In this special episode we hear about photosynthesis, forensics, peer review, and the past, present and future ofeLife.
In this episode
00:54 - Great expectations
Great expectations
with Detlef Weigel, eLife
Deputy Editor Detlef Weigel explains eLife’s ethos to Chris Smith...
Detlef: This really comes from my own experience over the last 30 years, how much more difficult it had gotten especially for young researchers to get published at the very highest level. When I started out, when I got my PhD in ‘88, it was essentially guaranteed when you did very good work, that would be published at a very visible level. And that has really dramatically changed over the last 30 years.
Chris: In what way?
Detlef: The scientific enterprise has grown enormously. Unfortunately, the outlets that are seen as being at the highest level have not kept the pace. They have grown a little bit but certainly, not at the same rate. What that has led to, you very often come across articles where this would not have looked out of place in one of the very general broad interest journals. Conversely, it’s still true that when you look at what some call ‘elite journals’, the work that is being published there is of course very good. But then we also realised that there could be probably 5 or 10 times as many articles that would be fit to appear there.
Chris: How do you see what you’ve been striving to do with eLife as addressing that need?
Detlef: Yeah. So certainly, not having any arbitrary limits very much helps. It’s difficult for me to know whether some of our competitors artificially restrict the number of papers that they publish every week or every month. It would seem so because they haven’t grown at the same rate as the scientific enterprise has grown over the last 30 years. One should not turn away manuscripts that are at the same level as other manuscripts that one publishes. Very regularly, students or post docs will show up and say, “Why did the journal turn away my paper? It’s not any different really or worse than this other paper published here.” They have the impression that what's turned away is inferior compared to what does get published at the very highest level. And that really is not the case. It’s often really the lack of the raw and this is something at eLife, we want to get away from. We strive to give much clearer guidance what is expected and that we do not string authors along or we tell them, “Well, maybe sometime in the future, we’d be more interested in publishing your work and why don’t you just try to add more stuff and convince us then?” That’s really completely contrary to the eLife ethos.
Chris: Yes, because some PhD students I have spoken to have spoken of their disenchantment when they have completed 3 years of work on a thesis, submitted a paper and then had back from the reviewers about another 3 PhD’s worth of additional experiments just to prove a point. Is that what you're getting at? You're saying, “We’re going to give you a direct answer. We’re going to give you a quick direct answer and if you fulfil those criteria, there's no holds barred after that towards getting your research actually out there.”
Detlef: Absolutely. The feedback that we provide after the reviews are much clearer I would say than what you receive from any other journal. For us, this is one of the most important things to be very, very clear what we expect in a revision. We normally list a couple of experiments if we think more experimental evidence is being done and if it comes back, the work has been done, then we very likely will accept it. No moving targets.
Chris: Finally, what do you think is on the horizon or what's next on the agenda? What are eLife going to be pushing to do in the next 5 years to carry on being adventurous, daring and trying to change the way that academic publishing is done?
Detlef: Something that is very high on my list of priorities is actually after having demonstrated at eLife that our process works to convince and if you will, convert as many other journals as possible to take a similar approach so that this really becomes the standard and that in the future, students and postdocs will say, “ If there’s not a transparent consultative process among reviewers, I will not agree to submitting my manuscript to such a venue, no matter how fancy that journal is.”
06:11 - Of mice and men
Of mice and men
with Jessica Metcalfe, Colorado State University
Jessica Metcalf is an early-career researcher who had just published a paper in eLife looking at whether the bacteria recoverable from the body of a decomposing mouse can be used forensically to predict the time since death. Since then she’s been appointed as an assistant professor at Colorado State University, and she’s moved on from mice to men, as she explained to Chris Smith...
Jessica: When we spoke last time 4 years ago, I had just published my first paper, looking at how repeatable the microbial succession during decomposition was, where we decomposed mice all of the same age, in the same lab, on the same soil type, and we sampled them during 8 time points and we found really it’s the exact same set of microbes at each time point for each mouse.
Chris: Why were you doing that?
Jessica: This was our first step in trying to understand whether microbial succession during decomposition is a repeatable enough and a predictable enough process to potentially be developed as a forensic tool to estimate how long a person had been dead. And that was the first paper that we published in eLife.
Chris: Where have you taken the research since? It’s obvious that things have gone in the right direction for you because you’ve achieved a significant university appointment and begun to publish more on this topic. So, how are you developing that initial eLife publication?
