July 11, 2020

The Niche

Knoepfler lab stem cell blog

In a pickle over STAP stem cells: top 5 reasons for skepticism

in a pickleIf you take an ordinary cucumber and soak it in a mild acid solution of vinegar for a few weeks you get a pickle, which is where we find STAP stem cells.

Recently, some scientists reported in Nature that if you take ordinary cells and soak them in a mild acid solution for 30 minutes, often the cells transformed into the most powerful type of stem cells known to science.

These newly incarnated pluripotent or totipotent stem cells, which they termed “STAP” stem cells, reportedly can make any known type of cell and maybe even an entire embryo along with its own placenta.

Now that’s no pickle.

The authors reported that it doesn’t even have to be acid, but any number of stresses will do the trick.

Just how amazing is this? It’d be like putting your cucumber in vinegar to make a pickle and instead finding the cucumber had changed into a living, swimming goldfish in the jar.

We’ve seen some amazing things in the stem cell field turn out to be completely true such as iPS cells, but somehow from day 1 I had no doubt about iPS cells.

Extraordinary claims require extraordinary evidence and independent replication. STAP stem cells aren’t there…at least not yet.

Five more specific reasons make me skeptical of STAP stem cells at this point.

  • 1. The STAP method & results are illogical. I’m not a Vulcan like Spock on Star Trek, but I believe logic and common sense are keys to science. To me STAP defies common sense. Illogical doesn’t necessarily mean wrong, but it raises doubts. STAP just seems too good to be true.
  • 2. The STAP team previously reported “spore” stem cells, which to my knowledge have not been independently replicated. They reported in 2001 the discovery of “spore stem cells” that are a micron or two in size, behave kind of like fungal spores, can take a beating, and may have a “minimal genome” contained in an atypical, tiny nucleus. Dr. Vacanti recently told me that STAP stem cells and spore stem cells are believed to be the same thing.
  • 3. The team also previously reported adult pluripotent stem cells. Drs. Vacanti and Obokata also published a surprising paper in 2011 reporting to have found pluripotent stem cells in adult tissues. I’m not a believer in such cells, but other folks do believe in such cells and call them VSELs or MUSE.
  • 4. Evolution should have selected against a hair trigger for conversion to pluripotency or totipotency. A process for any ordinary mature cell to go back in developmental time easily trigged by any one of a host of different stressors would be harmful, even deadly to organisms. In that reality, we should see teratoma or teratocarcinoma tumors–the kind that arise from pluripotent or totipotent stem cells–sprouting up all over the body after injuries or even just spontaneously, but that doesn’t happen. The key concept here is that in the wrong developmental context (in a child or an adult rather than in an embryo), embryonic-like stem cells would not behave normally just to fix tissues and then stop. Rather they’d make tumors. Evolution should select against that. Now if the authors had reported STAP stem cells as multipotent tissue specific stem or progenitor cells that might have made sense as a mechanism for tissue repair. But they didn’t.
  • 5. Why the delay to make human STAP cells?  The team says they made mouse STAP stem cells successfully in 2011, but only now in 2014 are they just starting to try to make human STAP stem cells. What the heck? Wouldn’t trying to make human STAP stem cells have been something they should have done immediately in 2011 or even done at the same time as trying to make the mouse ones? There may well be a good reason for this delay, but again it’s just something that is puzzling.

What’s the bottom line? In the end, right now we cannot be 100% sure either way about STAP stem cells. However, we’ll know if STAP cells are the real deal within as short as two months because quite a few labs are now trying the technique. Again, I believe the odds are it won’t work, at least not in a reasonably close fashion to what was reported in these Nature papers. Sure, we might see some people say to the media or even publish papers indicating that they can kinda sorta almost make STAP-like cells with certain stressors sometimes, but my prediction is that it still won’t be very convincing.

I really hope I am wrong and if I am you’ll read my happy mea culpa right here.

For additional background see my review of the STAP Nature paper here and more STAP-related thoughts here.

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