The PhD Route To Becoming a Science Writer

If you know that you want to become a science writer, should you even bother with obtaining a PhD in science? There is no easy answer to this question. Any answer is bound to reflect the personal biases and experiences of the person answering the question. The science writer Akshat Rathi recently made a good case for why an aspiring science writer should not pursue a PhD. I would like to offer a different perspective, which is primarily based on my work in the life sciences and may not necessarily apply to other scientific disciplines.

I think that obtaining a PhD in science a very reasonable path for an aspiring science writer, and I will list some of the “Pros” as well as the “Cons” of going the PhD route. Each aspiring science writer has to weigh the “Pros” and “Cons” carefully and reach a decision that is based on their individual circumstances and goals.

Pros: The benefits of obtaining a science PhD


1. Actively engaging in research gives you a first-hand experience of science

A PhD student works closely with a mentor to develop and test hypotheses, learn how to perform experiments, analyze data and reach conclusions based on the data. Scientific findings are rarely clear-cut. A significant amount of research effort is devoted to defining proper control groups, dealing with outliers and trouble-shooting experiments that have failed. Exciting findings are not always easy to replicate. A science writer who has had to actively deal with these issues may be in a better position to appreciate these intricacies and pitfalls of scientific research than someone without this first-hand experience.


2. PhD students are exposed to writing opportunities

All graduate students are expected to write their own PhD thesis. Many PhD programs also require that the students write academic research articles, abstracts for conferences or applications for pre-doctoral research grants. When writing these articles, PhD students usually work closely with their faculty mentors. Most articles or grant applications undergo multiple revisions until they are deemed to be ready for submission. The process of writing an initial draft and then making subsequent revisions is an excellent opportunity to improve one’s writing skills.

Most of us are not born with an innate talent for writing. To develop writing skills, the aspiring writer needs to practice and learn from critiques of one’s peers. The PhD mentor, the members of the thesis committee and other graduate students or postdoctoral fellows can provide valuable critiques during graduate school. Even though most of this feedback will likely focus on the science and not the writing, it can reveal whether or not the readers were able to clearly understand the core ideas that the student was trying to convey.


3. Presentation of one’s work

Most PhD programs require that students present their work at departmental seminars and at national or international conferences. Oral presentations for conferences need to be carefully crafted so that the audience learns about the background of the work, the novel findings and the implications of the research – all within the tight time constraint of a 15-20 minute time slot. A good mentor will work with PhD students to teach them how to communicate the research findings in a concise and accurate manner. Some presentations at conferences take the form of a poster, but the challenge of designing a first-rate poster is quite similar to that of a short oral presentation. One has to condense months or years of research data into a very limited space. Oral presentations as well as poster presentations are excellent opportunities to improve one’s communication skills, which are a valuable asset for any future science writer.


4. Peer review

Learning to perform an in-depth critical review of scientific work is an important pre-requisite for an aspiring science writer. When PhD students give presentations at departmental seminars or at conferences, they interact with a broad range of researchers, who can offer novel perspectives on the work that are distinct from what the students may have encountered in their own laboratory. Such scientific dialogue helps PhD students learn how to critically evaluate their own scientific results and realize that there can be many distinct interpretations of their data. Manuscripts or grant applications submitted by the PhD student undergo peer review by anonymous experts in the field. The reviews can be quite harsh and depressing, but they also help PhD students and their mentors identify potential flaws in their scientific work. The ability to critically evaluate scientific findings is further enhanced when PhD students participate in journal clubs to discuss published papers or when they assist their mentors in the peer review of manuscripts.


5. Job opportunities

Very few writers derive enough income from their writing to cover their basic needs. This is not only true for science writers, but for writers in general and it forces writers to take on jobs that help pay the bills. A PhD degree provides the aspiring science writer with a broad range of professional opportunities in academia, industry or government. After completing the PhD program, the science writer can take on such a salaried job, while building a writing portfolio and seeking out a paid position as a science writer.


6. Developing a scientific niche

It is not easy to be a generalist when it comes to science writing. Most successful science writers acquire in-depth knowledge in selected areas of science. This enables them to understand the technical jargon and methodologies used in that area of research and read the original scientific papers so that they do not have to rely on secondary sources for their science writing. Conducting research, writing and reviewing academic papers and attending conferences during graduate school all contribute to the development of such a scientific niche. Having such a niche is especially important when one starts out as a science writer, because it helps define the initial focus of the writing and it also provides “credentials” in the eyes of prospective employers. This does not mean that one is forever tied to this scientific niche. Science writers and scientists routinely branch out into other disciplines, once they have established themselves.


Cons: The disadvantages of obtaining a science PhD


1. Some PhD mentors abuse their graduate students

It is no secret that there are a number of PhD mentors which treat graduate students as if they were merely an additional pair of hands. Instead of being given opportunities to develop thinking and writing skills, students are sometimes forced to just produce large amounts of experimental data. 


2. Some of the best science writers did not obtain PhDs in science

Even though I believe that obtaining a PhD in science is a good path to becoming a science writer, I am also aware of the fact that many excellent science writers did not take this route. Instead, they focused on developing their writing skills in other venues. One such example is Steve Silberman who is a highly regarded science writer. He has written many outstanding feature articles for magazines and blog posts for his superb PLOS blog Neurotribes. Steve writes about a diverse array of topics related to neuroscience and psychology, but has also developed certain niche areas of expertise, such as autism research.


3. Science writer is not a career that garners much respect among academics

PhD degrees are usually obtained under the tutelage of tenure-track or tenured academics. Their natural bias is to assume that “successful” students should follow a similar career path, i.e. obtain a PhD, engage in postdoctoral research and pursue a tenure-track academic career. Unfortunately, alternate career paths, such as becoming a science writer, are not seen in a very positive light. The mentor’s narcissistic pleasure of seeing a trainee follow in one’s foot-steps is not the only reason for this. Current academic culture is characterized by a certain degree of snobbery that elevates academic research careers and looks down on alternate careers. This lack of respect for alternate careers can be very disheartening for the student. Some PhD mentors or programs may not even take on a student if he or she discloses that their ultimate goal is to become a science writer instead of pursuing a tenure-track academic career.


