Margie writes:

Greetings TWiN friends!

I am so excited to have a real reason to email you! (I have been trying to come up with an excuse since TWiN 10 when you didn’t have any letters & requested emails. — Come to think, do I get bonus points for non-Covid19 questions??? LOL.)

Background: I have multiple sclerosis (so a bit of familiarity with neuro-degeneration). I was an elementary school teacher & then an elementary school librarian. I am now medically retired.

Fair warning in advance— I am very good at unintentionally making short stories long. So apologies for the length!

Today (Wednesday 10/28/20), there was a report shared that caused quite a hopeful stir in my MS Gym FB group. 

Here’s the link shared for the report made on a local TV news show. I’ll also add screenshots of the transcript. 


Obviously, that report could be sensationalized, so I searched for the more specifics. 

It turns out that the news stir is caused because of a new publication from 26 Oct 2020 in Nature Immunology titled “A new neutrophil subset promotes CNS neuron survival and axon regeneration. “

Link to article: 

I’d like to suggest this as an article for you guys to discuss— especially as I have not yet found a way to read more than the summary. (Quite possibly I won’t understand it much without a lot of thinking & study, so not being able to access the whole paper might be a moot point anyway… which would make listening to you guys discuss it that much more useful & valuable to me!) (Ahem. Hint hint! 😃)

First question:

From what I read in the “Extended data” their in vivo experiments looked at the optic nerve. 

In TWiN 8 you guys discussed “Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice”

( — Which also looked at eye related neurons/cells. (Apologies for the simplification here & in future.)

The two papers look at different things (a protein vs white blood cell), but they seem parallel? 

Both seem to be looking at regeneration in nerve cells — but I can’t really tell if they’re looking at the same things or just similar things. Can you guys expound/explain it to me?

Also, both are looking at eye-related nerves. Is this because it’s easier/doable/simpler to get to & study optic nerves? 

Now let’s move on to questions where it will be even more apparent that my science is elementary school level. 

Second question:

Both papers used mice for their in vivo experiments. 

I’ve heard Vincent say that “mice lie, monkeys exaggerate, & ferrets aren’t humans.”

So why bother with mice if they lie? 

This is asked tongue-in-cheek because I do understand that we do have to start somewhere. 

Yet if mice (& other animals) are so very different structurally/molecularly/not-sure-the-right-words from humans, then what’s the value of doing the experiments in mice?

That is not asked facetiously. I’d really like to understand. 

Third question:

Apparently, the Sas et all group also did experiments in vitro using human cell lines. 

Since I can’t read the paper, I can’t tell the order.  

Is it usual to first experiment in cells in vitro then move to animal studies? 

They talk about next steps. Obviously this would be different depending on what you’re actually studying …  but would you progress to a different animal or to a different type of cells?

(Just FYI here’s a website publication that talks a bit about the in vitro stuff. )

Fourth question:

This is about authorship. 

From the Sas et all article’s website:

“Author Information 

These authors contributed equally: Andrew R. Sas, Kevin S. Carbajal.”

Why is it important to make note of that? And why only those 2 mentioned when there are more authors listed?

Fifth question:

Also about authorship. 

From article website-


A.R.S., K.S.C., A.D.J., C.Y. and A.L.K. performed experiments and data analysis. R.M. oversaw RNA-seq analysis. B.M.S. wrote the manuscript and coedited it with the help of the other authors. B.M.S., R.J.G. and A.R.S. directed the studies.”

In school librarian world, the person who does the writing is the author. 

But the person who wrote the manuscript isn’t the first author listed. 

I’m guessing maybe the principle investigators are listed first in the author list?

How do they decide who gets to be “first author” anyway? And why is that so important? (I hear it emphasized often in the different microbeTV podcasts.) Is it something to do with the “publish or perish” part of university professorship?

Sixth question:

This is about peer review & publication. 

The article website lists dates for submission, acceptance, & publication. 

Obviously the time gap between submission & acceptance is the time when peer review is done. 

I was able to read the peer review comments. At the end there’s a place for “Author Rebuttal to Initial comments” but it is blank. 

The journal’s letter to the manuscript authors does say:

“We invite you to revise your manuscript. 

“* Include a “Response to referees” document detailing, point-by-point, how you addressed each referee comment. If no action was taken to address a point, you must provide a compelling argument. This response will be sent back to the referees along with the revised manuscript.”

I can’t see the actual article to read their response to referees. 

I wondering:

  • Is this a usual request?
  • What if you don’t have funds to do the experiments the referees request?
  • What if you just don’t want to do them?
  • Do journals refuse to publish manuscripts if the authors won’t address the referees questions? Can the authors get away with justifications of why they don’t do the referees requests? (I’m assuming comment about “Do not hesitate to contact us if there are specific requests from the reviewers that you believe are technically impossible or unlikely to yield a meaningful outcome” might be two of the reasons authors try to use to not do the requests?)
  • Are the referees requests usually things that really need to be done or often things designed to delay or impede competitors?

I really don’t have much knowledge (much less understanding) of the peer review process. If you could point me to someplace to learn about it, I’d be obliged. 

Last question:

There seems to be a lot of hype generated by the University of Ohio — where the authors work — about the discovery & its potential. 

Cynical me wonders if generating hype is about creating reputation to encourage funding. 

But perhaps this really is a big discovery?

It seems to me, however, that there’s a lot of steps & research that have to happen before it might actually be something that could have an impact on my life. 

Don’t get me wrong. I’d be absolutely delighted for my CNS to heal its damage. But even if this discovery proves to be pivotal…. it can’t be applied to my brain any time soon!

So what do you guys think? Big deal or not? Worth the hype? Or important & encouraging but not more so than other advances. (Like the papers discussed in TWiN 8)

Thanks very much for the podcasts. 

Yes, they are always over my head. Or at least completely out of my experience. I do enjoy getting glimpses into a world so different from my own.  (Meaning the world where you know & study how the brain – or other science works – vs the world where you study how to get kids to read for pleasure or do their homework!)

Thanks again. And keep on TWiN-ning!



P. S. 

I did consider sending this email to Immune – but I thought the emphasis on nerves & the similarity to the article in TWiN 8 made this the more appropriate choice. If not, please feel free to use the email there.