[HN Gopher] Faked Crystallography
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       Faked Crystallography
        
       Author : mhb
       Score  : 73 points
       Date   : 2022-07-29 19:19 UTC (2 days ago)
        
 (HTM) web link (www.science.org)
 (TXT) w3m dump (www.science.org)
        
       | areoform wrote:
       | > One final note: the "authors" of all these current 992 papers
       | are from Chinese medical institutions, most of them appearing
       | only once.
       | 
       | I've observed something sociologically fascinating about China.
       | In multiple fields, gaming, research, academics etc, the
       | proportion of the population likely to cheat _seems to be_ higher
       | in China. Examples include,
       | 
       | https://www.theatlantic.com/education/archive/2016/03/how-so...
       | 
       | https://www.ign.com/articles/2018/02/16/99-of-pubgs-banned-c...
       | 
       | https://www.reuters.com/investigates/special-report/college-...
       | 
       | https://www.nature.com/articles/d41586-021-02587-3
       | 
       | There are cheating scandals everywhere, but, as an outsider, it
       | seems to be somewhat more endemic in China. The anomaly begs the
       | question, why.
       | 
       | Being born in China doesn't radically wire your brain in a
       | different way. People seem to cheat everywhere, but more people
       | are more likely to cheat here, in this specific environment, why
       | is that? What's causing them to adopt this behavior as an
       | acceptable strategy?
       | 
       | I can't seem to find any interesting research on the topic beyond
       | idle speculation. Does anyone know of anyone investigating this?
       | 
       | Note - this comment is not meant to be denigrating nor a
       | judgement, but an observation and a question. The question begs a
       | deeper attempt to ascertain a) if it's true and b) the factors
       | driving it.
        
         | timdellinger wrote:
         | this is a good place to start:
         | https://scholar.google.com/scholar?hl=en&as_sdt=0%2C47&q=aca...
         | 
         | e.g. https://eric.ed.gov/?id=EJ1178415
         | 
         | which describes cultural differences in cheaters
        
         | naniwaduni wrote:
         | Cheating on this scale doesn't (usually) happen because a
         | thousand people independently come up with this idea. Something
         | about this environment makes it possible for prolific cheaters
         | to _scale_ farther than they do elsewhere. There 's a deep dive
         | that could be done here, but at a high level, it comes out to:
         | there's money in it, incentive structures drive money here.
         | Follow the money.
        
         | blueblisters wrote:
         | If your peers in online classes are cheating and you're not,
         | you're at a material disadvantage when it comes to grading.
         | Unless the teacher decides to start reporting your peers for
         | academic integrity violations [1].
         | 
         | Same goes for academia I suppose. When incentives for academia
         | are aligned towards publishing, and if there is minimal or no
         | enforcement of cheating at an organizational level, you're at a
         | disadvantage if you don't cheat.
         | 
         | I don't think Chinese academic institutions have robust
         | academic integrity and enforcement policies and unless that
         | changes, you're likely to see Chinese academics stuck in a Nash
         | Equilibrium.
         | 
         | [1] https://news.ycombinator.com/item?id=31544634
        
           | thechao wrote:
           | In grad school I had to do a term paper; my three partners
           | were Chinese. Two of them approached me and asked what we
           | were going to do when the third one cheated/plagiarized his
           | part of the paper. Apparently, cheating is a phenomenon
           | specific to subcultures in China -- and this one student
           | belonged to that culture.
           | 
           | When we got his part of the paper it had just been copied
           | wholesale from academic sources; the professor had already
           | been prewarned. We all got an "F", and the one student was
           | put on probation, and lost his funding. It really sucked. The
           | rest of us were given a chance to rewrite the term paper.
        
       | naugtur wrote:
       | A friend of mine got his first programming job in 2010 as a
       | programmer assistant of a physics professor who needed to
       | automate the procedures of proving crystal structures from mass
       | produced PhDs impossible using graph theory. He was finding so
       | many fakes, mostly coming from Chinese PhD students he needed to
       | write (and optimize) the software to disprove them at scale.
       | 
       | These PhD papers were apparently the easiest to quickly edit from
       | someone else and push past the uninterested reviewers.
        
