Via Egon Willighagen, a truly bizarre article in Drug Discovery Today that appears to have been accepted for publication:
I am holding out hope that this paper is some sort of Sokal Affair-type hoax, or perhaps an incredibly convincing piece of elaborate performance art.
In drug discovery, de novo potent leads need to be synthesized for bioassay experiments in a very short time. Here, a protocol using DrugPrinter to print out any compound in just one step is proposed. The de novo compound could be designed by cloud computing big data. The computing systems could then search the optimal synthesis condition for each bond–bond interaction from databases. The compound would then be fabricated by many tiny reactors in one step. This type of fast, precise, without byproduct, reagent-sparing, environmentally friendly, small-volume, large-variety, nanofabrication technique will totally subvert the current view on the manufactured object and lead to a huge revolution in pharmaceutical companies in the very near future.Believe it or not, the author proposes the use of optical tweezers to synthesize drugs atom-by-atom (among other nanofabrication techniques.)
I am holding out hope that this paper is some sort of Sokal Affair-type hoax, or perhaps an incredibly convincing piece of elaborate performance art.
https://www.youtube.com/watch?v=CEDGCPFGuSM
ReplyDeleteWhew, boy...
Well, they claim they're only five years away from the prototype, and it looks like they've been making some progress, having managed so far to produce a video of a traditional Chinese egg-cake oven making egg cakes. I mean, they're almost there. And they had better hurry because, already, "there are some scientists trying to develop the apps for people to download and print their own drugs at home."
ReplyDeleteThe accepted date is listed as March 31, so maybe it was supposed to be an April Fool's joke, but for some reason there was a delay posting it? I hope? The only other thing that makes sense is if maybe it was written by a junior high school kid and he accidentally sent it to drug discovery today instead of his science fair committee, and they accidentally accepted it without reading it or sending it out for peer review....
Have you ever submit any manuscript to drug discovery today?
DeleteIt only accepted the invited manuscript.
Is that possible without peer review process? grow up and Don't show your low IQ here.
you can keep dreaming but remember wake up. Don't just die.
Invited or not, this article was obviously not peer reviewed by competent and critical reviewers. If it had to be an invited manuscript then it just leads me to believe they didn't care to double check the paper after they asked for it. Your personal insults to the other poster are unwarranted and show a lack of any real rebuttal.
DeleteLee Cronin also claimed this at a TED talk that was all over the internet http://www.ted.com/talks/lee_cronin_print_your_own_medicine#
ReplyDeleteYeah, but Cronin actually has a prototype of his 3-D printed reaction vessel.
DeleteHow do you know this guy without prototype?
DeleteThat TED talk also was conspicuously light on important details. What are these "inks," how is the chemistry done? Theoretically you could do stuff with basic building blocks if you used real chemistry techniques, but it wouldn't be universal by any means. This Chinese paper on the other hand proposes in quite a bit of detail a system that just doesn't make sense to anyone with a chemistry background.
Deletehttp://www.icbbe.org/2013/ShowKeyNoteSpeakerDetails.aspx?personID=2915&RoleType=KeynoteSpeaker
ReplyDeleteHe does seem to be inflated about his positions. PI at Harvard Medical and MIT?
Probably at Broad Institute, which is a coop of Harvard Med and MIT.
DeleteComing soon to Elsevier Journals:
ReplyDeleteCure cancer with Cloud Computing™ & Big Data™.
3D print world peace using Cloud Computing™ & Big Data™.
Build Cloud Computing™ & Big Data™ servers with 3D printers powered by Cloud Computing™ & Big Data™.
Lose 10 pounds and increase your 3D-printed manhood today with Cloud Computing™ & Big Data™.
@Anonymous - I work at the Broad and he is not an employee here.
ReplyDeleteWouldn't the moving parts on this machine have to exceed the speed of light to produce useful amounts of a substance in a reasonable amount of time? This is trippy stuff!