4. A day only has 24 hours

Obtaining a PhD is a full-time job. Conducting experiments, analyzing and presenting data, reading journal articles, writing chapters for the thesis and manuscripts – all of these activities are very time-consuming. It is not easy to carve out time for science writing on the side, especially if the planned science writing is not directly related to the PhD research.


Choosing the right environment


The caveats mentioned above highlight that a future science writer has to carefully choose a PhD program. The labs/mentors that publish the most papers in high-impact journals or that happen to be located in one’s favorite city may not necessarily be the ones that are best suited to prepare the student for a future career as a science writer. On the other hand, a lab that has its own research blog indicates an interest in science communication and writing. A frank discussion with a prospective mentor about the career goal of becoming a science writer will also reveal how the mentor feels about science writing and whether the mentor would be supportive of such an endeavor. The most important take home message is that the criteria one uses for choosing a PhD program have to be tailored to the career goal of becoming a science writer.


Image via Wikimedia Commons(Public Domain): Portrait of Dmitry Ivanovich Mendeleev wearing the Edinburgh University professor robe by Ilya Repin.

Great Expectations For Scientific Publication: How Digital Publishing Is Helping Science

I recently came across a rant that lamented the advent of digital publishing, open access publishing and self-publishing in science. The rant was published in the Huffington Post as a “digital” blog post (ah, the irony), entitled “50 Shades of Grey in Scientific Publication: How Digital Publishing Is Harming Science”. It was reminiscent of the rants that might have been uttered by calligraphers who were upset about the emergence of Gutenberg’s printing press or concerns of European aristocrats in the wake of the French Revolution about whether commoners could ever govern a country. Normally I ignore rants, but this one was written by Dr. Douglas Fields, an outstanding neuroscientist and an excellent writer, who also serves as the Chief of the Nervous System Development and Plasticity Section at the National Institute of Child Health and Human Development. It is very difficult to understand how someone who is such an eminent scientist and has an extensive experience with scientific publishing would make so many bizarre statements about open access publishing.

My initial reaction was that Dr. Fields wrote it as a satirical piece, mocking the opponents of open access publishing by listing phobias and biases of interest groups that are trying to prevent free public access to the results of scientific research. Upon further reading, I realized that perhaps Dr. Fields did consider the statements in his article to be a valid critique of open access publishing and that it therefore warrants a response to point out the errors. Dr. Björn Brembs has already written one excellent response, but I think the topic is rather important and would benefit from additional responses. My problem is figuring out how to respond to a rant that is rife with so many inaccurate statements and fallacies. I will first summarize three key flaws in Dr. Fields’ reasoning and then move on to giving specific examples.

Artwork for Charles Dickens' Great Expectations by H.M. Brock

1. Conflating digital publishing, open access publishing and self-publishing

The title of Dr. Fields’ article mentions “digital publishing”, but in the article itself, the issue of “digital publishing” is conflated with “open access publishing” and “self-publishing”, even though these are very distinct entities. Digital publishing refers to the medium of publishing, and can take the form of articles or E-books which are viewed online or downloaded. Most scientific articles that I now read have been published digitally. I am very happy about this development and I do not miss the days when I had to spend hours in the library, photo-copying hundreds of scientific articles from print journals, both wasting my time and helping commit arbocide. Some of my colleagues still like to read the paper copies of journals, but most of us prefer the convenience of being able to archive thousands of scientific articles on a single USB flash drive and not have to maneuver around large stacks of paper. When it comes to books (literary, philosophical or scientific), I feel a bit differently. I derive tactile pleasure from printed books and I still find it easier to thumb through a printed book than browse an E-book. I can sympathize with concerns regarding digital publishing of books. However, when it comes to scientific papers (the focus of Dr. Fields’ article), most scientists would agree that digital publishing has made it easier for them to stay abreast of scientific developments.

Open access publishing can be defined as the publication of articles that are freely available to everyone. Readers do not need to be affiliated with any specific organizations and they do not have to pay for reading the published material. Many digitally published articles are NOT open access. Some of the digitally published journals actually charge up to $30 for reading one article, if one does not have a personal or institutional subscription to the journal. Conversely, there are printed publications which are, in a certain sense, “open access”, such as free local newspapers or flyers with grocery coupons. Anybody can obtain these for free. These examples just highlight the difference between the medium of publishing (digital versus paper) and the access to the published material (pay-for-access versus open access).

The term self-publishing, or the more derogatory term “vanity publishing’, is used when an author pays a fee and is guaranteed publication of the manuscript. The item is published either in a paper format or a digital format, and the author does not require approval of editor or peer reviewers prior to the publication. Most papers in open access scientific journals that I have come across are NOT self-publications, because they do undergo a peer review and the editors ultimately decide whether or not the manuscript should be published.


2. Open access publishing and rigorous peer review

 The second major flaw is that Dr. Fields assumes open access publishing somehow impairs the peer review process and results in the publications of papers without scientific rigor. Much of my own experience stems from the PLOS family of open access journals, which include PLOS One, PLOS Medicine and PLOS Biology.  The PLOS journals are among the most widely read open access journals in biomedical research. The last time I was a peer reviewer for a PLOS One manuscript, I used the same standards to assess the validity and scientific rigor of the manuscript that I use for pay-for-access journals. The PLOS editor used my review and that of the other anonymous peer reviewers to reach a decision about the manuscript. The editor requested that the authors of the manuscript make significant scientific revisions based on our reviews, similar to what I have seen in other pay-for-access journals. I never got the impression that the open access nature of the journal in any way diminished the rigorous peer review process. Most of the academic editors and reviewers of the PLOS open access journals are scientists who also routinely review manuscripts for pay-for-access journals and I have never heard of any reviewer having separate scientific review standards for open access papers. The PLOS editorial board members, that I have spoken to, have never experienced any pressure to publish a paper that was considered to be of poor scientific quality.

