Stereo Chemistry discusses ChemRxiv

In the latest episode of C&EN’s Stereo Chemistry podcast, reporter Tien Nguyen checks in with chemists to find out how they’re reacting to ChemRxiv, a preprint server for chemists launched by the American Chemical Society in 2017. ACS also publishes C&EN and a suite of peer-reviewed scientific journals.

ChemRxiv has raised a lot of questions for chemists about how preprints fit into the publishing process, and to better understand those concerns, Nguyen followed Ryan Shenvi and Jeremy Roach of Scripps Research Institute California. Their team’s paper about the molecule shown here was one of the first manuscripts posted to ChemRxiv—which we covered in September. The team later published the work in ACS Central Science.

In addition to covering the pair’s experience from preprint to peer review, we also heard how others in the chemistry community are adapting to the server, including Science editor Jake Yeston, C&EN executive editor Lauren Wolf, and ChemRxiv manager Marshall Brennan.

UPDATE: On March 16, 2018, Angewandte Chemie announced on Twitter that its editorial board voted to allow submissions of papers that have been posted as preprints on ChemRxiv.

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The following is a transcript of this podcast.

Matt Davenport: I’m Matt Davenport.

Kerri Jansen: And this is Kerri Jansen.

Matt Davenport: It’s a very special day here at Stereo Chemistry.

Kerri Jansen: C&EN reporter Tien Nguyen has brought us a story and it’s kind of, well, would you say controversial?

Tien Nguyen: I think controversial is probably about right. The story is about ChemRxiv. A lot of our listeners may already know of it and judging from Twitter, they have opinions about it. ChemRxiv is a preprint server designed specifically for chemists to publish their work for anyone to see. This lets them share their data, methods, and conclusions before any of those things find a home in more traditional peer-reviewed journal.

ChemRxiv’s beta site was launched in August by the American Chemical Society. Around the same time, another preprint server, ChemRN, came online. ChemRN is run by Elsevier’s Social Science Research Network.

But today we’re focusing on ChemRxiv because I’ve been following a group that’s gone through the entire process, from ChemRxiv to peer-reviewed journal.

Kerri Jansen: And you should know that the American Chemical Society publishes C&EN, which, of course, makes this podcast. ACS also publishes a suite of traditional scientific journals and runs ChemRxiv, which was developed with guidance from the Royal Society of Chemistry, the German Chemical Society, and the Chinese Chemical Society.

Tien Nguyen: Although ChemRxiv is new, preprint servers have been around for years. There’s arXiv, probably the best-known preprint server used mainly by physicists that went online in the early 90s. Then came bioRxiv for biologists a few years ago.

Now chemists have ChemRxiv. ChemRxiv already has vocal supporters and detractors. That’s because it’s raised all sorts of tough questions about what having a platform that bypasses peer-review will do to chemistry. Will it undermine conventional publishing? How should news organizations cover chemistry that’s not been peer-reviewed? How should people treat the chemistry that’s published there? And what does it mean in terms of “establishing priority?” Like, if you publish to ChemRxiv first, will that get you the recognition for being the inventor, or just make you more likely to get scooped?

We’ll wade into the deep end with those big picture questions soon enough. For now, let’s start the conversation somewhere familiar: with chemistry and, of course, with chemists.

Ryan Shenvi: My name is Ryan Shenvi, I’m an associate professor of chemistry at the Scripps Research Institute.

Jeremy Roach: My name is Jeremy Roach and I’m a fifth year grad student in Ryan’s lab.

Tien Nguyen: Ryan, Jeremy, and their coauthors, posted one of the first preprints to appear on ChemRxiv. I actually covered it for C&EN, but even before that—in just a few days after publishing to the server—Ryan and Jeremy’s manuscript had thousands of views. Six months later that number has grown close to 10,000 views, which Ryan says makes it probably one of the most read papers from his lab. That’s a lot of traffic for a study that they essentially posted on a whim.

