manipulation. Instead, these cells were subjected to environmental stresses such as physical pressure or exposure to acid that, according to these papers, caused the cells to express genes associated with pluripotency. Culturing of these cells led to the derivation of pluripotent stem cells lines. Thus were born STAP or stimulus-triggered acquisition of pluripotency cells. Needless to say, these results were hailed as a remarkable advance in stem cell biology.

Unfortunately, as soon as the papers were published, several high-level laboratories tried to recapitulate these results and universally failed. Even more troubling were some of the inconsistencies that came to the forefront in the published papers that the reviews had apparently missed or were ignored by the journal. The RIKEN center where this work was done even launched an internal investigation that concluded that Dr. Obokata was guilty of scientific misconduct.  Obokata gave approval to formally retract her Nature papers.  However, the RIKEN Center gave Obokata and her colleagues until the end of November to prove that she could reproduce STAP cell derivation.

Now the jury is in – Obokata has been unable to replicate her results. In the original experiments, Obokata used a gene fusion that caused the cells to glow green if they expressed genes related to pluripotency. In her replication of her original experiments, Obokata produced such green glowing cells when she subjected to environmental stresses. However, this is only a preliminary test that only involved a few such cells. More rigorous tests that were conducted, however, failed. In this case, Obokata’s stressed adult cells were introduced into a mouse embryo to see whether they could contribute to the development of various tissues during animal development. Obokata’s stressed cells, however, were unable to integrate into the developing embryos. Since this is the ultimate test for pluripotency, and since these cells were not able to pass this test, it seems virtually certain that Obokata’s original results were completely bogus.

With her signature conclusions in tatters, Obokata has resigned from the RIKEN center. In a very emotional resignation letter, Obokata wrote she could not “find words enough to apologize… for troubling so many people at RIKEN and other places.”  The RIKEN president, Ryoji Noyori, wrote in an accompanying statement that Dr. Obokata had been subjected to horrible psychological stress as a result of this affair.  Noyori added that he accepted her resignation to hopefully save her from suffering further from a severe “mental burden.”  One the co-authors of the STAP papers, Japanese stem cell scientist Yoshiki Sasai, committed suicide a few weeks after the retraction of the paper.

Hopefully, RIKEN and the other scientists who were involved in this venture move on and continue with the business of pushing back the frontiers of science.  It is entirely possible that intentional fraud was involved, but ultimately, we will never know.  For now, it is clear that sloppiness and a lack of skepticism about one’s own results contributed to this fiasco.  I think most people simply want to put this whole sordid event behind them.  However, there are pointed lessons to be learned and we will be better investigators if we learn them.

For one, peer review is not omnipotent.  Post-publication review is important and will continue to be important.  Secondly, journals need to be willing to solicit outside opinions to ensure the quality of high-level publications.  Third, the majority of scientists publish in journals that most people will never read.  Their work is not glamorous, but instead document tedious, high-quality, detailed, scientific research.  The majority of such work will never appear in Nature or Science or Cell, but that’s alright because good solid research is still good solid research regardless of where it appears.  It is really too bad that the push for high-visibility publications can cause people to publish too quickly before results have been properly vetted.  The STAP episode might be a reminder for journals to take greater care with the review of original research.

STAP Papers Retracted


The two papers that appeared in the journal Nature that described the derivation of embryonic stem cell-like cells simply by exposing cells to environmental stresses have been formally retracted. In a notice of retraction from the Riken Center’s Haruko Obokata, who was the lead author of these papers, and her colleagues said that “[s]everal critical errors have been found in our Article and Letter.” The notice also pointed out that a subsequent investigation of those errors by an internal Riken Center investigation found evidence of research misconduct.

“The STAP technology, indeed, sounded too good to be true,” said Dusko Ilic, from King’s College London, to the Reuters news group. “I hoped that Haruko Obokata would prove at the end all those naysayers wrong. Unfortunately, she did not.”

In an editorial that appeared in Nature, Ivan Oransky from a blog site known as Retraction Watch, argue that it couldn’t have caught the errors. Oransky wrote: We at Nature have examined the reports about the two papers from our referees and our own editorial records,” the editorial notes. “Before publishing, we had checked that the results had been independently replicated in the laboratories of the co-authors.” Nevertheless, the journal says this incident has highlighted flaws in the peer-review publishing process.

“We — research funders, research practitioners, institutions and journals — need to put quality assurance and laboratory professionalism ever higher on our agendas, to ensure that the money entrusted by governments is not squandered, and that citizens’ trust in science is not betrayed,” it adds.

The simple fact is that reviewers examine data, figures and materials and methods, but they have no gift of ESP to determine is the authors are telling the truth.  Truth-telling and honesty are virtues without which science cannot exist.  What is the basis of honesty and truth-telling?  Well, the secular, pragmatic worldview would suggest that truth-telling works and without it we cannot do science without it.  However, if truth-telling gets the individual scientist ahead for a time, then why shouldn’t they prevaricate?  What should the individual worry about what the collective thinks or needs?

It is at this point that I must interject that the Christian worldview provides the foundation for honesty and truth-telling.  The Christian tells the truth because God is the author of all truth and is by His very nature, the truth (see John 14:6).  To not tell the truth is to dishonor God and not live in accordance with his revealed prescriptions.  Therefore, the Christian worldview explains why we should tell the truth when reporting our experiments.