ReplyDeleteThis got me thinking about how long something like this would actually take. Since there are no real details in the paper, I'll take my cue from the original author and just make stuff up:
DeleteSo let's say each set of optical tweezers can construct a molecule in one second. For the prototype, let's assume they're only aiming to have one set of tweezers in operation (a prep scale instrument would certainly have more operating in parallel, but, really, a few orders of magnitude here or there aren't going to do anything to this analysis). They talk about making benzene, so we'll use that, and target, say, 10 milligrams. OK, molecular weight, Avogadro's number, number of seconds in a year.... My arithmetic is a little rusty, but I'm coming in at around 2.4 trillion years. Since big numbers are hard to wrap out minds around, I guess this needs some context. It's about 170 times longer than the age of the whole entire universe.
Maybe I'm just missing something about how this is supposed to work. Afterall, I only did a quick, back-of-the-envelope analysis that anyone with a high school education could perform.
I really really want to see the reviewer comments for this paper.
(My estimation of the speed of the machine was based on something comparable to but a little faster than the egg cake machine we see in the video in the supplementary data).
DeleteIt will be referenced 100's of times in China and that will be grounds for promoting him to tenure, because the committee that grants it will be too lazy and stupid to know that this is BS. That's whats important to him.
ReplyDeleteWhy do you so mean? God is watching your word. How do you know all the truth? Maybe some patent is still ongoing. So he can not show all the detail. What's your problem? Are you happy to bullying Asia guy on the internet but acting like a fucking pusssy sisy girl in the reality?
DeleteWhy publish a paper of this dubious quality if you're patenting something. I don't think it's a case of 'bullying the Asia [sic] guy" but calling out uninformative stupidity combined with speculation. Sure it would be nice to piece together molecules atom by atom, but unless your handling radicals what's going to drive bond formation? If you are handling radicals what stops them from reacting with themselves? Supposing this kind of thing was possible, how would you get throughput to the point it's synthetically useful?
DeleteExtraordinary claims need extraordinary data to back them up. This paper is, basically, claiming to completely revolutionize the way every synthetic chemist does their work. There is absolutely no data to support that claim, and the conceptual framework, as it is presented in the paper, makes no sense. So, while it is conceivable that there are some details behind the scenes somewhere that make more sense, this paper is all we have to go on, and it has completely failed to communicate anything reasonable. So what is the point of this paper? And why am I taking the trouble to respond to a troll? I just don't like that he gets to add this relatively high profile publication to his list with no consequences, which contributes an air of legitimacy to what this guy is saying. Naive people will see these sorts of publications, but they're not going to see all of this discussion, and that can lead them to foolish conclusions to the general detriment of good science.
DeleteA couple of my random thoughts:
ReplyDelete1. This was the first article I've ever read from Drug Discovery Today. It will also be the last.
2. The National Science Council of Taiwan should really ask for its money back.
3. "According to my personal experience, cloud computing is easy but automatically dealing with the huge amount of chemical reaction data is difficult." Yes, and apparently it's so difficult that it precludes thinking about fundamental chemistry in a chemistry paper.
1 who care you read it or not? who are you? Mr. president!
Delete2 why? how do you know it is impossible in the future?
3 read more paper please! one guy is pick up a atom by optical tweezers.
http://arxiv.org/abs/1402.5329
it is really shame to critize people behind internet!
"it is really shame to critize (sic) people behind Internet!" Posted by "Anonymous".
DeleteCan you say "irony"? I knew you could.
OK, I'll take these one by one just for kicks.
Delete1. I'm expressing a personal opinion. Given your vitriol, apparently it is YOU who care whether I read the journal or not. Also, I am not the President of the United States or another country. Given that the current President majored in Political Science, rather than one of the natural sciences, he probably wouldn't be the best judge with respect to the quality of the current work. Just a guess.
2. Funding agencies, particularly in this day and age, typically want some sort of concrete result for their support. Experiments, data, that sort of thing. Science fiction is very entertaining, but it shouldn't be supported by such agencies. Without any sort of experimental support, this is indeed science fiction. Thought experiments are not substitutes for real experiments.
3. No thank you, I've had quite enough.
When one publishes a manuscript, people are free to comment upon it. That's the whole idea of publication. If you put your name on crummy work, you should expect criticism and plenty of it.
I don't read Elsevier journals -- I'm more of a Nature guy myself.
DeleteI'm more of a Car & Driver guy myself.