Ryan Shenvi: Yeah in retrospect, it was maybe a little too spontaneous. I’d love to portray it as this calculated and shrewd decision but it’s simply not the case. About two weeks before we posted the paper I presented the same work at a Gordon conference, sort of to beta-test the ideas because I didn’t know how they’d be received. Honestly, I was worried that the work might be misunderstood. I’d be run out on a rail for betraying the total synthesis community. Actually, to my surprise, this conceptual framework that I presented with was pretty well received.

So that was great but then I had the opposite problem, I thought maybe I had just torpedoed our intellectual property on multiple fronts by this presentation. I sort of sat and stewed on that for a couple weeks. And then I ended up chatting with my colleague Donna Blackmond and she has been heavily involved in the ChemRxiv setup and analysis. So she mentioned that it had just gone up the day before and I had just had my morning coffee so everything sounded like a great idea. I rushed upstairs, talked it over with Jeremy, quickly emailed our collaborator Laura Bohn and we posted the paper a couple hours later.

Tien Nguyen: For Jeremy, this was his first publication on his graduate work. I asked if he was nervous about putting it on this brand-new preprint server.

Jeremy Roach: Yea a little bit, Ryan was very gung-ho about it. And I was a little bit more skeptical when he brought the idea to me. But I think ultimately, the point is to disseminate your work and inform the field of what you’re doing, and what your ideas are. The potential pitfalls of it I thought were not so bad. It was worth getting around all the troubles we were having with the review process and getting the work out there.

Tien Nguyen: Ryan explained that the trouble with the peer review process for this paper stems from the fact that their paper is a departure from the norm in the natural product total synthesis field. It’s a field known for these making monstrously complex molecules that have valuable and documented medicinal properties, like anticancer or antibacterial activity. And Ryan’s lab, well, took a different approach.

Ryan Shenvi: What’s sacrosanct in natural product total synthesis is the structure. The whole point is to get to this structure, solve problems along the way, and end up making exactly what’s been made by cellular processes. Of course, we’re not doing that. We’re not even attempting to do that. The natural product itself is a fundamentally flawed molecule. What we’re doing is changing the target structure.

Tien Nguyen: What they proposed to do was make a molecule related to the natural product, a natural product called Salvinorin A. The molecule happens to be the most potent hallucinogen ever discovered. But more importantly, Salvinorin A binds selectively to receptors in the brain called kappa-opioid receptors. Kappa is a cousin of the mu opioid receptor that most opioid drugs target. Researchers have found evidence that drugs binding to kappa could provide pain relief without the accompanying feelings of euphoria that lead to opioid addiction.

Ryan and Jeremy reasoned that deleting one particular methyl group nestled in the center of Salvinorin A would make the structure more stable and much easier to make. So they decided to make that molecule instead. According to their calculations, this modified structure should still have Salvinorin A’s potent binding abilities. But they couldn’t, and wouldn’t, know for sure for almost four years.

Ryan Shenvi: So this was a long journey and this has been a real labor of love. Jeremy has worked on this pretty much his entire Ph.D. And it was an incredibly risky endeavor because we were making a compound for biological purposes, although the compound was not known to have any biological activity. So there’s a huge risk, and I have only great things to say for Jeremy’s fortitude, persistence,courage, and a little foolishness for undertaking and completing this project.

Jeremy Roach: I think second-year grad student Jeremy, when he made the decision to take this project didn’t know how naive he was being.

Tien Nguyen: Luckily for fifth-year Jeremy, his naiveté paid off. The Salvinorin analog showed selective binding to the kappa opioid receptor, and the 10-step synthesis they came up with gave them a way to make other related compounds as well. They wrote up these findings which ultimately made their debut in ChemRxiv.

Here’s where things get interested. A few weeks after they posted their manuscript on ChemRxiv, another paper related to Salvinorin A came out in Organic Letters, an ACS journal. At this point, Ryan and Jeremy’s paper was still under review at a more conventional journal, which I won’t name. The Org. Lett. paper was from Thomas Prisinzano’s group at the University of Kansas. The Kansas researchers also simplified the structure Salvinorin A, although they did so by using different chemistry and modifying more of the molecule. Still, they did delete the same pesky methyl group as Ryan and Jeremy. The Prisinzano group did not get back to our requests for an interview before we recorded this podcast.

