A couple of days ago I was saying that the problem with blogging (at least for me) is lack of discipline. So I figured that one way to become a bit more disciplined, and hopefully post stuff that people will find of interest, would be to write a brief entry every time I come across a paper that I think is particularly interesting. I'm calling this category of entries "Journal club" for lack of a better name, as I don't think I want to (nor could) write an extensive critique of the paper in question. Instead, the purpose of doing this is to flag a paper as something that is of interest to an editor of Nature Medicine, and let those of you who work in the relevant field do the detailed evaluation of the contribution.

To get things rolling, here's three papers:

1) A study by Stephen Hauser and his colleagues in the NEJM reports that rituximab, a drug used for the treatment of non-Hodgkin lymphoma and rheumatoid arthritis, could also be useful to treat multiple sclerosis. Their clinical trial involved 104 people, 69 of whom received two one-gram doses of the drug (which acts by depleting CD20+ B cells). The trial lasted 48 weeks and showed a reduction in the number of inflammatory brain lesions and clinical relapses in the treated patients versus the controls over this time period. Although the trial wasn't designed to establish long-term safety or efficacy, it is indeed promising for people with MS.

2) In Immunity, Jackson Egen and his colleagues report on their use of high-resolution multiplex static imaging and intravital multiphoton microscopy to give us an unprecedented look at granulomas -- masses of inflammatory cells that arise owing to the persistence of an infectious agent in host tissue and that are critical for host protection.

Granulomas, which are often seen in people with tuberculosis, contain different cell types including lymphocytes, macrophages and fibroblasts. In their study, the authors found that, after infection with Mycobacterium bovis, Kupffer cells in the liver capture circulating bacteria and subsequently form the nucleus of a new granuloma by recruiting uninfected liver-resident macrophages and blood-derived monocytes. Within the granuloma, these cells set up an immobile matrix that attracts a dynamic population of T cells in a TNF-alpha-dependent manner. You ought to check out their movies.

3) To continue with the microbiology theme and the topic of the interaction of bacteria with host tissue, Science just published a study on the mechanism whereby tissue abscesses can inhibit bacterial growth. Brian Corbin and his colleagues found that calprotectin -- a neutrophil-derived protein -- can stall the growth of Staphylococcus aureus inside an abscess. Mechanistically, the effect of calprotectin depended on its ability to chelate Zn2+ and Mn2+, thereby interfering with the transcriptional machinery of the bacterium. In vivo, mice lacking calprotectin had abscesses with higher levels of metals that seemed to favor staphylococcal proliferation. Whether metal chelation can work as a general strategy to inhibit bacterial growth inside an abscess remains to be seen, but the possibility is certainly tantalizing.

Posted by Juan Carlos Lopez at 02:02 PM | Permalink | Comments (0)

A couple of days ago we got a comment from one of our referees, saying that it's unreasonable for us to get more than three reviewers for any given paper that we consider for publication. He stated that having to deal with the comments from more than three referees places an undue burden on authors, which may put the community off from sending us new submissions.

We are certainly familiar with some (unfavorable) comparisons that are made between our journal and other publications that use only two reviewers per paper. I'd like to say, first, that we don't get more than three referees for any given paper as a matter of course. When we do, it's sometimes because one of the referees has not reviewed for our journal before. We aren't therefore sure how his/her comments will compare with what other, more experienced, referees may have to say about the paper -- sometimes new referees are either too tough or what we call "wet". So, as different journals have different standards and criteria, referees often go through a "training period" during which they come to be familiar with the kind of papers a journal looks for.

Second, a good number of submissions to Nature Medicine tend to be multidisciplinary, making it very difiicult for just two people to evaluate the full manuscript. For starters, most of our papers include human and animal data. So, right off the bat we may need one person with technical expertise on the animal experiments and another person to advise us on the potential relevance of the findings to human disease. If you then consider that you may want to have a second opinion about the same points, we're already talking about at least three reviewers and have not even started talking about papers that stretch over two or more disciplines.

Third, when we look at all of the referees' concerns, we don't necessarily ask authors to address every point, particularly if the criticisms bring up points that are clearly part of a subsequent study. So, two referees times two does not necessarily equal four sets of comments.

To finish, I should say that two or three years ago we followed up with people who had published in our journal, some of whom had to go through the "four-referee ordeal". We ask these authors if they felt that the review process had significantly improved their paper. The overwhelming majority of these authors agreed that the referees' criticisms had really made a difference and were frankly appreciative of our peer-review process. I guess you can't please everybody all of the time.

Posted by Juan Carlos Lopez at 12:14 PM | Permalink | Comments (0)

Our colleague Kate Jeffrey, who was one of the editors of Nature Medicine for most of 2007, went back to academia late last year, and it shows that she hasn't wasted any time in getting involved in exciting proyects within and out of the lab.

The other day she told me about a scientific film festival that she is co-organizing. The idea is to screen fictional films that have a scientific storyline or main character. The festival will feature some already existing films but, more importantly, they want to showcase the work of aspiring filmmakers who may be interested enough in science to make a fictional movie about it.

