The Radical-Free Corner

More on impact factor metrics: are we ready to get rid of them?

Submitted by redoxoma on Wed, 09/26/2018 - 21:20

The Radical-Free corner by Francisco R. M. Laurindo

Recently, a young investigator wrote to Nature [1] urging to "stop saying that publication metrics do not matter and tell early-career researchers what does" when rating the scientific achievements of young investigators. This message highlights that increasing awareness against the inappropriate use of impact factor (IF) metrics for evaluating CVs is bringing, as a side effect, undertainty and lack of clarity on how someone's career achievements will be evaluated. This boils down to the simple question of whether we are ready to get rid of IF metrics.

First of all, it is important to say that it is increasingly accepted that using IFs as the sole metrics to evaluate someones's achievements in science is flawed by a number of reasons [2]. This tendency has led to the San Francisco "Declaration on Research Assessment" (DORA) in 2012, which has been since signed by over 500 institutions and 12000 individuals, calling among other issues, to "the need to eliminate the use of journal-based metrics, such as Journal IFs, in funding, appointment, and promotion considerations" and " the need to assess research on its own merits rather than on the basis of the journal in which the research is published ". In fact, recent experiences indicate that hiring investigators on the basis of addressing their achievements and contributions with interviews rather than traditional publication-based CVs has led to improved results [3]. Indeed, the current NIH-type biosketch (not dissimilar to FAPESP) is centered on the value of each individual's contribution to science.

All these welcome advances may have raised the perception, expressed in the comment from the first paragraph, that IF-related metrics do not matter any more. I believe the cold fact is that they still do to a reasonable extent and presently there is no completely adequate replacement for them, including the evaluation of young investigators. The distortions of strictly adhering to IFs and numeric scores should not be taken to mean that we have clear validated alternative methods available. Looking to someone's specific contributions and having a holistic approach when comparing a few candidates for academic purposes may indeed prove successful even with today's tools due to the low scale of this task. But even so, many evaluators still run their parallel evaluations of IF metrics, as this is yet so much embedded into our collective unconscious and provides some numerical scores with a security blanket of objectivity. However, problems become particularly acute when competitively evaluating a large number of CVs, e.g., regarding scholarships or large-scale research awards. As unfair and innaccurate as it would be to blindly rely only on the metrics, it would also be unfair to ignore them. Despite the limitations, there is indeed some gross correlation at least between the highest journal IFs with the quality and completeness of published work and ensuing amount and quality of the effort put into it. Along this line, IFs and number of articles do tell something about the capacity of the individual to choose important problems, to focus deep into a given problem until the end, to work hard and intensively into scientific questions and to be able to finish coherent stories about them. For the early-career investigator, relying solely on citations can be innappropriate because many good articles take a long time to get cited. Thus, number of published articles and their IF-related metrics are still a default basis for early-career CV evaluation. In fact, much before IFs were invented, everyone knew the most prestigious publications and those who published on them were positively considered.

On other hand, the limitations of those metrics are real. I believe that down the road these numbers can only help separate candidates that are very good or excellent from those that are merely good or median. However, metrics can significantly fail when trying to separate the top candidates from those that are just not as excellent. So, what can be done to improve on these issues? The DORA followers are getting away with all the metrics, however this leaves everyone, specially the young investigators, uneasy about how they will be evaluated and what are the best career strategies [1]. Without having the illusion (or arrogance?) that I will set the last word on this complex subject, I believe we are not yet ready to get rid of IF metrics in general, but the system can indeed take several extra paths to perfect, reinterpret and at the end eventually ignore them. Here I list some features that are increasingly being taken into account in the evaluation of young investigator's CVs. In the absence of a better collective term, I will call them modifiers, that is, each of them can potentially enhance or decrease potential inferences derived from metrics.

An important modifier is the intrinsic quality of the work, that is, overall degree of innovation, extent of contribution, implications for novel ideas or for potential applications, accuracy and completeness of the investigative strategy, and so on. Logically, the works having these qualities will usually take much more time to be performed and this allows less time to publish other papers, potentially decreasing the number of published items. Additionally, in some cases, these works may be published in journals that despite their solid reputation and tradition, along with lengthy and demanding reviews, do not display proportionally high IFs. Such are the cases of Journal of Biological Chemistry, Journal of Molecular Biology, American Journal of Physiology… among others. Contrarily, some journals use a number of strategies to unrealistically maximize their IFs and the intrinsic value of the work they publish may not be proportionally as high (this is a good theme for future discussions). Evaluators should take all these issues into account. However, it is important that the scientist being evaluated does not assume that reviewers will appreciate the quality of someone's work by default: reviewers are uniformely very busy and may not be from the particular subarea that would readily understand the specifics. Thus, the intrinsinc qualities of each one's work have to be explicitly clarified by the author. The investigator's biosketches from many research agencies, including Fapesp, provide appropriate space for the investigator to write in a few lines what is the contribution and novelty of that paper, as well as anything else that can indicate intrinsic value (e.g., it is a pioneer work in specified aspects, it contributed to diagnostic or therapeutic advances, it served as a basis for public policies, etc) or the community's perception of value (e.g., it promoted the invitation for a relevant talk, it was the theme of an editorial comment or chosen as the cover article, etc). This will contribute to identify intrinsic qualities in published work, which will adjust and improve the interpretations of numeric scores, in some cases even allowing one to get totally out of them. Interestingly, for unclear reasons, investigators have rarely made use of this strategy at Fapesp, although the biosketch format allows that.