There are differences in terms of the criteria regarding novelty of the scientific papers that editors of open access journals may use to decide whether or not a manuscript is suitable for their journal. PLOS Medicine, PLOS Biology and the new open access journal eLife want to primarily publish ground-breaking, high-impact papers. Significant novelty and broad impact on the field of science have to be paired with high scientific rigor for these journals to consider a manuscript for publication. PLOS One, on the other hand, is more likely to publish papers that will not have such a broad impact on science, but it still requires scientific rigor and validity of the conclusions. This hierarchy of impact is not unique to open access journals. The pay-for-access journals Nature and Science also only consider manuscripts with a potentially high impact, whereas there are many other traditional pay-for-access journals that are willing to consider lower impact research findings as long as they demonstrate scientific rigor during the peer review process.


3. Open access publishing and corporate interests

 The third major flaw in the article is that Dr. Fields assumes open access publishing somehow plays into the hands of capitalist corporate interests. Since open access publishing does not generate any revenue from its readers, it requires authors of manuscripts to pay for the publication costs. This might be an incentive for open access publishers to publish large numbers sub-standard scientific papers, because this way they could collect the authors’ publication fees. This is a valid concern and many of my colleagues who support open access publishing are aware of this potential conflict of interest. My response is that the reputation of an open access journal would suffer if it were to publish sub-standard scientific papers. This would lead to the loss of readers as well as submissions from authors, which would not want their work to appear in a disreputable journal. Furthermore, the peer review process of open access journals provides the necessary checks and balances to prevent publication of shoddy science. It is true that open access digital publishers could decide to increase the total number of published papers per year from say 10,000 to 100,000 in order to make more money. However, the decision about the scientific validity of a paper rests with the scientific editors and not with the publishers, so increasing the total number of available publication slots should not result in the publication of poor quality science as long as the peer review process remains rigorous and independent.

One has to also look at Dr. Fields’ concerns in the context of the current pay-for-access publishing industry, which is actually run by large corporations that reap huge profits from subscription fees. One of the largest academic publishers is Elsevier, which had over 3 billion US$ in revenues and an astonishing profit margin of 37% in 2011. The truth of the matter is that the current pay-for-access model is catering to corporate greed and is impairing the free sharing of scientific results. In addition to generating revenue from subscription fees, current pay-for-access publishers often also charge fees to the authors of the manuscripts. This may explain the high profit margin. I will elucidate this using the example of the journal Blood, one of the leading pay-for-access journals in hematology and vascular biology (which happens to be my area of interest). A review of the publication costs for Blood reveals that this journal charges $62 per printed page and $620 for each color figure, as well as $105 per data supplement. Many papers that describe the immune system, blood cells or blood vessels need to show histology or immunofluorescence images, which are usually presented in color. A hypothetical average length paper of 8 pages with four color images and one data supplement would cost the author: (8x$62) + (4x$620) +$105 = $3081. In addition to collecting this fee from the authors, the journal also then collects annual subscription fees from its readers, which are either $975 for an individual in the US, $1,220 for subscribers outside theUS and altogether much higher for a site license granted to a university library. Needless to say, these subscription fees are quite high and especially difficult to pay for in underdeveloped countries.

This $3,081 fee for a typical Blood paper has to be compared with the fees of the open access PLOS journals, which charge authors of PLOS One papers a flat fee of $1,350 (no matter how many color figures or supplements are used). The more prestigious PLOS Medicine and PLOS Biology journals charge a higher flat-fee of $2,900 per published papers. What is quite remarkable is that authors submitting to PLOS from underdeveloped countries pay either no author fees or a nominal $500 fee, depending on which country they are submitting from. Due to the open access nature of the PLOS journals, anybody can access the articles without having to pay any subscription or access fees, which is especially helpful to researchers in countries with minimal financial resources for education and research. PLOS journals are published by a non-profit organization, so this may explain why they are able to offer such affordable prices to authors and free access to all readers. However, even the recently founded open access journal Scientific Reports published by the Nature Publishing Group only charges $1,350 to the authors.

Science was never meant to be conducted by the rich for the rich. The goal of scientists should be to communicate rigorous findings to as broad an audience as possible. Open access publishing is a step in the right direction, because it helps liberate the scientific enterprise from corporate interests of pay-for-access publishers that impair the broad dissemination of scientific knowledge to readers who cannot afford the high subscription fees.


4. Specific responses to Dr. Fields

In this section, I will just highlight some of the statements made by Dr. Fields that I disagree with and give brief responses:


“Scientific publication is undergoing a drastic transformation as it passes deeper into government and capitalistic control, while weakened from struggling simultaneously to cope with unprecedented transformations brought about by electronic publication.”

“The federal government has mandated that scientific research that is funded in part by federal grants be made freely available to anyone over the Internet.”


Scientific publication is not passing into government and capitalistic control. It has always been under capitalistic control. The government mandates do not concern the publication itself (i.e. the government does not interfere with peer review and editorial decisions), but governments are pushing for free access to the publications. The electronic publication is not a weakening, but a strengthening because it facilitates rapid sharing and communication of scientific results.


“In the absence of income derived from subscriptions, scientific journals must now obtain the necessary funds for publication by charging the authors directly to publish their scientific study. The cost to authors ranges from $1,000 to $3,000 or more per article. Scientists must publish several articles a year, so these costs are substantial.

The funding model fueling open-access publication is a modern rendition of the well-known “vanity” model of publication, in which the author pays to have his or her work printed. The same well-appreciated negative consequences result when applied to scientific publication. Because the income is derived from the authors rather than from readers, the incentive for the publisher is to publish as much as possible, rather than being motivated by a primary concern for quality and significance that would increase subscription by readers, libraries and institutions and thus income. In the open-access, “author-pays” financial model, the more articles that are published, the more income the publishers collect.”