I'm no filmmaker, but right off the bat I can think of a couple of ideas:

1) A scientist doing his second postdoc discovers that an experiment key to his whole project will not work. The film is about the aftermath of his disappointment, during which he entertains ideas such as dropping out of science, committing scientific fraud and starting a third postdoc. Surely there is a good drama waiting to be developed there.

2) The New Yorker published earlier this year a fascinating article on "human guinea pigs", who volunteer for clinical trials. There easily is a movie in the life of a ficticious guinea pig who is involved in a trial as unfortunate as TeGenero's TGN1412 trial in 2006. The side effects would have to be not as severe as in that trial, but something that allows the director to explore human nature more fully -- something like, say, infertility.

Anyway, congratulations to Kate and her co-organizers on such a great idea. I hope they get a lot of submissions from filmmakers inspired by the project.

By the way, have a look at the trailer they created to begin to advertise the festival:

Posted by Juan Carlos Lopez at 11:43 AM | Permalink | Comments (1)

I don't post much on this blog, but when I do, I'm like the bass drum in an orchestra -- it doesn't sound often, but when it does...

OK, the last entry of the day is about the lively debate between the Journal of Experimental Medicine and Thomson Scientific -- the creators of the Impact Factors (IFs). Have you been following it? In a nutshell, last December the JEM published an Editorial thoroughly criticizing Thomson for their lack of transparency in the way they calculate IFs. Thomson wrote a long rebuttal, to which the JEM subsequently replied.

I find it somewhat amusing that the JEM has started this cruzade against IFs. First, IFs are subject to the same competition rules that affect any other product available to researchers. If the product is useless, you stop using it, the same way that you stop using an antibody that gives you a high background or a journal that publishes bad science. If IFs are still in the market and are still going strong, it's because the alternatives aren't as useful. Why would they want to change the way they do business unless there is pressure from the marketplace?

Second, some of the arguments the JEM uses to criticize the IFs strike me as equally amusing. For example, they suggest that the median, not the mean number of citations would be a more reliable indicator of a journal's impact, and they wonder why IFs include citations to Review and News & Views articles instead of just focusing on primary research. As you can already imagine, if these changes were made, they would lead to a higher IF for the JEM. In fact, I once heard a talk from a member of the JEM staff in which the IFs of several journals (including mine) were recalculated using the median number of citations, taking out cites to Reviews and a couple other cosmetic fixes. Do I even need to tell you that the difference between the JEM and Nature Immunology or Nature Medicine wasn't too large any more?

All of this is well and good but it seems to me that, if we're not satisfied with the IFs, journals are not the right advocates for change, as we have a vested interest in having the highest impact for the communities we serve. In other words, it would be disingenuous for me to start advocating that citations to Reviews must stay in the calculation and suggest new things that will make my journal's IF be higher. To my mind, the scientists should be the ones fighting this battle, assuming they care. Alas, I suspect the care more about figuring out what they need to do to publish in a journal with a high IF as opposed to trying to find a way to level the field across journals.

To me, the situation is quite simple. IFs will carry on being influential until something else outcompetes them in the marketplace. In the meantime, if you want a higher IF and Thomson counts citations to Reviews, then publish more Reviews. And if they choose the mean over the median, then try to publish articles that will give you a higher mean number of citations. Everything else is commentary.

Posted by Juan Carlos Lopez at 12:26 PM | Permalink | Comments (0)

The other day I posted something about the ordeal my friend Andy Marshall was going through as a result of something he published about a researcher who works on genetically modified crops.

One of the many interesting comments we got on that entry had to do with the distinction between perceived and actual conflicts of interest. I mentioned at the time that we would discuss this matter at some point in our editorial, and we finally got around to doing it (click here to read it).

I'm sure this will not be sufficient to satisfy everyone, but we will be delighted to hearing your views about this question. We're constantly revising our Conflicts of Interest policy, and your views are certainly important to help us shape it.

Posted by Juan Carlos Lopez at 12:18 PM | Permalink | Comments (0)

Sorry we haven't been posting anything for the past few weeks. Blogging requires a degree of discipline that I have yet to develop. We'll try to be a bit more disciplined, though, as there's always interesting stuff happening that it's worthy of comment.

This time is Europe's decision to launch the Innovative Medicines Initiative, a joint effort of the European Union and big pharma to inject cash into Europe's biopharmaceutical industry.

The Initiative correctly stated that investment in Europe has lagged behind what the Americans spend in research and development, and the growth of the industry is nowhere near what you see in countries like China. Part of the solution is to increase investment, sure. But, as we stated in our February Editorial, one wonders if the kind of projects they intend to fund -- which they call "pre-competitive research" (research aimed not at directly developing a drug, but at generating tools that speed up the drug discovery process) will be all that helpful to the biopharmaceutical sector.

In addition to this question, there are other points that may be problematic as the IMI moves forward -- questions about funding, intellectual property and bureaucracy, some of which we discussed in the Editorial. As we wrote there, more money is always a good idea but, when it comes to the actual implementation of the IMI, the devil will be in the details.

Posted by Juan Carlos Lopez at 12:00 PM | Permalink | Comments (2)