On the opposite side, in some cases young investigators display a CV characterized by a large number of publications, however of intrinsic low value: incremental contributions, not-so innovative advances or questionable methodology. Given the conundrums of the scientific publishing scenario nowadays, these works do get published somehow. In other cases, the works are multiauthored without a clear contribution of the author being evaluated, which sometimes will appear as a middle-author amongst several others. There is nothing wrong – and actually it is good – to get involved in many investigations from a given group. Moreover, in some cases of multiple high-quality cooperative work, a middle position by no means indicates a negligible contribution. Again, disclosing the author's contribution for that particular work in the space provided in the biosketch is essential and will help understand the potential value of the author's contribution and how it differs from the so-called "salami-splicing" type of CV. Moreover, I suggest that the authors separately highlight, in their biosketches, only their few principal works by which they want to be evaluated and leave the others as a group of collaborations. That will avoid that noise from too many works obscures what really matters.

A further enhancer in a CV is what I would call "vertical coherence", that is, the connectivity accross each of the investigator's papers, allowing one to foresee the emergence of an investigative track. This multiplies the importance of each work, so their overall value is larger than the sum of each part. Again, these connections must be emphasized and explained by the investigator.

Another relevant aspect is that there are other dimensions of impact of a scientific work that transcend the scientific sphere. This is recognized now by many research agencies, including Fapesp, and comprise : 1) Social relevance and 2) Economic impact. Furthermore, in some areas, general metrics of impact are lower than those in other areas as a characteristic of the field. Again, in such cases, the relevant information will not be readily obvious for reviewers that are not too specialized and thus should be clearly highlighted by the investigator.

These considerations indicate that a number of parallel aspects can affect the perception and interpretation of the IF metrics, providing a more accurate and fair picture. Are these modifiers subjective? Perhaps yes to a good extent, but one has to balance the problems. Certainly, at this time we still face a paradox. As discussed above, IF metrics is still embedded into the system. On the other hand, it is likely possible that incorporating the modifiers described in this essay and trying more and more to have a systematic approach to them will enhance the capacity to select the best achievements while getting off the numerical score tiranny. Decorating the basic metrics with such a "systematic subjectivity" evaluation and perfecting it along time seems more realistic, feasible and less traumatic to early-career scientists than just abandoning metrics all of a sudden. While we love to hate IFs, they are still deep into our minds.

J. Tregoning. How will you judge me if not by impact factor? Nature, 558(7710): 345, 2018 | doi: 10.1038/d41586-018-05467-5
J. K. Vanclay. Impact factor: outdated artefact or stepping-stone to journal certification? Scientometrics, 92(2): 211-38, 2011 | doi: 10.1007/s11192-011-0561-0
S. L. Schmid. DORA Molecular Biology of the Cell, 28(22): 2941-4, 2017 | doi: 10.1091/mbc.e17-08-0534

Francisco R. M. Laurindo, Editor in Chief of Redoxoma Newsletter
Heart Institute (InCor), University of São Paulo Medical School, Brazil

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The Mismeasure of Science

Submitted by redoxoma on Tue, 11/22/2016 - 11:46

The Radical-Free Corner by Gregory A. Petsko

This article is reproduced from the IUBMB News, issue 1 (February 2016), with kind permissions of the author and IUBMB (Dr. Michael P. Walsh, Secretary General). Dr. Petsko is Adjunct Professor at Cornell University, a member of the National Academy of Sciences of the USA and a former president of the American Society for Biochemistry and Cell Biology (among many other positions). His research provided major contributions for understanding structure-function relations of proteins, including many related to neurodegenerative diseases (Ed. Note)

High on my list of things that need changing in the culture of science today – and it’s a list that gets longer by the week – is the obeisance being paid by people who should know better to the meaningless, pervasive metrics that have skulked into our community like a burglar in the rosebushes. I am referring to the ubiquitous citation number and its illegitimate offspring, the impact factor and the h-index.