       | Isamu wrote:
       | >One final note: the "authors" of all these current 992 papers
       | are from Chinese medical institutions, most of them appearing
       | only once. If anyone got a raise or promotion based on their
       | publication record off this stuff, what a waste of money that
       | was. . .
       | 
       | This is the result of mandatory publication requirements placed
       | on the Chinese medical professionals. Gaming the system with paid
       | fake publications is just another industry that popped up to meet
       | this requirement.
        
         | [deleted]
        
       | cdr6934 wrote:
       | I wonder if those structures were compared to what AlphaGo output
       | and found significant differences.
        
         | opticfluorine wrote:
         | These aren't protein crystal structures, they are metal-organic
         | frameworks (MOFs), so AlphaFold probably wouldn't work well on
         | these ones.
         | 
         | It would be really interesting to see an equivalent model
         | trained to predict these structures. The physical chemistry of
         | transition metal complexes, especially when multiple metals are
         | in close proximity to each other and connected by shared
         | ligands, is much more complicated than proteins. The reason is
         | because of multireference effects - essentially the quantum
         | entanglement of multiple possible electron configurations.
         | These are exceedingly difficult calculations to perform -
         | common approximations are O(n^8) or worse and require highly
         | specialized knowledge to apply correctly - so an ML model that
         | can efficiently make predictions in this space would be a major
         | transformative breakthrough.
        
       | zx8080 wrote:
       | I'm not a specialist in the field, though it could be obvious for
       | one, what makes criteria for paper to be fake one. There's no
       | process described to check against some criteria. Except for
       | weird generated wording.
       | 
       | There should be some border between an obviously fake paper and
       | obviously real one.
       | 
       | Fake papers could be used by someone to remove and cancel a real
       | papers together with them if no good criteria is used to separate
       | them. Chinese author name or address does not seem to be a good
       | one.
        
       | cyanydeez wrote:
       | Eh, I'm gonna posit something other that what's proposed: that
       | these articles are intended to raise someone's publishing record.
       | 
       | I'd say there's 2 reasons one might pollute the datastream:
       | 
       | 1. Obfuscate competitor's data queries
       | 
       | 2. Use "approved" articles as a tool to trick regulators in a
       | grander series of fraud.
        
       | opticfluorine wrote:
       | While pursuing my Ph.D. in chemistry, I was asked to peer review
       | an inorganic chemistry publication in which the author attempted
       | to fake crystallography data. In this case the telltale sign was
       | that they left the hydrogen atoms in the structure - X-ray
       | diffraction is unable to resolve the hydrogens, you need a more
       | sophisticated technique like neutron diffraction for that.
       | 
       | What it turned out they had done is optimize a predicted
       | structure of their molecule using density functional theory
       | (DFT), then draw it like a crystal structure would be displayed
       | (a 3D plot with error ellipsoids at each atom, with probable
       | bonds shown) and tried to pass it off as a true crystal
       | structure. My advisor missed this when he reviewed it first - if
       | you're reading quickly, you just see a crystal structure and
       | accept it for what it is. So I wonder how many like this slip
       | through the cracks every year. Apparently a lot, if the CCDC
       | identified ca. 1000 of them.
        
         | echelon wrote:
         | Does this not immediately destroy one's scientific career and
         | invalidate all past papers? It seems like it should.
         | 
         | Maybe there should be a bounty on uncovering these?
         | 
         | This shit has to stop. If _publish or perish_ is going to
         | continue to be a thing, maybe just switch to publishing
         | negative results. It 's not sexy, but it's valuable too.
        
