Reject, minor, major revision and the fourth option

Once a reviewer of one of our papers wrote that she/he did not understand our mathematical model. That's a honest submission. No one expect that every one will understand everything. But had not that affected the decision made on our paper? May be. May be not.

But every reviewer faces this problem. As science is getting more and more interdisciplinary, one often find some part of the paper bit difficult to understand and review. I am not talking of complete ignorance. Neither talking of a badly written paper. Am talking of a situation where you broadly understand the concepts and issues, but lacks clarity on particulars in that paper. The best option then is to ask the authors to explain and help you understand their paper better.

Once you have understood the paper, with clarity, then only you can make a rational judgment on the paper. Isn't that obvious? But not in practise. Journals does not allow you to post queries or make comments on a manuscript without making a judgment out of three choices: minor revision, major revision, or reject. 

There is no scope of a dialogue, albeit with anonymity, between the people who did the science and those who did the vetting. Yes, there exist the practise of post-review rebuttal. But that's only after the reviewer has made the decision. 

The purpose of publishing scientific papers has changed with time. So has changed the practise and culture of peer-review. Journal editors complain of shortage in serious reviewers, authors complain of lackluster reviews,  reviewers complain of lack of professional incentive in reviewing papers.

Even then, there are people who review each others papers and do that with all earnest. They still believe in the elementary purpose of peer-review of a scientific paper: to improve the manuscript and to improve the work reported there.

Won't it be wiser to help this lot scientists to do the job better? One step towards better review would be to provide a fourth option to a reviewer. Let the reviewers post questions or start a thread of discussion with the authors, before they decide on the manuscript.

Obviously, such interactions would be considered as part of the review documents and has to bounded by a specific duration. It would also be bounded by all legal and ethical guidelines of peer-review.

Am not sure, how many of my peers will use this option. But letting some use it judiciously, wont harm science, but make it better.

Everybody loves an anti-cancer drug

There are over 19000 papers, published till date, with the word anti-cancer in title or abstract. Over the years, funding for research on newer anti-cancer drugs has increased. So is the publications with this phrase (See the figure below). This phrase also have some magical power. It helps me to easily justify my research and grab a slice of funding pie. Unfortunately, the pie is never enough for all. 

Unfortunately, we are still far from wining the disease. 

Plot showing trend in publication of papers on "anti-cancer". Pubmed was searched for all the papers having the phrase "anti-cancer" either in abstract or in title. The numbers in parenthesis show the year of first report.

Working for drugs against cancer has some technical advantages over other diseases. Think about developing a new drug for an infectious disease, like Dengue or Malaria. It’s difficult to have a good in vitro model for many infectious diseases. When you have one, you need special laboratory facility and legal clearances to work on those. 

Cancer research has no such troubles; at least at the early stages of the project. Most of the in vitro assays are performed on cell lines. HeLa was the first human cell line, reported in 1952. Since then cell lines are the workhorse of anti-cancer drug development. These cells are treated with a drug and its ability to kill these cells is measured. Some time the drug does not kill the cell but just stops the cell division. That’s good enough for us. Measuring such cytotoxic or cytostatic effect of a drug is not so difficult. We have many cheap and reliable assays for this. One such is the famous MTT assay.

These experiments are simple, cheaper and you don’t have much legal and ethical issues. For a scientist, these are critical determinants. Social priority, science policy, academic fashion and ease of preliminary experiments, all these are behind the exponential growth in publications on anti-cancer agents.

But what is an anti-cancer agents? A search through the Pubmed throws up curious mix of items: plant extracts, nanomaterials to  atmospheric gas plasma. Most of these studies involve some form of in vitro cell culture-based experiment to show that these materials kill the cells, preferably through apoptosis. Essentially, the authors are checking cytotoxicity of these agents. Interestingly, some of these materials are also toxic to bacteria and often promoted as bactericidal agents, albeit in separate papers.

Most of these anticancer agents never makes to next step of evaluation. No body chase them further, not even the inventors. Authors move to another project, on another anti-cancer drug. Another paper is minted with the same key word. 

Cancer is a cellular disease. It is a disease with cells having genetic, epigenetic and phenotypic changes. To treat, either we have to convert these cells back to normal  or we have to get rid of them. For the time being, the first one seems improbable and our focus is on the other option.

In 1947, Sydney Farber used the same principle, when he used  aminopterin to treat children with leukemia. Aminopterin stops cancer by blocking cell division. Chemotherapeutic agents, developed subsequently, have the same property. They block proliferation of human cells through diverse mechanisms. Blockage of proliferation hits cancer cells and any other rapidly dividing normal cells. So, these drugs have some sort of inbuilt specificity: they block cell division and affect dividing cells more than those seating idle. 

