15 Years of PLOS ONE – Author Perspectives

November 29, 2021 Hanna Landenmark Interviews PLOS ONE 15th Anniversary

This December marks 15 years since PLOS ONE published its first papers. As we celebrate this milestone, we invited authors of some of the first papers to be published, as well as an author of a more recent paper, to share information about their careers, their perspectives on Open Science, and their experiences as PLOS ONE authors.

We spoke with Miriam Kolko (University of Copenhagen), Matthew Goddard (University of Lincoln), Andrej A Romanovsky (Arizona State University) and Seppo Ylä-Herttuala (University of Eastern Finland).

Their perspectives provide a fascinating insight into how their research careers have progressed in the past fifteen years, as well as the changes the research world has experienced. We hear about the importance of open science practices, and how open access publishing has gone from a relatively new idea fifteen years ago to an almost ubiquitous endeavor in the present day. They also discuss their experiences of both expected and unexpected discoveries, how they have stayed on track in pursuing their research goals, and the importance of being a good collaborator and keeping flexible in a dynamic research landscape.

Miriam Kolko

Miriam Kolko is a chief physician and glaucoma specialist at the Copenhagen University Hospital, Rigshospitalet-Glostrup and an author of the PLOS ONE paper “The Prevalence and Incidence of Glaucoma in Denmark in a Fifteen Year Period: A Nationwide Study [1]”.

Could you tell us a bit about what you are working on at the moment? What does your lab group look like?

MK: I am in the fortunate situation of leading the research group Eye Translational Research Unit, EyeTRU. We work with different aspects of glaucoma. All our research projects have the patient in mind and we thus have preclinical and clinical models to explore the pathophysiology behind glaucoma. In addition, we work to stratify and optimize existing treatments for glaucoma patients. We are particularly aware of the inappropriate side effects that occur with preservative-containing eye drops as well as the sparse regulation of generics. Finally, we work with big data to identify predictive factors for risk assessment and earlier detection of sight-threatening diseases, such as glaucoma. Currently, EyeTRU consists of 2 postdocs, 8 PhD students, a laboratory technician and several master’s and bachelor’s students.

It is essential to share knowledge, including sharing data, so that the most knowledge is obtained that can benefit patients
Miriam Kolko

What does a typical day at work look like for you?

MK: I am a clinician-scientist and spend half my time with patients and half time with teaching and research. I treat patients with glaucoma medically and surgically twice a week. The remaining time goes with research teaching and multicenter studies.

In your field, how important are open science practices? Do you have any success stories of having shared or re-used data, code, a preprint, or something else?

MK: Transparency is really important and creates the environment for original ideas and collaborations. The ability to publish preprints is one of many ways to share research at an early stage. Another very important prerequisite for knowledge sharing and innovative research is a safe working environment. Sure, competition is important, but teamwork is the key to ground-breaking research. In general, I believe that it is essential to share knowledge, including sharing data, so that the most knowledge is obtained that can benefit patients.

Can you tell us about an important moment in your career as a scientist, which helped shape you as a researcher?

MK: My research career started in the United States as a Fulbright scholar and later as a PhD student Under Professor Nicolas G Bazan. I spent a total of 5 years in the USA, which shaped me as a basic science researcher and has since given me the foundation to create a translational research environment in my research group Eye Translational Eye Research, EyeTRU.

PLOS ONE is celebrating 15 years as a journal this year. Can you tell us where you were in your career 15 years ago? If you could give advice to your former self as a researcher, what would you say?

MK: Believe in the impossible and keep going. Life as a clinician-scientist or full researcher is fantastic, but you face challenges along the way. The environment is harsh and the best advice is to stay behave as one would like others to behave.

Matthew Goddard

Matthew Goddard is a professor at the University of Lincoln and an author of the PLOS ONE paper “Invasion and Persistence of a Selfish Gene in the Cnidaria [2].”

Looking back at your paper, which was one of the first papers published in PLOS ONE, what did you learn from this study? Did you continue to work in this field and build on these findings?

MG: This paper was the first report inferring the dynamics of the evolution of homing endonuclease genes (HEGs: a type of ’selfish’ gene or non-Mendelian element) in metazoans. The surprising finding was they appear to have horizontally transferred between Cnidarian species. This was one of the final papers in my line of enquiry into HEGs and I moved on to other areas after this.