Jessica: So our first publication in eLife really showed us that if we control all variables that we see this really repeatable succession of microbes during decomposition, and so then this launched a number of other projects where we start focusing on different variables and start changing them, and ask the question, ‘do we still see this repeatable succession of microbes during decomposition?’ which is what we need if we’re going to be able to develop this into a forensic tool. In 2016, we published a paper in Science where we described two big sets of experiments. In the first one, we did a very similar mouse study as we did in the eLife paper, but we used 3 different soil types that had really different starting microbial communities. And there, we were using soil as a proxy for environment. If a person dies in Moab, Utah or in the mountains of Colorado, are they going to have the same succession of microbes or is it going to be completely different? And this helps us understand, is there a universal clock that we can develop to estimate the time since death or does it need to be regional? What we found there is that really, the soil type didn’t matter. We still get a very similar succession of microbes. And then the second part of that paper, we actually were able to work with a anthropological research facility down in Sam Houston State University where people donate their bodies to become part of a forensic science experiment after death. And so, we had the opportunity to decompose 4 human bodies – 2 in the spring and 2 in the winter. We sampled the skin in the soil over time and we again, asked the question: In this outdoor scenario, where there's rainfall events, there's insects, there's scavengers, do we still get a repeatable succession of microbes during decomposition? And what we found was yes, we do and it’s fairly impressive. That was a real shock because we went from a lab setting where we were controlling so many things to this outdoor setting, and we were still able to recover this pattern.
Chris: So what did you do? Did you just lay the corpse on the floor as though the person had died in situ and are they clothed, unclothed because that could make a difference too, couldn’t it?
Jessica: For the studies that we’ve done so far and that we have currently going right now, we’ve placed all the bodies in the exact same way. So we’re still controlling for that variable at the moment but at some point, we’ll probably test that as well. Everybody is outside, laid face up without clothes.
Chris: Now, why do you think that you see these results because the soil is such a strong driver normally for what's around and what it can support and sustain? Is it that the body is so nutrient-rich and so replete with its own microbial spectrum, that it just basically feeds and out-competes anything that could come in from the environment, and that’s why you see this very reproducible succession of microbes?
Jessica: What we found is that on average, most microbes appear to actually be coming from the soil. So you have to remember that soils have an incredible diversity of microbes and even though 2 soil samples may look very different overall as far as their microbial diversity, they still have some of the same microbes. And so, what I think is probably going on is that these are just really ubiquitous bacteria that are at a low abundance in a lot of places across earth, and they are very good at responding quickly to a new nutrient source. The body is this huge pulse of nutrients and there are microorganisms that have evolved to be really good and once they find that boom, they're growing like bonkers.
11:55 - Peer review under the microscope
Peer review under the microscope
with Drummond Rennie
Peer review is something that we all take for granted. We wouldn’t dream of publishing something credible these days without it. But the system wasn’t always robust and someone who’s helped to really shake things up over the last 30 years, founding in the process an internationally recognised conference series called “The Peer Review Congress”, is former medical doctor and high altitude physiologist Drummond Rennie...
Drummond: What happened was that I was working in a huge cardiac clinic in Guy’s Hospital in the early ‘60s and I got interested in problems from blue babies, kids with congenital defects in the heart, and they couldn’t have their blood fully oxygenated. Now, you get blue at high altitude and I did all the research I could do in London. I moved to the US in 1967 and the research I did that went very well indeed. This was high altitude in the Andes, in the Himalayas, and Alaska, and the Yukon, and so on. And an extraordinary thing happened to me.
我完成了一些研究在1970年代中期,我had what I consider in retrospect the luck to fall a long-ish way. Actually, a very long way down a mountain in the Canadian Yukon. From being a really second rate climber, I became, I suppose a fourth rate one and could no longer take full responsibility for experimental people who had agreed to be experimented on that I’d taken to high altitudes. The lucky part of that was that I was absolutely forced to change my career. I’d probably run out of ideas anyhow. It stopped me from getting killed later!
I became the first Deputy Editor of the New England Journal. Looking at what I had to handle and deal with, absolute abysmal standards, the shear weight of rubbish, it was astounding to me. This stuff would flow in and we’d flow it back again. The good research was superb but I’d say a third of the research sent to us were trite rubbish. One of the common features that occurred to me of these trite rubbish papers was that they’d all passed rigorous peer review.
One way or another, I became Deputy Editor of JAMA, the Journal of the American Medical Association. At that time, it was in a bad state and I was intrigued by the idea of helping to rescue it. I found that people there were interested in peer review also but were prepared to go a little further. In 1986, I wrote an editorial announcing that we would back a conference to discuss peer review. But I put in and insisted we would only present research. I was fed up with editors just saying, “We’ve had this disaster with peer review, but our peer review system, we declare to be excellent on basis of no evidence whatsoever.”
