Even though my background is in neuroscience, I rarely write about this topic. But wo papers on amyotrophic lateral sclerosis (ALS) from the latest issue of the Journal of Neuroscience struck me as interesting to talk about.

In the first one, Fiona Laird and her colleagues generated transgenic mice that express wild-type and mutant forms of the human protein dynactin p150-Glued. As mutant forms of this molecule had been linked to ALS, they decided to explore the mechanism whereby dynactin p150-Glued contributes to the pathology. They found that expression of dynactin p150-Glued carrying a mutation that had been linked to the disease in patients led to motor neuron disease in transgenic mice, something that was not seen in mice overexpressing the wild-type form of the human protein.

The paper is very nice in that it provides a very detailed account of the neuropathology the authors see in the mouse, including some intriguing evidence of autophagic cell death. The picture below, which comes from the paper, is a silver-stained section of the spinal cord from a mutant mouse, showing dark, presumably dying, motor neurons (arrowheads) that are not seen in control mice. Unfortunately, the authors didn't get to explore the hardcore molecular mechanisms that account for the motor neuron death. But they now have a useful system to ask more mechanistic questions to understand the role of dynactin p150-Glued in cell death and investigate its actual relationship to human ALS.

The second study deals with a question that has occupied the field for some time. We know that mutations in superoxide dismutase (SOD) are linked to familial forms of ALS, but where does SOD need to be expressed to cause disease: in neurons, in glia, in muscle? Dick Jaarsma and his colleagues tried to get at this question by generating transgenic mice that expressed mutant SOD only in neurons. The figure below, from the original paper, shows spinal cord sections from mice that expressed the mutant protein only in neurons (top left and bottom right) or ubiquitously (top middle).

This is not the first time that neuron-specific expression of SOD has been tried, but it is perhaps the first time in which it is found to effectively kill the motor neurons. In other words, these findings fly in the face of other studies reporting no motor neuron death in mice with neuron-specific expression of mutant SOD and of papers specifically identifying a contribution of extraneuronal SOD to ALS. Not unexpectedly, there is at present no definitive way to reconcile these disparate observations, other than invoking technical differences in the studies or stating that the cell-autonomous effect reported by Jaarsma et al. does not negate an additional contribution from glial SOD. What we can say for sure is that we don't yet understand the neuron/glia/muscle interplay in ALS, and that it will be quite hard to establish if the contributions of mutant SOD from each of these sources in transgenic mice are indeed relevant to the human condition.

Posted by Juan Carlos Lopez at 02:51 PM | Permalink | Comments (0)

Have a look at this report from Siri Carpenter that just came out in Science's "Science Careers". It's about how to publish translational research, focusing on what journals look for in the submissions they receive. It features interviews with (and pictures of) several editors, including yours truly.

Not a bad read to kick off the weekend, I reckon.

Posted by Juan Carlos Lopez at 10:43 AM | Permalink | Comments (0)

As I approach the age at which the word 'prostate' starts sounding like a funereal drum, I become more interested in studies such as those published this week in the NEJM and about three weeks ago in Nature Genetics.

The NEJM paper, by Lilly Zheng and colleagues, shows that single-nucleotide polymorphisms (SNPs) in five chromosomal regions, each of which had previously and independently been associated with prostate cancer, have a cumulative association with the disease when considered in combination. The authors estimate that the five SNPs and a family history of prostate cancer account for as many as 46% of the cases in the Swedish population they studied.

The three Nature Genetics papers, by Julius Gudmundsson et al., Gilles Thomas et al. and Rosalind Eeles et al., all of which are nicely summarized in the journal's March editorial, disclose multiple new susceptibility loci associated with prostate cancer that, together with other loci identified in 2006 and 2007, give us plenty of new avenues to explore in order to understand the disease.

The most immediate implication of findings of this sort is often diagnostic -- if you identify gene variants that are linked to a disease, you can ask questions about how good these variants are at predicting onset and/or progression of the pathology. Validating the diagnostic value of these genomic data often requires blinded samples analyzed in a prospective (preferably longitudinal) fashion.

The findings could also help us understand the biology of the disease, although this almost always takes more time and is not always pursued, as it is very challenging: you need to identify with precision the protein whose gene harbors the relevant SNP, then establish how the SNP affects protein function, and finally look at how this altered function modifies the physiology of the cell as it becomes tumorigenic in an in vivo setting.

This is what we at Nature Medicine look for when we evaluate submissions that report new associations of SNPs or mutations with disease, which is why we don't tend to publish too many of these kind of studies. That said, these ruminations do not take anything from the value of these four studies, which shine some more light on the black box that prostate cancer has turned out to be.