To meaningfully translate science done in university labs to the outside world is a hard but rewarding activity.
Matthew Goddard

Do you remember when you first heard of PLOS ONE? What made you first interested in publishing with PLOS ONE?

MG: This was back in the days before the explosion of journals occurred and most were still only accessible via subscriptions. I recall hearing the news of a new type of journal that was completely open access being suggested and I liked the idea of this very much. It was a gamble publishing in a new journal with a new format with no impact factor etc. but this was worth it as the ethos of the open access idea sat well with us.

Could you tell us a bit about what you are working on at the moment? What does your lab group look like?

MG: Mostly studying the effects of agricultural management (i.e. conservation agricultural approaches) and land-use change on soil biology (using DNA and classic methods) and physiochemical attributes (mainly C-sequestration and water retention). These are important areas, especially for the UK, to help understand how to best manage land given climate change and the desire to move to more sustainable agricultural approaches. There is a lack of data in this area.

In your field, how common are open science practices? Do you have any success stories of having shared or re-used data, code, a preprint, or something else?

MG: Very common, and pre-prints of any publication must be available to evaluated via the UK Research Excellence Framework (REF) system. I tend to conduct studies that generate data but we have used whole genome DNA sequence data from various microbes that are publicly available to better understand the genomes that we have sequenced. Such resources are invaluable to help understand the larger ecological and genetic picture.

MG: I had just completed my first post-doctoral position at the NERC centre for population biology at Imperial College’s Silwood Park in the UK. I am not sure about advice to my former self, but to someone at the first post-doc stage of their career it would be to expose yourself to and learn from as wide a diversity of scientists, ideas and places as possible.

Publishing papers is crucial to a career in research. Can you tell us of an event or memory that was not a paper, which influenced your career as a researcher?

MG: Hard: probably moving from the ‘blue-skies’ area where I mostly just interacted with other researchers during my PhD and post-doc to interacting with farmers/agricultural workers and gaining an appreciation of how to attempt to meaningfully translate science done in university labs to the outside world is a hard but rewarding activity.

Andrej A Romanovsky

Andrej A Romanovsky is a founder of Zharko Pharma and an Adjunct Faculty member at Arizona State University, and author of the PLOS ONE paper “Neural Substrate of Cold-Seeking Behavior in Endotoxin Shock [3]”.

Looking back at your paper, which was one of the first papers published in PLOS ONE, what did you learn from this study?

AAR: Actually, that was the very first paper published by PLOS ONE [3]. That study was conducted by two brilliant researchers, Camila Almeida and Alex Steiner, who at that time were postdocs in my FeverLab. Both were trained by Professor Guillermo Branco, a patriarch of Brazilian thermophysiology, and both have become highly productive independent scientists. Camila, who played a leading role on that study, and Alex made a remarkable discovery by showing that behavioral thermoregulation does not require the integrity of the brain structure called hypothalamus. Many textbooks on thermoregulation state that body temperature is controlled by a “central government” located in the hypothalamus. This widely spread erroneous view is allegedly supported by the fact that rats with lesions in a certain part of the hypothalamus cannot defend their body temperature against heat or cold. Camila and Alex reproduced these experiments. They found that rats with lesioned hypothalami indeed could not defend themselves against thermal challenges – but only when they were restrained in little cages and could not use behavioral thermoregulation. When the same rats were allowed to move freely and select a warmer or cooler environment, they exhibited fully competent thermoregulatory responses – no weakness whatsoever! That study was a blow to the idea that the hypothalamus is the “chief commander” of thermoregulation. If the readers of this blog are interested to learn more about how this idea was discrowned and what replaced it, please go to my review [5].

But most importantly, we enjoyed – and still enjoy and are proud of – being a part of the open access revolution.
Andrej A Romanovsky

Do you remember when you first heard of PLOS ONE? What made you first interested in publishing with PLOS ONE?