This problem may have reached its nadir (though I doubt it) with the appearance a couple of years ago of a sort of index of indices, the Q-index, which provides each academic member with individualised reports showing the key research and teaching performance data that are available from the university’s information systems. It also provides relevant benchmarks that support comparisons with average performance levels across the University and within units. The Q-index is comprised of two parts: the QR-Index focuses on measures of research performance and the QT-Index focuses on student evaluations of their teaching experience.

What amazes me is that faculty seem meekly to have accepted that their careers can be encapsulated in a single number – a number that is used to evaluate their performance comparatively with the performances of their peers. Could any administrator ask for a better tool to turn the faculty against one another? All the faculty energy that should, in a normal university, be expended in fighting their natural enemies, the bureaucrats, is now directed towards internecine competition for the best Q-index. Pay raises, promotions, and as far as I know even the selection of one’s mate will now be left to a bunch of paper-shufflers who can justify every decision by referring to a number whose validity is not only unproven but unprovable, yet has the same mystic authority as an IQ score.

Which brings me, of course, to the IQ score. The legendary evolutionary biologist Stephen Jay Gould devoted an entire book, The Mismeasure of Man, to debunking that particular metric and its abuse by racists and eugenicists. First published in 1981, revised and expanded in 1996, The Mismeasure of Man is a brilliant refutation of the idea that “scientific” data have proven – or can prove – the intellectual superiority of one group over another. What makes this book particularly relevant for our discussion is a concept that he introduces on page 27 in my copy of the 1996 edition: reification (from the Latin word res, meaning “thing”). Gould defines reification as a fallacy of reasoning that occurs when we try to convert an abstract concept (like intelligence) into a concrete entity (like an IQ score). I’ve traced the concept back to Alfred North Whitehead, who calls it the Fallacy of Misplaced Concreteness, and further back to William James, who in 1909 had this to say about it: “The viciously privative employment of abstract characters and class names is, I am persuaded, one of the great original sins of the rationalistic mind.” He called it the fallacy of Vicious Abstractionism.

Citation analysis marked the introduction of this fallacy into scientific discourse. At first, it seemed harmless enough: all it did was measure exactly what it claimed to, namely the number of times a paper was cited in the subsequent literature. But then reification set in. Citation number began to be conflated with the impact of a paper, even though “impact” is an abstract concept that should not – and cannot – be converted into a concrete entity. It was but a short step from that to the abomination of the impact factor, which purported to measure the impact of an entire journal by a single metric.

To make matters still worse, impact factor began to be conflated with the quality of the journal, even though impact and quality are two completely different things. Impact means the effect or influence of one person, thing or action on another; quality means the degree of excellence of something. You can be excellent without having much of an impact (see Bugatti, Ettore). You can have a huge impact without being excellent (see Trump, Donald). But most of all, neither of these completely different concepts, impact and quality, is a thing that can be quantified, especially in a single number.

Our European brothers and sisters appear to have sat by and watched while administrators seized upon the impact factor of where one publishes as a way to rank faculty. Promotion, salary increases and funding all became tied to how many papers one published in self-stylized “high-impact journals” – journals with impact factors considerably over 10.

Do you know how silly this is? The most important physics paper published in my lifetime, by a large margin I think, was published Feb 12 of this year: “Observation of Gravitational Waves from a Binary Black Hole Merger” by Abbott et al. (and, with over 1000 co-authors, there’s an awful lot of ‘et al.’). That paper was published in Phys. Rev. Lett., which has an official impact factor of 7.5; you could get fired in many European institutions for publishing in a place like that.

It’s not enough that worshiping at the altar of the impact factor has allowed bureaucrats with no scientific judgment to pass judgment on scientists by simple arithmetic. It has polluted the entire culture of science. Where you publish has now become an acceptable proxy for the content of the paper. I can’t count the number of times I have sat in a review panel for a grant or a fellowship or promotion and heard a fellow reviewer say, “So-and-so has published 2 Nature papers and one Cell paper”. And then when I, in my best fake innocent tone, ask that reviewer, “Uh, can you tell me what was in those papers and why they were important?” all too often I am met with the reply that the reviewer has not read them.

If the only thing that matters is to publish in a few journals, then of course everyone will want to publish in those journals, which gives said journals – and the non-practicing scientists who staff them – enormous power over the careers of people they have never even met.

