When I was a small child, I had an earache, so I asked my dad for a Band Aid. The source of my discomfort was an inner ear infection, so antibiotics would have been more on the mark—but a Band Aid seemed better than nothing. The placebo effect is powerful.

As reported in the New York Times this week, there is now a placebo pill designed for children that you can buy. The product is called Obecalp (placebo spelled backwards) and available online for $5.95 a bottle. Each cherry-flavored chewable Obecalp tablet is essentially a lump of sugar in a medicinal disguise. “Invented by a mommy,” says the website advertisement, featuring a headshot of the product’s inventor, a mother of three from Severna Park, Maryland. The implication is that, if a mom came up with the idea, then it must be okay to give fake meds to your children.

But how will mom (or dad) explain the situation when their children discover that the magical tablets they received for headaches, stomachaches and sore throats were always a hoax? The use of placebos sends an uncertain message to children. They will eventually know that their parents deceived them. Moreover, there is something unnerving about looking to pills for the answer to every ailment. There are other ways to comfort children. In some cases they simply need a dose of attention to feel better. Perceived physical ailments may also be a sign of emotional or mental distress that a sugar tablet cannot fix.

Doctors admit to prescribing placebos, according to a study published earlier this year in the Journal of General Internal Medicine. Researchers at the University of Chicago surveyed 466 physicians from three Chicago-area medical schools and found that nearly half of all respondents had used placebos in their clinical practice. One of their most common reasons for doing so: “to calm patients.” Something is wrong with a medical system in which patients need pills and injections to feel tranquil and reassured that they have received adequate care. It’s hard to imagine that adding more pills to the market, even if they are fakes, will help change this culture.

Posted on behalf of Coco Ballantyne

Image by Fillmore Photography via Flickr

Posted by Roxanne Khamsi at 10:21 AM | Permalink | Comments (2)

When it's not a trip, my day job gets in the way of my posting something to Spoonful. This week we closed the June issue of Nature Medicine, and right now I'm at the airport, about to start another 'tour'. So, while I wait for the PA system to herd us to the plane, I thought I would blog about my day as a juror.

For the second year running, a very dear friend of mine invited me to be part of the jury for an award that her organization gives to young scientists. And for the second year running, it turned out to be a fun day out.

The award recognizes young scientists in all disciplines. As a result, the jury (composed of nearly 40 people) was a very eclectic mix of basic scientists, engineers, physicists, matemathicians, you name it. There were even editors like me, whose only expertise lies on the inexact science of rejecting papers.

The discussion, which took the best part of the day to go over something like 40 finalists, was free-form. One of us would go over the candidate, and the rest would ask questions or bring up caveats about each of them, trying to understand the importance of their contributions.

I must confess that, halfway through the session, I started feeling sorry for those scholars who have to decide on, say, people's grants.

In the case of our jury, we found it was pretty tricky to decide how much weight to give to the candidates' letters of recommendation, to their number of papers and the journals in which they were published (someone referred to the high-profile journals as 'vanity journals', which struck a chord with me), to the number of citations, and to a plethora of factors that, one way or another, represent the blood, sweat and tears of a scientist.

Does a scientist who has three patents in the past five years, but only three papers, each of which had been cited just three times deserve more recognition than the scientist with five Nature papers and 1000 citations? Does a scientist who works in a hot field and has made nice contributions deserve more credit than another one who works in a less glamorous, lonelier field and has made equally profound contributions?

These questions aren't always easy to answer, but my friend got it right because she quickly realized that there's strength in numbers. So, if you have 40 judges from different fields and with different ways of evaluating science, chances are that the truly outstanding pieces of work will triumph over the rest. I'm therefore confident that our eclectic group made the right choices.

But returning to those grant evaluators, I was saying that I felt sorry for them because, if we managed to screw up and made a mistake yesterday, it won't make much of a difference for the scientists who should have won and didn't despite our best efforts. They'll carry on and will still be great scientists. In the case of grant decisions, though, getting them wrong can lead to a lab's shutdown, to fired postdocs and to truncated careers, which, alas, are becoming more and more common.