Dr. Fields is referring to the charges of open access journals, but he does not mention that the authors also have to pay substantial fees to traditional pay-for-access journals to have their work published. These charges are at times even higher than those of open access journals especially when researchers use color figures, which is common in research areas that rely heavily on fluorescence imaging (see example above for the journal Blood).  It is true that more articles may generate more profits for some open access publishers, but this is where the quality of the peer review process and editorial policies of a journal need to be evaluated. The open access PLOS journals are run by a non-profit organization and have no need to generate more profits. The problem pointed out by Dr. Fields applies to all for-profit publishing – whether it is open access or traditional pay-for-access. The best remedy is to ensure that the peer review process and editorial decisions are made by people who have no conflict of interest with the financial goals of the publishers.


In place of rigorous peer review and editorial oversight by the leading scientists in the field, these publishers are substituting “innovative” approaches to review submissions, or they apply no authoritative review at all. Some open-access journals ask reviewers to evaluate only whether the techniques used in the study are valid, rather than judging the significance or novelty of the findings.


Open access journals such as PLOS or eLife do have rigorous peer review in place and editorial oversight by some of the leading scientists in the field. There may be some open access journals which are not peer reviewed, but there are also pay-for-access journals that publish papers with minimal or no peer review. It is true that some open access journals such as PLOS One want reviewers to focus on the scientific validity of the research instead of whether or not it the research is deemed to be significant. This has advantages and disadvantages. By focusing on the validity instead of the significance, rigorous science gets to be published, independent of whether or not the area of research is “popular”. It also allows for the publication of studies that attempt to replicate previous work, instead of only focusing on new developments. The disadvantage is that a journal may publish multiple studies that merely re-affirm established scientific concepts or work on obscure species that are of no interest to the mainstream. On balance, I think it is a positive development, because I think that current journals under-emphasize the importance of replicating biomedical research and because I think that sometimes the “insignificant” areas of research may give rise to very new concepts that the mainstream of science would have otherwise ignored.


“The argument is made that the loss of rigorous scrutiny and validation provided by the traditional subscription-based mechanism of scientific publication will be replaced by the success of an article in the market after it is published — it’s the “cream-will-rise-to-the-top” theory.”

 “Now when a scientist writes up new research for publication in a prestigious journal, he or she must deal with all the contradictory findings of questionable rigor and accuracy being published by these vanity-publishing, open-access journals.”


As mentioned above, open access journals such as the PLOS family do have rigorous scrutiny. The open access allows for an additional mechanism of scrutiny, by allowing readers all over the world to read the article, replicate it and in some cases also comment on the article in the form of a post-publication peer review.

The phrase “vanity-publishing, open access journals” is quite bizarre. There are prestigious open access journals such as PLOS Medicine, PLOS Biology and the newly emerging journal eLife and there are prestigious pay-for-access journals such as Nature or Cell. But there are also many not so prestigious pay-for-access journals that publish work of questionable rigor or significance.


Similar changes are eroding literary publication as direct electronic publication by authors on the Internet has led to erotic and reportedly pornographic works like Fifty Shades of Grey and spinoffs sweeping bestsellers lists for months. The issue is not whether erotica or pornography is or should be popular; rather, one wonders what literary work might have filled those slots on the bestsellers lists if traditional mechanisms of editor-evaluated publication had been applied, which consider more than simply the potential popularity of a work in deciding what to publish.”


Responding to these assertions is again a daunting task. The preceding paragraph by Dr. Fields referred to “open access publishing” of scientific papers, but this paragraph now makes references to self-published erotica or pornography. I do not understand how peer-reviewed open access papers in journals such as PLOS One or PLOS Medicine are “similar” to self-published erotica or pornography. I have read published PLOS papers and I have been a peer reviewer for PLOS manuscripts prior to their publication and I can assure you that these open access scientific papers are not very erotic and not self-published. Open access scientific papers published in journals such as PLOS papers are free of charge, whereas even self-published erotica can require the payment of a fee. Erotica have been popular for as long as literature has been popular. Some of the great works of literature are erotica or have major erotic themes, so it is not clear to me why erotica and literary works are presented as being mutually exclusive. The “reportedly pornographic” phrase makes me wonder whether Dr. Fields has even read “Fifty Shades of Grey”. Neither have I, so I cannot comment on the quality of “Fifty Shades of Grey”, but I know that the book has received some pretty bad reviews. Its literary quality or lack thereof is not necessarily a function of being self-published. Many best-sellers released by established publishers are also routinely panned by literary critics. Furthermore, even famous authors such as Marcel Proust were occasionally forced to self-publish their works, because publishing houses did not think that the manuscripts were in keeping with moral standards or that they would have a high market value.

Self-publication is actually a platform to publish books that are rejected by traditional publishers who focus on profitability and marketability of books and are averse to taking risks. It is true that the loss of editorial review in self-published books can result in the publication of poor-quality books, but that is a function of poor writing and not of self-publication. Proust and others were able to produce literary masterpieces even though they used the self-publication route. Self-publication increases the volume of published books and articles and does put an increased burden on readers and reviewers to discriminate between “good” and “bad” work. This increased burden is off-set by the opportunity that self-publishing offers for innovative books that are not considered profitable or marketable by traditional publishers. However, open access scientific journals are not self-published. Therefore the discussion about self-published erotica in the context of open access scientific publications is an unnecessary and irrelevant distraction.


Scientists and the public are rightfully outraged and we all suffer when flawed scientific studies are published. Even with the most rigorous review at the best journals, flawed studies sometimes slip through, such as the “discovery” of cold fusion published in Science, but it is the rarity of this lapse that makes this so sensational when it happens. With the new open-access model of author-financed publication, the “outstanding” is drowned in a flood of trivial or unsound work.


We actually do not know much about how much flawed research is published in pay-for-access journals. The vast majority of retractions stem from pay-for-access journals and so far there is no evidence that open access publication is drowning out outstanding research.


“The logic for this government mandate is peculiar. Why do this to science? The scientific journals claim no rights to the results of publicly funded scientific research; they only seek financial compensation for the expenses required for editing, reviewing and producing the article to validate and disseminate the findings as effectively as possible.”


The huge profits made by academic publishers using the pay-for-access model, where they make authors pay submission fees and also generate huge revenues from subscriptions clearly contradicts that publishers are out to maximize their profits. The answer to “Why do this to science?” is simple: Science belongs to all humankind.