Think it can’t happen here (here being wherever you are, unless of course it’s already happened there)? Think again. The metrics are on the march, to the beat of reification. In the U.S., at Rutgers University, the state university of New Jersey (a state known for both the pharmaceutical industry and organized crime), the administration has contracted with a company called Academic Analytics to measure the productivity of its faculty. You can read about this stupidity, and the reaction from the Rutgers faculty, in this excellent article from Inside Higher Ed. The company, you will be frightened to know, has 385 institutional customers in the U.S. and abroad, representing about 270,000 faculty members in 9,000 Ph.D. programs and 10,000 departments. This is coming soon to a theater near you.

A Rutgers faculty resolution against the contract reads, in part, “the entirely quantitative methods and variables employed by Academic Analytics -- a corporation intruding upon academic freedom, peer evaluation and shared governance -- hardly capture the range and quality of scholarly inquiry, while utterly ignoring the teaching, service and civic engagement that faculty perform.” It also notes more practical concerns, such as that “taken on their own terms, the measures of books, articles, awards, grants and citations within the Academic Analytics database frequently undercount, overcount or otherwise misrepresent the achievements of individual scholars.” The contract, by the way, does not allow faculty access to data about themselves. Rutgers administrators say that the data are only used to evaluate departments and programs, not individuals. If you believe that, I have a bridge in Brooklyn I'd love to sell you.

The problem is not the use of any particular number, it’s the use of any number. Under the guise of improved accountability and outcomes assessment, people of questionable critical ability are usurping the rightful position of those who should be making evaluations, by relying on metrics that are not only unproven but also irrelevant. Numbers don’t know about people, nor do they care. That can be a good thing, but not when it comes to passing judgment. For that you need wisdom, insight, and sometimes compassion.

Ron DeLegge II famously remarked that “99 percent of all statistics only tell 49 percent of the story.” He was right, but only up to a point. Sometimes they tell none of it.

Dr. Gregory A. Petsko, Adjunct Professor
Cornell University, USA

[The views expressed in this article are those of the author and do not necessarily reflect the oppinion of all Redoxoma members.]

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The importance of a good laboratory Notebook

Submitted by redoxoma on Tue, 11/22/2016 - 11:45

Highlights by Paolo Di Mascio

A good scientist knows the importance of keeping all experimental records very well organized. Keeping a good laboratory notebook (LNB) is essential at the time of writing papers and reports, but can also save your time when repetitions are necessary some time later. In fact, this is a practice adopted in various industries where, by legislation, the laboratory procedure must be well documented.

LNBs are, also, important as legal documents to prove patents and defend your data against accusations of fraud. LNB is a Scientific Legacy in the laboratory of your Institution.

Currently, you can also keep an electronic LNB, but in those cases the creation date of the document and the authorship indication have to be very clear, otherwise it will not serve as a legal document. In US, for example, a person can use the LBN as evidence showing an earlier date of the concept of the patent.

How to start a LNB

The LNB should have a name on the cover for easy identification. Preferentially, there should be a signed record of who took each book.

On a separate cover page, you should WRITE YOUR FULL NAME and the YEAR you are starting the LNB, the NAME OF THE PROJECT, and THE E-MAIL ADDRESS WITH YOUR PRINCIPAL INVESTIGATOR’S NAME.

The LNB should record the procedures, reagents, DATA, etc., and thoughts that may be pass to other researchers. For this, explanation of WHY experiments were initiated, HOW they were performed, and the results.

The experimental entries, the Details of “How” and “Ethics”.

Entries: date, title, hypothesis or Goal, brief statement of purpose, background.

Protocols: calculations, reagents, equipment.

Observation: All that happens (planned or unplanned), raw experimental data, taped in information or reference to data location.

Data analysis: Processing of raw data, graphs and interpretations.

Ideas for future experiments!

Ethics: all data go in to the notebook, no pages come out of the notebook, correct mistakes, do not remove them and honesty is the best policy.

It is our scientific obligation, Science must be reproducible, the work should be reproducible faithfully by yourself and others. This will facilitate accurate reporting and publication. The NBL organizes how you do Science, formulate ideas clearly, specifying materials and methods, planning experiments well and obtaining maximum value from data.

This will protect also the intellectual property!

General aspect of the LNB

Bound notebooks, consecutive entries, no blank pages or spaces, fill in with line, use non-erasable ink pen, to delete simply strike through and write LEGIBLY (We can read and understand Leonardo’s notebooks from 500 years ago)!