Deletethis reads like a memo from Dr. Evil to Number 2
ReplyDelete"i have but one request and that is to have mini reactors with frickin' 3D printers to make benzene!"
who care you believe it or not? who are you? Nobel Prize winner?
ReplyDeleteThis is just a picture of future work not a research article.
And some of this work is indeed really work right now. Are you still living in Prehistory?
You are a troll and you suck at science.
Deleteare you ........introducing youself right now?
Deletenice to meet you!
Ahh, the old "I know you are but what am I?" argument. You solidify the time-honored stereotype that trolls are not mature.
DeleteYou ask if chemjobber is living in prehistory? Show us some data that this is nothing more than science fiction and I will eat my words and beg for your forgiveness for calling you a troll.
"This is just a picture of future work not a research article."
DeleteWell, duh, because a research article would have required, like, actual research and data, and been useful to someone else other than the authors (and DDT). I guess that wasn't a possibility.
It also lacks the interest or grounding in actual science that would qualify it for a science fiction magazine, and the titillation that would qualify it for Penthouse or related magazines. Could this have been published in Fractals or something?
"This is just a picture of future work not a research article." - then he should have submitted to science fiction instead of a peer-reviewed journal
DeleteReminds me of "The X-Files".
ReplyDelete"The truth is out there"
"I want to believe"
Also, consider the energetics of ripping a carbon atom from a material/molecule and then re-bonding. What will this be printed on? I imagine a single atom of carbon would be so reactive that it would bond to any substrate, which would make getting the 3-D structure of the drug quite difficult. Giving money and recognition to someone that makes ridiculous claims is a slap in the face to any real scientist who spends lots of time and effort doing real research. I still remember a news article from last year when a scientist (in the US I believe) said that in about 5 years he will have nanorobots that will go into your body and cure any disease. If I remember correctly he got a pretty big grant for this.
ReplyDeleteI totally agree with you. Scientist do the thing from 0 to 1. Engineering do the rest from 1 to 100.
ReplyDeleteThis is just provide another option to instead of traditional systhesis.
If it's supposed to provide another option to traditional synthesis, it would have to actually work. It doesn't and as proposed it would take far too long - the heat death of the universe would occur before a mole of compound was made. I know ChemEs and they wouldn't have anything to run if it weren't for chemists so let's not pretend its a 100-1 ratio of whatever your proposing.
DeleteIt does not provide an alternative to traditional synthesis. It does not even provide a feasible proof-of-concept project.
DeleteCurious as ever I thought of diving into this guys background; out of the 46 publications I received when checking PubMed, I'd say that most of his work is on traditional Chinese medicine and alternative medicine. When reading trough some of them it seems to me that all of these papers are rather "weak" attempts of computational chemistry, in which any form of experimental backup (e.g. mutational studies, empirical data etc) is not present at all. This explains all the publications in journals barely anyone will ever hear from (impact factors around 1 or less).
ReplyDeleteOne wonders, was this just a piece of craziness, in which he let is fantasy go wild, or is this just an extreme example of his whole publishing history.
On a sidenote: which position does he have at MIT, and does anyone there know he published this representing them as well?
this seems like someone's dopey april fool's article that got put in the wrong pile and forgotten
ReplyDeleteI noticed that this paper was published as Open Access. I wonder which funding agency footed the $3,750 bill for that? And I wonder if that price exceeds the total cost of the "research" the paper is based on?
ReplyDeleteThis must be an April fools joke or something. Has to be.
ReplyDeleteI mean, barring the fact that you'd need to somehow strip out a single atom from some ordered structure with optical tweezers (LOL), how would the actual chemistry be done, again? Simply putting some unstable and impossible to obtain isolated atom next to your center of interest does not mean you can magically form the bond you want... and how would this at all being energetically feasible, let alone efficient, anyways?
It would be like me publishing a (invited?!) paper that says in the future we'll "Chemputer" (C) ligands that not only act as biased agonists of GPCRs, but have spatial neuronal selectivity, whereby they only act upon one side of the neuron in one area of the brain. Magic! (DDT, I'll be waiting for that invite)
Reading and commenting on this paper here http://quintus.mickel.ch/2014/04/19/print-your-own/
ReplyDeleteand reading the comments above and at http://pipeline.corante.com/archives/2014/04/21/molecular_printing_of_drug_molecules_say_what.php#comments
I get the feeling that some of us think this is real stuff!
