There are I think a few causes. Number one is an immense labor-intensiveness of biomedical research. Unfortunately, we are far from fully automating the routine laboratory techniques, and good technicians are a luxury that only the richest labs can afford. In effect, great young minds in their most intellectually productive years spend most of their time doing mundane, mind-numbing tasks such as changing the wash on a Western blot, or doing minipreps of plasmids. Sure, you can try to think or read in between the washes or while your samples are spinning down, but then you will likely mess up your experiment and you have to start over.

Related to that is another cause – the extreme bottom-heaviness of the hierarchical pyramid. The overwhelming majority of researchers in biomed are required to do what their superiors “suggest” they should do, rather than following their own curiosity and exploring on their own. Only one in 10 graduate students in the US gets an independent position as a professor at a research university. That means again that most of these people will never have the freedom to go where they really feel their ideas are guiding them.

The third cause is the funding mechanisms for biomedical research. I am not very familiar with other countries, but the main funding agency in the US, the National Institutes of Health, doesn’t really want to fund innovative research guided by curiosity. Their agenda is to help fight diseases, not to sponsor some bright young wackaloons who think that the world is a fascinating place and want to discover how stuff works. And so there is a tendency in the NIH to select grant applications that are directly related to some sort of a disease, even if they are clearly not particularly innovative and will result in the humanity learning very few new things. The funny thing is that the grants are peer-reviewed and it is other scientists who rate grants based on these utility criteria, even if they realize that best science results from people being allowed to do exciting rather than utilitarian work. Grant mechanisms supposed to promote innovative, high-risk science, such as R21, are a total joke and they are graded according to the exact same criteria as R01s, ie. utilitarian value and feasibility first, then innovation and curiosity. In consequence, even the people at the top of the pyramid have their hands tied by their peers who prefer to promote incremental, low impact science.

Is the system broken? I don’t know. Just because I get frustrated at times with all the grind at the lab bench and with not getting to do what I want scientifically, doesn’t mean that the system is unfair or not optimally designed. Still, I feel a little robbed of my curiosity and my enthusiasm, and when I read about Levitt and Feynman, I can’t help wondering if there is a way to redesign the system so that people like myself could treat science as a never-ending adventure the same way they do.

WHAT????? Legalize cocaine, heroin, and amphetamine???? Let me quote some statistics: an estimated 3 million people in the US currently suffer from serious drug problems. That’s 1 in every 100  citizens, whose life is seriously impaired by use of illicit drugs. There is no doubt that drug use would increase after legalization – even the authors of the article don’t deny that. We don’t even have a ball park estimate by how much it would increase, but let’s say that it is 10%, which would be an extremely optimistic estimate. That would mean that by legalizing drugs you are basically condemning one in every 1000 otherwise perfectly healthy people to a serious debilitating disease which deprives them of their free will, distorts their perception of reality, and results sooner or later in a terrible humiliating death. Not only that – my prediction is that it is the children who would suffer the most. Hard drugs, such as crack, are not easy to come by for high school kids nowadays. Sure, if you really want to get them, you will, but for most kids the scare of talking to a dealer and the high price are enough of a deterrent. If these drugs were legalized, they would become as easily accessible to these kids as alcohol is right now – that is very easily. Would you rather your child/little brother/nephew got drunk with beer on their prom night and in the worst case scenario vomited all over the place, or that he or she got high on crack and died of overdose?

These deliberations aside, the statement that we are losing the War on Drugs, is simply FALSE. It all depends on how you define “losing”. If losing means being unable to completely eliminate the drug problem, than yes, we are losing. On the other hand, we are successful at keeping drugs hard to come by and expensive, we are preventing some poor kids from being lured into the vicious circle of addiction, we are saving some families from the terrible fate that is dependence of one of its members. In that way, we are winning. We should be thankful to all the people that fight this war for us – they are helping fend off evil that is drug dependence, and they are paying for it dearly, sometimes even with their lives. Saying that their noble efforts make no economic sense is not a good way to express our gratitude! The articles such as the one in The Economist show how much our money-driven thinking and tendency to put a number on everything makes us forget the basic differences between right and wrong.

If you are still not persuaded, let me ask you this question: If a group of terrorists said they would cease all violent actions if you agreed to poison one citizen in every thousand with a known deadly neurotoxin, would you even start to negotiate? The mythical Athenian hero Theseus would know the answer to that question. Are we going to have the guts to follow his example? Or are we going to listen to all these pseudo-economists and hippie-libertarians and just give up?

As for the arguments for drug legalization, I’ve heard them all – they range from total bullshit through conventional wisdom strawmen to libertarian “I should be able to hurt myself if I want to” rants. If there are real logical arguments against the war on drugs, I am not aware of them, so please be so kind as to enlighten me.

Nobody in their right mind will deny that there is a lot of things that are wrong with Big Pharma. Shameless lobbying, physician bribing, exorbitant drug prices all give pharmaceutical industry giants a bad rap. Are patents to blame? Boldrin and Levine argue that they play a big part.

A substantial portion of the chapter does not concern patents at all. The authors repeatedly go off on a rant on just about every aspect of the evil corporate culture of the pharmaceutical industry. All these issues are clearly off-topic, so I will concentrate on their rebuttal of the necessity for drug patents.