STAP Author Agrees to Retract Both Nature Papers


STAP cells or Stimulus-Triggered Acquisition of Pluripotency cells were allegedly derived from adult mouse cells by subjecting those adult cells to a variety of environmental stresses. Even though the derivation of STAP cells was not terribly efficient, the ability to make pluripotent stem cells without viruses or the introduction of new genes seemed to be a godsend for stem cell scientists. Unfortunately, further testing and inquiries into STAP cells has revealed multiple problems and several labs have been completely unable to recapitulate the results of the researchers who reported the derivation of STAP cells. These problems have led many scientists to question the factuality of STAP cell derivation.

STAP cells took another hit this week when genetic tests of STAP cells indicated that those cells do not match the mice from which they were allegedly derived, according to a report from Nature News Blog.

The derivation of STAP cells were initially reported by Haruko Obokata from the RIKEN center and her colleagues. Given the remarkable nature of the claims in those papers, many scientists were skeptical and moved to test the protocols utilized by Obokata and others in those paper to make STAP cells from adult mouse cells. Unfortunately, these independent tests universally flopped, and an internal investigation by the Riken Center came to the conclusion that Dr. Obokata was guilty of research misconduct, which she has denied.

Teruhiko Wakayama, a scientist from Yamanashi University and one of the co-authors on the STAP papers, subjected some of the cell lines that he derived using the STAP approach back in March to a battery of genetic tests. He was dismayed to discover that some of these cell lines did not match the adult mice from which they were supposed to have been generated. This raises the possibility that the STAP cells are the result of contamination, which is a perennial problem in cell culture laboratories. Wakayama did not observe any anomalies with the lines reported in the Nature papers, but, just to be safe, he sent those and other lines to an independent, and unnamed, lab for further examination and corroboration.

These independent tests, according to reports from Japanese media sources, have found that none of the STAP cell lines match the mouse strains they were supposed to be from. This calls “into question whether the STAP phenomenon has ever been demonstrated.”

Last week, the Nature News Blog reported that Dr. Obokata had agreed to retract one of the two STAP papers, even though the retraction has yet to appear in print. Now, according to the ScienceInsider, Obokata has consented to retracting both Nature papers. The ScienceInsider added this will not end the STAP story, since Riken is doggedly trying to determine whether the STAP phenomenon exists and as some critics are asking how these flawed papers were published in the first place.

“The science of the two papers was rigorously, robustly peer-reviewed as part of our usual editorial procedures. Any inaccuracies in the presentation of data that may have come to light since the peer review are being investigated,” a spokesperson from Nature told ScienceInsider.

Authors Agree to Retract One STAP Paper


Embattled stem cell scientist Haruko Obokata from the Riken Center for Developmental Biology in Japan has agreed, albeit reluctantly, to retract one of the two Nature papers that describes a controversial technique for generating pluripotent stem cells by stressing adult cells with acid or pressure.

Obokata and her colleagues pioneered the STAP protocol that generates Stimulus-Triggered Acquisition of Pluripotency or STAP cells in two papers that were published in the international journal Nature in January, 2014. When these papers appeared, they were regarded as a revolutionary finding in the field of stem cells. Nevertheless, these papers also generated more than a fair share of suspicions, and rightly so. After all, these papers challenged many previous observations. Therefore, many laboratories tried to repeat Obokata’s results, without any success. While in and of itself this was not a definitive refutation of these papers, further mining of the data in these papers revealed discrepancies and inconsistencies. Again, while this is not a definitive refutation of the results in the paper, it was enough to implement further investigation. Therefore an internal investigation by the Riken Center was conducted.

In their investigation, Riken found evidence of misconduct.  According to the Riken report, two pictures of electrophroresis gels were spliced together, and that data from Obokata’s doctoral thesis was reused in two images despite that fact that these data came from experiments that had been conducted under different conditions.

Obokata apologized for her errors, but insisted that these mistakes were unintentional and that they did not detract from the validity of her work in general. She also said she would be appealing the findings. That appeal, however, was rejected earlier this month.

Now, Obokata has agreed to retract one, but not both, of two Nature papers. According to the Nature News Blog, which is editorially independent of the research editorial team, the “Bidirectional developmental potential in reprogrammed cells with acquired pluripotency” paper is to be retracted. Riken told the Nature News Blog that each co-author either agreed to the retraction or did not oppose it.  According to the Japan Times:

Of the three researchers, her lawyer said University of Yamanashi professor Teruhiko Wakayama is responsible for the paper Obokata has agreed to retract. He was engaged in all experiments, and Obokata wrote the paper under his guidance, lawyer Hideo Miki said.

She e-mailed the other main co-author, Yoshiki Sasai, deputy director of the Riken Center for Developmental Biology in Kobe, that she would have no problem if Wakayama wants to retract it, Miki said.

Both papers were published in the Jan. 30 edition of the journal, one as a “letter” and the other as an “article.”

However, the journal Nature couldn’t confirm the request. “Nature does not comment on corrections or retractions that may or may not be under consideration, nor does it comment on correspondence with authors, which is confidential,” a spokesperson tells the Nature News Blog. “We are currently conducting our own evaluation and we hope that we are close to reaching a conclusion and taking action.”

According to the Japan Times, Obokata has said that she will not retract the other paper.

Lead Author On STAP Papers Publicly Apologizes in Press Conference


On April 9th, the Japanese scientist at the center of a controversy over studies purporting to turn mature cells to stem cells simply by bathing them in acid or subjecting them to mechanical stress, Haruko Obokata, publicly apologized for her errors associated with the published work.

In a press conference in Osaka, Japan, with a crowd of voracious reporters flashing their cameras, Obokata blamed her scientific immaturity and lack of awareness of research protocols for the errors that were found in her two high-profile papers on the studies that were published in the journal Nature in January, which included the use of a duplicated image. With Obokata were two lawyers who are representing her.

