Yesterday was a crazy day for the STAP cell situation. We had RIKEN releasing a scathing internal investigatory report and then some folks in the media got all worked up about a single PCR assay result that Dr. Ken Lee posted on ResearchGate. Some of the reporters/science writers hyped their headlines/articles on this situation as though STAP cells had been proven real. On the other end of the spectrum quite a few people thought that Ken was pulling an April Fool’s Day prank, which he wasn’t.
A few media folks did a great job like Monte Morin at the LA Times and Karen Weintraub at the Boston Globe.
Still others responded to constructive criticism of their arguably over-the-top headlines by changing them. Kudos to them. For example WIRED had a piece entitled “‘Fabricated’ stem cell paper may have just been proven valid” and I see now that the title seems to be changed to the far more accurate “‘Fabricated’ stem cell paper technique may yet be proven valid”. At least I think these WIRED articles with different headers are one and the same.
Ken has been doing the most rigorous attempts that I know of at replicating STAP cells since the Nature papers came out without any STAP success.
However, Ken’s new results just recently posted were just the tiniest, itty bittiest hopeful and different this time. The new result of a single PCR assay shows the levels of 2 pluripotency-related genes (Oct4 and Nanog) increased 8-10-fold in triturated cells, but oddly enough that change was not evident in the cells with both trituration plus acid treatment. Sox2 was not changed in any sample.
So this is extremely preliminary and as yet quite limited in scope.
One PCR assay on a few genes (even if interesting) shouldn’t cause people to hyperventilate or the equivalent in their media headlines.
As I told the LA Times, injured or dying cells can fire off random changes in gene expression that are hard to make sense of most of the time. These new results do not prove that STAP is real at this point and probably the odds are way against this ultimately replicating STAP.
Typically during other forms of induced pluripotency a whole slew of dozens of stem cell genes are turned on and can increase by 100-fold or 1000-fold in levels from the starting non-stem cells.
Ken also indicated that it appeared all the stressed cells were in the process of dying and would be dead by day 3, which is not supposed to happen when one makes STAP cells according to the STAP authors. To do stuff like form teratoma, contribute to embryos, and more, STAP cells need to be healthy and proliferative. Ken harvested all the cells and stopped the experiment because they were dead or dying.
I find this one experiment notable and definitely worth following as Ken’s lab continues this series of experiments, but I urge caution about interpreting this one result too broadly.
Finally, I want to give a big hat tip to Ken for all his hard work on trying out different STAP methods.
researchgate are spammers.
They desperately need positive media, so they market the sh*t out of this STAP case. But it all has been discussed before, and outside of researchgate.
I note that Dr Kenneth Ka-ho Lee has announced on Researchgate he has stopped analysing Stap cells, saying he does not believe they exist.
I suspect he thought by contributing the blog he was doing something interesting for his students, as well as addressing something well publicized in the media? However, the rather rapid gear changes he has performed indicate I suspect that he was not expecting the media pressure that comes with blogging. All of that plus the blog comments themselves I could well imagine threaten his reputation, and he thought ..what the heck!
I sense that it is the normal discourse within science to have rigorous debates when discussing controversial proposals. When blogging research commentary is added it may attract outgoing but naïve researchers to tip toe into difficult areas. However, there is a fine line between crowd and herd behaviour, so trying something new and reporting it depending on the nature of the subject, may bring a world of pain down on them, and then it seems it is better not to try anything new.
It seems there are many genuine questions about proving STAP cells, and due to the informative debate I have heard many different thoughts on how to test pluripotency. With the controversy regarding the Nature papers, it is going to be a brave person to ever think this is an area worth reinvestigating and thereby threaten their reputation and consequently their research funding.
Prof. Lee said that he would not continue reporting STAP cell research….
Dr. Lee’s result actually shows the opposite of what he claims: STAP method didn’t work again. I do not know why he was saying something as if it was a positive result. When I compare the mRNA level of parental cells and iPS, I observe THREE ORDER of MAGNITUDE, 1000-2000 fold increase of Oct4, Sox2. If you see only 7-8 fold, that’s a “noise”. Stressed cells, dying cells, damaged cells show lots of “noise”, or “error bars”. It’s funny that Dr. Lee’s result shows no error bar. In addition, he uses only one house keeping gene normalization control, which often result in skewed result. I always use 3-5 different genes to confirm the result.
But the cells were actually a mixture of dying and “STAP” cells so you wouldn’t expect the same increase in transcript levels that is seen in pure iPS cells.
“STAP cells need to be healthy and proliferative” The authors claim that STAP cells do not proliferate, in contrast STAP-stem cells do.
You are 100% right that that’s what they said, but that always struck me as a very bizarre statement since they also reported that STAP cells were totipotent.
How the heck can a non-proliferative cell be totipotent?
To my knowledge, that’s impossible.
I absolutely agree with you. The only possibility that comes to my mind is that STAP cells (if they exist) have to be modified by the environment (when injected in nu/nu mice or into blastocyst) and that makes them to proliferate.
You didn’t like my explanation?? =) I was just trying to find a way to explain the unexplainable. I’m not a STAP believer! BTW I like a lot what you’re doing with your blog for the field.
Actually, I did like it. Do you mean the thumbs up or thumbs down on comments? They can be from any reader of the blog.
Great points. The continued media sensationalism is ironic because I believe that media outlets, especially those in Japan, actually bear some culpability for the magnitude of the STAP debacle in the first place through their inaccurate and sensationalist reporting. When the STAP papers were initially published, the media (especially in Japan) heralded it as a Nobel-level advance, game-changing, paradigm-shifting, “epoch-making” (in the actual words of the Asahi Shimbun), etc, which was a huge exaggeration, even before we knew about all of the problems with the paper. The truly “epoch-making” concept of cellular reprogramming had already been established and the clinical relevance of STAP was questionable, as STAP was suggested to only work in neonatal cells, and even if the initial findings were replicable there was no evidence that it would work in less resilient adult cells or that that the generated STAP stem cells would be healthy or even “safer than iPS cells” as claimed. Most media reports ignored or minimized all of these aspects. Dr. Yamanaka’s recent complaint to RIKEN further highlighted that STAP (if it actually works) is not actually much more efficient than the latest iterations of iPS; however, media representations of such counterpoints have been scarce. Additionally, it is well known that papers in Nature (and other journals) are more than occasionally thought-provoking but not reproducible, but the media painted this preliminary study as something ironclad that had already changed the field; a writer from the Asahi Shimbun even told a friend of mine “if it is published by Nature, you would believe it.” The STAP concept is interesting, but the media exaggeration prematurely built STAP into something that it was not, resulting in a public perception that STAP was some kind of all-powerful messiah of regenerative medicine, which has given it a higher height to fall down from. It is therefore heartening to see the more balanced reporting you have described above, although I do believe that the coverage from the LA Times and the Boston Globe has been pretty good throughout. I hope that other media outlets (especially those in Japan) can learn from them and actually take the time to do a little bit of background investigation before writing to increase their accuracy, for the sake of the field.