First, they present a rather tedious (they themselves admit it) history of patentability of drugs throughout the world. By analyzing the history they attempt to show that there is either no correlation or a negative correlation between patentability of drugs and innovation in the industry. By means of such demonstration they hope to call in question the intellectual property supporters’ argument that patents are necessary to promote new drug discoveries. However, I would hardly call their examples scientific. They provide hearsay “evidence” that despite lack of patent protection, companies in Switzerland, Germany, and Italy innovated no less than companies in the UK and USA, where patent protection was present. Also, they analyze the example of Italy before and after introduction of patent protection for drugs. Supposedly, in the 20-year period before patent protection was introduced, Italy contributed 9.28% of the world’s newly discovered active chemical compounds, and in 3 years following that period, that percentage fell to 7.5%. These examples, however, are rather meaningless for the following reasons: (1) they completely ignore other economic factors in the same period of time, (2) they are hardly statistically sound (comparing 20-year period to a 3-year period seems rather ridiculous), (3) from the point of view of pharmaceutical technology and medical law they can be considered ancient history, and (4) most importantly, they ignore the fact that despite the lack of protection in their countries of origin these drugs DID have patent protection everywhere else, including the USA, arguably the biggest single world market for pharmaceuticals. So in effect it didn’t matter whether where the drug was made, but rather where it was sold.

After their analysis of historical cases, Boldrin and Levine cite an economic study on the social benefits of patents which they claim basically says that drug patents are not in the society’s best interest. I figured I was kind of dumb, because hard as I tried I didn’t understand what the hell they were talking about. And so like a proper scientist I decided to go to the source – the paper itself. I had a bit of a hard time finding it because Boldrin and Levine misspelled a name of one of the authors, as well as the name of the pharmaceutical company which sponsored the study (!!!), but I ended up actually finding the abstract. I am going to quote this abstract in its entirety for reasons that will soon become apparent (I added the emphasis):

“Napsterizing” Pharmaceuticals: Access, Innovation, and Consumer Welfare
James W. Hughes, Michael J. Moore, Edward A. Snyder
We analyze the effects on consumers of an extreme policy experiment — Napsterizing’ pharmaceuticals — whereby all patent rights on branded prescription drugs are eliminated for both existing and future prescription drugs without compensation to the patent holders. The question of whether this policy maximizes consumer welfare cannot be resolved on an a priori basis due to an obvious tradeoff: While accelerating generic entry will yield substantial gains in consumer surplus associated with greater access to the current stock of pharmaceuticals, future consumers will be harmed by reducing the flow of new pharmaceuticals to the market. Our estimates of the consumer surpluses at stake are based on the stylized facts concerning how generic entry has affected prices, outputs, and market shares. We find that providing greater access to the current stock of prescription drugs yields large benefits to existing consumers. However, realizing those benefits has a substantially greater cost in terms of lost consumer benefits from reductions in the flow of new drugs. Specifically, the model yields the result that for every dollar in consumer benefit realized from providing greater access to the current stock, future consumers would be harmed at a rate of three dollars in present value terms from reduced future innovation. We obtain this result even accounting for the stylized fact that after generic entry branded drugs continue to earn significant price premia over generic products and hence recognizing that Napsterizing does not completely eliminate the incentives to innovate.

What the hell? Turns out Boldrin and Levine took the study and arbitrarily changed the assumptions made by the authors in constructing their model, and came up with different numbers, which completely contradicted the authors’ original conclusions. What’s more, they made it seem like the assumptions were in the paper all along. If that’s not outright fraud, I don’t know what is.

Well, let’s move along. Next, Boldrin and Levine set out to attack one of the strongest arguments supporting pharmaceutical patents – high costs of clinical trials necessary to bring the drug to the market. They say that the costs of these trials can go as low as $6.5M. It doesn’t prevent them from stating at the beginning of the chapter that the average cost of clinical trials is $71M. Yes, that’s seventy-one million vs. six-point-five million – a 10-fold difference over a 13-page span. In reality, these costs can easily go up to over $100M (The Scientist ran an excellent article about it a few months ago). And that’s only for a single drug that actually reached clinical trials. Most of the drugs tested do not even go past the preclinical stage, and so all the money spent on R&D of these drugs is lost. Believe it or not that’s the fairly postitive scenario. Some drugs will fail to show benefits after tens of millions of dollars spent on clinical trials. So effectively, the cost of bringing a drug to the market, with all the risk of failure factored in, is enormous.

Boldrin and Levine  end their list of arguments by quoting amounts of money spent on biomedical research by private companies vs. the federal government. They claim that only about a third of all the costs of biomedical research are covered by the industry. However, they completely ignore the fact, that government-sponsored biomedical research is, to a very large degree, basic rather than applied. The hard, risky, expensive, and relatively more mundane work of taking basic research results and making them into actual drugs that patients will be able to benefit from, is almost entirely the domain of the industry. So from a purely pragmatic point of view, one might argue that it is the federal government that  is wasting money on studies that don’t immediately produce solutions applicable to patient care.

So that’s it? Do the authors of this treatise, academic scientists themselves, hope to persuade us with imprecise “conventional wisdom” arguments that don’t even have the pretense of scientific rigor, and then by hijacking a research paper and twisting it around so that it sounds like it supports their case? I’d expect a bit more of an effort on their part, seeing that their ideas are nothing short of revolutionary. But wait, there it is! In the final chapter they propose a genius solution, which will make patents completely  redundant in the pharmaceutical industry, regardless of their actual value right now. They finally acknowledge (despite demonstrations to the contrary in their previous chapter) that developing a drug is expensive. So in order to protect the company from huge losses in the absence of patents, they suggest that the Food and Drug Administration (the agency responsible for registration of new drugs in the USA) should set a price tag on that development process, and that any company willing to produce that drug must pay the inventor that price. In that, they basically reinvent licensing, except now it’s the government who decides what the value of the license is, not the owner of the patent. Just think of what a great opportunity for corruption that is! We are talking tens to hundreds of millions of dollars here, which could be gained or lost in a single transaction. And it would all depend on a signature of a single FDA official!