To her credit, Obokata took full responsibility for the errors in the papers and apologized to her co-authors for the messy situation in which they presently find themselves. She also apologized to the RIKEN Center for Developmental Biology, where she did her work, for the embarrassing press this ordeal had brought upon it. Additionally, she sought forgiveness from the RIKEN committee whose report earlier this month found her guilty of scientific misconduct. At the time, Obokata had attacked the report.

This is Obokata’s first public statement in more than two months, and she held the press conference to apologize for the errors and to make the case that her research, despite the caveats and mistakes, was still valid. Also, Obokata wanted to establish that the inaccuracies in the papers were not deliberate. The day before the press conference, Obokata submitted a formal appeal to RIKEN for their committee to retract its misconduct findings. She insisted that the “stimulus-triggered activation pluripotency” or STAP phenomenon, as it has been dubbed, exists. RIKEN has 50 days to respond to her appeal.

In the STAP work, lead author Obokata, along with Japanese and US colleagues, described remarkable experiments in which she reprogrammed mature mouse cells to an embryonic state merely by stressing them. Unfortunately, she her two papers soon fell under suspicion and last month a RIKEN-appointed investigative committee found in a preliminary report that they contained numerous errors. A further report on 1 April by the RIKEN committee concluded that two of the errors in this paper constituted a case of scientific misconduct. Obokata aggressively responded on the same day in a written statement in which she expressed “shock and anger” at these conclusions. She also thought that the committee had unfairly come to their conclusions without giving her a chance to explain herself. On this day, however, Obokata’s seemed to sing a very different tune in which she pleaded for forgiveness and presented several apologies. However, she steadfastly maintains that her primary findings are true.

Obokata continues to insist that the two problems that the committee declared cases of scientific misconduct (the duplicated image and the swapping of a diagram of an electrophoresis gel) were honest mistakes, and that she had not been given enough time to explain her side to the committee.

After her brief introductory remarks, Obokata’s lawyer gave a 20-minute presentation to make the case that neither problem constituted misconduct. Defining fraud as fabrication, he countered that in both cases Obokata had the original data that should have been used but merely added the wrong data by mistake. For the more damning finding — an image of teratomas that had appeared in her doctoral dissertation and then again in the recent papers — the committee had found that she had changed a caption, which made it look intentional. The lawyer however traced the image back to a slide, part of a presentation that Obokata had continually updated and reused, until its origin became obscured. In one of her many apologies, Obokata said, “If I had gone back to carefully check the original data, there wouldn’t have been this problem.”

After the lawyer’s presentation, Obokata responded to journalists’ questions for more than 2 hours. Why had she only handed two laboratory notebooks over to the committee looking into her research? She said that she said she had four or five more that the committee hadn’t requested. Obokata denied that she ever agreed to retract the papers. Had she asked to retract her PhD dissertation? No, she merely sought advice on how to proceed Obokata’s dissertation is under investigation at Waseda University, where she studied for her doctorate).

Obokata also denied the possibility that the STAP cells had resulted from contamination from embryonic stem cells, saying that she had not allowed embryonic cells in the same laboratory and that she had carried out tests which precluded that possibility.

She said that she had created STAP cells more than 200 times, adding that she knows someone who has independently achieved it but refused to give the name (citing privacy). She believes that a RIKEN group trying to demonstrate STAP cells will help her. She has not, she said, been asked to participate in those efforts. She added that she would consider doing a public replication experiment but that it was not up to her whether she could.

Two hours into the questioning, her lawyer cut off journalists, citing concern for Obokata’s frail emotional state, and said she had to return to the hospital where she has been staying. She bowed, apologized, then bowed again and left with the reporter’s cameras flashing away as she retreated.

I feel genuinely sorry for this young lady.  Her career in science is essentially over.  It is within the realm of possibility that her mistakes were unintentional and were the result of a hurry to publish.  In this case, her adviser does bear some of the blame for her mistakes.  However, at this point it seems more likely that her mistakes were probably intentional.  If that is the case she should have known that such a high-prolife paper describing such a novel finding would be subjected to intense scrutiny and repeated attempts to verify it.  I am reminder of Moses’ admonition to the tribes that had settled on the East side of the Jordan River if they do not help the other tribes fight for their lands.  In Numbers 32:22-24, Moses said, “then when the land is subdued before the Lord, you may return and be free from your obligation to the Lord and to Israel. And this land will be your possession before the Lord.  But if you fail to do this, you will be sinning against the Lord; and you may be sure that your sin will find you out. 24 Build cities for your women and children, and pens for your flocks, but do what you have promised.”

Indeed your sin will find you out, and if Ms. Obakata intentionally attempted to deceive her colleagues, then it would appear that her sin has found her out.  At the moment I am willing to give her the benefit of the doubt, but if further evidence emerges that the whole thing is bogus, then I will retract my half-hearted support.  It is entirely possible that she found something novel and interesting that happens to cells when they are stresses.  However, it seems equally clear that a conversion into an embryonic stem cell-like state is probably not one of these things.  I reiterate my original belief – the original STAP paper should be retracted.

RIKEN Institute Investigation into STAP Paper Concludes Misconduct was Committed


The STAP paper that generated so much excitement in Nature has been subjected to some pretty substantial knocks. Several labs have tried to replicate the experiments from this paper, and no one has consistently succeeded. Also, a detailed protocol was released, but the claims of this protocol contradict those in the published paper. Also, one of the authors on the original STAP paper, has even said that he no longer believes the results of his own paper.