“One wonders how many new advances in science will never have an opportunity to take root now that scientific publication is an increasingly corporate and government business rather than the scholarly academic activity that it was for centuries.”

Dr. Fields again forgets to mention that scientific publication has been a corporate run business in the past. The government is mandating free access to scientific research results, not running a business on the side.


In summary, Dr. Fields article is a diatribe against both open access and digital publishing, but few, if any, of the arguments are convincing. Many scientists who support both digital publishing and open access have great expectations for how it will help improve science. We think that digital publishing saves time and allows us to invest this time into conducting and analyzing research. Open access enables us to share scientific results with thousands and perhaps millions of students and scientists all across the globe. Scientific and medical developments published in open access journals are instantaneously available to everyone, whether it is scientists in Germany, patients in the USA or biology teachers in Mali. This allows everyone to partake in the scientific enterprise either by implementing the research findings or by enabling them to intellectually contribute to science. These are the reasons why science will improve in the new era of scientific publication. Even though we have great expectations, we also know that there will be many obstacles along the way. We have to continuously reevaluate the shift to open access publishing and we need objective and constructive criticism instead of rants to ensure that the new era of scientific publications maintains or even improves the quality of science that is published.


Image credit: Wikimedia / Public Domain – Artwork by H.M. Brock for Charles Dickens’ novel “Great Expectations”

The Healing Power of Sweat Glands

Two kinds of sweat glands are present in the human body. Apocrine sweat glands are located in arm-pits or rectogenital areas and are responsible for “smelly” sweat. Eccrine sweat glands, on the other hand, are distributed all over the human body and produce a non-odorous sweat. The eccrine sweat glands are primarily found in humans and certain primates. They also exist in some other mammals, but are usually restricted to the footpads of non-primate mammals. There is some controversy about the actual purpose of eccrine sweat glands in humans. The functions traditionally ascribed to eccrine sweat glands include promoting grip, generating a protective acid mantle for the skin as well as regulation of temperature or the electrolyte balance.

The recent article “Eccrine Sweat Glands are Major Contributors to Reepithelialization of Human Wounds” published in the American Journal of Pathology by Laure Rittié and colleagues proposes a novel and very interesting function for eccrine sweat glands. In this study, CO2 laser treatment was used to create superficial wounds in human subjects, either on their palm or on their forearms. The researchers performed biopsies during the subsequent days to assess the wound healing process. They observed significant proliferation of cells at the bases of hair follicles (pilosebaceous units) as well as proliferation of cells within the eccrine sweat glands. The outgrowths of cells from these areas merged together to regenerate the skin layer. Wound healing (re-epithelialization) in the palms of hands was primarily driven by cell proliferation of sweat gland cells, because the palms do not contain hair follicles.

The findings suggest that wound healing and regeneration of damaged skin may be an important function of cells that reside within human eccrine sweat glands. The study did not quantify the exact contribution of the sweat glands to the wound healing process or compare it with the contributions of other cell types. It also did not address whether the sweat production itself regulates or facilitates the repair process. This would be an intriguing possibility, because we all know how our palms become sweaty when we are under stress. Is it possible that the eccrine sweat production is a way of preparing the body for potential wounds and the need for repair or regeneration? Is there a way to enhance the wound healing emanating from the eccrine sweat glands? These and other questions will need to be addressed in future studies.

In summary, the work by Rittié and colleagues presents an important new perspective on how sweat glands can participate in wound healing. It is also an important reminder of how some animal models of wound healing may have their limitations when their results are translated to the human setting. Most laboratory animals that are used for wound healing studies do not have eccrine sweat glands. Results derived from such animal wound healing studies may thus not be readily applicable to the human setting and should be interpreted with a grain of sweat (salt).


Image credit: Wikimedia / National Institutes of Health – Anatomy of Skin

Somatic Mosaicism: Genetic Differences Between Individual Cells

The cells in the body of a healthy person all have the same DNA, right? Not really! It has been known for quite some time now that there are genetic differences between cells within one person. The expression to describe these between-cell differences is “somatic mosaicism“, because cells can represent a mosaic of genetic profiles, even within a single organ. During embryonic development, all cells are derived from one fertilized egg and ought to be genetically identical. However, during every cell division errors and differences during DNA replication can occur and this can lead to genetic differences between cells. This process not only occurs during embryonic development but continues after birth.

As we age, our cells are exposed to numerous factors such as radiation, chemicals or other stressors which can causes genetic alterations, ranging from single nucleotide mutations to duplications and deletions of large chunks of DNA. Some mutations are known to cause cancer by making a single cell grow rapidly, but not all mutations lead to cancer. Many spontaneous mutations can either result in the death of a cell or do not even impact its function in any significant manner. DNA copy number variations (CNVs) is an expression used to describe a variable copy number of larger DNA segments of one kilobase (kb). Most recent studies on CNVs have compared CNVs between people, i.e. how many CNVs does person A have when compared to person B. It turns out that there may be quite a bit of genetic diversity between people that had previously been overlooked.

A new paper published in the journal Nature takes this one step further. It not only shows that there are significant CNVs between people, but even within a single person. In the study “Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells“, Alexej Abyzov and colleagues found significant CNVs in induced pluripotent stem cells (iPSCs) that they had generated from the adult skin cells of human subjects. Importantly, most of these CNVs were not the result of reprogramming adult skin cells to the stem cell state. They were already present in the skin fibroblasts obtained from the human subjects. Most analyses of CNVs are performed on whole tissues or biopsies, but not on single cells, which is why so little is known about between cell CNV differences. However, when iPSCs are generated from skin fibroblast cells, they are often derived from a single cell. This enables the evaluation of genetic diversity between cells.

Abyzov and colleagues estimate that 30% of adult skin fibroblasts carry large CNVs. This estimate is based on a very small number of fibroblast samples. It is not clear whether other cells such as neurons or heart cells also have similar CNVs and whether the 30% estimate would hold up in a larger sample. Their work leads to the intriguing question: What percentage of neighboring cells in a single heart, brain or kidney are actually genetically identical? Cell types, such as heart cells or adult neurons cannot be clonally expanded so it may be difficult to determine the genetic diversity within a heart or a brain using the methods employed by Abyzov and colleagues.