AAR: The history of science is the history of illusions (like the one about the hypothalamus controlling body temperature)… In 2006, we published in PLOS Biology a study conducted in FeverLab by Alex Steiner (mentioned above) and Andrei Ivanov (now Professor at Cleveland Clinic), with the help of multiple collaborators [6]. This study, which found that fever is initiated outside of the brain, in the lungs and liver, was well-received. Encouraged by this success, we submitted our next study to PLOS Biology – again! Soon we received good reviews and an invitation to move the paper to … PLOS ONE. At that time, PLOS ONE did not exist, and this is where illusions enter our story. Listen, everybody knows that there are many Nature journals, right? Nature Neuroscience, Nature Immunology, Nature This, Nature That… But among all the Nature journals, there is one that stands like Gulliver among the Lilliputians: Nature! Camila, Alex, and I tried to imagine what type of journal PLOS ONE would be. And we came to the conclusion, or should I say illusion, that PLOS ONE would be the same to the PLOS journals as Nature was to the Nature journals! It was due to this illusion that we accepted the invitation, and this is how the very first PLOS ONE article [3] was born! And although PLOS ONE did not turn into the most prestigious PLOS journal (and was not designed to do so), our article seeded what has grown to become the Gulliver of all Gullivers in scientific publishing – the journal that has published more papers than any other academic journal in the history of mankind. But most importantly, we enjoyed – and still enjoy and are proud of – being a part of the open access revolution.

Could you tell us a bit about what you are working on at the moment?

AAR: I retired from laboratory research in 2019 to dedicate my remaining professional life to making several new drugs. The ideas for all these drugs came from or are closely related to my past research. Together with my colleagues, we have launched a couple of startups, including my favorite, Zharko Pharma. The name is a transliteration of the Russian adverb жарко (žárko), which means hot, like in feeling uncomfortably hot. Zharko’s goal is to develop a drug for treating the thermal discomfort experienced by menopausal women – hot flashes. Hot flashes are a widely spread condition that are debilitating in some women, and no effective non-hormonal treatment is currently available.

Publishing papers is crucial to a career in research. Can you tell us of an event or memory that was not a paper, which affected your research?

AAR: Yes, I can tell you about a silly event in FeverLab’s life that gave us a cover of the Journal of Neuroscience. When Andras Garami (now Head of Thermophysiology Department at University of Pécs Medical School in Hungary) worked with me as a postdoc, we were studying the role of the so-called TRPV1 channel in thermoregulation. The latest Nobel Prize in Physiology or Medicine was given to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature…”, including TRPV1. This channel is expressed on sensory nerves and is responsible for the burning sensation we have while eating chili peppers. Being a Hungarian, Andras was not a stranger to spicy foods, but he wanted to experience first-hand how spicy “spicy” can be and was looking in grocery stores for the hottest peppers. Eventually he found a habanero so spicy that blisters covered his lips after he tasted it. Not a surprise that many mammals avoid eating spicy peppers! Soon thereafter we needed to confirm the absence of the TRPV1 channel in TRPV1-knockout mice. We realized that these mice should not feel the hotness of habanero and would be expected to be able to eat this pepper, whereas “normal” mice (those with a functional TRPV1) should avoid this blister-inducing “poison”. Andras then ran experiments in mice, and these experiments confirmed our expectations. We later published an article about thermoregulation in TRPV1-knockout mice in the Journal of Neuroscience [7], a knockout mouse devouring a habanero stares out at you with hungry eyes from the cover of this issue.

Seppo Ylä-Herttuala

n Academy Professor at the University of Eastern Finland and author of PLOS ONE paper “Short and Long-Term Effects of hVEGF-A165 in Cre-Activated Transgenic Mice [4]”

Looking back at your paper, which was one of the first papers published in PLOS ONE, what did you learn from this study? Did you continue to work in this field and build on these findings?

SYH: We have a long history in therapeutic angiogenesis studies and this PLOS ONE paper was one of the first to realistically study long-term safety concerns of VEGF-A overexpression in vivo. The results were very important since they showed that even a low-level VEGF-A expression in vivo for an extended period of time (> one year) can cause significant side effects, such as cancer, thus preventing the use of vectors leading to long-term transgene expression in clinical VEGF-A studies. Also, Cre-loxP technology was quite new at that time and the paper showed how useful it is for in vivo safety and efficacy studies. We still use this mouse model for retinal angiogenesis studies.

Do you remember when you first heard of PLOS ONE? What made you first interested in publishing with PLOS ONE?

SYH: I think that it was from PLOS website.

For younger researchers, I would say that “Be brave and aim high to reach your vision and goals but be also realistic and prepared for sharp turns and surprises in your research”.
Seppo Ylä-Herttuala

Could you tell us a bit about what you are working on at the moment? What does your lab group look like?