Posted by Juan Carlos Lopez at 04:58 PM | Permalink | Comments (0)

Today's paper in PLoS Medicine reporting on a meta-analysis of clinical data on SSRI inhibitors for the treatment of depression really made a splash.

The article, by Irving Kirsch and his colleagues, showed that, when you look at data from 35 randomized clinical trials testing the efficacy of four of these "new-generation antidepressants", the only differences between the drug and the placebo groups are seen in severely depressed patients.

Although this is not the first time that a meta-analysis has provided evidence against the eficacy of SSRIs, it is perhaps the largest study of its kind available so far, immediately fuelling existing concerns about their widespread use in medical practice.

Not unexpectedly, the companies that sell the drugs have already issued statements supporting the efficacy of their products, pointing out that the meta-analysis didn't look at all of the available data. It wasn't clear, however, if the companies were referring to postmarketing surveillance data, something that is entirely possible, as the paper was based strictly on data received by the US Food and Drug Admnistration (FDA) before approval of the drug.

In any case, this is not the first time that we experience this scenario. You can bet that we will now start hearing accusations of negligence against the FDA for approving medicines that don't work. The public image of pharma companies will be further tarnished by negative claims against their products. Psychiatrists will have to reassure their patients, trying to encourage them to remain compliant. Iin fact, some associations of psychiatrists have already issued statements urging patients not to stop taking their medications until they discuss the situation with their doctors.) And people with depression? Well, I guess they'll have every reason to be depressed.

Now, is it really the case that these drugs don't work but in a small subset of patients? These drugs are globally available, and several world regions have their own regulatory agencies, each of which carries its own analysis of efficacy before approving a drug. Are we supposed to accuse not only the FDA, but every other regulatory agency of not doing a good job making sure that a drug works? It's possible, but unlikely.

OK, let's say that the lack of efficacy could not be detected with the data submitted to the regulators, but only with the large number of patients that you look at when you do a meta-analysis. Should the regulatory agencies then ask for much larger (and therefore much more expensive) trials before approving an antidepressant? Maybe, but then it might be too harsh to use a post hoc analysis that had the opportunity to look at data from at least four different companies to then rebuke the FDA for their approval of the drug or each of the individual companies for their trial design.

To my mind, the key issue now is to see what the regulatory agencies are going to do after the publication of these findings. Will they look at postmarketing surveillance data to try to confirm or rebut the alleged lack of efficacy? Will they modify their approval of the drug so that it is only prescribed to the small subset of patients in whom an effect was observed? In several Nature Medicine Editorials, some of which are here (1, 2, 3, 4, 5), we have been critical of the FDA's leadership and commented on the need of the agency to regain the confidence of consumers. So, the publication of the PLoS Medicine paper should not necessarily be construed as a new embarrassment for the FDA, but as a fresh opportunity for the agency to show that it can respond to public concerns, and handle the situation efiiciently and wisely.

Posted by Juan Carlos Lopez at 03:39 PM | Permalink | Comments (2)

It's always gratifying when something you published in your journal is regarded by others as an important contribution. This report in yesterday's New York Times discusses extensively the trial we published last year showing that an agonist of metabotropic glutamate receptors was beneficial in people with schizophrenia.

It's a shame that the NYT didn't identify Nature Medicine as the place in which the original paper was published, but so be it. I'm delighted to see that the findings are receiving the attention they deserve.

Posted by Juan Carlos Lopez at 04:35 PM | Permalink | Comments (2)

"How did you get into publishing and how do I pursue a career in that field?" As the cliché goes, I wish I had a nickel for every time I've heard that question.

So, lazy as I am, I thought I would write down an answer to the second part of the question (how I specifically got into publishing is too uninteresting to write about), so that next time I get an e-mail asking me for advice on the subject I simply send a link to this post.

There are different ways to get into publishing. Let's start with copy editor. In broad terms, copy editors are in charge of correcting the style and language of the articles we accept prior to publication, as well as making sure that the changes made by the authors when they review their proofs are correctly incorporated. As language is such an important part of the job, employers tend to prefer people whose first language is English. In the case of scientific journals, scientific training is definitely a plus. However, if you have a PhD or postdoctoral experience, this position may not be for you, as you may not find it particularly stimulating from the scientific point of view. Furthermore, employers may find you overqualified for the position.

If you want to stay in closer contact with the science, there are several options.

In journals that have professional editors, such as the Nature journals, titles from the Cell Press stable and Science, research editors read submissions and decide whether something is worth sending out for external review by experts in the field. For this job, a broad understanding of and interest in science is very important. It is also necessary to be able to express your ideas (scientific and otherwise) clearly. And crucially, you must have a very thick skin, as authors don't like it when you send them a rejection letter (which happens most of the time), and they can be very aggressive in their interactions with you. For this position, we normally hire people who have 4-5 years of postdoctoral experience, but there have been cases of people who join us after relatively brief postdocs.

