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Most scientists 'can't replicate studies by their peers'

bbc.co.uk

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Re: Most scientists 'can't replicate studies by their peers'

#261
post #47
post #28

"all you have to do is read the methods section in the paper and follow the instructions." I wish science was that simple. The methods section only contains variables the authors think worth controlling, and in reality you never know, and the authors never know. Secondly, I wish people say: "I replicated the methods and got a solid negative result" instead of "I can't replicate this experiment". Because most of the t…

So why aren't mouse studies done in acoustically isolated rooms? Too expensive or lack of forethought? I know metrological laboratories that are mechanically insulated with all sorts of contraptions making the space vibration free so it'd not as if buildings could not be adapted for their intended scientific use as a matter of principle.

In my experience, you're lucky if you can get space for your equipment at all.

One week, they're moving your growth cambers out into the hallway to work in the ceiling. The next, they had to cut power for 8 hours for maintenance, and by the way, it wasn't plugged into an outlet with emergency power. Oops.

Hell, they can't even keep the lab temperature steady. Solutions sitting on your bench will start to precipitate out.

So yeah, the issue is money. It's also planning; you never know what the needs of researchers are going to be in a few years.

In the end, nice facilities can certainly help with a lot, but they don't address the core issues of experimental variables and combinatoric complexity. The way you deal with this is skeptical peers that understand the methods, reliance on robust methods wherever possible, and independent methods to confirm results. Even with all this replication difficulty, it is quite possible to make compelling conclusions.

Re: Most scientists 'can't replicate studies by their peers'

#262

Earlier quoted context omitted.

I'm sorry, but given that we're gold fish looking out of the bowl from the inside; trying to predict the future from vague memories of the immediate past; we have no clue what's causing what in this mess. Any one who claims otherwise is an ignorant prostitute, doesn't matter if they're aware or not. There are huge monetary incentives to pushing this agenda, and plenty of bullying to get people to walk in line. Have a…

"Have a look around today, and most scientists seem to agree that we're rather heading into the next ice age." What scientists are you talking about? Also, didn't you JUST claim "we have no clue"? By the way, global warming is not the case of some weird uptick in data correlating with some other data being interpreted as causally linked. In the case of global warming, it's really common sense (if you're trained in ph…

This to me is a really compelling argument, I wish this approach was more common.

A nitpick:

> I laugh at the idea that scientists...have a "huge monetary incentive" to push this "agenda"

I'm guessing a bit at what you're thinking here, but I think it could be argued that not losing your job could be considered a "huge monetary incentive". I've certainly experienced extreme "peer pressure" to sign off on something that I disagree with before, the idea that office politics literally doesn't exist in the field of science seems quite unlikely to me.

Re: Most scientists 'can't replicate studies by their peers'

#263
post #98

Earlier quoted context omitted.

The classic ideal of controlling a single variable at a time is nice but largely impossible. Especially in biological sciences but that's true even down in chemistry and physics the systems scientists are trying to control are complex and it's not always possible to modify one variable without affecting others.

How can you possibly draw any useful conclusions when your experiment's parameters are so fluid as to be uncontrollable?

Independent experiments and controls. AKA, literally the basis of experimental science.

Let's say you want to know where a protein localizes in a cell, of a given tissue, in both mutant and wild-type organisms.

* Immunolocalization. You develop antibodies to the protein of interest, fix and mount tissue, perfuse it with the antibody, and use a secondary antibody to make it detectable.

* Fluorescent tagging. You make a construct with your protein fused to a fluorescent protein. Usually this involves trying a few different tagging strategies until you find one that expresses well. Then you can make a stable transgenic, or try a transient assay. If it works, then you see some nice glowy confocal images. Be careful, though, as the tagging can affect protein localization.

* Fractionation. In some cases, you can get a rough idea by e.g. extracting nuclei and doing a simple Western blot to see where the protein shows up.

In the real world, you might start with the FP-tag and see that your protein is absent from the nucleus in your mutant. Which would be cool, and interesting in terms of figuring out it's function. If that was presented as the only result, I'd reject the paper and think the authors are terrible investigators. I'd want to see, at least, some nuclei preps that detect the protein in the WT, and don't in the mutant. I'd love to see immunos, too, as FP often does mess up the localization.

You can take it even further and start doing deletions. You take the protein and crop bits out to see what happens. You should see stuff like removing the NLS makes it stop going to the nucleus. That's a good sanity check and a sign your methods are working. You can also try to mess with active sites, protein-protein interaction domains, etc. etc. All within a theoretical model of what you think is going on in the cell.