At any rate, the Organic Letters paper doesn’t cite Ryan and Jeremy’s ChemRxiv preprint. I asked Ryan if he thought they should have cited his paper, and he says that it’s not for him to say.

Citations are just one of many new and confusing issues that preprints present for researchers.

When I reached out to Ryan and Jeremy for an interview to write up their preprint in C&EN in September, they actually declined to speak with me. Ryan said he was dying to talk about the work but he didn’t think he could without jeopardizing his student’s chances of landing a high-profile publication.

Now every journal has their own policy for dealing with preprints. Some journals like JACS and Angewandte don’t deal with them at all, having decided not to accept any manuscripts that have appeared on ChemRxiv. Other journals do take preprints, but subject to certain stipulations that can be confusing to researchers. Science is one such journal. We invited our neighbor Jake Yeston, Science’s chemistry editor, into our studio, to help dispel some of that confusion.

Jake Yeston: So what we tell authors what we actually tell authors is not to seek out press coverage …

Tien Nguyen: Jake is part of the team at Science responsible for getting manuscripts peer reviewed and ready for publication. So although he’s not setting Science’s preprint policy, he’s familiar with it. Jake understands that sometimes the press, such as myself, seek out scientists, which can lead to some sticky situations.

Jake Yeston: I would say the really complicated nexus is between not journals and Rxivs alone, but journals, Rxivs, and the news media. When you write a story about a paper on arXiv and the comments that you get when you write your story are this is great. It doesn’t matter all that much what the author says to you. The real problem comes when you’re writing a story in the papers on arXiv and it gets severely critiqued, and then, I think we are really disadvantaging the authors by saying to them, well you’re not allowed to defend your work.

Tien Nguyen: And that disadvantage isn’t unique to preprint servers. For example, Jake says this has happened before with work presented at conferences. I asked him what he would say to researchers who found themselves in this tough position where their work was on an Rxiv, being debated in the press, but not yet published in Science, and they wanted to respond.

Jake Yeston: Honestly, at this point, it’s hard for me to envision a scenario where we would proactively reject a paper because journalists decided of their own accord to cover it on a preprint server and the author commented in that context. I think we understand that telling people they are allowed to post papers on arXiv presupposes that these situations are going to arise. If we never wanted this to happen we would have to tell people not to put their papers there.

Tien Nguyen: But he can envision some scenarios where the mixing of preprints, journals, and journalists could create problems for chemists.

Jake Yeston: The other challenge of a journalist covering a paper on Rxiv is that there’s still a lot of confusion over what constitutes priority. And by priority, I mean who got there first. You can imagine two different research groups. One of the research groups is a little sloppy, and they rush to finish their paper so that they can get it up on Rxiv so that C&E News can write a piece. The other group is meticulous. They do all of their control experiments. They scale up all their reactions instead of just characterizing them. They try to look at the broader implications, maybe study the mechanism. Then they send the work to a journal and get it reviewed. So it’s possible that in that circumstance if those two papers were sent to the journals at the same time, the more meticulous paper would probably end up getting published sooner because the sloppier paper would have to get revised extensively. But if you cover the sloppy paper when it’s on the Rxiv and you don’t write a very long article that says, well this is OK because it’s first past the post, but you know there’s a lot of things that they could have done better. There’s a lot of things that they could have paid a little more attention to. Then in some sense you’ve, you’ve privileged people for being first at the expense of being careful.

Tien Nguyen: Jake wraps up by saying, is it really journalism’s problem? He’s not sure. But you know, since we’re journalists, we’ll talk a little bit about how we handle covering ChemRxiv.