However, many anti-cancer agents reported in academic literature do not follow the same logic. Something can be cytotoxic for different reasons. It may kill cells by blocking essential  processes like protein production. Cells can be killed by forming pores on the membrane or by oxidative damage. Many so called anti-cancer agents kill cells by these mechanisms. These methods have no specificity towards cancer cells and would affect every other cells in body. Even then, authors call those as anti-cancer agents. 

In fact. we really don’t have shortage of such non-specific cytotoxic or cytostatic agents. I will say, we have enough of such arsenals; enough to stop further search for new one. The focus should be more on developing strategies to deliver those specifically to cancer cells, sparing the normal one.

Academic research has its own dynamics. Some works on basic “blue sky” questions on how nature works. Others prefer to work on issues that has immediate social relevance. Discovery of a new cancer drug would have immediate social impact. Many of us may have such high goal, but we are mostly lost in closed alleys. 

Drug development is always an uncertain endeavor. Something that worked well in vitro may fail miserably in animal experiments or in clinical trials. Even then, our efforts should start with clear logic. Our strategy should have clear rationality based on our existing knowledge of other ant-cancer drugs. Unfortunately "logic" is loosing to the rush to get published. It is loosing to the fashion in academics. 

As the rogue cells keeps dividing within millions of people, we keep trying new methods to checkmate them. We keep trying, often, even without rationality. And the printing press churn out "Anti-cancer" in black and white. 

How to stay updated with latest literature

When I was doing Ph. D, online publishing of scientific journals had just learned walking. We were more dependent on hard copies of journals in libraries. For many of us, it used to be a ritual to regularly visit the library and flip through the pages of our favorite journals, to catch the new and relevant to our work. But, the Internet has changed the way we access journals now. It has democratized access to knowledge and also overwhelmed us with information. Hundreds of papers get published every day. Though you may have access to most of those, it’s difficult to keep track of papers of interest. Thankfully, there are tools that can help you to keep you informed about the latest literature in your field. 

E-mail alert by PubMed: NCBI PubMed has changed the way we do biomedical research. You must be searching this database at least once every day. Do you know that you can make an personal account with NCBI to save your searches? Visit MyNCBI page to make an account. Log in your account. Perform a search using a keyword suitable for your research. This time you will get a link for "Save Search", near the top of the search results page. Click it. It will take you to a page to save your search result with option to activate email alert for new results on this key word. You can select the frequency of such update. I select to get update daily, so that whenever there is a new paper, I get informed immediately. You can anytime come back to your MyNCBI page and edit your saved searches. The key of this email alert is the key word(s) used for the search. Therefore, you have to be very careful in choosing them. Use different key words and create saved searches for those. Subsequently, based on the email alerts, you may change the keywords. 

Twitter: Do you Tweet. No am not asking you to use Twitter to add spice to your social life. You can use it as a powerful tool to keep updated with what's happening in your field of study. Most of the reputed journals use social media, including Twitter, to spread news about important papers published by those. Even, scientific associations use Twitter to announce breakthrough in specific fields. Even many scientists use regularly Tweet about latest papers published by them and their peers. So join Twitter. Find out Journals and organizations of your interests in Twitter. Start following them. See if any of your peers is there in Twitter. Follow them too. Then make a habit to scroll through the tweets once daily. And don’t be just an observer. Reciprocate. Tweet about your new publication. Tweet about a recent paper that you found interesting. Build a social network around your science. 

Faculty of 1000: This is what you have always dream of. A bunch of experts reading and flagging latest literature for you. Obviously, this does come with a cost. Subscribe to F1000Prime. Choose particular topics of your interest and even experts to follow from the list. F1000 will send you email alerts whenever your experts review a brilliant paper of your interest.  One day, maybe your paper will also get reviewed by F1000 and get the prestigious badge of F1000 in the PubMed. Till then enjoy reading.

Trajectories in Open Access

Scientific research is a social endeavor and throughout the world, it is funded primarily by public money. Therefore, there should be no barrier to the knowledge developed through such research and it should be accessible to everyone. The primary sources of such knowledge are the articles published in scientific journals. So, to spread knowledge, these articles should be freely available to everyone. The Open Access movement, which is  spreading through the academic world, is preaching this philosophy.