Let me now share a few personal thoughts that the lecture of Boldrin and Levine’s pamphlet (I am now reluctant to call it a book) provoked. I think their ideas stem from a basic misconception about patents. Ideas are a dime a dozen – here the authors and I will agree. However, the patent is not meant to only protect the idea itself, but, more importantly, the investment an inventor (or their licensee) makes once he or she starts developing an idea into a finished product. In the case of some ideas, the investment may be close to non-existent, in others, such as drugs, it can be gigantic. Getting rid of patents altogether is throwing the baby out with the bath water – it removes the crucial protection every investor will expect before betting their money on an idea. At the risk of disclosing my ignorance about patent law, I would like to propose a solution slightly less drastic than completely getting rid of patents. Instead, we could simply put a clause on every patent that if the inventor cannot prove that either they, or any of their licensees have made substantial investments to bring the product to the market within a set period of time, their patent would be revoked. That would take care of a lot of patent trolling and would allow only truly “expensive” ideas to be protected. Maybe somebody has already come up with that scheme, I don’t know – I am far from an expert in the field. In any case, it seems like a reasonable compromise between promoting innovation and protecting investments.

The whole case reminds me a bit of my discussion with supporters of Open Access publishing. Both them, and Mrs Boldrin and Levine, think they have simple solutions to complicated problems. The simplicity of their solution is so appealing, that their perception of reality becomes completely skewed to support it. They will stop at nothing to prove that their solution is best, because the pink spectacles they view the world through make them completely impervious to all the evidence to the contrary. How amazingly fragile a human mind is!

To wrap up, let me quote Thomas Jefferson, a one time ardent opponent of the patent system, who later changed his mind:

An act of Congress authorising the issuing patents for new discoveries has given a spring to invention beyond my conception. Being an instrument in granting the patents, I am acquainted with their discoveries. Many of them indeed are trifling, but there are some of great consequence which have been proved by practice, and others which if they stand the same proof will produce great effect.

Either Eric Schadt doesn’t know what he is really doing, or he is not saying everything, but the impression I got was that of vagueness. There are some encouraging signs. Both the interview, and lists of publications on Rosetta Inpharmatics’ (the subsidiary of Merck most strongly tied to the new project) website, and on Sage’s (almost empty) website suggest that the data behind Sage will be three-fold: genetic (SNP, copy number variations), RNA expression (mRNA, miRNA, other non-coding RNA), and clinical. Schadt claims that the amount of data donated initially by Merck is comparable to NCBI GEO, which is almost too good to be true. In addition, the data is more coherent and was collected in a more consistent way than the data on GEO, which is a big advantage. The way I understood it, this seed data is supposed to jump-start a wider initiative where investigators will be attracted by the data already available and will want to expand the platform using their own data. In order to expand the database in an orderly fashion, Sage is supposed to enter into an incubation phase of a few years, where only selected few institutes will be able to contribute and make use of the database, so that potential problems can be identified and tools can be adjusted to be most useful to the wider audience. Apparently, Sage founders want to avoid the situation Novartis created a while back, where they just dumped raw data onto the web and let everybody use it as they saw fit. Sage is aiming for something bigger – they actually want to create a social network of scientists all putting their heads together to tackle important disease-related questions based on widely-available public domain data and tools. I kind of see where they are going with it, but I can envisage a few problems with their approach:

• Difference in culture between academia and industry. The collaborative team-oriented efforts characteristic of pharmaceutical industry may not work out in academia. Academics are very individualistic beings and a very wide collaboration may not appeal to them as much as to industry-bred scientists.
• Problems with keeping the data coherent. They will have to develop ways to accommodate various experimental paradigms under the same umbrella. It is very unlikely that investigators in academia will want to use the exact same protocols they used at Merck, and on the other hand it will be difficult to keep the dataset consistent with the existing database if they allow too many variations in experimental methods. In other words the more scalable the system will be, the less coherent.
• Investigators’ unwillingness to work on improving the system. I’m guessing that Friend and Schadt are hoping that members of the scientific community will keep improving the system and they are planning to build tools that will facilitate it. My concern is that PIs will simply not have the time on their hands to do that kind of a job, which will carry no clear immediate benefits to themselves. Schadt actually acknowledges that as one of the problems they will have to tackle, so I am hoping they will manage to develop some kind of a reward system where people will actually be incentivized to help out.
• The cost. Schadt seems to think that the costs will only be substantial in the beginning, and after that, when all the tools are created, and the community pretty much takes over with very little involvement from the company itself, the enterprise will be pretty cheap to run. I am not so sure. If they intend to keep the system more-or-less coherent, more than a little supervision will be required, and that is never cheap, especially on a scale that they are hoping to achieve.
• Merck involvement. I’m wondering how much will Sage be able to cut off its ties with Merck. Schadt actually admits that they will “maintain some strong collaborations with Merck”. Will that mean that Merck will be eavesdropping on how the community uses the data?

That last point brings up another question: Why would a pharma giant like Merck donate data probably worth tens to hundreds of millions of dollars to the public domain? Here’s a few ideas, some of them recycled from other people’s blogs and comments:

• They desperately need new ideas from basic research to fill in their drug discovery pipeline and so they are trying to facilitate basic research. They cannot, within their own company, get through the wealth of data they have created and cannot follow every lead, so they want other people to do it for them, and then use the results for their more applied research.
• They may count on attracting new talent to Merck from the users of the database (think of the contact list they will be able to create).
• They may be able to “spy” on researchers by “supervising” the effort. I am really looking forward to seeing that User Agreement and Privacy Policy.
• They are trying to earn some good will from the scientific community and the powers that be in hope of future gains.

That is pretty much all that can be said at this point about the initiative. Until anyone outside of Merck/Sage actually gets access to the data, and until plans for the new platform are crystallized and the big grey light bulb actually starts putting on some colors, there is really no point in blogging about it. Oh, wait… I just did, didn’t I? Crap!