As examples, see the LNBs from Leonardo da Vinci, Marie Sklodowska Curie , Charles Darwin, Albert Einstein, Linus Pauling, Francis Crick, Gregor Mendel and Thomas Edison)

Leonardo da Vinci, Studies of reflections from concave mirrors. Italy, probably Florence, from 1508.
Source: British Library, Public domain

Marie Sklodowska Curie (1867-1934). Impressions of America. Autograph manuscript, 11 leaves, 1921. - RBML, Meloney-Curie Papers
Source: Rare Book & Manuscript Library, Columbia University

Charles Darwin, 1837. First Notebook on Transmutation
Source: Wikimedia, Public domain

Albert Einstein: Click to see an Einstein's notebook, image protected by copyrights:
The Albert Einstein Archives, The Hebrew University of Jerusalem

Linus Pauling: Click to see a page extracted from Linus Pauling's Notebook, image protected by copyrights:
Special Collections & Archives Research Center, Oregon State University Libraries

Francis Crick (1954). "Model Building"
Source: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers, licensed under a Creative Commons Attribution 4.0 International license

Gregor Mendel (circa 1864)
Source: Mendel Museum, apud Strong Brains

Thomas Edison (1873). [NE1691] Notebook Series -- Experimental Researches: Cat. 994 Vol. 1 (1875-1876, 1877-1878) [NE1691005; TAEM 3:196]
Source: The Thomas Edison Papers, Rutgers

Comments

Rhian Touyz (not verified)

Thank you for this very important report. I will share it with all my lab members. One can not stress enough the importance of accurate documentation and honest reporting

Sun, 12/04/2016 - 10:11 Permalink

Jalen jenkins (not verified)

I think its important to keep a ISN because of all the info you can store in it. If you don’t take notes then how are you going to be able to go back and take a look at what you have been doing. I also think its important because if you make a mistake you can record what you did and then it will teach you a lesson for next time.

Tue, 08/28/2018 - 13:35 Permalink

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How I see the future of redox research

Submitted by redoxoma on Sat, 10/31/2015 - 20:06

With this issue, we start a series of short texts about the theme “How I see the future of redox research”. The radical-free corner was really radical in this regard and invited several prominent colleagues from Brazil and abroad. These comments are meant to be highly personal accounts, by known experts, of the directions they foresee redox research. We are sure these short insertions will kick on our minds to help our thinking.

And we started in great style, with no one less than Prof. Henry Jay Forman, a long-standing investigator of the area. Prof. Forman is the Distinguished Professor of Chemistry and Biochemistry, University of California, Merced, and the former President of the Society for Free Radical Biology and Medicine.

The Radical-Free Corner by Henry Jay Forman

Based on nearly a half century investigating redox biochemistry, I have observed repeatedly how trendy approaches have affected progress. Some still think “omics” are the what we should all be focused upon to generate hypotheses; however, now “omics” are just tools for those who have an actual hypothesis. I see a great future for mitochondrial biology, which was once the “thing," fade (I was told that my discovery of dihydroorotate driven superoxide production was “an uninteresting artifact”), and then return when new techniques allowed greater insight. But, the greatest advances will be made in understanding how redox signaling works in both normal and pathophysiology. It is likely that pathophysiology associated with aging involves greater inflammatory signaling responses partially due to decreased signaling that increases antioxidant defenses. This, rather than some kind of “redox signaling gone wild” may even have something to do with the aging process per se. While I don’t have a pet theory of aging, I think the speculation of others is fun to watch, as it is an area we must pursue as the population itself ages.

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Free radicals: should clinicians pay attention to them?

Submitted by redoxoma on Fri, 05/29/2015 - 20:03

The Radical-Free Corner by Protasio L. da Luz*

Within the Cepid-Redoxoma, we are deeply involved in redox research and we consider this very important, of course. However, it is interesting at times to see how some meaningful outsiders interpret the area. The Radical-Free Corner challenged a highly experienced academic clinician-scientist, who kindly accepted this task (he happens to have been the Editor’s doctorate supervisor – a minor conflict of interest, I confess)
(Editor's comment)

Oxidative stress pervades several areas of Medicine: aging, cancer, atherosclerosis and other degenerative conditions, principally. Several studies claim that it is the cause of aging. But while there is evidence for oxidative footprints in aged cells [1], this seems far from being the end of the story. Recently, for instance, Gladyshev [2] questioned this theory and suggested that oxidative stress is only part of a general process of biological imperfectness, in which several players are involved in aging and the whole process is influenced by many variables such as species or environmental circumstances. In atherosclerosis, several evidences indicate the importance of oxygen species in vascular pathophysiology. For instance, inactivation of NO by superoxide impairs arterial vasodilation and LDL oxidation is recognized as a fundamental mechanism in foam-cell formation and plaque development. There is even a specific receptor in macrophages to which oxidized LDL binds - LOX-1.