The RIKEN institute, where this research was conducted, convened an internal investigation to determine what went wrong. Even though they do not call for the paper to be retracted, they do conclude that deliberate falsification did occur in the paper. There report can be read, in English, here.

The report examines six problems with the original paper:
1. Unnatural appearance of colored cell parts shown by arrows in d2 and d3 images of Figure 1f.
2. In Figure 1i, lane 3 appears to have been inserted later.
3. A part of the Methods section on karyotyping appears to have been copied from another paper.
4. A part of the procedures described in the Methods section on karyotyping appears to be different from the actual procedures used in the experiment.
5. The images for Figures 2d and 2e appear to be incorrect, and closely resemble images in Dr. Obokata’s PhD dissertation.

The first problem is chalked up to what happens to microscope pictures when they are compressed into JPEG files and sent with an electronic copy of a manuscript. Having had figures sliced, diced, shrunk and compressed, blurred, and converted to black and white after submitting them to journals, I can vouch for Dr. Obokata on this one. Therefore, they do think that this one is a problem.

Problem 2 they think is due to true tampering. Lanes in gels, western, southern and northern blots are sometimes cut and pasted in papers, but Nature, apparently has a policy about this and their policy is that this is a no-no. Also, they conclude that the gel lane pasting “created the illusion that the data of two different gels belonged to only one gel, but may also lead to the danger of misinterpretation of the data.” I think they are completely correct on this one.

Problem 3 was probably a dunderheaded mistake. They think that Dr. Obokata plagiarized the protocol, but in all honesty, it could have simply been the result of being in a hurry and having a deadline that you have to meet to finish your Ph.D. and get your papers submitted by a certain date. To my reading, this one sounds like a lack of sleep and being in a hurry. But honestly lady, couldn’t you have at least cited the other paper from which you took the protocol in the first place?

Problem 4 they think is a simple case of someone else did the work and you didn’t check with them first before including it in the paper.  Thus it is an oversight and not a case of falsification. On this one, I think the senior author has to bear a lot of the blame. It’s his butt on the line if the paper has anything wrong in it, and he simply did not read the submitted paper carefully enough before submitting it.

Problem 5 is a pretty flagrant case of bait-and-switch. The original figure in the paper was supposed to be STAP cells made from spleen. However, Dr. Obokata said that these were pictures of bone marrow blood cell-making stem cells instead of spleen stem cells. Also the pictures she substituted came from her Ph.D. dissertation, and were of cells that had not been treated with acid, but had been subjected to shear forces by forcing them through a narrow pipette. This is a different experiment than the one she reported. Also, her statements that she had forgotten that these figures of cells treated completely differently are hard to believe. I think we are justified in calling this one a whopper.

Problem 6 is a mislabeling of two figures of cells that came from the same experiment. It is a classic case of the paper being rewritten before publication, the figures being completely reworked, and the labeling getting all messed up. This one is not falsification but it is negligence.

All in all, the paper is a mess. Whatever might have been observed has been fogged over by fraud, negligence, and too many cooks in the paper-writing kitchen. This sounds like too many people were involved in the preparation of the paper and they did not properly talk to each other. This is a black eye for the Riken Institute, which has done so much very fine work. They are to be commended for speedily convening the investigation and for expeditiously examining the evidence. However, large efforts need to have one clearing house for data and all that data needs to be checked, checked and rechecked after every rewrite and before submission.

I think the papers clearly need to be retracted. The investigation does not make that recommendation, but it is the honorable thing to do under the circumstances.

STAP Paper Author Urges that the STAP Paper Be Withdrawn


Japanese scientist, Teruhiko Wakayama, a professor at Japan’s University of Yamanashi, who was part of the research team that described the production and characterization of STAP cells, has called for his own headline-grabbing study on stem cells to be withdrawn from publication. Wakayama says that the main findings of this paper have been thrown into doubt.

When the STAP cells came out in January it was hailed as a game-changer that could herald a new era of medical biology. The paper was published in the prestigious journal Nature and was also widely covered in Japan and across the world.

Since that time, however, there have been reports that several other scientists have been unable to replicate the Japanese team’s results. Also there seem to be some disparities with some of the paper’s data and images.

“It is no longer clear what is right,” Wakayama told public broadcaster NHK.

STAP or stress-triggered acquisition of pluripotency cells seemed to represent a simple way to reprogram mature animal cells back into an embryonic-like state that would allow them to generate many types of tissue.

From these STAP cell papers, various editorials dreamed big and suggested that just about any cell in your body could be simply and cheaply reprogrammed back into embryonic cell-like cells, and be used to replace damaged cells or grow new organs for sick and injured people.

Wakayama even said, “When conducting the experiment, I believed it was absolutely right.” However, now he is not so sure. He continued: “But now that many mistakes have emerged, I think it is best to withdraw the research paper once and, using correct data and correct pictures, to prove once again the paper is right. If it turns out to be wrong, we would need to make it clear why a thing like this happened.”

A spokesperson from the journal Nature has said that they were aware of, “issues relating to this paper,” and that an investigation was underway. However, at this point, the journal had no further comment to make.

Robin Lovell-Badge, a stem cell expert at Britain’s National Institute for Medical Research, cautioned against premature assumptions on whether the research was flawed. “I have an open mind on this,” he told Reuters. “I’m waiting to hear from several serious stem cell labs around the world on whether they have been able to reproduce the methods.”

Wakayama’s co-researcher Haruko Obokata, the first author on the STAP paper, became an instant celebrity in Japan after she spoke during a Nature media briefing to science reporters all over the world about her findings.