But, before we get there, Jake says he still sees some fundamental, unresolved questions lingering around ChemRxiv. For example, what is the financial incentive for running a free preprint server in the land of paid subscription journals? Like, will people see that a new Science paper has come out online and say, oh I’ll just go read it for free on ChemRxiv? He also points to the ever-growing number of journals and wonders how many more we actually need? As he’s going through the list of all these journals, it occurs to me …

Tien Nguyen: So let me ask you, do we need ChemRxiv?

Jake Yeston: ... the answer to that question is really not clear to me yet.

Tien Nguyen: After the break, us media types will finally weigh in on ChemRxiv and we’ll hear from someone at the ChemRxiv mothership. But not before diving into the civilized slugfest that was the ChemRxiv session at the ACS meeting in DC this fall.

Dorea Reeser: Hey everyone. It’s Dorea from C&EN and we need your help assembling this year’s Talented 12, presented by ThermoFisher Scientific. The T12 is a group of a dozen up-and-coming scientists that the chemistry community needs to know about. C&EN will feature those chemists in a cover story later this year.

We enlisted Alex Spokoyny of UCLA to help us make our appeal, not just because he’s a T12 alum, but he’s also used ChemRxiv. Small world, right? Some of Alex’s upper-level undergraduates published work from a lab class to the preprint server. Here’s Alex on the thinking that made that possible.

Alex Spokoyny: We decided that we were going to try to essentially change the classes from the old-school way how they’re taught. You know, the students go in the lab they have developed protocols for them when they sort of learn a technique and some sort of methodology and kind of repeat something that has been done already.

Dorea Reeser: Alex and his TAs developed a 10-week program in which groups of undergrads developed new catalysts for aminations. The students then learned how to write up the work for a manuscript—instead of just a lab notebook—and the group published it to ChemRxiv. That work also just appeared in the journal Dalton Transactions, but Alex is happy with his decision to go with ChemRxiv first.

Alex Spokoyny: Many of the students graduated and they, for example, don’t have access to academic literature anymore and they want to share it with their friends and families. So the fact that, you know, these ChemRxiv submissions are publicly available right, anybody can click on it and access the manuscript and the data. I think it’s a great thing.

And I think they you know for undergraduates appreciated the fact that you know you can come up after you know a relatively short research stint in a lab like this with something that can potentially affect how other researchers think about science and you know provide something useful to them.

Dorea Reeser: And Alex has actually changed how he thinks about science since he was named one of C&EN’s Talented 12 in 2016.

Alex Spokoyny: One of the cool things is that I was just able to meet people and researchers in so many different fields that I might not have met if I wasn’t part of the Talented 12. We’ve met with Karena Chapman, who is a really talented are both literally and because she’s part of the Talented 12 spectroscopist, beamline scientist at Argon. We also started collaborating recently with a few other folks from T12. Renee Frontiera, she’s at Minnesota and also Fikile Brushett, he’s at MIT. So I think just the overall experience of being able to network with some phenomenal scientists, it’s been absolutely priceless.

Dorea Reeser: Alex and Karena actually just published a paper together in Nature Materials. And now you can help us put together the next chemistry dream team by visiting talented12.cenmag.org and clicking on “Nominate candidates for 2018.” We’re looking for best and brightest early-career chemists from all over the world, working in academia, government, and industry. The deadline for nominations is April 8 at 11 PM Eastern.

Tien Nguyen: Before the break, we were talking to Jake Yeston of Science, who thought that the most interesting new wrinkles introduced by ChemRxiv would be those involving scientists, journals, and journalists. And those three groups were all present last fall in Washington, D.C. at a symposium about ChemRxiv at the ACS national meeting. Lauren Wolf, the leader of C&EN’s science and technology team was there, so we asked her to fill us in.

Lauren Wolf: I think he big ticket session was the one where they had some ACS journal editors talking about ChemRxiv because there is some controversy. I don’t know what precisely the number is now, but back at that time only about 80% of ACS journals were accepting preprint papers. Notable among those is that JACS, you know, the flagship journal of the ACS, still does not accept papers that have been preprints. And so there was a JACS editor there, Chad Mirkin, and also an editor from ACS Nano, Paul Weiss, was there. Now, ACS Nano does accept preprint papers, but they had made a pretty formal statement that if they were going to accept a preprint paper that it had to have more novelty than the average paper. And so there was some backlash about that online. And so up until this meeting, people were looking forward to hearing what these editors, some pro-ChemRxiv some con ChemRxiv, were going to say.