           | 2muchcoffeeman wrote:
           | > _This shit has to stop. If publish or perish is going to
           | continue to be a thing, maybe just switch to publishing
           | negative results. It 's not sexy, but it's valuable too._
           | 
           | I had an argument recently about why fundamental research was
           | important. The other person insisted that money should only
           | be spent on endeavors where the outcome is known to benefit
           | humanity. They couldn't accept, despite not having any
           | science or math training, that sometimes we study things that
           | start off seemingly useless and become important, or that we
           | sometimes stumble upon things. (And this is why we should
           | spend money on science in general).
           | 
           | Think about all the scientifically illiterate politicians who
           | control money and funding who probably have similar views.
           | 
           | I can totally understand how we let things get this bad. If
           | you don't provide a positive result, you might be facing
           | unemployment. It's not about advancing our knowledge anymore.
        
           | shishy wrote:
           | Yes, they'd get retracted if caught and be a black mark /
           | destroy a career if someone did something like this and it
           | was proven they intentionally faked it.
           | 
           | What often happens though is that the paper will get
           | retracted but then the authors play hot potato in blaming
           | different people for faking it and it turns into a whole mess
           | where you don't always know (i.e. cannot prove) exactly who
           | did the faking.
           | 
           | "Someone else faked it and I missed it, just like all the
           | reviewers!!"
        
           | logifail wrote:
           | > If publish or perish is going to continue to be a thing,
           | maybe just switch to publishing negative results. It's not
           | sexy, but it's valuable too.
           | 
           | If we are to be allowed to publish papers from negative
           | results then I should go and dig out my PhD notes and get
           | writing!
           | 
           | Seriously, though, I started noticing the many broken
           | incentives early on, after a explanation about "impact
           | factor" from an older PhD student in our lab.
        
             | opticfluorine wrote:
             | Same here - I went into science thinking that it would be
             | all about trying new ideas and pushing the boundaries of
             | what we know. And while in a certain sense that is still
             | present, it takes a back seat to the perverse incentives
             | you describe.
             | 
             | This was one of (and unfortunately not the only) reason I
             | decided to leave academia after my Ph.D., leaving my field
             | entirely and going into software engineering rather than
             | taking a postdoc position. Academia isn't for everyone, and
             | neither is industry... but wow, I sure am happier where I
             | am now.
        
         | kergonath wrote:
         | > the author attempted to fake crystallography data
         | 
         | That is _not_ what fake data is. It might be a
         | misrepresentation is the author tries to pass it out as
         | experimental results, but it is not fake, i.e. it came from a
         | real study and actually has some meaning (though not much if it
         | is indeed an unstable structure that can just be observed in a
         | computer, and it is ground for rejection depending on the
         | journal).
         | 
         | I mean, I don't have much patience with people over-hyping
         | their results, but fake data of the common sort is either
         | photoshopped graphs, re-used spectra coming from other studies
         | or compounds, or things like that. And this definitely happens.
         | But the "it came from a simulation, therefore it's fake"
         | argument is very unhelpful in general.
         | 
         | A spectrum from a simulation is _not_ fake, it's just a
         | simulation result.
        
           | DiggyJohnson wrote:
           | Intent to deceive is what makes it a fake/fraud. No?
        
           | raverbashing wrote:
           | It is fake if it's being misrepresented as experimental
           | results instead of just a simulation
        
             | kergonath wrote:
             | Again, that is not what this word means. It's
             | misrepresented data, not fake. And yes, the distinction
             | matters.
             | 
             | This is also not what the article is about. The problem
             | they face is completely fabricated data, not DFT structures
             | in a poorly worded paper.
             | 
             | Of all places, this is probably the last one where I would
             | expect this argument.
        
           | 1vuio0pswjnm7 wrote:
           | It is arguable that it is more than a misrepresentation if
           | the author's intent is to fool the reveiwers. If so, it is
           | "fraudulent data".
        