What are the implications of this work? On a practical level, this study suggests that it may be important to derive multiple iPSC clones from a subject’s or patient’s skin cells, if one wants to use the iPSCs for disease modeling. This will help control for the genetic diversity that exists among the skin cells. However, a much more profound implication of this work is that we have to think about between-cell diversity within a single organ. We need to develop better tools for how to analyze genetic diversity between individual cells, and more importantly, we have to understand how this genetic diversity impacts health and disease.

Image Credit: Wikimedia / Alexander Mosaic (Public Domain)

Abyzov A, Mariani J, Palejev D, Zhang Y, Haney MS, Tomasini L, Ferrandino AF, Rosenberg Belmaker LA, Szekely A, Wilson M, Kocabas A, Calixto NE, Grigorenko EL, Huttner A, Chawarska K, Weissman S, Urban AE, Gerstein M, & Vaccarino FM (2012). Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature, 492 (7429), 438-42 PMID: 23160490

Recent Study Raises Questions About Using Adult Stem Cells for Chronic Heart Disease

A recent clinical study (POSEIDON Randomized Trial) investigated the effects of transplanting bone marrow derived adult stem cells into patients with known heart disease. The results were presented at the 2012 American Heart Association (AHA) meeting in Los Angeles and also published in the article “Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy: The POSEIDON Randomized Trial“. The article by Dr. Joshua Hare and colleagues appeared in the online edition of the Journal of the American Medical Association on November 6, 2012.

The primary goal of the study was to compare whether adult stem cells from other donors (allogeneic cells) are just as safe as the stem cells derived from the patients’ own bone marrow (autologous cells). Thirty patients with a prior heart attack and reduced cardiac function received either allogeneic or autologous cells. The injected cells were mesenchymal stem cells (MSCs), an adult stem cell type that resides within the bone marrow and primarily gives rise to bone, fat or cartilage tissue. MSCs are quite distinct from hematopoietic stem cells (HSCs) which are also present in the bone marrow but give rise to blood cells. In the POSEIDON study, patients underwent a cardiac catheterization and the MSCs were directly injected into the heart muscle. Various measurements of safety and cardiac function were performed before and up to one year after the cell injection.

The good news is that in terms of safety, there was no significant difference when either autologous or allogeneic MSCs were used. Within the first month after the cell injection, only one patient in each group was hospitalized for what may have been a major treatment related side effect. In the long-run, the number of adverse events was very similar in both groups. The implication of this finding is potentially significant. It suggests that one can use off-the-shelf adult stem cells from a healthy donor to treat a patient with heart disease. This is much more practical than having to isolate the bone marrow from a patient and wait for 4-8 weeks to expand his or her own bone marrow stem cells.

The disappointing news from this study is that one year following the stem cell injection, there was minimal improvement in the cardiac function of the patients. The ejection fraction of the heart is an indicator of how well the heart contracts and the normal range for healthy patients is roughly 55-60%. In the current study, patients who received allogeneic cells started out with an average ejection fraction of 27.9% and the value increased to 29.5% one year after the cell injection. The patients who received autologous cells had a mean ejection fraction of 26.2% prior to the cell transplantation and a mean ejection fraction of 28.5% one year after the stem cell therapy. In both groups, the improvement was minimal and not statistically significant. A different measure of the functional capacity of the heart is the assessment of the peak oxygen consumption. This measurement correlates well with the survival of a patient and is also used to help decide if a patient needs a heart transplant. There was no significant change in the peak oxygen consumption in either of the two groups of patients, one year after the treatment. Some other measures did indicate a minor improvement, such as the reduction of the heart attack scar size in both patient groups but this was apparently not enough to improve the ejection fraction or oxygen consumption.

One of the key issues in interpreting the results is the fact that there was no placebo control group. The enrollment in a research study and the cell injection procedure itself could have contributed to minor non-specific or placebo benefits that were unrelated to the stem cell treatments. One odd finding was that the patient sub-group which showed a statistically significant improvement in ejection fraction was the group which received the least stem cells. If the observed minor benefits were indeed the result of the injected cells turning into cardiac cells, one would expect that more cells would lead to greater functional improvement. The efficacy of the lowest number of cells points to non-specific effects from the cell injection or to an unknown mechanism by which the injected cells activate cardiac repair without necessarily becoming cardiac cells themselves.

The results of this study highlight some key problems with current attempts to use adult stem cells in cardiovascular patients. Many studies have shown that adult stem cells have a very limited differentiation potential and that they do not really turn into beating, functional heart cells. Especially in patients with established, long-standing heart disease, the utility of adult stem cells may be very limited. The damage that the heart of these patients has suffered is probably so severe that they need stem cells which can truly regenerate the heart. Examples of such regenerative stem cells are embryonic stem cells or induced pluripotent stem cells which have a very broad differentiation potential. Cardiac stem cells, which exist in very low numbers within the heart itself, are also able to become functional heart cells. Each of these three cell types is challenging to use in patients, which is why many current studies have resorted to using the more convenient adult bone marrow stem cells.

Human embryonic stem cells can develop into functional heart cells, but there have been numerous ethical and regulatory concerns about using them. Induced pluripotent stem cells (iPSCs) appear to have the capacity to become functional heart cells, similar to what has been observed for human embryonic stem cells. However, iPSCs were only discovered six years ago and we still have a lot to learn more about how they work. Lastly, cardiac stem cells are very promising but isolating them from the heart requires an additional biopsy procedure which can also carry some risks for the patients. Hopefully, the fact that adult bone marrow stem cells showed only minimal benefits in the POSEIDON study will encourage researchers to use these alternate stem cells (even if they are challenging to use) instead of adult bone marrow stem cells for future studies in patients with chronic heart disease.