Tien Nguyen: Here are some of the pros that she heard in the room and on Twitter: Preprint data can be used in grant applications; preprints benefit younger researchers who are under more pressure to quickly establish themselves; preprints are free to access, meaning more people around the world can read them; And preprints let you “put a stake in the ground.”

Now on the flipside, the cons: Some people thought that once you post a preprint, your work is no longer novel and journals want to publish novel work. Another concern was that posting a preprint might lead to you getting scooped. Think back to Jake’s example where group A is less thorough but publishes to ChemRxiv quicker. But now imagine that another group working on something similar sees that preprint and decides, ‘We’ve got to publish, like now.’ So to some people preprints are a stake in the ground, but a stake that gives away your position letting others try to rush past you to publication in a journal.

So I’ve been thinking about these concerns while working on this podcast for a few months now. It seems that there’s one main question at heart of the uncertainty around preprints. And that is: when scientists discover something new, who should get to break the news first? Should the scientists get to do so before peer review? Or should it be the journals or journalists who can vet the work with outside reviewers?

Honestly, I don’t think anybody involved with this podcast, myself included, can answer that. And certainly not in an unbiased way. I don’t think any one person can.

But what I can tell you about is how C&EN decided to approach covering the papers on ChemRxiv. Writing about Ryan and his gang’s preprint last fall took me into uncharted territory. At that point, I had never written about scientific work that had not been peer reviewed and gotten that gold star of academic approval. So I turned to my editor, Lauren, with my questions. What was our policy for covering preprints?

Lauren Wolf: My thought was, hmm I’m kind of making this up as I go. It’s not like we’ve never covered preprint papers before, it’s just hasn’t been a frequent occurrence. There are others preprints that have been out there for physics and bio and engineering and other things, but we chemists haven’t had one thus far. This was sort of the first time where I had to sit down and think, ok well, what should our policy be about this, what should our aims be, how do we make a decision about whether we’re going to cover a paper like this. So yeah, uncharted territory.

Tien Nguyen: What Lauren told me was that first, we needed to know if Ryan would even talk to us. And as we quickly found out, the answer was no. So I went back to Lauren.

Lauren Wolf: My thought was, well there has to be some way where we can still write about this paper, because if we don’t, you know, it’s in the public, people are tweeting about it, people are blogging about it, we need to be part of this conversation. And so how we can get around this. Which was why we sort of settled on this strategy that we did, which was, you know, if he can’t tell us about the science, then let’s talk to a whole bunch of experts in the field who can help make sure we understand how they did the science in the paper.

Tien Nguyen: I ended up contacting about 8 organic chemistry professors, 4 of whom responded with comments. All of which were pretty positive. I also fielded questions like, how did you get the paper prior to peer review and what journal is it going to appear in? To which I explained our thought process, and basically said, we’re all on new ground here.

In the meantime, we discovered that certain journals do at least allow researchers to fact-check any news stories written about their work. We told Ryan, and he fact-checked the scientific accuracy in our piece, and we included a line in our story that said, “the authors declined to discuss the work with C&EN for this story except to confirm its factual accuracy.” The story, titled “Synthetic simplification of hallucinogen pays off,” came out a little over two weeks from when the manuscript first appeared on ChemRxiv. That’s a longer turnaround than usual. Typically, we’ll cover a paper on the day it comes out if we know about it beforehand or at least within a few days of its online release.

Looking back on the whole experience, I asked Lauren if there was any part of the process that she’d do differently.

Lauren Wolf: I don’t think so, I mean, I think you handled it really well. I think the lessons learned are that if we’re going to cover a preprint server paper, it’s going to take more time and more effort, but that potentially the payoff is a really big one because we’ve got a story that not everyone else has.