Well after the bit about using optical tweezers I stopped reading and commenting.
Obviously an April Fool's spoof! But someone at "in the Pipeline" has it correct, "this author will be cited 100 times and get tenure"!
Well if anyone has a patent on the way on this stuff it is now broken.
From the cover page of the pdf:
Delete"Received date: 2-12-2013
Revised date: 12-3-2014
Accepted date: 31-3-2014"
Seems like too lengthy and elaborate a process to be an April fool, especially since it didn't even make it out by April 1st.
My opinion remains that the author is a lunatic. A commenter ('Seriously') at In The Pipeline also claims that the rest of this guy's output, while not as off-the-wall as this, is pretty woeful.
So this is after four months of revision...what did it look like before?
DeleteIn the future molecules will use social networking websites to construct themselves.
ReplyDeleteI just received this:
ReplyDelete"Comment:
I am the author of this paper. I think it time to stop this discussion so I decide to withdraw this accepted paper to avoid be insult any more. I wish our team can really construct a prototype of this technique even only a little progress. I had got tenure for more than five year and I really do not need this kind of non-constructive discussion. Please end of this discussion since I had email to the editor to ask withdraw this paper. BTW, this paper had been reviewed by three reviewers and revised for third version and revised by two editor. So I had revised it more than six version and check all the references. So please do not insult drug discovery today’ judgment. Just blame on me. I wish I can publish again five years latter with a solid evidence and experiment. Thank you all. You guy are really hurt me very badly."
I am the author of this paper. I think it time to stop this discussion so I decide to withdraw this accepted paper to avoid be insult any more. I wish our team can really construct a prototype of this technique even only a little progress. I had got tenure for more than five year and I really do not need this paper to get tenure. Please end of this discussion since I had email to the editor to ask withdraw this paper. BTW, this paper had been reviewed by three reviewers and revised for third version and revised by two editor. So I had revised it more than six version and check all the references. So please do not insult drug discovery today’ judgment. Just blame on me. I wish I can publish again five years latter with a solid evidence and experiment. Thank you all. You guy are really hurt me very badly.
ReplyDeleteThe discussion will never end. Welcome to western culture.
DeleteGod, I wish it was so easy to get tenure in the US. Just imagine: publish improbable stuff, get a paycheck. That would completely rock!
That is why i chose just been a Co-PI in USA. and leave USA without any hesitate. I know I can not get R01 and tenure in USA. however, mostly,
ReplyDeletei can not stand any racism. such as chinese fool day. it too mean for me and i can not accept it since i was in USA even now on the internet since I go back to my howntown. So i would rather to withdraw this paper and please stop insult me, I beg you guys!. without this paper, i still can retire very safe. I just tired of do the same research or me too research. try to do somrthing different...that's all. anyway, thank you all the criticism. Since my knowledage (someone say i just a highschool student, but i had been a professor for 14 years, i should study from high school again) and english is poor, so i had better not response any more and stop publish anymore.
The United States has a lot of problems and is not a perfect country. Frankly, I would not be surprised at stories of prejudice and outright racism against Chinese or Taiwanese nationals within the US academic system.
DeleteHowever, despite the existence of those problems, there are many, many, many Chinese nationals and Taiwanese nationals who have come to the US academic science system and succeeded in gaining grants and tenure.
你應該检讨自己
DeleteYes, you are right. My boss also a very successful professor in USA. However, I am not as good as they are. Actually, I am still far from them. Anyway, I had withdrawed this paper even some idea is really feasible right now. I know this tech is very difficult and maybe never success. However, thanks all the comment truly. I had learned a lot from some very useful comment and link.
Deletewouldn't hurt to let us know who your boss is in USA so people have better understanding where is the training from. maybe it's us that should go back to school and relearn all the fundamentals.
Delete> i can not stand any racism. such as chinese fool day.
Deleteyou're not exactly doing your country any favors publishing this shit.
YC, I can understand and appreciate your wanting to explore something outside of your normal field, and I am sorry that much of this criticism has hit you personally. On the other hand, you need to be much more careful about investigating topics when you don't have substantial experience in that particular field.