Ultimately, the difficulty of replication isn't that troublesome. An inability to do so is, but science has never been easy. That's what you sign up for, and that's why you need to read papers critically. You get a sense of distrust for data unless there's really solid evidence of something. And when you find that solid evidence, you get a big smile and warm feeling in nerd heart.

Re: Most scientists 'can't replicate studies by their peers'

#264
post #28

"all you have to do is read the methods section in the paper and follow the instructions." I wish science was that simple. The methods section only contains variables the authors think worth controlling, and in reality you never know, and the authors never know. Secondly, I wish people say: "I replicated the methods and got a solid negative result" instead of "I can't replicate this experiment". Because most of the t…

a load of variables that are needed to be controlled in order to get the original experiment to work is kind of a red flag tho. like someone could just keep trying the experiment and then adding another variable they are controlling in order to get the experiment to work. but really they are just running a bunch of experiments and getting lucky at some point. assuming they stop trying to control variables or try and…

It's not a red flag, it's reality. Biology is complicated, and no matter what the synthetic biologists tell you :)

You use independent methods and good controls to deal with this. This is nothing new, it's been the basis of experimental science for decades. If you're allowed to publish without doing this, the field has failed. Molecular biology, in particular, has flourished because of the effectiveness of genetic controls. Mutants are highly reproducible (you just send out seed, cultures, or live specimens), verifiable (sequencing), and combinatoric (crossing).

Re: Most scientists 'can't replicate studies by their peers'

#265
post #256
post #230

Earlier quoted context omitted.

Respectfully, I think you're missing the complications outlined in the rest of the thread. The difficulty in the biosciences and even in chemistry and some physics is that they can't really be formalized in the way that is necessary to construct these "chains of proof". The scientific literature is an ongoing conversation anchored by rigorous experimental facts and data. But rigorous doesn't mean it's clean like a ma…

I thought that statistics is the right tool to handle uncertainity? I had the impression that all the "soft" science is based on statistics. We can't prove that smoking kills people. But, given a certain confidance interval (or whatever equivalent measure for baysian statistics?), we can state that smoking is not a good idea if you want to live longer than mean expected years... Sure, some unforseen event may interfe…

Statistics is also the way to look at data in the "hard" sciences. Every measurement has error, and that's how you deal with it.

However it's not a simple thing that automatically combines different studies. It takes skilled application to understand how data connects, what's comparable, what's not, etc. Traditionally, "meta-analysis" is the sub-field of statistics that combines studies. But that only combines extremely simple studies, such as high-controlled clinical trials. It's inappropriate for the complex type of data that appears in a typical molecular biology paper is a chain of lots of different types of experimental setups.

Those who don't know the body of stats, trying to reason about application, is a lot like an MBA trying to reason about software architecture. The devil is in the details, and the details are absolutely 100% important with application of statistics to data.

Re: Most scientists 'can't replicate studies by their peers'

#266
post #49
post #34

I thought the reproducibility crisis was limited to the social sciences and some areas of health/medicine, this is the first article I've seen that claims it is a general problem through all of academia. The Wiki article on the Reproducibility Crisis cites a Nature survey that makes it seem like the issue is widespread through every industry, including the hard sciences like physics and engineering: https://en.m.wiki…

Oh it's general. Apart from anything else, a majority of all scientific papers rely on some form of software, be it simple R statistical scripts, to complex programs. None of those programs ever have bugs in them, right? Then to be fair to the authors, scientific papers follow a fairly fixed format, often with hard limits on paper length (cf. Nature, etc.). Putting all the detail necessary for replication, and a dece…

It is not a completely general problem. In the field I work in (computational physics) we very often reproduce results published by other research groups. It's very common in our field to see plots in a new paper overlaid with data from old papers showing where our results agree (where they disagree is not a reproducability issue but is instead due to our ability to do more accurate calculations).

Here is a paper where some colleagues of mine wrote a benchmark paper explicitly to check various methods against each other (with good agreement): https://journals.aps.org/prx/abstract/10.1103/PhysRevX.5.041...