So, what a nice thing to gather evidence and an even nicer thing to get clever people out there – if there were any – to find this evidence. And so in 1989, we held the first conference on this and it was an amazing event – angry arguments and a great deal of excitement. So, we’ve been having them every 4 years since. The first thing that happened was the amount of rubbish being printed was confirmed. So, these conferences during the ‘90s and the 2000s, early 2000s, gave a tremendous impetus to the idea that the literature was full of biases and to the literature that said, “These are ways of correcting all of these biases and then of helping journals follow guidelines that would enable evidence based reporting.” So, that is what happened very broadly.
The last thing I’d say is something a little different. There was one woman for every ten men at the first congress. That ratio has changed completely. My parents got married in Cambridge around 1933. Before that, my mother put herself through medical school in the 1920s. She had been very happy with that ratio, don’t you think...?
17:11 - The evolution of photosynthesis
The evolution of photosynthesis
with Julian Hibberd
Julian Hibberd is based in Cambridge and he’s been trying to unpick how the more advanced “modern” form of “C4” photosynthesis evolved. Chris Smith first met him 4 years ago when Julian published evidence that C4 photosynthesis had probably evolved not once but many times, a story he’s since been able to refine and build upon…
朱利安-光合作用的祖先的形式是effectively unchanged since bacteria initially evolved the ability to fix carbon so probably, 3.6 billion years ago. The majority of land plants still use that system and that system relies on an enzyme which sounds unfortunately like a breakfast cereal called rubisco. rubisco is great. It fixes CO2and makes carbohydrates. But some of the time, it makes a mistake. Instead of taking CO2, it takes oxygen. Because the concentration of oxygen in the atmosphere is now very high compared to that 3.6 billion years ago, those mistakes happen more often that waste energy generates a toxic compound. The C4 pathway is a system which effectively abolishes those mistakes by generating a little turbo-charger around this rubisco enzyme, such that more CO2is supplied to it.
Chris - So back in history then. The bacteria that evolve this in the first place were living in an environment which was dominated by carbon dioxide, hardly in the oxygen around. So they didn’t need an enzyme that really could discriminate between an oxygen molecule and a carbon dioxide molecule. And it’s only in the latter era now, this is more a problem so there is this pressure to adopt this turbo-charged form.
Julian - That’s exactly right, yes. Over evolutionary time and geological time, the CO2has come down because photosynthesis has been so successful, and we’re now in a completely reverse situation where CO2is relatively scarce and there's huge amounts of oxygen. And that’s led to this conflict between fixation of oxygen by rubisco and the fixation of CO2.
Chris - How has it changed in order to make it a better discriminator between an oxygen molecule and a carbon dioxide molecule?
Julian - So in the C4 pathway, plants have developed a complex suite of traits which allows CO2to be pumped from one cell type to another cell type. And in that second cell type, we have the rubisco enzyme and that increases the concentration of CO2specifically around Rebisco which basically abolishes then the oxygenation reaction.
Chris - So it’s like a sieve.
Julian - It is a bit like a sieve, yeah. So that sieve involves a specific set of enzymes which initially fix the CO2into a different form. The CO2is then released at high concentrations around rubisco and that’s what's improving the efficiency of photosynthesis.
Chris - And if I look at all plants that do this, have they all got one common ancestor then or does it happen with the same common end-product, you get lots of CO2around your rubisco, but the way you get there is different in all these different plants?
Julian - There are multiple ancestors of C4 plants, so we estimate it’s evolved at least 60 times. And we think there's a general set of machinery and C3 plants which is sort of nascent and it allows C4 photosynthesis to develop. So, a lot of the regulatory structure associated with turning genes on or turning genes off, we have discovered more recently that quite a lot of that is sitting there in the C3 situation. It’s not being used exactly as it would be in a C4 leaf but in a way, it’s ready to be used.
Chris - And so, because it had that machinery, it’s a bit like me, walking into a kitchen and saying, “Well, that’s a knife and fork where we usually use that for eating but actually, I'm going to beat an egg with that.” And so, you're using a fork which is already made as a fork but you can do a different job with it, and it’s useful for both.