SYH: We are continuing our pioneering work in cardiovascular gene therapy. After several advances in vector design, transgene optimization and improved local cardiac delivery methods, we have continued to apply therapeutic angiogenesis for the treatment of severe myocardial ischemia and have now conducted five clinical phase 1 and 2 trials with adenoviral vectors. Our most recent multicenter trial is currently recruiting patients in five cardiology centers in the EU for the treatment of severe coronary heart disease. We also have a very active research program for new vector development and in VEGF signaling mechanisms. My research group currently has 35 members.

In your field, how common are open science practices? Do you have any success stories of having shared or re-used data, code, a preprint, or something else?

SYH: Open access practices are very common in biomedical and clinical research. Most of our papers are now open access. This is also a requirement of EU and ERC grants which we have had during the last 10 years. Also, we have used open access data archives to identify new non-coding RNAs and gene expression profiles in mouse, pig and human heart and other tissues. From these sources we have identified new short hairpin RNAs and miRs which can regulate endogenous VEGF expression.

SYH: Fifteen years ago I was a just-appointed professor of Molecular Medicine with a very enthusiastic research program in angiogenesis and cardiac ischemia, extending from VEGF signaling studies to translational and clinical studies. Most of these goals have now come through, albeit with several surprises and new turns in the research direction over the years. For younger researchers, I would say that “Be brave and aim high to reach your vision and goals but be also realistic and prepared for sharp turns and surprises in your research”.

Publishing papers is crucial to a career in research. Can you tell us of an event or memory that was not a paper, which influenced your career as a researcher?

SYH: I so well remember the moment in 1996 when we, as the first in the world, did the first adenoviral gene transfer to human arteries with percutaneous catheter technique. This paved the way for my further research career in angiogenesis and cardiac ischemia.

Author biographies

Miriam Kolko

Miriam Kolko is chief physician and glaucoma specialist at the Copenhagen University Hospital, Rigshospitalet-Glostrup. She is also professor in translational eye research at the Department of Drug Design and Pharmacology at the University of Copenhagen. Prof. Kolko is president of the Danish Glaucoma Society and board member of Fight for Sight, Denmark. During medical school Prof. Kolko completed a Fulbright Scholarship at the Neuroscience Center of Excellence, Louisiana State University, US. Here she became interested in basic neuroscience. After medical school, she completed a Ph.D. and a postdoctoral position in the same laboratory. In 2003, Prof. Kolko returned to Denmark after a total period of 5 years in the United States. She completed another postdoctoral position, after which she underwent residency in ophthalmology followed by a 3-year glaucoma fellowship. From 2014 to 2017, Prof. Kolko directed glaucoma in the Region of Zealand until she was assigned to her current position. At the University of Copenhagen, Prof. Kolko is heading the research cluster “Personalised Medicine”. In addition, Prof. Kolko is heading the research group, Eye Translational Research Unit (EyeTRU). The research in EyeTRU concerns cellular, translational, epidemiological and clinical models for understanding glaucomatous neurodegeneration. Prof. Kolko has received more recognitions. Among these, she has received the first “Award of excellence” from the Danish Ophthalmological Association and the Lions Prize. Prof. Kolko is co-chair of the neuroprotection SIG in the EGS and member of the EGS membership and national society committee. Recently, Prof. Kolko was elected to the WGA, Associate Advisory Board and as EVER glaucoma chair. Finally, Prof. Kolko was elected member of the board of directors of ACTA Ophthalmologica. All in all, Prof. Kolko is one of the few clinician-scientists that bridge between a clinical career with medical and surgical treatment of glaucoma patients and basic and translational research models to understand the pathophysiology behind as well as the current management of glaucoma.

Matthew Goddard

Professor Matthew R Goddard, PhD, BSc hons, DIC, FHEA undertook a PhD and post-doctoral fellowship in evolutionary and ecological biology at Imperial College (Silwood Park), then moved to a Faculty position at University of Auckland (New Zealand) in 2004 and then gain a Professorial position at the University of Lincoln (UK) in 2015. Mat has worked extensively with the agricultural sector and spearheaded microbial ecology revealing the differential distribution of microbes associated with agriculture and how this may effect agricultural outputs. Mat now has a strong focus on soils and runs large scale agri-ecosystem projects fusing next-generation DNA sequencing to evaluate biodiversity (not just microbes) with soil physics and chemistry to both understand the effect of agricultural managements and land-use change to provide evidence to inform decisions by land owners that aim to minimise disease and elevate agricultural and ecological health and quality.