Photo by JasonUnbound

Posted by Juan Carlos Lopez at 06:39 PM | Permalink | Comments (6)

Time to return to the issue I brought up the other day regarding the open-access debate. Some people think that publishing firms rip people off by taking scientific information from the community and selling it back to the very providers of this information. This ignores, of course, that some journals such as the Nature titles, Science and the Cell Press stable add value to the content they publish by filtering scientific information in such a way that their imprimatur is (in most cases) guarantee of quality. Ironically, as these journals have professional editors, who are the public face of the titles, they tend to receive most of the negative feedback regarding our business model.

But, fine, let's play along and ignore the fact that we at the Nature journals add value to what we publish. The purpose of this post is to illustrate that, even though we charge for our content, our publications are very cost-effective for our readers.

Take a look at this figure from an independent study by Credit Suisse/First Boston. It shows how much the University of California system (a very important user in terms of sheer volume) had to pay every time a member of their community used our journals online, and it compares this cost across different publishing companies.

As you can see, whereas the cost of using our journals is approximately one nickel per use, other publisher's products cost well over an order of magnitude more (almost two orders of magnitude in one case).

I'm sorry that I had to blank out the name of the other publishers; I didn't feel comfortable fully disclosing them. In any case, I'm sure you suspect who they might be.

So, next time you think that the Nature journals rip you off, think about this graph. Do the Nature journals really deserve all the flak they receive, or do we actually give people their money's worth?

Posted by Juan Carlos Lopez at 05:54 PM | Permalink | Comments (2)

The other day a friend of mine sent me this link to an somewhat somber article in the UK's Independent, which wondered if we should stop looking for an AIDS vaccine, following the failed Merck trial of a few months ago.

The article polled 35 British and American AIDS researchers and found that, in general, they were markedly less optimistic about the short-term prospects of finding an HIV vaccine than they were five years ago. The Independent published the results of their poll one month after a US government-sponsored summit on HIV vaccine research, about which our very own Roxanne Khamsi wrote in the new issue of Nature Medicine.

I don't know that one has to be so pessimistic. In fact, it seems that the meeting was very helpful in pointing to the limitations of the existing animal models as predictive of efficacy in humans, something that, sadly, is the rule rather than the exception when it comes down to creating models of human disease. In the context of the Merck trial, this past December we wrote this editorial, in which we indeed agreed that the field faces serious problems, but tried to conclude on an optimistic note pointing to the fact that the development of the polio, measles and hepatitis B vaccines took 47, 42 and 16 years, respectively.

Sure, the failed trial was a setback and one must take a hard look at the direction in which the AIDS vaccine field is going (in fact, very soon we'll publish a Perspective on this topic), but this is hardly enough of a reason to call it a day. Paraphrasing Mark Twain, I'd say that rumors of this field's death are being greatly exaggerated.

Bust of Mark Twain. (Image by wallyg)

Posted by Juan Carlos Lopez at 10:07 AM | Permalink | Comments (3)

The 'News and Views' section of Nature Medicine has a new look!

This month you’ll see we’ve introduced three new columns: Bedside to Bench, Bench to Bedside, and Community Corner. These columns are available this month without a subscription.

Cancer researchers Daniele Krause and Richard Van Etten anchor the new section with a 'Bedside to Bench' column examining how recent clinical trials hint at how to kill the cancer stem cell in certain blood disorders; eliminating this source of tumor cells has the potential to lead to improved cancer treatment. Their analysis exemplifies the goal of the new column: to examine the basic research implications of a recent clinical finding.

So far the response from the community has been positive about the ‘Bedside to Bench’ column. One of our readers, Evan Snyder, a physician-scientist at the Burnham Institute in La Jolla, California, said he has initiated a seminar series with this same intent, examining how to develop testable hypotheses about basic science from clinical observations. We’d love to hear if others in the community have similar programs, or how they feel about this approach to asking the right scientific questions.

The other new column, ‘Bench to Bedside’ takes the more familiar route of examining the clinical implications of a basic research study. This month, Neil Shah complements Van Etten and Krause's column by highlighting how resistance to chemotherapy develops in tumors deficient in the well-known cancer genes, BRCA1 and BRCA2. Shah takes the assignment to heart, examining in depth how patient treatment might change given this greater mechanistic understanding.

Our third column, ‘Community Corner’, scans a small segment of the research community for their response to a recent biomedical study—in this case two reports suggesting how environmental toxins might affect the development of autoimmunity. Experts with three different backgrounds each found something unique about the study.