Oxidative stress is traditionally regarded as an imbalance between reactive oxygen species (ROS) production and their inactivation - or removal by natural antagonists (superoxide dismutase, for instance). The distinct ROS include some highly reactive chemicals that act upon specific molecular sites of proteins and other cellular chemical constituents, altering cellular signaling pathways in a way to interfere with their function. They are ubiquitous and inherent to essentially all living species. This fact by itself makes one think that reactive species might to a good extent be necessary, because nature does not do silly things; we believe there is always a purpose.

One characteristic of redox systems is that they are confined to specific compartments and organelles, such as mitochondria, endoplasmic reticulum and others. This makes them specially difficult to approach from a therapeutic point of view. There are thousands of sites where redox processes occur. Which of them participates in one specific disease, plus when or how, is far from well understood. Also, redox systems are part of the defense mechanisms of the human body, for ex., in killing pathogenic bacteria. Further, many if not most of the informations we have today are derived from in vitro experiments in cultured cells, or in non-human species. Although homology is a feature of living beings, even small genetic differences make huge distinction between phenotypes, such as between men and rats. As a consequence, it is not entirely clear how many of these experimental findings are relevant to men.

Given these characteristics, some relevant clinical questions remain:

what is the real contribution of oxidative stress to the pathophysiology of human diseases? Are they the cause, a marker or just an epiphenomenon?
do chemical measurements in plasma reflect intracellular phenomena?
can specific targets be identified? can these targets be reached with present therapeutic agents?

One disturbing observation comes from lessons of populations who live longest under natural conditions such as the Japanese from Okinawa. They never even heard of supplemental antioxidants and just adhere to a healthy life with appropriate food, exercise, religion, no smoking, no stress and long lasting family ties. Furthermore, when controlled studies with antioxidant vitamins were performed in high-risk patients such as in the HOPE trial [3] (in which 9542 men and women randomly received vitamin E or placebo for 4.5 years), results were bluntly negative. Those complex physiopathological issues and disappointing clinical results generate skepticism among doctors and in practice put anti-oxidants aside. Should clinicians just forget about this?

Following from basic research, at the end it is essentially required that good clinical, randomized trials are addressed towards answering these questions. A possibly informative trial would be to assess the effects of an innovative anti-oxidant upon the intima of coronary arteries in patients with stable coronary disease, using Optical Coherence Tomography (OCT), which is a recent, very sensitive method to analyse the intima; a specific question could be: “does an anti-oxidant prevents progression of coronary atherosclerosis?”. While being a surrogate variable to clinical events, OCT measurements are a powerful indicator. If such trials result negative, it would not be the first time. Hormone replacement therapy, e.g., is just as well firmly justified according to countless experimental studies; however, it only does not work when applied to women! It reminds me of the old story: “According to the laws of aerodynamics the bumblebees cannot fly. The extension of their wings and disproportionate body weight makes flying impossible, as it can be easily demonstrated in a wind tunnel. However, being unaware of these scientific facts, the bumblebee does fly and makes some honey too” . Or as Shapeskeare said: “There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy”. (Hamlet 1.5.167-8) Hamlet to Horatio.

D. P. Jones Redox theory of aging. Redox Biology, 5: 71-9, 2015. | dx.doi.org/10.1016/j.redox.2015.03.004
V. N. Gladyshev The free radical theory of aging is dead. Long live the damage theory! Antioxidants & Redox Signaling, 20 (4): 727-731, 2014. | dx.doi.org/10.1089/ars.2013.5228
S. Yusuf, G. Dagenais, J. Pogue, J. Bosch, P. Sleight. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. The New England Journal of Medicine, 342 (3): 154-60, 2000. | dx.doi.org/10.1056/nejm200001203420302

*Protasio Lemos da Luz, MD, FACC Senior Professor of Cardiology, Heart Institute (InCor), School of Medicine, Faculty of Medicine, University of São Paulo, Brazil e-mail: protasio.luz@incor.usp.br

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A radical-free talk about the scientific career: 3 Ds that allow for an E

Submitted by redoxoma on Thu, 02/05/2015 - 21:05

The Radical-Free Corner by Francisco R. M. Laurindo

Can professionalism be learned? Certainly, to some extent, but likely not in the way you learn Chemistry or Biology, for example. But you can – and you should – discuss it, in order to trigger further thoughts that can help to achieve personal improvement. This is the idea of this short essay, derived from lectures given at our annual retreats over the years. While written with the young student in mind, I think it fits other ages as well... It should not be read rationally, but emotionally, just like it was written.