The Japanese team was joined by other researchers from Brigham and Women’s Hospital and Harvard Medical School in the United States in this research. They took skin and blood cells from mice, grew them, and then subjected them to stresses that brought the cells “almost to the point of death.” They exposed the cells to a variety of stresses, including trauma, low oxygen levels, and acidic environments.

One of these “stressful” situations used by these researchers was to bathe their cells in a weak acid solution for around 30 minutes. Within days, the scientists said they had found that the cells had not only survived but had also recovered by naturally reverting into a state similar to that of an embryonic stem cell.

Unfortunately, other research teams have yet been able to replicate the findings, and the RIKEN Center for Developmental Biology in Japan, where Obokata works, said last week it had “launched an independent inquiry into the content of the paper.

That inquiry will be conducted by a panel of experts from within and outside RIKEN, it said, and would be published as soon as it was concluded.

A spokesperson from the RIKEN Institute declined to comment on Wakayama’s call for the paper to be withdrawn.

STAP Cells: The Plot Thickens Even More


You might remember that Charles Vacanti and researchers at the RIKEN Institute in Japan reported a protocol for reprogramming mature mouse cells into pluripotent stem cells that could not only integrate into mouse embryos, but could also contribute to the formation of the placenta. To convert mature cells into pluripotent cells, Vacanti and others exposed the cells to slightly acidic conditions or other types of stressful conditions and the cells reverted to a pluripotent state.

Even though Vacanti and others published these results in the prestigious journal Nature, as other scientists tried to replicate the results in these papers, they found themselves growing more and more frustrated. Also, some gaffes with a few of the figures contributed to a kind of pall that has hung over this research in general.

The original makers of these cells, stress-acquired acquisition of pluripotency or STAP cells, have now made a detailed protocol of how they made their STAP cells publicly available at the Nature Protocol Exchange. Already. it is clear that a few things about the original paper are generating many questions.

First of all, Charles Vacanti’s name does not appear on the protocol. He was the corresponding author of the original paper. Therefore the absence of his name raises some eyebrows. Secondly, the authors seem to have backed off a few of their original claims.

For example one of the statements toward the beginning of the protocol says, “Despite its seeming simplicity, this procedure requires special care in cell handling and culture conditions, as well as in the choice of the starting cell population.” Whereas the original paper, on the first reading at least, seemed to convey that making STAP cells was fairly straightforward, this seems to no longer be the case, if the words of this protocol are taken at face value.

Also, the protocol notes that cultured cells do not work with their protocol. The authors write, “Primary cells should be used. We have found that it is difficult to reprogram mouse embryonic fibroblasts (MEF) that have been expanded in vitro, while fresh MEF are competent.”  This would probably explain inability of several well-regarded stem cell laboratories to recapitulate this work, since the majority of them probably used cultured cells. This, however, seems to contradict claims made in the original paper that multiple, distinct cell types could be converted into STAP cells.

Another clarification that the protocol provides that was not made clear in the original paper is that STAP cells and STAP stem cells are not the same thing. According to the authors, the protocol provided at Nature Protocol Exchange produces STAP cells, which have the capacity to contribute to the embryo and the placenta. On the other hand, STAP stem cells, are made from STAP cells by growing them in ACTH-containing medium on feeder cells, after which the cells are switched to ESC media with 20% Fetal Bovine Serum. STAP stem cells have lost the ability to contribute to extra-embryonic tissues.

Of even greater concern is a point raised by Paul Knoepfler at UC Davis. Knoepfler noticed that the original paper argued that some of their STAP cells were made from mature T cells. T cells rearrange the genes that encode the T cell receptor. If these mature T cells were used to make STAP cells, then they should have rearranged T cell receptor genes. The paper by Vacanti and others shows precisely that in a figure labeled 1i. However, in the protocol, the authors state that their STAP cells were NOT made from T-cells. In Knoepfler’s words: “On a simple level to me this new statement seems like a red flag.”

Other comments from Knoepfler’s blog noted that the protocol does not work on mice older than one week old. Indeed, the protocol itself clearly states that “Cells from mice older than one week showed very poor reprogramming efficiency under the current protocol. Cells from male animals showed higher efficiency than those from female.”  Thus the universe of cells that can be converted into STAP cells seems to have contracted by quite a bit.

From all this it seems very likely that the STAP paper will need to go through several corrections. Some think that the paper should be retracted altogether. I think I agree with Knoepfler and we should take a “wait and see” approach. If some scientists can get this protocol to work, then great. But even then, multiple corrections to the original paper will need to be submitted. Also, the usefulness of these procedure for regenerative medicine seems suspect, at least at the moment. The cells types that can be reprogrammed with this protocol are simply too few for practical use. Also, to date, we only have Vacanti’s word that this protocol works on human cells. Forgive me, but given the gaffes associated with this present paper, that’s not terribly reassuring.

Results of STAP Cell Paper Questioned


Reports of Stimulus-Triggered Acquisition of Pluripotency or STAP cells has rocked the stem cell world. If adult cells can be converted into pluripotent stem cells so easily, then perhaps personalized, custom stem cells for each patient are just around the corner.

However, the RIKEN institute, which was heavily involved in the research that brought STAP cells to the world has now opened an investigation into this research, since leading scientists have voiced discrepancies about some of the figures in the paper and others have failed to reproduce the results in the paper.