Tien Nguyen: Wired did cover Ryan and Jeremy’s work … but, a few months after we did.

Lauren Wolf: I think the interesting thing about preprint servers actually comes for news outlets. If a journal doesn’t want you to write about something they have a lot of ways of making that happen, as we discussed, right, not letting researchers talk to us. Could a story be a thousand times better if the researcher gave us the backstory of how they made the discovery? Yes, and that would be a better news story every time, but we’re sort of in the meantime working within this construct of being restricted. It’s the game we play, it is the construct that’s in place.

Tien Nguyen: Preprints on the whole, however, are not new to scientists or to journalists. Matt reached out to some other science writers to see how they cover preprints such as those on arXiv or bioRxiv.

Matt Davenport: Yeah and I honestly was not that surprised to find out that how you covered Ryan and Jeremy’s work is basically how those other folks are covering preprints. Once science is out in the public—whether it’s in a journal or on a preprint server or talked about openly at a conference—it’s fair game for coverage. But in cases where the work is not peer-reviewed, reporters tend to be more cautious and/or rigorous, by sending the work to more experts for comments, for example.

What did surprise me, though, was hearing how other reporters feel about preprints.

Erika Check Hayden: I love covering preprints. They often spark, real-time lively discussions among scientists on social media and elsewhere. So I get to peek in at these conversations about science that are usually happening out of sight, during the peer-review process.

Matt Davenport: That was Erika Check Hayden, who covered biomedical research for Nature for 15 years before becoming the director of the science communication program at UC Santa Cruz. She was one of my instructors when I went there.

We also heard from Emily Conover, who covers physics for Science News. She said that arXiv is one of her several go-to spots when she’s looking for new papers to cover. So I’m really curious to see if we start feeling the same way about chemistry preprint servers in the future.

Tien Nguyen: OK, let’s take stock of who we’ve talked to about ChemRxiv. We’ve got scientists, someone who works for a chemistry journal, someone who works for a chemistry magazine. Who are we missing?

Marshall Brennan: So I am Marshall Brennan, I am the publishing manager for ChemRxiv.

Tien Nguyen: Marshall is a former Nature Chemistry editor and joined ChemRxiv in September. He’s spent a lot of time talking to chemists about the role of ChemRxiv. I asked him, how does he view ChemRxiv’s role in the publishing landscape?

Marshall Brennan: So in terms of where it fits into the hierarchy of things, is that it should be somewhere between a conference either paper publication/poster and your final journal article. When you’re making the decision about whether or not to preprint something, it ultimately should be the same thought process that you take when you decide, should this student talk about this project at conference Y? Because most conferences don’t have a NDA that you sign, so it is public disclosure in a lot of cases, but it’s public disclosure on a smaller scale.

Tien Nguyen: Basically, if you’re really worried about getting scooped by the competition, you would probably be more careful about what you present at a conference they’re attending. That same thinking applies to preprints. I also asked Marshall about the elephant in the room, or building rather. Marshall works one floor above us here at the American Chemical Society headquarters in D.C. And ACS publishes some of the journals that don’t accept preprints. So if ACS is supporting ChemRxiv, can’t Marshall and his team just tell the journals to fall in?

Marshall Brennan: So this is obviously a very complicated issue that people can read into any way they’d like. What I think is most telling about how this has gone over is that when the press release came out in 2016 saying that ChemRxiv was going to be a thing, about I think it was less than half of all of the ACS journals would consider a submission that had gone to a preprint server. Now it’s really just down to a handful of journals. Primarily, it’s JACS, Organic Letters, one of the journals in our toxicology portfolio, and the other sort of high profile journal that currently doesn’t take preprints is Angewandte Chemie.

We respect our community and our community is involved in our journals via the editorial boards, and so we respect our editors to make decisions about content because they are proxies for our community.