To make room for the changes we have largely discontinued news and views on papers published outside of Nature Medicine. I’ve been wondering what to do with this format ever since, to my dismay, finding that Nature Medicine, Nature Immunology and Nature had all published a news and views on the same paper. A speaker at a conference—rightly, to my mind—mocked such excess. Since the launch of Nature Medicine more than ten years ago many other journals have begun to present commentaries on their strongest papers, particularly those with a biomedical slant. Although I like to think I provide superior editorial and screening functions as an editor, that is mostly vanity---basically, with a click on a web browser you can find the commentary you need. In my mind, too much duplication risks redundancy and stretches the editorial resources of the scientific community.

Although we’ve dropped some news and views, we still have a duty to our readers to alert them to the hottest biomedical research in the previous month. So we’ve expanded our research highlights section to two pages, and added a short column highlighting papers within the Nature Publishing Group. One drawback to our process is that we rarely highlight papers that we have rejected, in order to avoid sending mixed signals to researchers who submit their papers. I must admit though, we do sometimes reject some interesting papers—often for reasons unrelated to their overall coolness, but for reasons nonetheless appropriate for our journal, such as a lack of mechanistic insight or poor in vivo data. So, these papers aside, I like to think we provide a quick snapshot in the research highlights section of the papers most relevant to that elusive beast dubbed 'Translational Research.'

Our aim with the research highlights is to provide breadth in our coverage.

Our aim with the three new columns is to provide the depth—exploring the biomedical literature with quality synthesis.

We’d like your help in this venture. If you are a researcher who has formulated a testable, reasonable—and compelling—hypothesis about the mechanistic basis of disease, based on recent clinical findings, consider submitting a proposal for a 'Bedside to Bench' column. And if you get a chance to read the new columns, send us your feedback. This is a work in progress and we hope it develops in a way to best serve the biomedical community.

Posted by Charlotte Schubert at 03:32 PM | Permalink | Comments (0)

A couple of people were asking me the other day why it is that I post some comments that we receive on this blog that are frankly bizarre. I must confess I don't know. I guess I must have a soft spot for people who are "out there", if you know what I mean.

Come to think of it, it must have started back when I was a student and needed to read the print edition of Nature, as there simply was no internet. After the classifieds, at the very end of the book, there was a section called "Scientific announcements". And every month or so, a man called D.B. James, based somewhere in Wales, would publish his scientific ideas, which, presumably, didn't meet with much support from the Nature editors. Does anyone else remember him? This is a sampler of his work, collected from issues of Nature as recent as late 2001.

When I lived in Britain, I met a scientist from the MRC who had the intention to create the D.B. James Appreciation Society, but I don't think his plan prospered. Or at least I think so, as I never got an invitation to join, and soon after that Nature decided to stop publishing James' snippets. Too bad.

At around the same time, during my stint at Nature Reviews Neuroscience, I had a closer interaction with an author whose writings were also difficult to categorize. Based somewhere in Georgia, in the US, and signing under the pseudonym Ken Al Sifr, our correspondent used to write to us every month. His letters were always flawless, even though he wrote them in a typewritter, and I seem to recall that he was particularly fond of using green ink whenever he needed to make a note on the margins of his text. In his letters, which he also sent to Nature, Nature Neuroscience, Nature Medicine, and surely to Science and Neuron, he would criticize in no uncertain terms many of the papers published by said journals, pointing us in the direction of findings published decades ago, which, according to him, compromised the novelty of the new contributions and showed that we had no idea about what we were doing running the journals.

I now regret the fact that I didn't keep any of his letters; I destroyed all of them when I move to my current job at Nature Medicine. I do remember, though, that some of them had drawings that could be construed as sexually explicit. Others included pictures of the NRN editors (which, as per the style of our reviews journals, continue to appear in every print issue). In yet others, he would paraphrase famous poems such as Marvell's 'To his coy mistress':

"The brain's a fine and private place
But none, I think, do there embrace."

However, not all is lost. Ken Al Sifr is the author of two books, "Too many neurons" and "Your brain glossary for the brain decade", published by Vantage Press. I managed to purchase both of them, and can share with you two of his definitions from the second book. I hope they give you an idea of the content of his letters. Enjoy!

P.S. Incidentally, as far as I know he continues to write to the NRN editors. Hopefully they don't make the same mistake I made, and choose instead to keep such jewels.