Last week, Friday (February 14, 2014, spokespersons for the RIKEN centre, which is in Kobe, Japan, announced that the institute is looking into alleged irregularities in the work of biologist Haruko Obokata, who works at the institution. Obokata was the lead author listed on two papers that were published in the international journal Nature. These papers (Obokata, H. et al. Nature 505, 641–647 (2014), and Obokata, H. et al. Nature 505, 676–680 (2014) described a rather simple protocol for deriving pluripotent stem cells from adult mouse cells by exposing them to acidic conditions, other types of stresses such as physical pressure on cell membranes. The cells, according to these two publications, had virtually all the characteristics of mouse embryonic stem cells, but had the added ability to form placental structures, which is an ability that embryonic stem cells do not have. The investigation initiated by the RIKEN centre comes at the behest of scientists who have noticed that some of the images used in these papers might have been duplicated from other papers. Also, several scientists have notes that they have been unable, to date, to replicate her results.

These concerns came to a head last week when the science blog PubPeer, and others, noted some problems in these two Nature papers and in an earlier paper from 2011. Obokata is also the first author of this 2011 paper (Obokata, H. et al. Tissue Eng. Part A 17, 607–15 (2011), and this paper contains a figure that seems to have been used for one of the figures in the 2014 paper. Also, there is another figure duplication.

Harvard Medical School anesthesiologist Charles Vacanti who was the corresponding author of one of the Nature papers has said that has learned last week about a data mix up in the paper and has contacted the journal to request a correction. “It certainly appears to have been an honest mistake [that] did not affect any of the data, the conclusions or any other component of the paper,” says Vacanti. Note that Vacanti is a co-author on both papers and a corresponding author on one of them.

In the other paper, Obokata serves as the corresponding author and this paper contains an image of two placentas that appear to be very similar. Teruhiko Wakayama works at Yamanashi University in Yamanashi prefecture, and he is a co-author on both of these papers. According to Wakayama, he sent more than a hundred images to Obokata and suggests that there was confusion over which to use. He says he is now looking into the problem.

Additionally, ten prominent stem-cell scientists have been unable to repeat Obokata’s results. One particular blog listed eight failures from scientists in the field. However, most of those attempts did not use the same types of cells that Obokata used.

Some scientists think that this could simply be a case of experienced scientists working with a system that they know very well and can manipulate easily, unlike outsiders to this same laboratory. For example, Qi Zhou, a cloning expert at the Institute of Zoology in Beijing, who says most of his mouse cells died after treatment with acid, says that “setting up the system is tricky; as an easy experiment in an experienced lab can be extremely difficult to others, I won’t comment on the authenticity of the work only based on the reproducibility of the technique in my lab,” says Zhou.

However, others are more deeply concerned. For example, Jacob Hanna, a stem-cell biologist at the Weizmann Institute of Science in Rehovot, Israel, however, says “we should all be cautious not to persecute novel findings” but that he is “extremely concerned and sceptical”. He plans to try for about two months before giving up.

It could be that the protocol is far more complicated that thought. For example, even Wakayama has been having trouble reproducing the results. To be sure, Wakayama and a student of his were able to replicate the experiment independently before publication, but only after being coached by Obokata. But since he moved to Yamanashi, he has had no luck. “It looks like an easy technique — just add acid — but it’s not that easy,” he says.

Wakayama says that his own success in replicating Obokata’s results has convinced him that her technique works. “I did it and found it myself,” he says. “I know the results are absolutely true.”

Clearly one way to clear this up is for the authors of this groundbreaking paper to publish a detailed protocol on how to make STAP cells. This should clear up any problems with the papers. Vacanti says he has had no problem repeating the experiment and says he will let Obokata supply the protocol “to avoid any potential for variation that could lead to confusion”.

The journal Nature has said that there are aware of the problems with the papers and looking into the matter.

For now, that’s where the issue sits. Frustrating I know, but until we know more we will have to just “wait and see.”

Histones Might Hold the Key to the Generation of Totipotent Stem Cells


Reprogramming adult cells into pluripotent stem cells remains a major challenge to stem cell research. The process remains relatively inefficient and slow and a great deal of effort has been expended to improve the speed, efficiency and safety of the reprogramming procedure.

Researchers from RIKEN in Japan have reported one piece of the reprogramming puzzle that can increase the efficiency of reprogramming. Shunsuke Ishii and his colleagues from RIKEN Tsukuba Institute in Ibaraki, Japan have identified two variant histone proteins that dramatically enhance the efficiency of induced pluripotent stem cell (iPS cell) derivation. These proteins might be the key to generating iPS cells.

Terminally-differentiated adult cells can be reprogrammed into a stem-like pluripotent state either by artificially inducing the expression of four factors called the Yamanaka factors, or as recently shown by shocking them with sublethal stress, such as low pH or pressure. However, attempts to create totipotent stem cells capable of giving rise to a fully formed organism, from differentiated cells, have failed.  However, a paper recently published in the journal Nature has shown that STAP or stimulus-triggered acquisition of pluripotency cells from mouse cells have the capacity to form placenta in culture and therefore, are totipotent.

The study by Shunsuke Ishii and his RIKEN colleagues, which was published in the journal Cell Stem Cell, attempted to identify molecules in mammalian oocytes (eggs) that induce the complete reprograming of the genome and lead to the generation of totipotent embryonic stem cells. This is exactly what happens during normal fertilization, and during cloning by means of the technique known as Somatic-Cell Nuclear Transfer (SCNT). SCNT has been used successfully to clone various species of mammals, but the technique has serious limitations and its use on human cells has been controversial for ethical reasons.

Ishii’s research group focused on two histone variants named TH2A and TH2B, which are known to be specific to the testes where they bind tightly to DNA and influence gene expression.