Update: There is a nice story in this month’s The Scientist about predictive models in systems biology, a field that could benefit most from a project like Sage. Mind you, the article is about some exotic bacteria, but scientists have been relatively good in the past about scaling things up.

In my last three posts (Part 1, Part 2, Part 3) I have talked about several aspects of Open Access publishing, mostly criticizing what I felt were weaknesses in the model as it stands today. If you haven’t read my posts, I invite you to do so now, before you proceed. I also recommend related posts by Coturnix and Cameron and the discussions that followed, as well as the discussion of my posts in the Science 2.0 friendfeed room.

The feedback I got was mixed – ranging from cautious support, to ridicule and outrage. Most comments, however, were very informative and insightful, if not always supportive of my way of thinking. I enjoyed the whole experience thoroughly. It is a rare pleasure for me to have an intelligent discussion with extremely bright and passionate people and I hope that through the attention my blog got in the process I will be able to enjoy that pleasure on a more regular basis.

To conclude the discussion, I would like to share my last thoughts in the form of an appeal to all of you actively engaged in the great Open Access experiment. You are doing an immensely useful job and you are all contributing to the betterment of the scientific publishing field, and for this I am grateful to you. Even if OA doesn’t take the publishing world by a landslide, the benefit of additional pressure on traditional closed access publishers will ultimately result in their more fair, less exploitative behavior towards subscribers. However, please keep in mind, that OA is a means not an end in itself, the final goal being wider dissemination of scientific information and more efficient communication between scientists. Maybe OA will turn out to be the best way to reach this goal, maybe there will be better ways, I don’t know.

In any case, in order for you to be successful at introducing OA on a larger scale, you will need all the help and good will you can get. Don’t dismiss voices of disagreement as “journalistic curmudgeonism” or “snippy little rants”. I found one statement by Coturnix particularly disturbing in that context: “Reading Peter Suber’s archives first […] is necessary requirement for discussing this topic before opening one’s mouth – he has covered every detail […] and noted all proposed solutions to all the problems”. Did I get that right? Is the self-proclaimed visionary of OA and ardent supporter of free circulation of information really denying me my constitutional right to speak my mind on my own blog just because I haven’t read his friend’s opinions on the subject? This question aside, I doubt that even Peter himself, doubtless one of the most brilliant and hard-working supporters of OA, would be vain enough to subscribe to Coturnix’s notion that he has predicted and solved all the problems of OA. One man, even as intelligent as Peter, cannot possibly see the whole problem of Open Access in all its staggering complexity and have all the answers, while at the same time being actively engaged in promoting the model. People like me, on the other hand, don’t have an agenda, they haven’t invested their lives into supporting either model, they don’t carry the burden of dogmatism reinforced by being among the same people and hearing the same opinions all the time, and so they sometimes see things more clearly and can provide a much needed fresh perspective. That is why I am asking you to listen to cynical and uneducated naysayers like myself. In order for the system to work you will have to persuade us about its utility and feasibility, and so far, at least in my case, you have failed. Treat us like partners in the process, rather than trying to ignore us, ridicule us, scold us, or proselytize to us with an air of superiority*.

What I have also noticed is that many of you focus on situations confirming their views, repeating them like some kind of mantras, while completely ignoring examples to the contrary. Try to learn from failures of the system, rather than constantly reveling in victories. Analyze the reasons why journals such as BMJ and JCI said “no” to open access, while in some other fields, such as physics, OA and CA seem to coexist peacefully. Try to take into account all the cultural and psychological factors that underlie differences between fields and their inclinations to adopt the OA model.
Unbounded optimism often clouds your judgment. Be realistic about what you can and cannot accomplish. Yours is not an all or nothing game. You may have to settle for less than you have dreamed of and it will still be better than what you started off with. The seemingly perfect solutions sometimes turn out to be impractical or plain disastrous, and the danger is not realized until much later. At the risk of being yet again being accused of Godwin-ing, let me remind you of the example of David X. Li, a brilliant Wall Street quant, who thought he had the perfect solution to the problem of high-risk loans. He thought he could make both lenders and bankers happy thanks to his magical formula. We are all feeling the consequences of his mistake right now. Don’t be David Lis of scientific publishing. Don’t ignore the basic facts about human nature and assume that people will do what you want them to do. Keep in mind, that the ones with most power and influence in science are the ones who will benefit least from the OA revolution and have the most to lose by it.
If you feel that there is at least a grain of truth in all my rantings, feel free to discuss any or all the issues covered on my blog or in private. I hereby volunteer for the position of the Open Access Movement’s first Official Devil’s Advocate***. If you ever require my services, just pop me an e-mail and I will do what I can to help bring your lofty visions back down to earth. Finally, If there is one take-home message I would like you to remember from this whole discourse it is this: Open Kool Aid** may impair your long-range vision and objective judgement. Please drink responsibly.

Sincerely,
Niewiap

* Yes, Coturnix, I am talking to you
** a phrase used by Bill Hooker in the Science 2.0 friendfeed discussion about my post; it is meant to signify infatuation with the Open Access ideology
*** Update: Sadly, I’m being told that the position is already taken. I congratulate David Crotty on his appointment, and I am relieved that the OA movement is in good hands. Nevertheless, I will keep blogging on OA from time to time in an unofficial capacity.

During the aforementioned council Mr. Gunn called my scholarly discourse here and here a “snippy little rant”. Well, Mr. Gunn, you ain’t seen me rant yet! But now rant I shall, because (1) you are virtually begging for it (2) I have come across a totally rantable statement, namely that upfront editorial decisions are a thing of the past and that the future belongs to post-print open access review process (I may have simplified it a little, but this is that’s the gist of it). Read on at your own risk.