DeleteMuch of the criticism is really directed at the journal's editorial board and referees, who should have realized that the material really didn't fall within the scope of the journal. They could have more gently directed you in another direction and/or pointed out the weaknesses in the material before publication, saving you from embarrassment. In my opinion, their errors were much more severe than yours.
Dear Iron Chemist,
DeleteThanks for your advice. it seems one of my postdoc who had be fired by me in this board. Whatever, I had type many answer in another blog
http://quintus.mickel.ch/2014/04/19/print-your-own/
I am sorry using "racism" this word because I had very bad experience in USA before. Of course most of people are friendly! Let's go back to science and peaceful.
to Anonymous,
Deleteif you wanna insult someone. please Show your name.
I dare to show my name, and you?
you can insult me but leave out my country.
I know who you are.
you the postdoc that be fired by me three years ago!
"without this paper, i still can retire very safe."
ReplyDeleteYup. That's what its all about. The world over.
Or you can be honest to a fault like me, but make the mistake of being an American PhD from a second-tier institution, and retire in a double-wide by the lake.
life is not easy in anywhere. I wish you can get tenure very soon. I am a oldman almost can retired within five years. Wish you luck.
Delete(I also posted this on Quintus's blog, since the conversation appears to be spread out).
ReplyDeleteYC, I do feel bad that many of us who made jokes about this did so in a way that included you as a person rather than just focusing on the ideas, and I apologize about that.
However, the reason this has received so much attention is that you are proposing a system that would completely revolutionize how most of us do our everyday work, but the way you have described it appears to contradict the fundamental rules of chemistry as we learned them. It is great to imagine things, and I understand that this journal does not require experimental data, but a lot of the things you said don't make sense to most synthetic chemists. Is there is any data to back any of this up, or even a reasonable conceptual framework to help us believe that it really is feasible?
The major questions I had were: (1) How does the actual chemistry work? I've never seen a reaction where naked carbon atoms and naked hydrogen atoms were selectively combined by being positioned next to each other to make a specified compound. (2) How would the molds be constructed and what would they be made out of? (3) How do you actually position single atoms in a mold with this sort of precision? (4) If you are making things one molecule at a time with this sort of machine, can you achieve a rate that is actually useful? Above, you say one nanosecond each, but what is that based on? Is there a known manmade machine that works like this and which approaches that kind of turnover?
And maybe the fault is on me that I'm just not very widely read (and I'll certainly admit that), so if there are answers to these questions, just tell us what they are. The whole tone of the paper is completely speculative.
Exactly this. Civility needs to be maintained in scientific discourse. I regret my earlier, anonymous comment calling the paper "trippy." It was the wrong tone. It's easy to lose sight of the fact that there are actual people with actual careers on the other end of the connection. As has been shown now, the words on this blog to reach researchers. Keep the person separate from the ideas. At the same time, no matter how sincere the author's intentions, that his paper made it this far into the review process is baffling.
DeleteProf. Chen's hypothetical implementation of the "DrugPrinter" was half-baked but the idea may have merit. I'm thinking of something along the lines of automated peptide and oligonucleotide synthesis, wherein a narrow class of compounds can be assembled using a limited set of reagents. Adapt that to small molecule frameworks that can be elaborated using new, late-stage synthetic methodologies currently being developed by dozens of researchers in the US and abroad. This could be useful for discovery chemists investigating a series of structurally-related compounds. Instead of a "3D Printer," it would be more like a benchtop chemical plant, complete with automated production. Of course, this would have to be a very modular system, impossible to encapsulate into a single product. As far as the "draw molecule and print" appeal goes, that also doesn't seem unreasonable. Recall that retrosynthetic analysis was originally developed by EJ Corey to be a computer algorithm, one that would devise synthetic routes to complex targets. Is it time to revisit that idea with modern computing power? I mean, why shouldn't organic synthesis become the work of robots the way that chemical analysis has? It's not as if it leads to lucrative careers for human chemists anymore.
-DDTea
Thank you very very much for your tone. what's a pitty, I had withdraw this paper. i am trying to reveal it right now. you have my word. i will have a little evidence in the very near future.