Histones are proteins that bind to DNA non-specifically and act as little spool around which the DNA winds.  These little wound spools of DNA then assemble into spirals that form thread-like structures.  These threads are then looped around a protein scaffold to form the basic structure of a chromosome.  This compacted form of DNA is called “chromatin,” and the DNA is compacted some 10,000 to 100,000 times.  Histones are the main arbiters of chromatin formation.  In the figure below, you can see that the “beads on a string” consist of histones with DNA wrapped around them.

DNA_to_Chromatin_Formation

There are five “standard” histone proteins: H1, H2A, H2B, H3, and H4.  H2A, H2B, H3 and H4 form the beads and the H1 histone brings the beads together to for the 30nm solenoid.  Variant histones are different histones that assemble into beads that do not wrap the DNA quite as tightly or wrap it differently than the standard histones.  Two variant histones in particular, TH2A and TH2B, tend to allow DNA wrapped into chromatin to form and more loosely packed structure that allows the expression of particular genes.

When members of Ishii’s laboratory added these two variant histone proteins, TH2A/TH2B, to the Yamanaka cocktail (Oct4, c-Myc, Sox2, and Klf4) to reprogram mouse fibroblasts, they increased the efficiency of iPSC cell generation about twenty-fold and the speed of the process two- to threefold. In fact, TH2A and TH2B function as substitutes for two of the Yamanaka factors (Sox2 and c-Myc).

Ishii and other made knockout mice that lacked the genes that encoded TH2A and TH2B. This work demonstrated that TH2A and TH2B function as a pair, and are highly expressed in oocytes and fertilized eggs. Furthermore, these two proteins are needed for the development of the embryo after fertilization, although their levels decrease as the embryo grows.

Graphical Abstract1 [更新済み]

In early embryos, TH2A and TH2B bind to DNA and induce an open chromatin structure in the paternal genome (the genome of sperm cells), which contributes to its activation after fertilization.

These results indicate that TH2A/TH2B might induce reprogramming by regulating a different set of genes than the Yamanaka factors, and that these genes are involved in the generation of totipotent cells in oocyte-based reprogramming as seen in SCNT.

“We believe that TH2A and TH2B in combination enhance reprogramming because they introduce a process that normally operates in the zygote during fertilization and SCNT, and lead to a form of reprogramming that bears more similarity to oocyte-based reprogramming and SCNT” explains Dr. Ishii.

Human STAP cells – Troubling Possibilities


Soon after the publication of this paper that adult mouse cells could be reprogrammed into embryonic-like stem cells simply by exposing them to acidic environments or other stresses , Charles Vacanti at Harvard Medical School has reported that he and his colleagues have demonstrated that this procedure works with human cells.

STAP cells or stimulus-triggered acquisition of pluripotency cells were derived by Vacanti and his Japanese collaborators last year. These new findings show that adult cells can be reprogrammed into embryonic-like stem cells without genetic engineering. However, this technique worked well in mouse cells, but it was not clear that it would work with human adult cells.

Vacanti and others shocked the world when they published their paper in the journal Nature earlier this year when they announced that adult cells in mice could be reprogrammed through exposure to stresses and proper culture conditions.

Now Vacanti has made good on his promise to test his protocol on human adult cells. In the photo below, provided by Vacanti, human adult cells were reprogrammed to a pluripotent state by exposing them to stresses, followed by growth in culture under specific conditions.

Human STAP cells
Human STAP cells

“If they can do this in human cells, it changes everything, said Robert Lanza of Advanced Cell Technologies in Marlborough, Massachusetts. Such a procedure promises cheaper, faster, and potentially more flexible cells for regenerative medicine, cancer therapy and cell and tissue cloning.

Vacanti and his colleagues say they have taken human fibroblast cells and tested several environmental stressors on them to recreate human STAP cells. He will not presently disclose which particular stressors were applied, he says the resulting cells appear similar in form to the mouse STAP cells. His team is in the process of testing to see just how stem-cell-like these cells are.

According to Vacanti, the human cells took about a week to resemble STAP cells, and formed spherical clusters just like their mouse counterparts. Vacanti and his Harvard colleague Koji Kojima emphasized that these results are only preliminary and further analysis and validation is required.

Bioethical problems potentially emerge with STAP cells despite their obvious potential. The mouse cells that were derived and characterized by Vacanti’s group and his collaborators were capable of making placenta as well as adult cell types. This is different from embryonic stem cells, which can potentially form all adult cell types, but typically do not form placenta. Embryonic stem cells, therefore, are pluripotent, which means that they can form all adult cell types. However, the mouse STAP cells can form all embryonic and adult cell types and are, therefore, totipotent. Mouse STAP cells could form an entirely new mouse. While it is now clear if human STAP cells, if they in fact exist, have this capability, but if they do, they could potentially lead to human cloning.

Sally Cowley, who heads the James Martin Stem Cell Facility at the University of Oxford, said of Vacanti’s present experiments: “Even if these are STAP cells they may not necessarily have the same potential as mouse ones – they may not have the totipotency – which is one of the most interesting features of the mouse cells.”

However the only cells known to be naturally totipotent are in embryos that have only undergone the first couple of cell divisions immediately after fertilization. According to Cowley, any research that utilizes totipotent cells would have to be under very strict regulatory surveillance. “It would actually be ideal if the human cells could be pluripotent and not totipotent – it would make everyone’s life a lot easier,” she opined.

Cowley continued: “However, the whole idea that adult cells are so plastic is incredibly fascinating,” she says. “Using stem cells has been technically incredibly challenging up to now and if this is feasible in human cells it would make working with them cheaper, faster and technically a lot more feasible.”