In the current model of publication, researchers submit their articles to journals and the journals publish the selected few after peer-review. In this process, the author voluntarily transfers the copyright of the article to the publisher. The publisher does not pay the author. But the reader, whether a researcher or a layman, has to subscribe the journal to read it. That's what most of our libraries spend money on. Over the years, the subscription fees have ballooned to such an extent that even libraries in the developed world are falling short of their budget.  

The Open Access movement strikes at this very issue. It promotes two models, to achieve open access to published work. In the first, any body is free to access the journal over the Web. Such journals are called open access journals. For publication in such a journal, authors have to pay a article-processing fee. The cost for editorial manpower, formatting, typesetting and server management are covered by that fee collected from the authors. Over the years, number of open access journals has increased exponentially, with many having doubtful reputation. Even then, several open access journals are well respected for consistently publishing high quality work. Though such journals are promoting open science, article processing charges are often very high and prohibitive for researchers working in developing countries.

The other model, for open access, is creation of public funded open access digital archives for scientific papers. PubMed Central, developed by  U.S. National Institutes of Health's National Library of Medicine, is one such digital archive, where publishers or the authors voluntarily submit a copy of their articles. In fact, such submission has been made mandatory for every work funded by NIH of USA. Some other funding agencies are also promoting the same model. Anyone having an access to the Web can read all the papers stored in such archives. Such archiving does not violate the copyrights of most of the publishers, as authors submit only their copy of the final peer-reviewed draft without having any editing and formatting by the publisher. ResearchGate, a social networking site for scientists, also follows a similar model for sharing scientific articles.

Very recently, DBT and DST, funding bodies for scientific research in India, has released the second draft on their open access policy. They have proposed establishment of open access digital archives, in different institutions as well centrally. Any publication coming out of a work funded by these agencies must be deposited in such archives. Like other such archives, authors will deposit only their own copy of the final peer-reviewed draft. Interestingly, the proposed policy explicitly discourages author-paying model of open access journals and has made it clear that they would not provide financial support for article-processing fees. This makes sense, as article-processing fees of many journals are exuberantly high for most Indian labs. Additionally, this will also discourage spread of predatory journals, many of which are published from India.

It will be interesting to follow how India's open access policy shapes eventually. But for the time being, let me imagine the evolution of the publishing industry in the age of open access. The open access digital archiving makes sense for every country and most of the major players in science would eventually move to this model. But that may trigger a trouble. A publisher takes care of peer-review, editing, formatting and publishing. They charge the fee to the reader or the author to cover the expenses for this process. The final published articles are usually smartly edited and eye candies to readers. The authors copy of the final draft deposited in open access archives are not adequately formatted but contains all the scientific contents. Therefore, though reading such a draft is bit cumbersome, but that does not affect the science. In fact, every scientist is well trained to read such drafts. If we get such final draft without any cost, why should we pay to read a well-formatted copy of the same, published by the journal? Obviously not. Eventually this will reduce the number of subscribers to such journals. So journals running on subscription based model will not survive in the world of open access. In fact all major publishers for science journal are offering some form of open access for their journals and testing the water. But we need publishers to manage the whole process of publishing scientific articles through peer-review. At least some one has to run the peer-review process and that also have a cost though the reviewers do not get paid. If the reader does not pay, the cost has to be covered by the author. And that brings us to author-paying model of current open access journals. Therefore, institutionalized discouragement to such journals may not be a good idea as we do not have an alternate model that will sustain in long run.

There is another model of science publishing. It involves post-publication peer review. In this, authors deposit articles that are published online without any peer-review. The readers can access those articles freely and can comment on those. In a variant of this model, the journal invites peers to review, once the paper is published online. arXiv, an open access server, publishes articles without peer-review and without any charges. However, it does not allow commenting or review by readers and in essence it is merely a repository.  Even then, this server is quite successful and authors regularly submit high quality articles, particularly in physics and allied subjects. Recently established PeerJ PrePrint archive is an attempt to replicate that for bio-medical sciences. It allows readers to review and comment in articles archived there. Most online journals also allows readers to comment on published peer-reviewed work. However, till now peer review by readers has not catch up the scientific world and very few readers express their opinion online. Even when they comment, those are not detailed like thorough peer-review. Currently, post-publication peer-review by readers doesn't seems to be a viable option. Over-reliance on reader's opinion may also bring  the vices of social media in science publishing. In essence, the current practice of organized peer-review managed by editors is still the gold standard. In the age of open access,  quality peer-review can be sustained only through the author-paying model. Therefore, rather than rejecting author-paying model, we need to develop technologies to reduce the cost of running the show and have to establish some peer-based mechanism to regulate this industry to maintain high standards.