One factor that makes it difficult to interpret the POSEIDON trial is the lack of a placebo control group. This is a major problem for many stem cell studies, because it is not easy to ethically justify a placebo group for invasive procedures such as a stem cell implantation. The placebo patients would also have to receive a cardiac catheterization and injections into the heart tissue, but instead of stem cells, the injections would just contain a cell-free liquid solution. Scientifically, such a placebo control group is necessary to determine whether the stem cells are effective, but this scientific need has to be weighed against the ethics of a “placebo” heart catheterization. Even if one were to ethically justify a “placebo” heart catheterization, it may not be easy to recruit volunteer patients for the study if they knew that they had a significant chance of receiving “empty” injections into their heart muscle.

There is one ongoing study which is very similar in design to the POSEIDON trial and it does contain a placebo group: The TAC-HFT trial. The results of this trial are not yet available, but they may have a major impact on whether or not bone marrow stem cells have a clinical future. If the TAC-HFT trial shows that the bone marrow stem cell treatment for patients with chronic heart disease has no benefits or only minor benefits when compared to the placebo group, it will become increasingly difficult to justify the use of these cells in heart patients.

In summary, the POSEIDON trial has shown that treating chronic heart disease patients with bone marrow derived stem cells is not yet ready for prime time. Bone marrow cells from strangers may be just as safe as one’s own cells, but if bone marrow stem cells are not very effective for treating chronic heart disease, than it may just be a moot point.


Image credit: Wikipedia

Science Journalism and the Inner Swine Dog

A search of the PubMed database, which indexes scholarly biomedical articles, reveals that 997,508 articles were published in the year 2011, which amounts to roughly 2,700 articles per day. Since the database does not include all published biomedical research articles, the actual number of published biomedical papers is probably even higher. Most biomedical researchers work in defined research areas, so perhaps only 1% of the published articles may be relevant for their research. As an example, the major focus of my research is the biology of stem cells, so I narrowed down the PubMed search to articles containing the expression “stem cells”. I found that 14291 “stem cells” articles were published in 2011, which translates to an average of 39 articles per day (assuming that one reads scientific papers on week-ends and during vacations, which is probably true for most scientists). Many researchers also tend to have two or three areas of interest, which further increases the number of articles one needs to read.

Needless to say, it has become impossible for researchers to read all the articles published in their fields of interest, because if they did that, they would not have any time left to conduct experiments of their own. To avoid drowning in the information overload, researchers have developed multiple strategies how to survive and navigate their way through all this published data. These strategies include relying on recommendations of colleagues, focusing on articles published in high-impact journals, only perusing articles that are directly related to one’s own work or only reading articles that have been cited or featured in major review articles, editorials or commentaries. As a stem cell researcher, I can use the above-mentioned strategies to narrow down the stem cell articles that I ought to read to the manageable number of about three or four articles a day. However, scientific innovation in research is fueled by the cross-fertilization of ideas. The most creative ideas are derived from combining seemingly unrelated research questions. Therefore, the challenge for me is to not only stay informed about important developments in my own areas of interest. I also need to know about major developments in other scientific domains such as network theory, botany or neuroscience, because discoveries in such “distant” fields could inspire me to develop innovative approaches in my own work.
In order to keep up with scientific developments outside of my area of expertise, I have begun to rely on high-quality science journalism, which can be found in selected print and online publications or in science blogs. Good science journalists accurately convey complex scientific concepts in simple language, without oversimplifying the actual science. This is easier said than done, because it requires a solid understanding of the science as well as excellent communication skills. Most scientists are not trained to communicate to the general audience and most journalists have had very limited exposure to actual scientific work. To become good science journalists, either scientists have to be trained in the art of communicating results to non-specialists or journalists have to acquire the scientific knowledge pertinent to the topics they want to write about. The training of science journalists requires time, resources and good mentors.
Once they have completed their training and start working as science journalists, they still need adequate time, resources and mentors. When writing about an important new scientific development, good science journalists do not just repeat the information provided by the researchers or contained in the press release of the university where the research was conducted. Instead, science journalists perform the necessary fact-checking to ensure that the provided information is indeed correct. They also consult the scientific literature as well as other scientific experts to place the new development in the context of the existing research. Importantly, science journalists then analyze the new scientific development, separating the actual scientific data from speculation as well as point out limitations and implications of the work. Science journalists also write for a very broad audience, and this also poses a challenge. Their readership includes members of the general public interested in new scientific findings, politicians and members of the private industry that may base political and economic decisions on scientific findings, patients and physicians that want to stay informed about innovative new treatments and, as mentioned above, scientists that want to know about new scientific research outside of their area of expertise.
Unfortunately, I do not think that it is widely appreciated how important high-quality science journalism is and how much effort it requires. Limited resources, constraints on a journalist’s time and the pressure to publish sensationalist articles that exaggerate or oversimplify the science in order to attract a larger readership can compromise the quality of the work. Two recent examples illustrate this: The so-called Jonah Lehrer controversy, where the highly respected and popular science journalist Jonah Lehrer was found to fabricate quotes, plagiarize and oversimplify the research as well as the more recent case where the Japanese newspaper Yomiuri Shimbun ran a story about the use of induced pluripotent stem cells to treat patients with heart disease, which turned out to be a fraudulent claim of the researcher. The case of Jonah Lehrer was a big shock for me. I had enjoyed reading a number of his articles and blogs that he had written and, at first, it was difficult for me to accept that his work contained so many errors and evidence of misconduct. Boris Kachka has recently written a very profound analysis of the Jonah Lehrer controversy in New York Magazine:

Lehrer was the first of the Millennials to follow his elders into the dubious promised land of the convention hall, where the book, blog, TED talk, and article are merely delivery systems for a core commodity, the Insight.

The Insight is less of an idea than a conceit, a bit of alchemy that transforms minor studies into news, data into magic. Once the Insight is in place—Blink, Nudge, Free, The World Is Flat—the data becomes scaffolding. It can go in the book, along with any caveats, but it’s secondary. The purpose is not to substantiate but to enchant.