It has been said that if ACS is in JACS title, why don’t you just tell them to take preprints, right? Well that kind of goes against our mission of respecting authors, respecting chemists by respecting the decisions that their editors make. So yes, I personally and I think a lot of people involved with ChemRxiv would love if JACS would change their policy but ultimately, we respect that that’s not our decision to make because of how we structure those journals.

It’s a new thing and not everybody understands it. And there’s this sort of elephant in the corner of, “Hey, JACS might not accept your paper.” It’s something we need to talk about it, right? Because that’s a very real thing. But we’re not out to say everyone needs to preprint everything. We’re not here to destroy journals. We really like journals.

Tien Nguyen: Peter Stang, editor-in-chief of JACS, has said that their editorial board will revisit their policy on preprints at the fall 2018 ACS National Meeting. If any changes do happen, we’ll be sure to let you know.

Since ChemRxiv’s start, about 220 preprints have appeared on its site. For comparison, bioRxiv had about 340 preprints in the same length of time after they launched. Highly recognizable groups have been preprinting their work, and others have used the server in unique ways, such as UCLA’s Alex Spokoyny.

And Ryan Shenvi, who we began our story with, has since posted another paper, a follow-up to their first one, on ChemRxiv. We caught up with him just as he was getting ready to post the second preprint to talk about why he was going back.

Ryan Shenvi: Oh, I just like ChemRxiv, I don’t know. Because it’s so satisfying to finish your work and just put it out there. I mean because I don’t know maybe it’s the little kid in me but I want, you know, my kids always come up me and say like, “Hey daddy, look at this look what I did.” And they want some feedback. I don’t know, I haven’t done enough internal psychoanalysis. I just like to finish something in and get it out.

Tien Nguyen: Cool. So have you gotten much feedback from the community then?

Ryan Shenvi: You know, I have not! I’m so bummed, not from the people within my community.

Tien Nguyen: He says most of the feedback he receives is typically through giving seminars in other departments. He had hoped to get more feedback by putting the paper on ChemRxiv. He’s heard from people on Twitter, but says he didn’t get any in-depth comments.

I asked Marshall if ChemRxiv had a commenting system and he said they did at first, but they had such huge problem with spam that they were forced to shut it down. They’re working on bringing it back, though he wasn’t at liberty to say when it’ll be back or how exactly it’ll work.

But it’s also unclear if once it’s online, people will actually use it. Jake says Science and Nature, which publishes a lot more than just chemistry, have commenting systems that people rarely use.

Jake Yeston: I mean, Science and Nature have both had open commenting systems for about two or three years.

Tien Nguyen: Oh they do?

Jake Yeston: Yeah. And nobody ever uses them. You know I mean literally I mean you could go up to one of Phil Baran’s papers published in Science now and you could say, “This is great. I love it.” You know or you could say, “How come you take so many papers from Phil?” You know, whatever you want to say, you could go up there and you can say it. And it’s very lightly moderated you know as long as you use polite language and don’t link to your website selling purse knock-offs.

Tien Nguyen: So no one comments on synthesis papers?

Jake Yeston: No one comments on anything! It’s prohibitively rare for us to you know I mean once in a while I mean if a paper is clearly going south then we’ll get some comments but it’s prohibitively rare for us for people to use that commenting system. When we set this up we had hours of meetings about how we were going to moderate it. Oh, I’m serious. I mean, we came up with countless hypotheticals of the notional kind of comment that we would really struggle to figure out whether to allow somebody to post or not. And we had you know our legal adviser come and talk about it and then nothing happened.

Tien Nguyen: Because we’re dedicated reporters, Matt Davenport and I went to onto Science’s website and left a comment, or what they call an e-letter, on a Phil Baran paper, in an attempt to realize Jake’s hypothetical scenario.

Matt Davenport: Oh, here it is. E-Letters. Submit a response to this article.

Tien Nguyen: Oh hey, there you go. So a text box just opened up.

Matt Davenport: Ok. Compose E-Letter. (Typing) This is a test for C&EN, the news magazine of the American Chemical Society.

Tien Nguyen: Just say that Jake said that we could do this.