Re: Most scientists 'can't replicate studies by their peers'

#267

An alternative headline would be "Most Published Studies Are Wrong" Am I wrong for considering this not-quite-a-crisis? It has long been the case that initial studies on a topic fail to get reproduced. That's usually because if someone publishes an interesting result, other people do follow up studies with better controls. Sometimes those are to reproduce, sometimes the point is to test something that would follow fr…

>That's usually because if someone publishes an interesting result, other people do follow up studies with better controls. No, no, a thousand times no! Most studies do not have follow up studies that confirm/refute the original. Often such a followup study is hard to publish. If you manage to reproduce it, you cannot publish unless it presents a new finding. If you fail to reproduce it, it often doesn't get publishe…

There's a really good Google talk on this subject full of many concerning statistics and anecdotes:

John Ioannidis: "Reproducible Research: True or False?" -- https://youtu.be/GPYzY9I78CI

Re: Most scientists 'can't replicate studies by their peers'

#268

Earlier quoted context omitted.

Soft sciences actually dont have a greater problem with replication. It is just more publicized, in part because those researchers are actually addressing the problem and making large scale replication attempts.

Well that depends. What kind of reproducibility are you talking about? If we talk about something like Higgs then it was definitely reproduced. Same with gravitational waves. But the other problem is that the soft sciences have a compounding problem. The one I mentioned about the foundation not being as strong. As a comparison psychology needs a p=0.05 to publish. Particle physicists need 0.003 for evidence and 0.000…

The huge huge huge majority of published papers aren't CERN-style monumental efforts with bazillions of repeated experiments that you can use to get insanely good stats on.

From my own experience in my PhD I've seen outrageous replication problems in CS, microbiology, neurology, mechanical engineering, and even physics on the "hard sciences" side of things. I've seen replication problems also in psychology, sociology, and political science on the "soft sciences" side of things.

People who come from a "hard science" background seem to have this belief that it is way more rigorous than other fields. I disagree. If anything, the soft sciences are actually making a movement to address the problem even if that means more articles being published saying that 40% of psych papers are not reproducible or whatever.

Re: Most scientists 'can't replicate studies by their peers'

#269
post #256

Earlier quoted context omitted.

I thought that statistics is the right tool to handle uncertainity? I had the impression that all the "soft" science is based on statistics. We can't prove that smoking kills people. But, given a certain confidance interval (or whatever equivalent measure for baysian statistics?), we can state that smoking is not a good idea if you want to live longer than mean expected years... Sure, some unforseen event may interfe…

Statistics is also the way to look at data in the "hard" sciences. Every measurement has error, and that's how you deal with it. However it's not a simple thing that automatically combines different studies. It takes skilled application to understand how data connects, what's comparable, what's not, etc. Traditionally, "meta-analysis" is the sub-field of statistics that combines studies. But that only combines extrem…

Amen. You can google the controversy around the StatCheck program to really dive into why stats and their applications are beyond lies and damned-lies in their falsehoods (because you can prove the lie is right). Doing something as simple as smoking causes cancer is a very very simple experiment to interpret (hard to fund/preform though). It's the pernicious little studies on 8 cells total that get messy. Preforming a lot of experiments is hard.

I knew of a student that graduated with only 8 cells of data out of his 7 years in grad school. That may sound like a small amount, but to his committee, it was a very impressive number. He (very very) basically sliced up adult rodent brains and then used super tiny glass pipettes to poke the insides of certain cells. He chemically altered these cells' insides in a hopefully intact network of neurons, shocked the cells, and then recorded the activity of other cells in the network using the same techniques. Then he preserved and stained the little brain slice so he could confirm his results anatomically. From start to finish, it took him 13 hours total, no lunch or restroom breaks, every day, for 7 years. He got 8 confirmable cells worth of recordings total.

That is a hard experiment. But due to his efforts in adding evidence we now suspect that most adult hearing loss is not due to loss of cells in the ear, but in the coordination of signals to the brain and their timing mis-match. It is not much, bu it adds to the evidence and will for sure help out people someday.

To add, he is now a beer brewer in Bavaria and quit science. This shit takes sacrifice man.

Re: Most scientists 'can't replicate studies by their peers'

#270
While I understand that the life sciences dominate science research right now, it still annoys me when I read a headline about "most scientists" and the article is exclusively about the life sciences. Even if the physical sciences have reproducibility issues of their own, those issues may be different enough to frustrate lumping all of the sciences together.

I suggest that future articles about the reproducibility crisis should either: a) Specify "life science" in the title, or b) demonstrate that the generalization is justified.

My field (physics) is certainly not perfect, but we do have a reasonable body of reliable knowledge including reproducible effects. I work for a company that makes measurement equipment, and we are deeply concerned with demonstrating the degree to which measurements are reproducible.

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