A general feeling among scientists is that science is not for everyone and that the scientific career is unusual in many aspects. To a good extent, this is true. Successful scientists work very, very hard, often under deadline-induced pressures, generally under lower than average financial rewards, and are submitted to an unsurmountable amount of frustrations, which include: grant rejections, paper rejections, negative results, inconclusive results, incomplete papers, failure to attract and keep good students, incomprehension, lack of support, lack of recognition, and…bureaucracy, actually extreme bureaucracy. Yet, despite occasional downs, which hopefully will be shallow and transient, most just love their career choices. Passionately. Persistently. As a scientist, I wonder why this is so. In no other career one is thrilled by the excitement of discovery, of sharing the understanding of nature, even as an extremely small and humble part of it. In few other careers, every single day is completely unique and allows for novel challenges. Few other careers push your capabilities to your very extreme. In no other career one can form people through an individualized process that allows shaping each other’s minds. Also, the scientific career, at all levels from academy to industry, continuously exposes the scientist to gifted and intelligent colleagues from whom we can learn quite a lot. In a word, we can say that science provides a sense of …enchantment. This is not felt always. Sometimes it is absent for long periods and even for very long periods. But from the moment it is revived, even if briefly, the previous hardships will seem to have been worthwhile. Even though a few scientist colleagues of mine will disagree, I will shamelessly use my advantage as the Newsletter Editor to state, on a personal note, that I still firmly believe that enchantment is what brings most students to science – at least the best - and the perspective of enchantment will keep them going on. So, …enchantment. That is the “E” of the title.

Just like paper reviews, which often start praising the work and then kill it, you may be wondering….go ahead with the bad news! You are right. The first one is that there is a false enchantment, which is quite dangerous. By false, I mean the pseudo-enchantment feeling of superficially scratching the possible gold, but just making a phantasy and not effectively digging to touch it. It is similar but less legitimate than the fascination of a non-scientist for science. This associates with being unfocused, procrastinator, superficial…and unproductive. It can be quite insidious and only reveal itself when it is too late. The second bad news follows logically: enchantment does not come for free. Neither in science nor anywhere else. Versions ranging from the prosaic “there is no such a thing as a free lunch” to the sophisticated “per aspera ad astra” provide the same message: one needs to cultivate qualities that require significant effort to get the prize, the gold. These qualities make up the “Ds” of the title.

The first “D” is easy to guess. Dedication. If you quickly think “Oh! of course I am dedicated”, chances are that you are not. Those that are truly dedicated are often uneasy with their levels of commitment and at least will stop and think deeper over this question. That is because dedication does not equal accomplishing your duties in a bureaucratic doggish way. It is true that a prime issue is indeed how many weekly hours you work in scientific matters. Unwritten universal experience indicates that nothing substantial is accomplished even in the best research centers if someone does not work a minimum of around 60 hours/week. Even if you are a genius. However, it is also true that even working above normal and “doing my maximum” is not enough, first because quality of the work is essential (wait for the other Ds) and second, because your perceived maximum is much less than your real maximum. That is, true dedication involves working a lot, working well and continuously looking yourself for new solutions, and new challenges as well. Dressing, eating , dreaming, sweating, talking, thinking over and over your scientific questions. As an integral part of this process, one has to find and cultivate new capabilities that allow progression in a given field of interest. In other words, dedication involves continuously rediscovering yourself to match given challenges. This carries another D, determination, which I will not single out at this time. Dedication is highly individual, but many individuals are highly influenced or dominated by the milieu in which they act. Thus, you can also talk about a “group mood” or an “institutional mood” of dedication, either one important determinants of the perceived level to which a member (especially a newcomer) feels like dedicating her/himself. While it is difficult to generalize about group moods of dedication, I believe it is safe to say that the mood of most institutions in our country is still quite precarious (I will arbitrarily assign this statement a p<0.05), for a number of reasons I will skip saying. It quickly follows that if you want to seriously dedicate yourself to scientific questions you have to detach yourself from the mass. That happens for many other things (the other Ds, by the way) and you can survive very well to that. Actually I would simply call this …maturity, and I have seen this quality emerge in many students independently of their age. Invariably, this characteristic is a good marker of success in science.

The second D is hard to swallow. Discipline. And it is ugly because discipline translates into doing at the precise moment what you know well that has to be done but you do not feel like doing it. If you are still reading this article (from the beginning, I mean) you probably have a minimum of it. Most of those that approach the scientific career have this minimum. The problem is that this minimum is not enough. The challenges to be surpassed in the pursuit of quality science require a whole lot of discipline. This means things like regular hours in the experiments, routine extended hours in the lab, holiday/weekend working hours, thinking over results and analyzing data before the next experiment is repeated, not leaving the housekeeping work for tomorrow, keeping record books, reading papers in-between experiments, shorter lunch hours to enhance lab work productivity…. and so on. Moreover, the true discipline is really put to a challenging test when things are not going straight. The fatal circle in the lab is to decrease dedication and discipline when things start to go wrong. Considering that all works go through longer or shorter periods of negative and inconclusive results (I like to call these periods as “going through the cloud”), it follows that discipline is a direct factor determining the best possible outcome from this cloud, allowing you to get even a short glimpse of the surrounding landscape that is essential to keep going on.