This is all true, but Robert Lanza from Advanced Cell Technology in Marlborough, Massachusetts, a scientist with whom I have often deeply disagreed, noted: “The word totipotent brings up all kinds of issues,” says Robert Lanza of Advanced Cell Technology in Marlborough, Massachusetts. “If these cells are truly totipotent, and they are reproducible in humans then they can implant in a uterus and have the potential to be turned into a human being. At that point you’re entering into a right-to-life quagmire”

A quagmire indeed, for Vacanti has already talked about using these STAP cells to clone human embryos. Think of it: the creation of very young human beings just for the purpose of ripping them apart and using their cells for research or medicine. Would we allow this if the embryo were older; say the age of a toddler? No we would rightly condemn it as murder, but because the embryo is very young, that somehow counts against it. This is little more than morally grading the embryo according to astrology.

Therefore, whole Vacanti’s experiments are exciting and novel, they hold chilling possibilities. Lanza is right, and it is doubtful that scientists would show the same deference or sensitivities to the moral exigencies he has shown.

Stimulus-Triggered Acquisition of Pluripotency Cells: Embryonic-Like Stem Cells Without Killing Embryos or Genetic Engineering


Embryonic stem cells have been the gold standard for pluripotent stem cells. Pluripotent means capable of differentiating into one of many cell types in the adult body. Ever since James Thomson isolated the first human embryonic stem cell lines in 1998, scientists have dreamed of using embryonic stem cells to treat diseases in human patients.

However, deriving human embryonic stem cell lines requires the destruction or molestation of a human embryo, the smallest, youngest, and most vulnerable member of our community. In 2006, Shinya Yamanaka and his colleges used genetic engineering techniques to make induced pluripotent stem (iPS) cells, which are very similar to embryonic stem cells in many ways. Unfortunately, the derivation of iPSCs introduces mutations into the cells.

Now, researchers from Brigham and Women’s Hospital (BWH), in Boston, in collaboration with the RIKEN Center for Developmental Biology in Japan, have demonstrated that any mature adult cell has the potential to be converted into the equivalent of an embryonic stem cell. Published in the January 30, 2014 issue of the journal Nature, this research team demonstrated in a preclinical model, a novel and unique way to reprogram cells. They called this phenomenon stimulus-triggered acquisition of pluripotency (STAP). Importantly, this process does not require the introduction of new outside DNA, which is required for the reprogramming process that produces iPSCs.

“It may not be necessary to create an embryo to acquire embryonic stem cells. Our research findings demonstrate that creation of an autologous pluripotent stem cell – a stem cell from an individual that has the potential to be used for a therapeutic purpose – without an embryo, is possible. The fate of adult cells can be drastically converted by exposing mature cells to an external stress or injury. This finding has the potential to reduce the need to utilize both embryonic stem cells and DNA-manipulated iPS cells,” said senior author Charles Vacanti, MD, chairman of the Department of Anesthesiology, Perioperative and Pain Medicine and Director of the Laboratory for Tissue Engineering and Regenerative Medicine at BWH and senior author of the study. “This study would not have been possible without the significant international collaboration between BWH and the RIKEN Center,” he added.

The inspiration for this research was an observation in plant cells – the ability of a plant callus, which is made by an injured plant, to grow into a new plant. These relatively dated observations led Vacanti and his collaborators to suggest that any mature adult cell, once differentiated into a specific cell type, could be reprogrammed and de-differentiated through a natural process that does not require inserting genetic material into the cells.

“Could simple injury cause mature, adult cells to turn into stem cells that could in turn develop into any cell type?” hypothesized the Vacanti brothers.

Vacanti and others used cultured, mature adult cells. After stressing the cells almost to the point of death by exposing them to various stressful environments including trauma, a low oxygen and acidic environments, researchers discovered that within a period of only a few days, the cells survived and recovered from the stressful stimulus by naturally reverting into a state that is equivalent to an embryonic stem cell. With the proper culture conditions, those embryonic-like stem cells were propagated and when exposed to external stimuli, they were then able to redifferentiate and mature into any type of cell and grow into any type of tissue.

To examine the growth potential of these STAP cells, Vacanti and his team used mature blood cells from mice that had been genetically engineered to glow green under a specific wavelength of light. They stressed these cells from the blood by exposing them to acid, and found that in the days following the stress, these cells reverted back to an embryonic stem cell-like state. These stem cells then began growing in spherical clusters (like plant callus tissue). The cell clusters were introduced into developing mouse embryos that came from mice that did not glow green. These embryos now contained a mixture of cells (a “chimera”). The implanted clusters were able to differentiate into green-glowing tissues that were distributed in all organs tested, confirming that the implanted cells are pluripotent.

Thus, external stress might activate unknown cellular functions that set mature adult cells free from their current commitment to a particular cell fate and permit them to revert to their naïve cell state.

“Our findings suggest that somehow, through part of a natural repair process, mature cells turn off some of the epigenetic controls that inhibit expression of certain nuclear genes that result in differentiation,” said Vacanti.

Of course, the next step is to explore this process in more sophisticated mammals, and, ultimately in humans.

“If we can work out the mechanisms by which differentiation states are maintained and lost, it could open up a wide range of possibilities for new research and applications using living cells. But for me the most interesting questions will be the ones that let us gain a deeper understanding of the basic principles at work in these phenomena,” said first author Haruko Obokata, PhD.

If human cells can be made into embryonic stem cells by a similar process, then someday, a simple skin biopsy or blood sample might provide the material to generate embryonic stem cells that are specific to each individual, without the need for genetic engineering or killing the smallest among us. This truly creates endless possibilities for therapeutic options.