Even the most hardened OA geeks will admit nowadays that editorial process is an expensive task, especially if you want to keep the impact of the published science high. So they came up with a brilliant idea: “Let’s publish everything we get and then the community will do the reviewing for us. HaHa! Cheap!” WTF??? Anyone who seriously considers this a good idea must be a [having an intercourse*][not very wise person*]. I don’t know what kind of science you do, but do you really want a high school kid to make the tenure decision for you (i.e. rank your paper) by saying “Kewl!!!1!!1! I didn’t no that bacteriums could do zat!”??? “Well, it will be moderated then!” you say. How much moderation is good? Just a little bit – meaning everyone with a sound scientific argument can post? Well then the discussion boards for papers will turn into a bloody [having an intercourse*] inferno with your competitors asking their whole labs to post negative reviews based on bullshit pseudo-scientific concerns, while you will be recruiting all your buddies to +1 you. “Hey, maybe we should do some heavier moderation, then!” you propose “like, with only experts in the field being able to comment and score papers.” And who will be making the decision? The moderator? Or maybe let’s call him editor and forget about this “moderation” [excrements*]. These people will have to be paid, right? Except editors in CA journals have the motivation to select the most objective and knowledgeable reviewers, because they care about the level of science that is published, while your moderator/editor could care less. What is he/she gonna do if she gets a phone call from you proposing $1000 in return for the trouble of removing this “idiotic review by [enter the name of your scientific archnemesis here]“? And how would revisions be handled? Would your moderator take care of that as well? “Hey, this is getting kinda expensive” you realize. Or maybe we don’t need revisions at all???? Or, if we need them, how do you handle the distribution of revisions, ie how do we make sure that everybody has the latest version? How about retractions? Errata?????

Then there is the non-trivial problem of how the hell are you going to coerce good reviewers to give a damn about rating your papers? Right now they have multiple reasons to help you. If you are a high IF paper, they will want to boast that they do reviews for you. They get access to the latest science much earlier than anyone else. From a purely egoistic point of view, they have the feeling of power over the authors, and they can show how [having an intercourse*] smart they are. All these key motivations are gone when you just leave the paper out for discussion and hope that anyone will leave their comment. Many people critique the current review/impact factor system as biased and prone to abuse. The argument goes that tenure/recruitment/funding commitees don’t bother reading the candidates papers and evaluating their value themselves and rather rely on IF as the ultimate measure of a paper’s worth. And in most cases THEY ARE RIGHT. What would you rather have: an immunologist evaluating the worth of your paper on plant cell biology, or three plant cell biologist doing the same? Some of the members of these committees don’t have the slightest idea about the kind of research you do and cannot possibly make an informed decision about its worth based on reading about it in a paper. Will some bad and unjust decision be made based on such shortcuts? Sure, but I will buy a six-pack of the best [having an intercourse*] imported Belgian beer to the first person who shows me a system that works better (a real, not imaginary one).

Last, but not least, I, and many people I know, like to peruse tables of contents of the most prestigious journals just to get the idea of what is currently at the very forefront of scientific discovery. The papers published in these journals are usually very good science and are a pleasure to read, whether they are directly related to my research, or not. I don’t want to give that pleasure up and get a scientific del.ic.ious-like sexiness contest instead.

OK. So I think I know why you guys don’t get it. You are good, noble people and you think, after a Greek philosopher or another, that if you show people the right thing to do, they will do it, just like you would. Well surprise, surprise: You are WRONG! Modern psychology makes it clear that people need a stick or a carrot to move anywhere and counting on their intrinsic goodness and noble instincts will get you nowhere. Sure, there will be people like yourselves who will do the RIGHT THING, but if you are set out to take over the world, you’d better have your stick and carrot business sorted out. As an unquestionable authority in the art of rant, Comrade PhysioProf, once said “Academic science is not a Care Bears fucking** tea party!“. I’ll Amen to that.

* adult language censored
** adult language uncensored for quotation accuracy
*** Update: Coturnix actually answered my plea and posted about my feeble attempts to bring reason into the world of OA publishing. In his post he calls me a “journalistic curmudgeon” and praises the valiant struggles of his OA allies to convert me to their faith. Nevertheless, I am flattered and delighted, because to me it means that my voice, liked by some, villified by others, is not just some delusional ranting that can be totally ignored. Thank you, Coturnix, and I hope to see some more constructive discussion on my blog thanks to your courteous gesture towards me.

First, allow me to explain one thing. My post was not an advocacy piece, but an opinion piece. I am all for open dissemination of knowledge as long as it doesn’t interfere with the quality of the final product, ie. the research paper itself. I come from a country where access to the latest research literature was very limited, so nobody needs to tell me about how much difference OA would make for poorer scientific communities. That said, I don’t really see OA as a viable option for addressing all the problems with knowledge dissemination. I am also far from proclaiming that OA is dead, but I do think that it will not play a significant role in the prestigious high-impact journal area.

After that disclaimer, let me address some of the comments that I got to my previous post. I think Peter Suber made a few very important points. First, he says that most OA journals don’t charge author-side publication fees and that there are plenty of OA journal business models. I must agree with both these statements, but retort: “What difference does it make?”. Three major players in the OA field: Hindawi, BMC and PLoS all charge publication fees and neither uses any of the more exotic business models pointed out by Peter. What it probably means is that theirs are the only models that really work on a larger scale. I mean, OA has been around for a while, you would think that publishers would have come up with a better way to make money if there was one.

