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Retrospection and Direction: A Q&A with Peter Walter

“In our panel it is the stated and adhered to policy that we will not consider where a paper is published. Rather, in our evaluations we assess its real impact in a field. Change of this sort and defiance of the status quo is badly needed in all committees and panels that make decisions that impact the future of our next-generation scientists, even if it entails a bit more work.”-from “On Publishing and the Sneetches: A Wake-up Call?

These are words written by Dyche Mullins and Peter Walter, in 2016. Walter is one of this year’s Breakthrough Prize in Life Sciences recipients and a leader in the scientific community not only for his scientific investigations but also for his continuous dedication to mentoring and teaching younger scientists, and for taking a progressive but circumspect stand on issues that impact the quality of scientific life. As a follow-up to last month’s Breakthrough Prize overview, PLOS interviewed Walter on some of the broader issues surrounding his work and publishing in general. Walter has strong opinions related to impact factors and Open Access; he remains open minded regarding preprints. His valuable and modest insights are below, with minimal editing.


Image courtesy of UCSF

PLOS: Which of your PLOS articles were most impactful for your work related to the prize, and why?

Walter: The Brickner and Walter paper [“Gene Recruitment of the Activated INO1 Locus to the Nuclear Membrane”] stands out, in my view, as this story organically grew out of our ongoing work on the unfolded protein response, yet opened an entirely new field: that the physical location of a genetic locus inside the nucleus can be dynamic and affect gene regulation. This paper also served to seed Jason Brickner’s independent career: Shortly after this publication, he was recruited to Northwestern University. Since then, his lab has vastly expanded upon this topic and he is now internationally recognized as one of the very leaders of cell biological mechanisms that control transcriptional memory.

PLOS: Do you have a personal favorite among your PLOS publications? Perhaps one that was either controversial or that sparked scientific debate/conversation at time of publication?

Walter: The Pincus et al. paper [“BiP Binding to the ER-Stress Sensor Ire1 Tunes the Homeostatic Behavior of the Unfolded Protein Response”] is one of my all-time favorites: It demonstrates the power of computational modeling for generating new hypotheses and then experimentally testing them. In this case, modeling suggested experiments that we would not have thought of otherwise, and the results showed beyond reasonable doubt that BiP dissociation from the ER-resident stress sensor Ire1 is not the regulatory switch that activates the UPR. The work inspired rethinking, and it is now clear that in both, yeast and metazoans, unfolded proteins per se are agonists that bind directly to the stress sensors Ire1 (and PERK). Despite the seminal insights provided in this publication, the field remains attached to the notion that BiP dissociation is causal for Ire1 activation—providing an important insight into the surprisingly inflexible thinking of established scientists (including myself, at times…).

PLOS: In your experience speaking with the public or non-scientists in general, what concept(s) about the unfolded protein response pathway do they typically find most interesting or resonates strongly?

Walter: Trained as a chemist, I personally cherish the many unorthodox molecular mechanisms by which the unfolded protein response regulates ER [endoplasmic reticulum] homeostasis. However, beauty at a molecular scale is mostly appreciated by aficionados and only rarely resonates with the public and non-scientists. We are now in a most fortunate era where our work tangibly links to a broad spectrum of diseases, including cancer and neurodegeneration, where our knowledge has become foundational to the exploration of new treatment strategies. As such, our work provides a wonderful platform on which to demonstrate the power and value to society of curiosity-driven research in which we seek understanding of how healthy cells work in disease-agnostic approaches and then use that knowledge to learn what goes wrong in disease and how to fix it.

PLOS: Our readers span the range of career stages. What is your opinion of the value or challenge to publishing in Open Access journals?

Walter: The challenge for the next generation of researchers is to break out of the stranglehold that the for-profit publishing industry has put on our community. The misguided emphasis on abstruse metrics, e.g., impact factor, in addition to the poorly transparent review procedures by our “vanity journals” and their hand-me-down cousins distort our most fundamental values. My colleagues and I have clearly laid out our views on this topic [in addition to the ASCB Newsletter referenced in the opening quote see the commentary co-authored with Martin Raff and Alexander Johnson, entitled “Painful Publishing”].

Just as with scientific models, old patterns are hard to break. We need our young scientists to recapture control. The myth that one can only get a job/grant/promotion with [high impact factor journal] papers has been debunked internationally (e.g., Jason Brickner and Liang Ge in China). The challenge ahead is to spread the word and make sure that no young scientist who made an important discovery will ever be held back by the name of the journal where ground breaking findings were published.

“Open-access and publishing (to “make public”) are synonymous in my view, and scientist-run non-profit open-access journals that manage to deliver consistently customer-friendly, transparent, and constructive reviews and timely feedback are destined to lead the movement.”

PLOS: Finally, have you or collaborator ever posted a preprint? If not, would you consider doing so, and why/why not?

Walter: To date, we have posted two preprints—I consider them experiments with the new forum. For now, I remain agnostic to the process. Science is moving fast enough for my taste (if not too fast sometimes), and I remain unsure whether an invitation to put un-reviewed stories out there will be that beneficial overall. Many things will need to be worked out: Does a preprint establish priority for a discovery? How will “better-first-and-sloppy-than-second-and-who-cares” science be regarded by the community? How will we deal with predatory scientists who appropriate ideas and results from our students or postdocs and then race to scoop them? Also, personally, I read most papers only once, and it is the first impression that sticks. The concept of looking at evolving versions rather than a final, best-as-can-be product is rather vulnerable in my opinion. We’ll see; I remain open-minded.


Editor’s Note: Some of the issues Walter raises above are covered in the PLOS Computational Biology article “Ten simple rules to consider regarding preprint submission.” Major funders including Wellcome Trust and NIH, and publishers such as PLOS, PeerJ and eLIFE are actively working on external policies and internal practices to facilitate authors’ use of preprints; PLOS Biology has formalized a policy whereby complimentary studies (those submitted within six months of publication or preprint posting and already addressing the same question) will be considered for publication. Newly minted scientists are encouraged to use preprints as a way of, as Walter recommends, recapturing control. The cartoon above on use ideas for preprints from the group PREreview is available for download on figshare.


Peter Walter is Professor, Department of Biochemistry and Biophysics at the University of California, San Francisco (UCSF) and Investigator, Howard Hughes Medical Institute. He served as President of the American Society of Cell Biology in 2016 and as Department Chair in Biochemistry and Biophysics at UCSF from 2001 until 2008. He is an elected member of the German Academy of Natural Scientists Leopoldina, the US National Academy of Sciences, the National Academy of Inventors, the American Association for Arts and Science, and the European Molecular Biology Organization. He is recipient of multiple awards including the Breakthrough Prize in Life Sciences (2018), Vilcek Prize in Biomedical Science (2015) and Lasker Basic Medical Research Award (2014). He is co-author of the widely-used textbooks Molecular Biology of the Cell and Essential Cell Biology and alumnus of the Djerassi Artist-in-Residence program.


Image Credit: Peter Walter lab; University of California, San Francisco

The Editor’s Note was updated on 1/30/3018 to indicate the policy at PLOS Biology is formalized and to provide the link to the Criteria for Publication on the journal’s information page.

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