Julian - Yes, and I think that’s a great analogy. Actually, some of the work we’ve done more recently is a little bit more nuanced than that. Maybe it’s like, there's a fork sitting there and we would normally use it for our dessert. We’re going to carry on using it as a fork but maybe for a different course. Sounds terribly Cambridge, doesn’t it? But if we’re thinking about these forks and we say, “Well actually, this is a gene for a fork” and the ancestral C3 plant, those genes are very poorly expressed. In the C4 pathway, they're very highly expressed. And to our surprise, what we found is that in the ancestral C3 state, a lot of those genes are already regulated by cues which turn on photosynthetic genes. So such as light, they're actually sitting there as part of that photosynthetic architecture, regulatory architecture for photosynthesis. But they're not responding to it fully, so all you need to do is amplify that response as you go from C3 to C4 and hey presto! You have the full system working.
Chris - And is your ultimate goal then to understand photosynthesis, understand how plants work so that we can do it even better?
Julian - That’s one of the potential outcomes. There's a broad consensus now that despite millions or billions of years of evolution of photosynthesis, it’s not optimised for current agricultural practice. There's a broad consensus that there are multiple ways of improving photosynthesis. And so, if we understood it enough to be able to engineer it into a C3 crop such as rice or wheat, we should be able to dramatically improve crop yield, so up to 50 per cent improvement.
22:41 - Back to the future
Back to the future
with Eve Marder, eLife
eLife Editor Eve Marder talks to Chris Smith about what makes a great paper...
Eve: My name is Eve Marder and I'm Professor in the biology department and neuroscience program at Brandeis University.
当我还是一个年轻的科学家,论文目的是to be complete and full descriptions of a piece of work and to lay out the data, lay out the controls, lay out the methods, and then to allow the authors to articulate what they thought the work meant. Over the years, a lot of that became lost as people pushed for publications of higher and higher impact to the detriment of clarity, thoroughness, and to my mind, eLife is a way of going not back to the past, but forward to the future. We can write papers the way they should be written.
Chris: Do you think that’s happening?
Eve: I think that’s happening not perfectly. Many of the papers we publish are papers that I'm very proud of, papers that have enough depth, enough scope, enough clarity that they allow the reader to really see what the important findings are and how the work was done.
Chris: How is eLife competing with other journals though that still do subscribe to what science publishing had become with people submitting papers and then being given another 5 PhD’s worth of experiments to do before they get their paper revisited?
Eve: Many eLife papers are quite substantial so it’s not that other journals are publishing more substantial papers. But eLife refuses to send authors back for 6 or 9 months, or 2 years of work. We basically follow the policy that authors should send the paper when they consider it done and then we try to evaluate it as it is. And so, we might ask for minor modifications or a small bit of additional work if for example, a reviewer says that a specific figure has too much noise in the recording or someone thinks that a Western blot is fuzzy, we might ask them to redo something like that. But we will not provisionally accept a paper and ask them for 9 months’ worth of work because we think it’s really unfair to the young scientists who are doing the work to stretch out their careers and leave them in scientific limbo for a very long time.
Chris: How are you doing that though without potentially compromising on the quality?
伊芙:很简单。我想告诉你一个little anecdote that tells you the difference between eLife and what's happened to a lot of other publishing. Very early on in eLife, we sent a paper to a young man who was a very fine scientist who was beginning as assistant and he reviewed the paper, and he listed 6 or 8 experiments that should be done, probably a year’s worth of work. And in the consultation session, I pointed out to him that we were trying to avoid doing that so I asked him whether those experiments were necessary to support the point of the paper and he said, “Oh no. I just thought the job of the reviewer was always to suggest more experiments.” And so, what we do, if experiments are really necessary to prove the point of the paper and they would take 6 months, we reject the paper. And we tell the authors that they're free to take the paper elsewhere. They're free to do the experiments and maybe resend it to us or elsewhere, but basically, we don’t play those sorts of games with authors.
Chris: When you say to colleagues who were suggesting to you that they might have some work they want to publish and you say, “What about eLife?” Have you noticed that people react differently now compared with say, 5 years ago when things were just getting going?
Eve: Absolutely. I've noticed something else which is really important. Now, when I go to seminars or a conference, oftentimes, you see people showing slides where the work was from an eLife paper. I have some very, very prestigious scientists now are routinely citing work that they had published in eLife. So I feel like we’ve really crossed a very important threshold.
Chris: Where are you going next? What's going to be the sort of strategic direction for the next 5 years? You’ve honed down the peer review process that seems to be bearing fruit, you're attracting some very high calibre publications. You always have, but the numbers are definitely going up. What are you targeting next?
Eve: We’re hoping to grow in certain areas. eLife has been more successful at attracting the best papers in some subfields than others. I feel like we’ve grown eLife tremendously in the past 5 years and that we’ve done it gradually enough so that we haven’t lost the essential eLife ethos...
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