DeleteOk, I just love the "Danger" section of the paper:
ReplyDelete"Just imagine if one day you could simply download an app from the internet and then print your own drug out at home, it would be a worldwide disaster. Chronic drug abusers or gangsters would produce amphetamines or other narcotics in abundance. The drug abuse problem would soar beyond all comprehension if DrugPrinter was available to the general public–policeman and lawyers would be as busy as the chemists."
You just don't see enough cautionary tales about gangsters in JACS...
I just tell my Dean that i had withdraw this paper because of these discussion and make fun on me. My Dean only reply my email one word, "coward！"
ReplyDeleteYes. I admit i am. to publish is made fun on y everyone. To withdraw to be scold. seems do anything is all wrong.
Tell the Dean to "Shut the Fuck up!"
ReplyDeleteWell, maybe not.
I apologize for being so hard on you earlier. You are trying and thinking creatively, which is very important. As someone said before, your work needs to go to a different journal.
Part of its a cultural thing, I think. In the west, everything is up for discussion and criticism. I guess what I have seen is that people not raised in the western tradition have trouble, at times, getting used to that.
I am sorry. But I am totally not on-board. "I apologize for being so hard on you earlier."
DeleteWhy apologize? The guy is so far removed from science and the scientific method. And here you apologize to have called a clown a clown.
I don't get it. Let the crazies rule the world!! After all, we don't want to hurt their feeling by calling them crazy!
It is ok right now.
ReplyDeleteIn the fact, this is only a concept before few years ago in my mind. However, if you really got the Drugprinter funding, it is a lot of pressure rethink everyday and night. I had thinking it over and over and check the references for almost 2 years. however, to date, only some part is possible right now. Can you imagine how huge amount of permutation combination and of different kind of bond-bond interaction? How to collect all the information? I am not in charge in the part D. However, i must collecting all the reactin condition one by one. How many year it will take? i don't know. I just know we had a tcm database collecting for 13 years. it is a huge work and boring.
Is it even possible to get a printer with such precision? Having done a lot of scanning probe microscopy, I've never seen a probe go exactly where it was told to go. Atom by atom assembly would require outstanding precision. And there tends to be a lot of drift, particularly when you are working at small length scales. Imagine the quality control issues you would have. This of course assumes the atoms wouldn't stick tenaciously to the printer and that the energetics wouldn't destroy equipment or the molecules you are assembling. How many "printed" molecules would have the right structure? And let's not forget about chirality...
DeleteThe problem is that your "idea" is simply not possible as you have written it. Even if it were, you wouldn't have workable amounts of material in any reasonable time frame.
ReplyDeleteThe World's Greatest Traditional Chinese Scientist in Taiwan
ReplyDeleteThere is another great scientist in Taiwan.
He published 38 papers on two of Hindawi(BioMed Research International and Evidence-Based Complementary and Alternative Medicine) in half year.
The key point is that both editors, Chung Y. Hsu & Fuu-Jen Tsai, are his bosses.
http://www.hindawi.com/search/all/calvin+yu-chian+chen/
...............................................................................................
retractionwatch.com/2014/07/08/sage-publications-busts-peer-review-and-citation-ring-60-papers-retracted/
London, UK (08 July 2014) – SAGE announces the retraction of 60 articles implicated in a peer review and citation ring at the Journal of Vibration and Control (JVC). The full extent of the peer review ring has been uncovered following a 14 month SAGE-led investigation, and centres on the strongly suspected misconduct of Peter Chen, formerly of National Pingtung University of Education, Taiwan (NPUE) and possibly other authors at this institution.
YC claimed here he got a "tenure" position.
ReplyDeleteJust like the title "I CANNOT believe this....."
Many people know that YC's position of associated professor was withdrawn in 2012 du to his some academic cheating behavior.
Now YC has no position in CMU(www.cmu.edu.tw) and ASIA-U(www.asia.edu.tw), how could he dare to claim he has tenure and will retire safely in 5 years.
YC also claimed in Taiwan that he is an associated professor (even above) of Howard, MIT and Oxford University.
Just again like the title "I CANNOT believe this....."
Nobody can prove that.
YC, how about show your certificate document to prove your tenure and your position of associated professor in Howard, MIT and Oxford.
Otherwise, we will take these words from you to the court!