Peter also pointed out that BMC is actually making a profit and so it is possible to combine profitability for the publisher with the greater good of universal access. However, this profitability comes as a cost, and in this case it is the cost of lower impact. Again, let’s look at the three major players: PLoS, BMC, and Hindawi. The first one that reported profitability was Hindawi, but virtually all of their journals are super-low on the IF scale. The allegedly profitable BioMed Central has very few journals above IF 5, and only one above 6. They however, took over 9 years to turn a profit and I am guessing it is not exactly a cash cow for Springer. PLoS, on the other hand, is still bringing lossess despite huge endowments and a “bulk publishing” supporting e-journal PLoS ONE. Their journals, however, are very high impact and PLoS is sweating to keep them that way. I am not buying the argument that it takes time for a journal to gain impact, because PLoS Pathogens is a little over 3 years old and it sports a mighty IF of 9.3, while the flagship journal of BMC, Genome Biology, IF 6.59, is 9 years old. Also confirming the “high-impact=low OA profitability” hypothesis is the fact that two highly prestigious journals, British Medical Journal and Journal of Clinical Investigation, after flirting with OA for a while, reverted back to CA because they couldn’t make ends meet.

Peter, and especially Stevan Harnad brought up another issue. They revealed a seemingly fool-proof scheme to go around the limitations of OA journals: the OA archives. The scheme goes as follows: if all the authors agreed (or were more or less forcefully incited) to submit their final post-referee drafts of papers to their institutional archives, which is typically allowed by copyright policies of most journals, we could link all these archives together using a common search engine and circumvent the access barriers that the publishers set before us without recoursing to OA journals per se. While the system is still in the works, I don’t see a reason why it should not work out from a technical standpoint. However, this idea is still missing the main point of my discourse: these papers still must be reviewed and the review process still costs a lot of money, especially for high-quality journals. Why a publisher would incur all these costs just to see the final product of their hard work distributed for free in an OA archive is beyond me. The reason why publishers are lax with their post-publication archiving policies is precisely because the inter-archive search system is not yet up and running, and so it is almost impossible to find a paper you need online without subscribing to the journal. Once this system becomes operational, two possible scenarios are possible: (1) the publishers put their collective foot down and make post-print archiving policies much stricter, in effect bringing the situation back to where it is now, or (2) the powers that be prohibit the publishers from doing (1) and so the publishers pack their things and get out of the scientific journal business because it is not bringing them the bucks they expect from it. That, trust me, is not in the best interest of the scientific community. The 2003 Wellcome Trust Report on scientific publishing, which many OA enthusiasts bear almost like a flag before them without actually taking the time to read it, actually says something very similar, and gives an example of a very restrictive archive system in the Netherlands (see point 4.28) which is enough of a pain in the ass to use that most people will still want to get a subscription, but which, if need be, provides open access to all published manuscripts.

Finally, Anders said something I have a hard time agreeing with. He proposes that CA publishers are monopolies and that they are “government-enforced”. I hope that by now my dear readers see clearly that there is no need to enforce the CA publishing model – it is the one that works out quite well for all the players in the market. On the contrary, introduction of OA to top-tier scientific publishing would require quite a bit of enforcement and would probably end in a massive disaster, as many experiments not taking common sense into account do. Also, scientific publishing is an extremely complex market, as the Wellcome Trust Report analysis makes clear (3.41-3.44), and while it is characterized by price-inelasticity of demand, which puts publishers in a position of power over subscribers, it also puts a lot of competitive pressure on the publishers to deliver highest-quality product (papers) and services (revision/editing), which is clearly in the best interest of the scientific community. Funding agencies and governments can and do exert quite a lot of pressure on the publishers in order to prevent them from abusing their privileged position in relation to libraries. I wholeheartedly support these actions, as well as antitrust investigations of major mergers in the scientific publishing field, which might result in a true monopoly, but I would advise caution when squeezing the commercial publishers’ profits, lest they might leave the field altogether and leave us, the scientist, with a big void to fill.

Thus, it is with sadness that I must conclude I am still skeptical about the chances of the diverse OA initiatives to completely substitute for the current CA publishing models. Call me doubting Thomas, but I want to see proofs of the feasibility of profitable high-impact open access publishing before I jump on the bandwagon and sing songs in praise of OA. All I can see right now is a lot of unfounded hope and plenty of examples to the contrary. Convince me if you can.

OK. So here’s the argument: Science needs to be made known through publishing. In order for science to be published, we need a team of people who will do the job of supervising the review process, editing, storing, and distributing bite-sized pieces of science called papers. These people need to be paid. Traditional closed access (CA) journals pay their employees from revenues they generate by selling their journal or the right to access it online. OA journals accomplish the same through selling space in their journal to people who want to publish in them. The main question is “Can OA journals publish high impact science, and also break even financially?“. On John Wilbanks’ blog on nature network there was a discussion a while ago on the profitability of OA journals, and I particularly enjoyed Martin Fenner‘s comment. He said that there he only sees four ways how high-impact OA journals could be making a profit (comments are mine):

Additional sources of income, e.g. ads on the website. The problem here is that the whole idea of OA is that anyone can download the paper and make any use of it they want. But that means that anyone can just post the paper on their website, and, by adding value, say automatic indexing of keywords iHop style, have people come to their website rather than the journal website to download it. And there goes the advertising money.

Much higher author fees (e.g. $5000-7500) or an author fee apply to every submitted rather than every accepted paper. From the point of view of authors, both solutions are fundamentally the same. Since a high-impact journal will have a high rejection rate, you will need to submit several times to such a journal to get accepted, so it doesn’t really matter whether you pay a few grand for the final accepted result or whether you pay a few hundred each time you submit. As long as you are being realistic about what will fly and what will not, you will be spending about the same amount per paper. But the trouble is, authors will not go for that. Imagine you have a piece of really hot, high impact data that you want to put on display. Are you going to go to a CA journal that will gladly accept your paper without making you pay a dime, or are you going to flesh out $5000 to have it published in an equally prestigious OA journal? I mean, c’mon. Let’s be realistic here for a moment. Of course you will pick CA. If you will excuse a little parable, papers in CA journals are like art exhibitions, while papers in OA journals are more like paid ads – if the stuff people have is worthy of an exhibit, they will very likely not pay for an ad. Also, the incentive on the side of the journal is all upside-down in the OA model. CA journals want to publish the best science possible, because that’s what their clients, the readers, will pay for. OA journals want to publish as much as possible, irrespective of the impact, because that’s what generates income for them. The client is different here – it’s the authors, not the readers.