         | dekhn wrote:
         | Not to say this disproves anything, but you can definitely see
         | hydrogen atoms in extremely high resolution crystal structures-
         | typically with resolution below 1A, which is rare for proteins
         | but should not be uncommon in inorganic crystals (right?)
         | 
         | ANy time you have a 3D structure (model) you can run the
         | equations in forward mode to create the structure factors of
         | the crystal that would have created that model.
        
           | HarryHirsch wrote:
           | Most of the time hydrogens are placed in calculated positions
           | because you know where they are and it also reduces the
           | number of parameters needing refinement. In good datasets
           | hydrogens will show up in the density map (aren't all
           | datasets good now in the age of area detectors), and you can
           | refine (possibly with restraints) those hydrogens that you
           | are uncertain about.
        
           | COGlory wrote:
           | Raleigh's criterion says hydrogens should be just on the
           | cusp, at least with home source xrays. Not sure about
           | synchotron.
        
         | hidroto wrote:
         | "optimize a predicted structure of their molecule using density
         | functional theory (DFT), then draw it like a crystal structure
         | would be displayed (a 3D plot with error ellipsoids at each
         | atom, with probable bonds shown)"
         | 
         | why not just publish this instead. surely an optimized model is
         | still valuable.
        
           | opticfluorine wrote:
           | Typically not on their own - it's very easy to calculate an
           | optimized structure that is incorrect, so you typically want
           | some sort of justification for your structure. Typically you
           | would be calculating one of these geometries along the way to
           | calculating other interesting properties to either compare
           | with experiment or make new predictions (or both). The "gold
           | standard" is... comparison with a crystal structure from
           | X-ray diffraction.
           | 
           | In my field (small inorganic molecules used as catalysts), I
           | typically calculated the structure along the way to
           | calculating the molecular orbitals for describing the
           | electronic structure (important for understanding many
           | properties of the catalyst and its reactivity) and predicting
           | the infrared and visible spectra (useful for comparison with
           | experiment and for explaining the electronic and magnetic
           | properties of the molecule). It's the whole picture that's
           | valuable, not just the structure - and the more experimental
           | properties you include, the harder it is to fake the whole
           | thing.
        
           | chaxor wrote:
           | I absolutely agree. Most of the time, getting very good DFT
           | results is actually far more difficult that getting the
           | experimental results of cystollography itself. They're both
           | quite hard, and it depends on which techniques are applied,
           | but getting computational methods to match with great quantum
           | accuracy is _very_ , *very* difficult. I know more about
           | condensed matter physics and GW Bethe Salpeter approaches
           | etc, than proteins, but the difficulty in getting good
           | computational methods to work is still out of reach for ~95%
           | of scientists even in that field.
        
         | muaytimbo wrote:
         | I published a number of crystal structures using a powerful X
         | ray diffractor and high quality crystals where H density was
         | both found and modeled. Modeling H density in and of itself is
         | in no way a sign of fake data, it is just a rare occurrence.
        
           | verisimi wrote:
           | Hang on, isn't a model by necessity not the same as the thing
           | it's modeling? Obviously a photo is sort of a model, but
           | depending on what the subject is, you can visually verify it.
           | If it's a software model, and say you enter lots of
           | parameters, I have to wonder how valid that model is.. How
           | can it be verified?
        
             | ta988 wrote:
             | The way you solve x-ray diffraction structures is that you
             | refine your model until the electron density matches.
        
         | Jensson wrote:
         | Most of these are probably not even possible to catch, if the
         | perpetrator has a basic understanding of the theory they could
         | generate those correctly no problem.
        
           | type0 wrote:
           | Hence why _fake it till you make it_ is so popular
        
         | ta988 wrote:
         | You can see the hydrogens if you have enough resolution (below
         | 1A). These days you start to see such good resolutions pretty
         | often.
        
