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Comment by moh_maya | Hacker News Reader

There is good reason to be skeptical of the claims in the article. This twitter thread [1] is a good, articulate criticism of the issues around the paper.

To quote a segment from the series of tweets by the author, Kevin Mitchell (a neurogeneticist from Trinity College, Dublin)[2] :

"1. A supposed mechanism in search of a phenomenon... (What is the microbiome supposed to explain here?)

2. No actual mechanism.

3. No actual findings. Just lots of exploratory blips, unconstrained by prior hypotheses, uncorrected for multiple tests, and unreplicated.

4. Massive hype.

Just because the genetics of complex disorders is complex and just because the neuroscience of the highest functions of the human mind is complex, doesn't mean we need to go looking for new kinds of biology to explain them"

[1] https://threadreaderapp.com/thread/1095012297200844800.html

[2] https://www.kjmitchell.com/

[edit: formatting]

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Shameless ad-hominem here, since there's not much to grab onto in that guy's argument:

Be careful who you believe. This grumpy genetic determinist is clearly out of touch with an entire field of emerging research about the gut-brain axis.

Apparently this guy you're quoting is also skeptical of epigenetic inheritance. (http://www.germlineexposures.org/blog/no-convincing-evidence...)

Why should I listen to him again?

He's hung up on finding a singular "actual mechanism" in a complex, nonlinear system? I know almost nothing about this guy but I suspect he's another a drug company biologist, desperately holding onto shattered dreams of genetic determinism.

So, if you actually read the 3-4 blog articles [1,2,3,4,5] on epigenetics that he's written, I don't interpret them as him suggesting epigenetic changes do not occur.

Rather, I think he is challenging the notion that epigenetic inheritance is the driver of / underlies behaviour change in mammals.

I disagree with your assertion that he is skeptical of epigenetic inheritance. I think he's skeptical that epigenetic inheritance can drive multi-generational neuro / psychiatric behaviour change, which is a far more nuanced position to take.

For instance, had you made the effort of actually checking his blog, [5] is a response to the article you linked / cited:

To quote him:

"So, in case I have come across as merely unpleasantly grumpy, let me spell out my general grounds for being skeptical of the claims of TGEI in mammals."

And further, in the context of behaviours and neuro disorders, and their inheritance in humans.

That's what he is commenting about. Not epigenetic inheritance in general. In as much as you didn't actually check his writings and painted his position with such a broad brush and value judgements, then yes. I would agree this was shameless and an ad-hominem attack indeed.

Now, I don't know this guy. But his arguments, especially the lots of different ways in which biologists mis-interpret and mis-apply statistics rings true. His arguments are cogent, and his analysis reasonable and conservative. Which, in science (the conservative interpretation) is an excellent thing, IMO. So yes, I do choose to consider his opinion carefully.

I think, in all this hype and buzz-wordy social media noise that appears to be driving everything including research and politics, it's important to identify and defend the voices that are saying, slow down, let's not read too much into these things yet; let's not get carried away.

Jill Escher, whose article you linked to, is a lawyer by training. This guy is a neuro-biologist and a professor at Trinity College, Dublin. Who do you think has more credibility here?

This suggests to me that you didn't even look the people you were citing up, or who you were criticising. Surely, you can do better?

[1] http://www.wiringthebrain.com/2013/01/the-trouble-with-epige...

[2] http://www.wiringthebrain.com/2013/01/the-trouble-with-epige...

[3] http://www.wiringthebrain.com/2014/04/the-trouble-with-epige...

[4] http://www.wiringthebrain.com/2018/05/grandmas-trauma-critic...

[5] http://www.wiringthebrain.com/2018/07/calibrating-scientific...

[Edit: added excerpt and replaced "crap" with "noise"]

I don't think a Twitter thread is an adequate response to an academic paper. Twitter is the equivalent of the homeless man yelling at the bus stop.

Eh, homeless people are occasionally right and a little less hysterical. Twitter is the equivalent of a small dog yapping at the homeless man yelling at a bus stop.

Various polls over the last few years show Twitter is the 2nd or 3rd most popular social media site for news. Right behind The FB.

This is as good as it's probably going to get from here on out.

I think the most obvious question is “does schizophrenia cause an abnormal gut microbiome or does an abnormal gut microbiome causes schizophrenia?”

My bet is it’s the former, not the later.

Then you need to explain how the fecal transplants triggered similar symptoms.

Maybe schizophrenia is not a sickness, merely a epi-genetic adaption to bad circumstances. Have a little civil war? Turn yourself into a twitching little zombie and walk it off?

So if you transport the message, you get a universal reaction.

Definitely. Eating patterns, sleep and many other things change. Even medications like lithium. What's lithium do to bacteria? My anxiety makes eating hard sometimes so i eat bad foods just to get calories in.

It is sad, because there is certainly a link, it’s not just the direct one that all academia is jumping to conclusions.

You pretty much nailed all those studies. Those type of hard to characterize, very complex, and poorly understood diseases, are the only candidates that you will see a “microbiome can cause/cure it” type of paper.

At the end of the day, they see a mouse, bearing a set of mutations that is not even close to mimic the disease population, adopt some new behaviors, and then they miraculously cured everything.

On top of that, VC have started to invest massively in that field, even starting their own company. On one side, I hope this will bring some much needed robustness to the current lack of rigor. On the flip side, since the biotech VC model is to IPO whithin 5 years, I doubt they will do better.

Or, more likely, they are both effects of the same root cause...

Or is there some third factor that causes both such as stress, high levels of innate immunity activation, etc.

Or it could be a feedback loop with multiple possible starting points.

I don't understand how these could possibly be mutually exclusive.

The professors behind this work are well known and credible.

Which is good but also not enough.

It’s a different league than a twitter thread.

It's reasonable for a twitter thread to point out methodological issues in a study even without prior credibility.

If the original research were in a twitter thread rather than a publication, it would be unreasonable to consider it seriously.

Where we'll known and credible.

Then they reversed causality for some wild theories.

Also worth mentioning that Science Advances is a relatively new open-access journal, which is distinct from and significantly lower status than the journal Science. Although I can't speak to the reputation of Science Advances, Nature has a very similar sister journal, Scientific Reports, that is distinctly mediocre.

Aside: I think this whole "status thing" is hurting scientific progress. You want to work in academia? Better publish x papers a year in a "reputable journal". This attitude is what leads to quantity over quality approach, and results in all the p-hacking and overhyping. Negative results are likely to go unpublished.

Here reputable = discriminating

And these low-reputation journals are poorly discriminating. Status here has a reason.

>Just because the genetics of complex disorders is complex and just because the neuroscience of the highest functions of the human mind is complex, doesn't mean we need to go looking for new kinds of biology to explain them

After decades of looking for brain abnormalities and finding none it really is time to look elsewhere.

Not to mention that "new kinds of biology" are becoming hugely credible. There's a massive body of work emerging about the gut-brain connection.

This Mitchell guy is in denial.

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