Subsidies by other journals. That’s the PLoS model. They have a few high impact journals, and they have PLoS ONE, where anyone can publish any work irrespective of impact, as long as it contains broadly understood “good science”, and as long as they are willing to pay for it. Their high-impact journals generate losses, and PLoS ONE is supposed to generate enough profit to make up for that. That this is not yet the case was widely discussed in the blogosphere after an extremely inflammatory article in Nature. Never mind that, I don’t necessarily doubt that PLoS will break even in the upcoming years, but there is another major flaw in their model – there are only so many people willing to pay to publish low impact data. That doesn’t mean that PLoS will run out of customers, but it does mean that any other publishing group who wants to repeat PLoS’ (still uncertain) success will. Also, any for-profit OA group based on the PLoS model will be tempted to expand low impact bulk publishing and shrink high impact loss-generating journals.

Government/charity donors (I added this one). That’s how a lot of OA community efforts run right now (Science Commons, for example). That is not the way to go, because at some point the donors will want to see some tangible effects of their donations, and there aren’t likely to be many. Besides, any organization based on government subsidization is likely to become less efficient and end up sucking more and more of the taxpayers money.

And so I hope you see by now that there are fatal flaws to all possible solutions of the high-impact OA publishing perpetual money problem. There are people who point out that from a macroeconomic perspective CA and OA are really equivalent, because it is all taxpayers’ money, whether it goes for paying publishing fees or buying subscriptions for CA journals. But it’s microeconomic effects where OA breaks down. It’s a question of individual scientists deciding where to publish and individual editors deciding whether to accept a paper and whether to charge for it and how much.

From what I have said so far you might think I have become an opponent of open access. That I have turned to the dark side, so to speak, and become a minion in the hands of the evil Nature empire. That is, most emphatically, not the case.

First, I think that OA is a great paradigm for a lot of areas other than scientific publishing. I am really looking forward to the expansion of OA data and biological materials repositories, such as GEO for microarray data and Developmental Studies Hybridoma Bank for antibodies. I hope that the whole Semantic Web hype will turn out to be well founded and that it will prove practical.

Second, I don’t deny that OA has its place in scientific publishing, but for the reasons I have outlined above, that place will probably lie in the low-impact end of the spectrum. We may see PLoS-like hybrids emerge, but it is extremely unlikely that they will take the publishing world by a landslide. Also, I acknowledge that the attempts to introduce the OA model in publishing are noble and carry a lot of potential benefits if by some miracle they succeeded. However, a lot of these benefits can be achieved much more easily without turning the whole world of publishing upside-down. For example if we want to give more people access to the newest scientific papers, let’s subsidize electronic subscriptions of high-impact CA journals to public libraries. If we want to hyperlink papers between one another, let’s expand current CrossRef schemes to not only include citation data, but also semantic realtionships between papers. And so on, and so forth… If only rather than dreaming of OA revolution all these intellectuals started thinking of how to do without it, we would do just fine.

And so to finish up I would like to make another parable. OA publishing is in a lot of ways like socialism. They are both intellectually and morally appealing at first glance, but they have some well hidden fundamental flaws, which make them unsustainable in the long run, unless enforced. Is OA publishing going to share the fate of the communist regime? Is it going to stay in vestigal form at the low-end margins of the scientific publishing world? Or maybe I am not getting it? Maybe OA is the best thing since sliced bread after all? Let me know what you think.

Here’s some more links to OA publishing discussion:

• a nice list of pros and cons on Informationsplattform Open Access
• on Bench Marks blog
• on Open Access Now
• on Medscape (pretty old)
• on Nonoscience

There are many, many more websites and blogs, mostly supporting OA, but the arguments are becoming repetitive after a while, so I will break up here, and leave the floor open to discussion.

Update: Please see Part 2, Part 3, and Part 4 of the series. Happy reading!

First, John explains what the main goal of Science Commons is:

[...] get the law out of the way, and let the traditional norms of science, which really are the ideals of community and of sharing of information, apply [...]

More precisely, John envisions nothing short of a revolution in science communication:

[We would like to] bring those norms into the Internet age with things like standard copyright licenses that Creative Commons has developed, [...] new ways to track impact, bringing ideas like trackback that came from the blog world to the scientific communication world. [We want to] help convince people that the public domain is something to be cherished, and not a thing to be avoided at all costs when it comes to things like data [...] make biological material and other sorts of physical research materials move around the world, the way that Amazon moves books around.

And the means to bring this about is developing “legal, technical, and policy tools”.

Well, so far all is well. These are very lofty ideals and they get all my moral support (I am a little too poor to make financial contributions just yet). However, a little later John makes a statement that I have a bit more of a hard time agreeing with:

I think [that the dense, passive voice style of scientific publications gets in the way]. I think there’s a little bit of a Guild mentality [...] in terms of the language and structure and flow of these papers. It’s taken me some time to learn how to read them. And it’s artificially idealized I think. [...] the reality is much more ambiguous. [...] the way that we write those papers [...] really keeps people out of science.