Posted by Juan Carlos Lopez at 03:46 PM | Permalink | Comments (9)

Today's Boston Globe ran a profile of Ram Sasisekharan, the MIT-based senior author of the papers published on 23 April in NEJM and in Nature Biotech., identifying the contaminant in heparin that caused adverse effects and even killed scores of people earlier this year.

Through careful structural analysis, Sasisekharan and his colleagues found that the culprit was oversulfated chondroitin sulfate and that, owing to the chemical nature of the contaminant, conventional screening methods cannot differentiate between clean and tainted lots. Then, using in vitro and in vivo approaches, they went on to show that the mechanism of action of the contaminant involved the activation of the kinin-kallikrein and the complement systems.

It was an remarkable tour de force, particularly considering that, according to the profile, the FDA approached Sasisekharan with the project only in late February, the published submission date of the Nature Biotech. paper is 21 March, and the mechanistic work had apparently been finished by early April. Pretty impressive stuff that, I hope, will inspire those prospective Nature Medicine authors whom we invite to resubmit their work and, alas, are occasionally scooped.

Ram Sasisekharan (Photo: David Shopper, The Boston Globe)

Posted by Juan Carlos Lopez at 02:06 PM | Permalink | Comments (0)

As I was saying yesterday, several people have made comments on the talk I gave in Madrid last month, as well as on the related blog post. Considering that we don't really censor people who write to us and that we are very receptive of feedback, I find it amusing that few of these comments have been posted on our blog, and that people prefer to cut and paste from what I wrote on their own blogs, but so be it.

Most of the comments have centered on what I wrote about the fact that open-access publishing is not the only alternative to scientific publishing, but just one of several models. Some people take strong exception to this idea to the point of feeling violated by the fact that we "sell back" the science they produce. Others acknowledge that we provide a filtering service, but point to the fact that the peer-review process is free. And a third group of critics argue that the problem with scientific publishing can be summarized in three words: Nature, Science and Cell. Each of these criticisms deserve some comment, and I'll start with the concept that peer-review is free.

Last August we published an editorial and a blog post called "Why review?". In them, we went over some of the reasons why people choose to review articles for scientific journals despite the myriad of other things they could do with their time. Particularly relevant to our current discussion is the fact that, although it is true that scientists don't get any money in exchange for their effort, they get enough compensation from the access they gain to privileged information about what their colleagues and their competitors are doing. For many scientists, to exert influence on the direction and standards of their field not only through their own work, but also through the comments they give their colleagues on their research is enough reward to make reviewing papers worth their while.

Now, there is information and there is information. If scientists choose to review papers for a given journal, it is because, a priori, they think that what they're gonna read will be of legitimate interest to them. So, many scientists have different thresholds to agree to review for certain journals. Indeed, I've met scientists who may agree to review for Nature, but nor for Nature Medicine, and others who agree to review for Nature Medicine, but not for more specialized journals. Why? Because, when they receive an invitation to review from us, their initial expectation is that they are likely to read something of broad interest or "otherwise, Nature Medicine would not be considering this paper for possible publication".

A corollary of this is that, if we send too many papers out for review, including some that may not be particularly interesting from the start, then we'll start finding that more and more people turn down our invitations to review manuscripts. In other words, being less selective on what we send out for review will quickly erode the expectation of quality that our reviewers have developed. They'll start feeling that the compensation they get from reviewing for Nature Medicine is not enough, and will find something else to do with their time.

A second corollary is that, in the absence of a certain guarantee that the paper will be of interest to a reviewer, the reviewer will almost certainly not touch it. This, in fact, is one of the reasons why those initiatives to publish papers online to let the community read them and evaluate them have not been successful so far -- many of the most thoughtful reviewers will choose to not spend time on those manuscripts in the absence of some initial screening that separates the wheat from the chaff.

In summary, the peer-review process is free, but only in a most superficial way. Reviewers get compensation from evaluating manuscripts for high-profile journals, provided that an initial screening of manuscripts takes place and truly identifies the contributions that will be of interest to the reviewers. The golden rule that there is no such thing as a free lunch also applies to our trade.

Definitely not Nature Medicine's idea of lunch. (Image by malias.)

Posted by Juan Carlos Lopez at 09:46 AM | Permalink | Comments (7)