Andrej A. Romanovsky

Andrej A. Romanovsky, MD, PhD, FAPS, is a physiologist and neuroscientist with primary expertise in body temperature regulation. In 2019, he left his Professor position at St. Joseph’s Hospital in Phoenix, Arizona, to work on the development of drugs for disorders of thermoregulation and hot flashes. Dr. Romanovsky helped to found the pharmaceutical startups Zharko Pharma, Catalina Pharma, and Synventa and currently works with these companies as an officer, Board member, or consultant. His current primary affiliation is with Zharko Pharma in Olympia, Washington; he also holds an Adjunct Faculty position at Arizona State University. Dr. Romanovsky has published more than 130 articles in peer-reviewed scientific journals. He is the Editor-in-Chief of the journal Temperature and the Editor of two volumes on Thermoregulation: From Basic Neuroscience to Clinical Neurology published by Elsevier within the Handbook of Clinical Neurology series in 2018. In 2019, he was elected as a Fellow of the American Physiological Society. Andrej’s hobby is tree farming. He has co-founded the family partnership Tree Fever: Forestland Conservation and Development and since 2011 has been operating a Douglas-fir tree farm growing timber in western Washington. He is married to Nancy L. Romanovsky, an oil painter, and they have four children and two grandchildren.

Seppo Ylä-Herttuala

Dr. Seppo Yla-Herttuala, MD, PhD, FESC is a world leader in cardiovascular gene therapy for ischemic diseases. His team was the first to use adenovirus-mediated gene transfer to human arteries already in 1996. Since then, he has conducted five phase 1-2 clinical trials in cardiovascular gene therapy. He is also the originator of the concept of epigenetherapy. His group has been widely recognized for basic biology, translational and epigenetic research of the vascular endothelial growth factors (VEGFs), especially focusing on the new members of the VEGF family. Previously he worked with oxidized LDL and atherosclerosis and was the first to show that OxLDL exists in human atherosclerotic lesions. His list of publications includes over 600 peer reviewed scientific articles.

References

1. Kolko M, Horwitz A, Thygesen J, Jeppesen J, Torp-Pedersen C. The Prevalence and Incidence of Glaucoma in Denmark in a Fifteen Year Period: A Nationwide Study. PLoS ONE. 2015;10(7): e0132048. doi: 10.1371/journal.pone.0132048

2. Goddard MR, Leigh J, Roger AJ, Pemberton AJ. Invasion and Persistence of a Selfish Gene in the Cnidaria. PLoS ONE. 2006;1(1): e3. doi: 10.1371/journal.pone.0000003

3. Almeida MC, Steiner AA, Branco LGS, Romanovsky AA. Neural Substrate of Cold-Seeking Behavior in Endotoxin Shock. PLoS ONE. 2006;1(1): e1. doi: 10.1371/journal.pone.0000001

4. Leppänen P, Kholová I, Mähönen AJ, Airenne K, Koota S, Mansukoski H, et al. Short and Long-Term Effects of hVEGF-A165 in Cre-Activated Transgenic Mice. PLoS ONE. 2006;1(1): e13. doi: 10.1371/journal.pone.0000013

5. Romanovsky AA. The thermoregulation system and how it works. Handb Clin Neurol. 2018;156: 3-43. doi: 10.1016/B978-0-444-63912-7.00001-1

6. Steiner AA, Ivanov AI, Serrats J, Hosokawa H, Phayre AN, Robbins JR, Roberts JL, Kobayashi S, Matsumura K, Sawchenko PE, Romanovsky AA. Cellular and molecular bases of the initiation of fever. PLOS Biol. 2006;4: e284. doi: 10.1371/journal.pbio.0040284

7. Garami A, Pakai E, Oliveira DL, Steiner AA, Wanner SP, Almeida MC, Lesnikov VA, Gavva NR, Romanovsky AA. Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis. J Neurosci 2011;31: 1721-1733. doi: 10.1523/JNEUROSCI.4671-10.2011

Disclaimer: Views expressed by contributors are solely those of individual contributors, and not necessarily those of PLOS.

Featured image: https://doi.org/10.1371/journal.pone.0000009

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