Dis·cern·ment (noun \di-ˈsərn-mənt, -ˈzərn-\): the ability to see and understand people, things, or situations clearly and intelligently (Merriam-Webster Dictionary). The third D, and a capital one. For scientists, discernment has a very broad meaning, going from attitude, perception and maturity to a technical understanding of the scientific question being targeted. Acquiring discernment is at the core of scientific formation (and of personal growth as well, but I will not talk about it, as this is not a self-help pamphlet). I could say many things about discernment, but here I stick to two. First, making the best choices in science requires educated and profound information. That means reading and studying a lot. Considering that the scientific background of most beginner students in our system is below the desirable level (I will arbitrarily assign a P<0.01 to this statement),.it follows that the average brazilian student would have to read even more than the corresponding student at the most traditional internacional centers. Reading one paper a day is a good goal for essentially every student. What I usually see, however, is the opposite, with our students reading and debating science at levels clearly insufficient (I will arbitrarily assign a p<0.001 to this statement). It follows that their correct decision/time coefficient tends to be quite low. So, even if correct solutions are found, they tend to be too late and to compromise the whole final work. And time is crucial and runs very very fast. A sense of urgency, that everything is for yesterday, is actually a very good sign at discernment. The second touchstone of discernment is efficiency. That involves cleverness and wisdom in planning and organizing the flow of the investigation. The wisdom of asking the right questions and designing the right experiments. And, back to the previous D, also discipline and patience to dissect step-by-step the most crucial experimental steps of your work. And also organization in the experiments and the most efficient use of time. A general law, especially for our labs in Brazil, is: talk less, think more and read much more. Although sometimes you have to talk a lot, but to the right person.

I guess it is about time to finish writing this. But I still have two messages I want to leave. The first is that, although you construct all the above “Ds” over your lifetime, they can be cultivated during your scientific training. And to a good extent learned from scratch. This requires focus and determination, but it is necessary. This means also that mentors and mentees should talk about this individually and as a group. A good “mood of dedication” of a group can also be enhanced, although this is a slower process. Of course, talking has limited efficacy. The supervisor her/himself is the first to provide good examples of dedication, discipline and discernment. And you should start by choosing a supervisor and a group that indeed shows these qualities – yes, you should look hard for a group, do not take the first one that crosses your path. Now, frankly speaking, everything I talked so far has to do with achieving the good scientific contribution you dreamed about when you looked at science. That is, the quality science that we pursue so much in our country at this precise moment. For students, I am not talking about finishing your thesis. This is (sadly) easy in the brazilian system (I will arbitrarily assign a p<0.0001 to this statement – how many failures have you heard about on your program?). For post-docs, I am also not talking about just getting “another job”. If those are your only goals, you have wasted your time reading this article.

The second take-home message might surprise you: you are NOT a genius (I will arbitrarily assign a p<0.00001 to this statement – this is pure statistics!). Yes, you probably have a reasonable portfolio of qualities that are needed for science and which made you get where you are now. But at the bottom you and me are ordinary people that only happen to like science. In this context, I believe the statement of the beginning of this text, i.e., that “science is not for everyone and the scientific career is unusual in many aspects” should not be misinterpreted to mean that you can stay above the ordinary daily hardships of a normal profession (which translate in heavy work and studying……) and solutions will come miraculously to you or to your supervisor. Well, that happens to very few people that are extraordinarily gifted, but even for them, if you look hard, somewhere into their lives there was a lot of work and dedication. To me, that is exactly the beauty of science: the scientific contributions and enchantment we talked above can be achieved by people having talents that are not particularly extraordinary. However, a premise is that they cultivate the “D” qualities. I will leave you with the original (and personal favorite) quotation that inspired the last paragraph [1]: “It is the discipline of science that enables us as ordinary people…to go about doing ordinary things, which, when assembled, reveal the extraordinary intricacies and awesome beauties of nature. Science not only permits us to contribute to the progress of grand enterprises but also offers a changing and endless frontier for exploration of nature”.

A. Kornberg. Basic research: the lifeline of medicine. The FASEB Journal, 6 (13): 3143-45, 1992. | http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=1397835

Francisco R. M. Laurindo
Editor in Chief of Redoxoma Newsletter
Heart Institute (InCor)
University of São Paulo Medical School

Comments

Lia (not verified)

Once more, Chico Laurindo expressed with awesome words all our feelings!

Thu, 02/12/2015 - 23:40 Permalink