       | stevenjgarner wrote:
       | Reminiscent of "Two decades of Alzheimer's research was based on
       | deliberate fraud" (also published by science.org):
       | 
       | https://news.ycombinator.com/item?id=32212719
       | 
       | https://news.ycombinator.com/item?id=32183302
        
       | AzureShill420 wrote:
        
       | HarryHirsch wrote:
       | What's staggering is that small-molecule crystallography is so
       | _cheap_. A x-ray diffractometer with area detector is maybe 50
       | kUSD, and after 8 hours you have a dataset, the full hemisphere.
       | It 's baffling why anyone would cheat!
        
         | murphyslab wrote:
         | Growing good, X-ray quality crystals is more art and luck than
         | science.
         | 
         | It's particularly difficult with most proteins and other
         | biomolecules. [0] But even for small molecular compounds, it
         | isn't always easy. I'm not sure about growing high quality
         | crystals of metal-organic frameworks, but they could easily be
         | limited by defects. Some compounds might be too waxy if there
         | are long aliphatic chains involved.
         | 
         | Even if you do get decent-looking crystals, they might be
         | twinned. If you are working with air or water sensitive
         | compounds, they need to be handled with extreme care and might
         | degrade before the data collection is complete. Some might also
         | have temperature sensitivity, such that they need to be kept at
         | -20 C to prevent melting or another phase transition.
         | 
         | Overall it can be a real make-or-break issue for someone
         | engaged in chemical research.
         | 
         | [0] Check out this PDF of a PowerPoint on the topic:
         | https://hamptonresearch.com/uploads/documents/ramc/RAMC2011_...
        
           | muaytimbo wrote:
           | Growing high quality crystals of Organometallic compounds is
           | easier than many other disciplines in chemistry, orders of
           | magnitude easier than proteins, as an comparison.
        
             | COGlory wrote:
             | Depends. A random metallo-organic compound vs a random
             | protein? Yes. But the problem can be further up the chain.
             | Synthesis can be expensive and difficult, and you need a
             | relatively large crystal (at least for X-ray). If you have
             | low symmetry, you need several relatively large crystals
             | all of which need to collect enough data before they die to
             | integrate across the datasets. It typically isn't thought
             | to be as challenging, but it can be.
        
         | gus_massa wrote:
         | I guess the hard part is making the real substance and then
         | making nice crystals to put in the device. I think they are
         | just lying about everything.
         | 
         | Also, it looks like they are changing the topic each year to
         | follow the current fashion, and they are publishing like 200
         | papers per year, so $50K is like $250 per paper. My (totally
         | unsupported) guess is that they are charging a few hundred
         | bucks per paper, so using a real diffractometer to make a new
         | unique fake image for each paper would duplicate the price of
         | each paper.
        
       | throwawaymaths wrote:
       | I remember in grad school a principal investigator that was
       | notorious for driving his grad students and postdocs hard: he had
       | set up a cot for them to sleep on in the office, if the
       | bioreactors we're turning making protein he would ask wtf was
       | going on (got to keep the pipeline filled)
       | 
       | Anyways they reported a structure of a very important protein,
       | the pump involved in exporting antibiotics from a bacterium. But
       | none of the data made sense, there were known mutations that
       | changed activity that were in strange places in the molecule. He
       | chalked it up to "allosteric interactions".
       | 
       | The problem with crystallography is that we can't directly
       | measure the phases of the diffraction pattern (we can measure the
       | intensities) and as anyone who does Fourier transforms knows, the
       | phases contain more information than the intensities. So we
       | typically bootstrap a guess of the phases using a similar
       | protein, then calculate a rough structure, then assign more
       | detailed locations for specific atoms based off of chemical
       | constrainst, then recalculate phases of the model, then apply
       | these fake phases to the known intensities to get a refined
       | electron density, and so on iteratively.
       | 
       | The risk is you can think your shit smells like roses, and use
       | math to support your claim .
       | 
       | Anyways someone didn't bite the bs, and actually redid all of the
       | phases using three orthogonal methods (xenon soak, gold soak,
       | selenomet) and showed that three transmembrane helices were
       | totally misassigned. The original pi wrote an apology, chalking
       | it up to his python script he'd written hastily flipped the signs
       | of some of the rows.
       | 
       | This is bullshit. I cannot imagine how flipping some of the signs
       | could have resulted in this error. What is more likely is that
       | the PI bootstrapped with a premature model of the protein, that
       | made the threading errors, where he threaded the sequence through
       | the electron density completely wrong, as a guess, to beat
       | competitors to the punch.
       | 
       | Anyways the pi, Geoffrey Chang, was never called out on this
       | bullshit or his toxic workplace. He's still a professor in
       | academia, at a highly ranked institution.
        