There is esentially two things I disagree with here: (1) that scientific jargon and style is a bad thing for the papers and (2) that this is what keeps people out of science. The style of scientific papers has evolved over years and years of scientific communication and it has reached the point where it is both efficient and precise – two essential things for communicating research results. Maybe there is a “Guild mentality” but it is just the same as with any specialized occupation, such as computer programmers, fighter jet pilots, and car mechanics – it is secondary to the language they use, not the reason why they developed their jargon. As for keeping people out of science, this is, with all due respect, just ridiculous. Science has long passed the point at which self-taught geniuses, like Leonardo da Vinci or Charles Darwin, could make seminal contributions to its progress. Nowadays, any sort of impactful research requires years of study of intricate details of the subsubsubfield you specialize in, and of the larger context of your studies. That, in turn, requires reading of hundreds of papers, and just about anyone will very quickly get used to their style after perusing just a few. If people just want a more gentle introduction into resarch subjects of importance, there is an abundance of magazines,  websites and blogs which offer a pre-digested amateur-readable versions of research papers.

Well, enough ranting, let’s give the floor back to John. He later talks about patents, and how he really doesn’t mind people making profit out of their intellectual property, but what he really has a problem with is:

[...] people who try to lock up taxpayer funded literature. The way that we have had this difficulty in getting the clinical trial papers that our tax dollars have funded [...] makes it very hard to [...] A) first read the stuff you paid for with your tax dollars, but B) take that information and really make it digital. Hyperlink it. Convert it. Mix it. Rip it. Spindle. Mutilate.

Fair enough. Taxpayers should have access to the science they paid for. Very good point, and important in arguing for open access. Let’s just maybe leave the “mutilate” part out, OK?

Then we are back to patents, and how to make the system work better by making use of standardized licenses, by crowd-sourcing of prior art, and by making it easier for people to estimate the costs of licensing before they start innovating on top of patented solutions. All important issues, especially for biotech startups, but I found John’s explanations rather fuzzy, maybe because I am not exactly an expert in the patent field.

After that, John has some really interesting things to say about open access publishing:

I would say that it’s become an adolescent? Which means it’s trying to steal dad’s car, and it’s acting up. It’s made it out of early childhood, that’s for sure. The Public Library of Science has become a very high-impact, very respected journal publisher. It’s at the highest levels of scientific quality. And their business model is still developing. And I think that their new PLoS ONE venture, which is a new online only thing, and their upcoming hubs work which is going to build communities, those are going to be really interesting things to watch.
In terms of sort of proving itself from a business perspective, BioMed Central, who has nearly 250 journals, I believe, under Creative Commons licenses, was sold in December to Springer. My understanding is that BMC’s annual revenues were in the 15 million pounds per year range. Again, not using any sort of copyright transfer when they were bought by Springer. And so that really was, I think, a vindication of the capability of a for-profit model that was open. And I love to point to Hindawi, which is in Egypt, which is also profitable, which has another few hundred journals under C.C. by license. So we’re certainly seeing some proof points that this can be high-quality and this can be profitable. But there’s still a lot of uncertainty as to how the existing journals adapt to that. It’s much easier to start from scratch with a new model than it is to change midstream.

Couple important points here. First, according to John Open Access can be profitable. So far as I can tell the numbers are not (yet???) convincing. Neither PLoS nor BMC journals are breaking even, despite relatively large author fees and, in the case of PLoS, major donations. That is not to say that they will never generate profit, but we don’t have a proof of concept right now that would suggest that. Second, existing closed-access journals are going to have to completely rethink their current strategy if they ever plan to become OA. John goes on to talk about how Science Commons works to facilitate this transition by helping out with building business models and publishing models, but he is silent about reasons why any journal might want to risk going under for the noble cause of open access. I find the paragraph above a bit too optimistic for my taste.

Next up is discussion of Semantic Web:

[...] communities involved [in handling large amounts of experimental data] have got to come to some agreement on meaning. And by meaning, I mean sort of standard names for things and relationships between things. Ontologies. Hierarchies. Taxonomies.

Now this is something really fascinating. A web of data, all interconnected by semantic relationships, enabling automated data mining, and true computer-assisted research. A nerdy scientist’s dream-come-true. Is that really going to work? John talks about several potential problems, such as figuring out who will be responsible for storing the data, and what kind of data to store:

[...] Is it the raw data? Is it the processed data? Is it the software used to process the data? Is it the normalized data? Is it the software used to normalize the data? Is it the interpretation of the normalized data? Is it the software we use to interpret the normalization of the data? Is it the operating systems on which all of those ran? What about genome data? [...] ideally, what we could say is, “Okay. Well, we can delete the old data if there’s a physical sample.” Right? Because we can go back and recreate the genome data from an even smaller piece of it [...] So suddenly, we’ve gone from the world of the digital back to the world of the physical samples as well.

The interview then moves on to a topic less science-y and more geeky – privacy and data security. Nihil novi – yeah, we need to focus on privacy blah, blah, blah. I am going to skip over that part, since I didn’t find it particularly enlightening.

Finally John discusses the challenges for his project (Science Commons) and for Open Access Science in general:

[...] there’s a constant challenge of funding because funding non-profits is always hard. In this economy, it’s almost lethally hard. But beyond that, I think the biggest challenge is what we started with which is that the existing systems for science are pretty robust against disruption [...] the biggest challenge because you’ve got to do so many things simultaneously. You’ve got to deal with legal problems, both contract and intellectual property problems [...] incentive problems [...] workload and labor problems[...] Guild culture and the Guild communication systems, all of that at once.

Then the interview finishes with a short discussion of current Science Commons projects:

• NeuroCommons, an open source data integration project, meant to be an experiment in Semantic Web
• collection of biological materials under licenses resembling CC licenses
• project with Nike and BestBuy about how to share patents and recreate the research exemption
• partnership with a large technology company (to be announced)
• acquisition of a large scientific database from a major pharmaceutical company

So that’s all, folks. The post is long enough as it is, so in my next blog entry I will try to serve you more food for thought along with some tasty links and a more personal perspective on this interview and on Open Access, so stay tuned for more.