Another class of professional editors are reviews editors, whose job is to think about review ideas, commission articles from suitable authors, developmentally edit the papers and organize the peer-review process. Scientifically, the requirements for the position are similar than those for research editors, although our company has sometimes hired people straight from their PhD with no post-doctoral experience. The reviews editor job can be construed as more creative than the job of a research editor -- you try to develop a useful review article, as opposed to trying to find what's wrong in someone's work as a reason to turn it down. Owing to your need to develop the articles you receive, your command of English and your attention to detail need to be very good, probably more than in the case of a research editor. At Nature Medicine we don't have a reviews editor, but we have a News & Views editor, whose job is similar to what I just described.

For both jobs, it's very useful to be socially skillful, as you need to develop good relationships with the community so that they agree to write review articles, act as referees and/or submit their research to your journal. Last, all of the above jobs (particularly copy editor) require you to have the ability to work to tight deadlines -- the journals need to come out on dates that have been established at least a year in advance, and these deadlines are rather firm.

In none of these jobs appeals to you, some publishing firms recruit other types of editors, which are variously referred to as managing editor, executive editor and so on. These people may or may not make scientific decisions on papers. Instead, they often act as liaisons between authors and the editorial board of the journal -- the scientists who ultimately decide what can be sent out to peer review and choose the referees. Depending on the journal, the managing editor may also be responsible for coordinating the production process of the publication, acting as manager of the copy editors and production staff, interact with the advertising and marketing departments, and other activities that don't necessarily require you to have a PhD. For this kind of position, in fact, it varies a lot whether your scientific background is relevant or not, although I'd say that, more often than not, it is relevant.

Last, but certainly not least, there are science journalists -- people who often work for a newspaper or other periodical, either as member of staff or as freelance writer, and whose job is to report on scientific advances for the readership of the publication. Some of these journalists have a very sophisticated understanding of science, whereas others are generalists who write about science the same way they write about politics or art -- in very broad terms for a very broad audience. The key issue here is that these people tend to be journalists, not scientists. In other words, you need a degree from journalism school to get one of these jobs. That said, if you want to be a freelance writer, you can get away without a journalism degree, provided you can write in a journalistic style. Some of the people who have written in the past for Nature Medicine's News section fall in this category of scientists turned journalists, but our News editor, who is responsible for choosing the stories we'll cover every month and for editing the work of our contributors, is a journalist by training.

In part II of these post, assuming there's interest and that my colleagues in the journal don't veto the idea, I'll tell you a bit about how we go about recruiting someone when there is an opening, in case you ever need to interview for one of these jobs.

Posted by Juan Carlos Lopez at 04:30 PM | Permalink | Comments (1)

In addition to the Insight on Cardiovascular Disease, edited by Nature Medicine's own Michael Basson, a couple of papers caught my attention from this past Thursday's issue of Nature.

First, the analysis of multiple sclerosis (MS) lesions by laser-capture microdissection and proteomics, which led May Han and colleagues to identify two potential therapeutic targets for the disease -- tissue factor and protein C inhibitor -- both of which participate during coagulation. Indeed, the authors went on to show that blocking the action of thrombin (which signals downstream of tissue factor) or administering activated protein C (to counter the increased levels of its inhibitor) ameliorated pathology in an animal model of MS. The image below, from the Nature paper, shows astrogliosis in a chronic MS plaque, revealed by and anti-GFAP antibody.

Second, the discovery by Xiaoyong Yang and colleagues of a link between O-GlcNac transferase and insulin resistance. We already knew that glucose flux through the hexosamine biosynthetic pathway leads O-GlcNac transferase to attach the sugar O-linked beta-N-acetylglucosamine (O-GlcNac) to proteins, thereby acting as a nutrient sensor. The new study shows that O-GlcNac transferase has a binding site for phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3), a key mediator of insulin signaling. Upon binding, PI(3,4,5)P3 recruits O-GlcNac transferase to the plasma membrane, where it sticks O-GlcNac to proteins of the insulin signaling pathway, reducing their responsiveness to insulin (see the figure below, which I borrowed from the paper; O-GlcNac transferase is labeled as OGT). In vivo, liver overexpression of O-GlcNac transferase causes insulin resistance, pointing to the likely functional relevance of this mechanism.

Posted by Juan Carlos Lopez at 03:25 PM | Permalink | Comments (0)

Two sets of papers caught my attention over the past couple of days. Apologies if they are old hat for those of you who work in these fields. It's hard to keep up with all the ToC alerts I get.