         | opticfluorine wrote:
         | That's unfortunately all too common of a story. And with the
         | way peer review works - where the leaders of any niche topic
         | are the ones who will be asked to peer review articles in the
         | same area - the system makes it very easy for an established
         | professor to shoot down dissenting voices.
         | 
         | Now, sure, if you can prove that there was deliberate
         | misconduct on the part of the PI, then you can go through
         | channels and hopefully get an investigation opened. There was
         | an article on HN recently (linked in another comment here)
         | where this happened/is happening with Alzheimer's research. But
         | it's often not so clear cut, as you've pointed out - you leave
         | enough room for ambiguity, then "apologize" and retract the
         | paper. There's no (significant) negative consequences for the
         | retraction if you're already an established leader of your
         | field (and you can still use your influence over the peer
         | review process to shape the field to continue favoring your
         | research). Meanwhile, the accuser is all but guaranteed to be
         | blacklisted from their field for the same reasons - and if they
         | don't have tenure yet, then game over, hope you had a backup
         | career in mind.
         | 
         | The current incentives in academic research are broken.
         | Sometimes I wonder if the tenure system is partly to blame -
         | does it go too far in creating these protected positions of
         | power that can be abused? Then again, tenure exists for a very
         | good reason - to protect dissenting voices by being pushed out
         | by these same forces. It seems more and more however that
         | tenure is no longer sufficient to protect against this (or
         | maybe it never was), and we need broader reform of the peer
         | review system in order to foster healthy and open discussion in
         | the research community.
        
           | throwawaymaths wrote:
           | I don't think it's tenure. Chang did not have tenure at the
           | time.
        
         | COGlory wrote:
         | Here is a link to some commentary on the ABC transporter
         | debacle.
         | 
         | http://xray0.princeton.edu/~phil/Facility/Guides/ABCtranspor...
         | 
         | I'm not 100% sold that it was malicious, but imo that doesn't
         | change much. Chang's job was to be a PI and vet these things
         | and whether he failed in his duties intentionally or
         | unintentionally, he should lose his job.
         | 
         | The Xray data and model bias and handedness is so complex and
         | hard to deconvolute that since that incident I've always
         | wondered if we are doing enough to vet the huge amount of xray
         | structures on deposit. I'm very glad to be primarily in cryo
         | instead...
        
           | throwawaymaths wrote:
           | Just to be clear: I don't think it was malicious, I just
           | think the excuse he gave was bs. I could be wrong -- I'm not
           | a crystallographer, just a nonprofessional expert (I have
           | given talks) at the Fourier transform. I just can't see how a
           | centrosymettrically inverted structure would get _some_ of
           | the helices correct
           | 
           | Ok, downvoted. Can someone explain to me how a
           | centrosymettrically inverted structure will get some of the
           | helices correct?
        
       | gilleain wrote:
       | Previous discussion :
       | https://news.ycombinator.com/item?id=32290497
        
         | dang wrote:
         | That one was posted later, while this one was (independently)
         | picked by a mod to go in the second-chance pool
         | (https://news.ycombinator.com/pool, explained at
         | https://news.ycombinator.com/item?id=26998308), so it got a
         | random placement on HN's front page.
         | 
         | Probably the thread is interesting enough to deserve a merge,
         | so we'll move the comments thence hither.
        
       | what-imright wrote:
       | Someone did this with intent to prevent a discovery
        
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       (page generated 2022-07-31 23:01 UTC)