Kachka’s expression “Insight” describes our desire to believe in simple narratives. Any active scientist knows that scientific findings tend to be more complex and difficult to interpret than we anticipated. There are few simple truths or “Insights” in science, even though part of us wants to seek out these elusive simple truths. The metaphor that comes to mind is the German expression “der innere Schweinehund”. This literally translates to “the inner swine dog”. The expression may evoke the image of a chimeric pig-dog beast created by a mad German scientist in a Hollywood World War II movie, but in Germany this expression is actually used to describe a metaphorical inner creature that wants us to be lazy, seek out convenience and avoid challenges. In my view, scientific work is an ongoing battle with our “inner swine dog”. We start experiments with simple hypotheses and models, and we are usually quite pleased with results that confirm these anticipated findings because they allow us to be intellectually lazy. However, good scientists know that more often than not, scientific truths are complex and we need to force ourselves to continuously challenge our own scientific concepts. Usually this involves performing more experiments, analyzing more data and trying to interpret data from many different perspectives. Overcoming the intellectual laziness requires work, but most of us who are passionate about science enjoy these challenges and seek out opportunities to battle against our “inner swine dog” instead of succumbing to a state of perpetual intellectual laziness.
When I read Kachka’s description of why Lehrer was able to get away with his fabrications and over-simplifications, I realized that it was probably because Lehrer gave us the narratives we wanted to believe. He provided “Insight” – portraying scientific research in a false shroud of certainty and simplicity. Even though many of us look forward to overcoming intellectual laziness in our own work, we may not be used to challenging our “inner swine dog” when we learn about scientific topics outside of our own areas of expertise. This is precisely why we need good science journalists, who challenge us intellectually by avoiding over-simplifications.

A different but equally instructive case of poor science journalism occurred when the widely circulated Japanese newspaper Yomiuri Shimbun reported in early October of 2012 that the Japanese researcher Hisashi Moriguchi had transplanted induced pluripotent stem cells into patients with heart disease. This was quite a sensation, because it would have been the first transplantation of this kind of stem cells into real patients. For those of us in the field of stem cell research, this came as a big surprise and did not sound very believable, because the story suggested that the work had been performed in the United States and most of us knew that obtaining approvals for using such stem cells in clinical studies would have been very challenging. However, it is very likely that many people who were not acquainted with the complexities of using stem cells in patients may have believed the story. Within days, it became apparent that the researcher’s claims were fraudulent. He had said that he had conducted the studies at Harvard, but Harvard stated that he was not currently affiliated with them and there was no evidence of any such studies ever being conducted there. His claims of how he derived the cells and in how little time he supposedly performed the experiments were also debunked.
This was not the first incident of scientific fraud in the world of stem cell research and it unfortunately will not be the last. What makes this incident noteworthy is how the newspaper Yomiuri Shimbun responded to their reporting of these fraudulent claims. They removed the original story from their page and issued public apologies for their poor reporting. The English-language version of the newspaper listed the mistakes in an article entitled “iPS REPORTS–WHAT WENT WRONG / Moriguchi reporting left questions unanswered”. These problems include inadequate fact-checking regarding the researcher’s claims and affiliations by the reporter and lack of consultation with other scientists whether the findings sounded reasonable. Interestingly, the reporter had identified some red flags and concerns:

–Moriguchi had not published any research on animal experiments.
–The reporter had not been able to contact people who could confirm the iPS cell clinical applications.
–Moriguchi’s affiliation with Harvard University could not be confirmed online.
–It was possible that different cells, instead of iPS cells, had been effective in the treatments.
–It was odd that what appeared to be major world news was appearing only in the form of a poster at a science conference.
–The reporter wondered if it was really possible that transplant operations using iPS cells had been approved at Harvard.
The reporter sent the e-mail to three others, including another news editor in charge of medical science, on the same day, and the reporter’s regular updates on the topic were shared among them.
The science reporter said he felt “at ease” after informing the editors about such dubious points. After receiving explanations from Moriguchi, along with the video clip and other materials, the reporter sought opinions from only one expert and came to believe the doubts had been resolved.

In spite of these red flags, the reporter and the editors decided to run the story. The reporter and the editors gave in to their intellectual laziness and desire of running a sensational story instead of tediously following up on all the red flags. They had a story about a Japanese researcher making a ground-breaking discovery in a very competitive area of stem cell research and this was the story that their readers would probably love. This unprofessional conduct is why the reporter and the editors received reprimands and penalties for their actions. Another article in the newspaper summarizes the punitive measures:

Effective as of next Thursday, The Yomiuri Shimbun will take disciplinary action against the following officials and employees:
–Yoshimitsu Ohashi, senior managing director and managing editor of the company, and Takeshi Mizoguchi, corporate officer and senior deputy managing editor, will each return 30 percent of their remuneration and salary for two months.
–Fumitaka Shibata, a deputy managing editor and editor of the Science News Department, will be replaced and his salary will be reduced.
–Another deputy managing editor in charge of editorial work for the Oct. 11 edition will receive an official reprimand.
–The salaries of two deputy editors of the Science News Department will be cut.
–A reporter in charge of the Oct. 11 series will receive an official reprimand.

I have mixed feelings about these punitive actions. I think it is commendable that the newspaper made apologies without reservations or excuses and listed its mistakes. The reprimands and penalties also highlight that the newspaper takes it science journalism very seriously and recognizes the importance of high professional standards. The penalties were also more severe for its editors than for the reporter, which may reflect the fact that the reporter did consult with the editors and they decided to run the story even though the red flags had been pointed out to them. My concerns arise from the fact that I am not sure punitive actions will solve the problem and they leave a lot of questions unanswered. Did the newspaper evaluate whether the science journalists and editors had been appropriately trained? Did the science journalist have the time and resources to conduct his or her research in a conscientious manner? Importantly, will science journalists be given the appropriate resources and protected from pressures or constraints that encourage unprofessional science journalism? We do not know the answers to these questions, but providing the infrastructure for high quality science journalism is probably going to be more useful than mere punitive actions. We can also hope that media organizations all over the world learn from this incident and recognize the importance of science journalism and put mechanisms in place to ensure that its quality.

Image via Wikimedia Commons/ Norbert Schnitzler: Statue “Mein Innerer Schweinhund” in Bonn