The first is a doublet from Nature on the mechanism whereby certain tumors acquire resistence to chemotherapy. The studies, by Wataru Sakai and colleagues and by Stacey Edwards and colleagues focused on tumors that carry mutations in BRCA2 and are therefore sensitive to platinum compounds like cisplatin. In some cases, these tumors develop resistance to cisplatin, and what both studies show is that the development of resistance depends on the appearance of new mutations in BRCA2, which restore the open reading frame of the protein. Although this is perhaps not incredibly surprising, particularly because similar secondary mutations had been observed in cases of resistance to imatinib in leukemia, this finding has obvious clinical implications for people who become unresponsive to cisplatin.

The other paper, by Marielle Gold and her colleagues in PLoS Pathogens, reports on the existence of a novel population of human T cells that innately recognize Mycobacterium tuberculosis (Mtb). These cells, which the authors isolated from newborns who were very unlikely to have ever been exposed to the bacterium, exist at relatively high frequencies and respond to Mtb-infected cells by producing IFN-γ. The authors assert that this is the first demonstration of a human innate pathogen-specific T cell and refer to preliminary experiments showing that other thymocytes can also respond to other pathogens including Staphylococcus aureus and Escherichia coli. How this innate recognition comes about in the fisst place strikes me as a pretty interesting question for follow-up studies.

Posted by Juan Carlos Lopez at 03:43 PM | Permalink | Comments (0)

The AAAS meeting last weekend was abuzz with events related to the US elections, including a forum where representatives of the Clinton and Obama campaigns presented their viewpoints of science policy.

I've been having trouble figuring out the difference between the two candidates' positions on any issue, so was eager to learn something from from the source.

Perhaps reflecting the stereotypes of the two campaigns, the Clinton representative, Tom Kalil, presented a more detailed, wonky set of proposals. Kalil was Deputy Assistant to former President Bill Clinton for Technology and Economic Policy. He said Clinton would double the budgets of specific agencies, including the National Institutes of Health, the National Science Foundation and the National Institute of Standards and Technology. She also would establish a $50 billion "Strategic Energy Fund" in part to promote renewable energy.

Obama's representiative, Alec Ross, looked about 20 years old and is the exective vice-president of One Economy, a nonprofit corporation that seeks to expand broadband technolgy. Perhaps in keeping with that, he emphasized computer technology advances, such as an expansion of high speed internet access. But he also said Obama planned to double funding of basic research and establish a $150 billion ten-year energy program.

Both candidates proposed programs to create electronic medical records--something that could also aid researchers conducting clinical trials.

I must admit I left still wondering essentially what the difference is between the two candidates. And I also wish someone from the McCain campaign could have been there (his campaign said they had scheduling conflicts). So I'm all for an effort to get the candidates together for a "Science Debate" an idea that is gaining a lot of momentum (although maybe not among the candidates themselves).

What do you think? Is science important enough for it's own debate? Are you ready to get behind the effort?

http://www.sciencedebate2008.com/www/index.php

Posted by Charlotte Schubert at 12:41 AM | Permalink | Comments (0)

It has been too long since I have blogged, and going to a meeting seems like a good reason to start up again. I spent the weekend in Boston at the annual meeting of the American Association for the Advancement of Science. 



The most interesting talk, by Angela Belcher at MIT, had on the surface very little to do with medicine. But it was so cool I have to blog about it.  Well, Belcher says she is applying her techniques to medical devices. And she does work on viruses—bacteriophage, to be more exact. 



Phage are viruses that infect bacteria, and it’s easy to make zillions in a test tube.  Belcher is using phage engineered to produce various proteins on their coats that nucleate the formation of inorganic materials—such as the building blocks of a solar cell, or lattices of cobalt oxide to create a battery electrode. 



She uses a technique often used by biologists, called ‘phage display’ in which phages within a large population each display unique peptides on their coats.  She can then screen for the phages that have the properties she is interested in, such as the ability to seed the formation of inorganic lattices of a particular confirmation. She further hones the properties of her phage—and the materials they seed—by natural selection.

She says she is inspired by the designs of nature—such as that of the abalone. Abalone shells are primarily calcium carbonate, a substance that by itself is soft and chalky. It's proteins within the shell that prompt the calcium carbonate to assume a particularly tough and resilient conformation. 



Her goal is to generate materials that are ecologically friendly, replicable, and assemble at room temperature. She also wants her materials to be upscalable—something her lab could achieve, for instance, with successive dips of an electrode in a beaker of phage, and a beaker of inorganic material that assembles into place using the phage as a template. 

Posted by Charlotte Schubert at 12:22 AM | Permalink | Comments (0)

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)