Matt Davenport: (Typing) Jake Yeston said that we could do this.

Tien Nguyen: Well, I’m also curious if the author gets pinged that someone commented on their article. And if that’s the case, we should you know say, “Shout out to Phil.”

Matt Davenport: (Typing) P.S. Shout out to Phil?

And about a week later, it appeared!

So ChemRxiv hasn’t yet been the crowd-sourced peer-reviewing destination that optimists hoped for. But neither has it been the self-scooping, novelty-killing platform some feared. But maybe this is what we should have expected all along. Preprints may be new to us chemists, but they’re not new. And physicists and biologists seem to have made it work.

So what is the reality of ChemRxiv as we understand it right now?

Jake of Science says the preprint server isn’t a bad idea and that he’s curious to see how many people use and where it goes from here.

Marshall at ChemRxiv is excited to keep improving the server through community feedback. He and his team are also looking for ways to add revenue, like offering a service that transfers preprint papers to journals. Journals would pay for this service, which there is precedent for. The idea is actually from bioRxiv.

Lauren at C&EN say she thinks ChemRxiv is here to stay but that it’ll take a culture change, which may come with some growing pains. And we at C&EN will be reporting all along the way.

Ryan at Scripps says his main hope for ChemRxiv is that it will develop into a way to crowd-source peer review. He also has an interesting take that because the ChemRxiv muddles the meaning of what constitutes priority it might actually lessen the focus on being first.

Overall, he says he’s glad he decided to post his group’s Salvinorin A paper on ChemRxiv.

Ryan Shenvi: It was really gratifying, actually. It was a real sense of empowerment. Anybody that does scientific research knows the excitement of sharing your work with the world and especially work that you’re really proud of. And then all the sudden, when the work is done, you’re limited by the publication process. You’ve got capricious referees, there’s slow turnaround times. It takes the timeline completely out of your own hands. ChemRxiv is empowering because, throughout the whole discovery process, you move at your own pace, right? You’re limited only by the speed at which you can solve problems. A preprint server, despite all the possible problems that could arise, at least returns the freedom of movement and speed to the researcher.

That Salvinorin A paper is now published in an open access ACS journal, ACS Central Science.

All right folks, that’s our episode. If you liked this episode, or if you didn’t like it, though that’d be surprising that you made it this far, subscribe to Stereo Chemistry. We’ll be coming out with stories monthly. Until then, you can connect with us on social media. Find me on Twitter at @mustlovescience.

Kerri Jansen: I’m at @absolutekerri. That’s K-E-R-R-I.

Matt Davenport: And I’m @MrMattDavenport. If you’ll be at the ACS national meeting in New Orleans, come find us. We will all be there.

Tien Nguyen: The music you heard in this podcast is by Lee Rosevere. You can find links in the description. Thanks for listening.

End transcript.

All music in this podcast is by Lee Rosevere and licensed under CC BY 4.0.

The music you heard first and most often was “Puzzle Pieces.”

The music just before the break was “Sad Marimba Planet,” and the music playing during the call for T12 nominations was “Southside.”

And the music at the end of the episode is “Credit Roll.”

Here are the links to the publications we mention in the podcast.

10-step Synthesis of 20-nor-Salvinorin A | ChemRxiv

Modular Approach to pseudo-Neoclerodanes as Designer Kappa-Opioid Ligands | Org. Lett.

O6C-20-nor-SalA is a stable and potent KOR agonist | ChemRxiv

Buchwald-Hartwig Amination Using Pd(I) Dimer Precatalysts | ChemRxiv

Buchwald–Hartwig amination using Pd(I) dimer precatalysts | Dalton Trans.

A molecular cross-linking approach for hybrid metal oxides | Nat. Mater.

Synthetic simplification of hallucinogen pays off | C&EN

RE: A general alkyl-alkyl cross-coupling enabled by redox-active esters and alkylzinc reagents | Science

Dynamic Strategic Bond Analysis Yields a Ten-Step Synthesis of 20-nor-Salvinorin A | ACS Cent. Sci.