Nicholas Mrosovsky

Uncompromising Scientific Integrity

Those three words encapsulate what I most admired about Nicholas Mrosovsky (NM). In the early 2000s he hosted what we informally called the Toronto Clock Club at his home, a journal club where we had the privilege of getting NM’s critical judgement on the latest paper or our own data. This was an exclusive club, by invitation only, where NM banned graduate students to keep the scientific discussion at the highest level. What impressed me were his rigorous approach to dissecting papers and experiments and his complete disdain for academic and scientific politics. He is the only person I have ever heard of who refused tenure on the grounds that he should only hold his position as long as he was productive. It was an attitude that felt anachronistic in the modern scientific milieu of spin and hype.

“To strive, to seek, to find, and not to yield” (from “Ulysses” by Alfred Lord Tennyson). This was part of a poem that Nicholas himself cited at a dinner in his honor at Massey College, Toronto, in 2005. I find it describes Nicholas’s work ethic and scholarship quite well.

My recollection of Nicholas can be summed up by saying that he had many of the virtues and attributes of Old School: direct, logical, unruffled and meticulous, and extremely independently minded. Allied to his biological imagination, these were the keys to his success, I feel. . . . He was clear on what he wanted and took the personal responsibility of doing science correctly very seriously. This lesson of personal ethics is an important one that needs continuous repetition and Nicholas was a terrific example of this to others.

Early Career and Contributions to Physiology

NM was born in 1934 in Romania to British parents and was educated at Winchester College in England. His undergraduate degree was from Magdalene College, Cambridge, and his PhD in Psychology was earned at University College London. In 1967 he joined the University of Toronto and spent the remainder of his career there as a faculty member in the Departments of Zoology, Psychology, and Physiology. His earliest research concerned the physiology of fat in relation to hypothermia, and his first paper was published in Nature in 1962, foreshadowing a prolific publishing career. This interest led to work on the physiology of hibernation and the publication of his first book in 1971, Hibernation and the Hypothalamus.

The work on body fat and hibernation continued in parallel with the entry of circadian work into the lab (see below). In 1990, his book Rheostasis: The Physiology of Change was published, looking at the concept of homeostasis in physiology and medicine from an evolutionary perspective.

He influenced me enormously, and he made me think. He made me think hugely, both in our discussions, by my reading of his papers, and from his wonderful book Rheostasis.

His book Rheostasis is wonderfully written; I recommend it to all of you.

Chronobiology

NM’s work in chronobiology began in the 1970s with circannual cycles in ground squirrels. Rhythms in hamsters entered the lab in 1980 with a study of simultaneous splitting of drinking and locomotor activity rhythms (Shibuya et al., 1980). The discovery that forced activity could accelerate re-entrainment to light-dark cycles (Mrosovsky and Salmon, 1987) opened up the study of nonphotic phase shifting (Reebs and Mrosovsky, 1989), which became the most highly productive and influential area of chronobiological research for NM’s lab.

Nicholas made landmark observations on nonphotic resetting by arousal and we followed his work closely. I was especially blown away by the idea that a clock output—behaviour—could be a clock input.

Roelof Hut, who was a graduate student when NM held the G.P. Baerends Chair at the University of Groningen in 1997 while on sabbatical from the University of Toronto, proposed looking at nonphotic phase entrainment in ground squirrels, a diurnal mammal, based on the hypothesis that their phase response curve should be 180° out of phase from nocturnal mammals. To avoid 24-hour environmental variables that might entrain the animals, he had the idea of advancing the treatments by a half hour every day.

Nicholas really pushed that idea, but I was wary because I had to do the experiment. It turned out that it was a horrible experiment. We had to run this protocol over 40 days to cover every circadian phase and it shifted also through my circadian organization, and I was messed up. The results (Hut et al., 1999) showed that diurnal mammals have the same phase response curve as nocturnal mammals, so we still don’t know what this non-photic phase shifting actually means.

Questions about the reality of nonphotic phase shifting required a demonstration that it was not just a masking effect, and this led to further work on masking (Mrosovsky, 1999). NM’s lab also made contributions to describing clock gene expression in relation to nonphotic resetting (Maywood et al., 1999) and in diurnal mammals (Mrosovsky et al., 2001). In the latter part of his career in the lab, the availability of retinally degenerate mouse models led to the dissection of the roles of different photoreceptors in visual functions including masking (Hattar et al., 2003). His final papers in chronobiology continued the study of photoreceptors and masking (Thompson et al., 2008).

Sea Turtle Biology, Behavior, and Conservation

Those of you who know NM’s work as a chronobiologist might be surprised to discover the other side of his scientific life: sea turtles. His interest started early in his career in the 1960s and included collaborations with his wife, Sara Shettleworth (Professor, Department of Psychology, University of Toronto). He published seminal work on the sea-finding behavior of hatchlings (how do they make their way off the beach and into the sea?) (Mrosovsky and Shettleworth, 1968), and he continued throughout his career to publish on the effects of temperature on hatchling sex ratios. It became clear that his work had important implications for sea turtle conservation, and he became passionately involved in sea turtle politics. His work is respected worldwide by the sea turtle conservation community and is influential in conservation efforts today. Even after he closed his circadian lab near retirement, he continued the work on turtles, advocating for their protection and conservation by collecting data to inform policy.

As with everything else, he did not shy away from controversy in his conservation work. His 1983 book Conserving Sea Turtles raised the contentious suggestion that scientific data should be collected to inform the debate over whether populations might be sustainably exploited. He took on the conservation establishment when he criticized the famed IUCN Red List of endangered species for basing listings on information not publicly available (Mrosovsky, 1997), and he argued for removing certain sea turtle species from the list based on data showing large, stable populations.

Rather than take sides, Mrosovsky suggested that the best approach would be to study each problem empirically, and develop testable hypotheses that would serve to resolve the debate.

Getting out of the rodent lab and into the field to study sea turtle nesting beaches was clearly the work that gave him the greatest professional joy. You can see it in the photographs of NM lying in a hammock on a tropical beach or holding up a baby turtle near the sea; he was never photographed smiling that way at a hamster in a running wheel!

OPEN IN VIEWER

Nicholas Mrosovsky in 2000 visiting the hawksbill turtle project, Mona Island, Puerto Rico. Photo by permission of Robert P. van Dam.

“Remember Behaviour”

Everyone who worked in NM’s lab recalls a sign with the motto “Remember Behaviour,” held up by two cartoon hamsters, posted on the wall of the lab.

He hoped everyone would remember that even the smallest manipulation could have far-reaching consequences. That was a life lesson as well as a lab lesson; I think everyone who came through our lab took a little bit of that with them.

The whole idea of behavior was important to Nicholas. Now, lots of people put their animals in cages with running wheels, shut the door, and have no idea what the animals are actually doing. You put a mouse in a running wheel and you get counts and you think that the animal is actually running when instead it’s playing.

In the days before telemetry, when Nicholas was studying hibernation, he would put a spoonful of woodchips on the back of the sleeping ground squirrel and see if they were still there the next day to confirm that the animal was indeed hibernating.

—Peggy Salmon

It was this attention to the actual behavior of the animal that led to some of his most influential findings in chronobiology: for example, the landmark 1988 paper on nonphotic entrainment:

. . . when it was noticed in this laboratory that phase shifts in the free-running activity of hamsters sometimes occurred on days after cage changes, it was decided to study the phenomenon, rather than to try to eliminate or ignore it. (Mrosovsky, 1988)

Meticulous Experimentation

He was meticulous about performing his own experiments, checking animal well-being, analyzing data.

In the early days, all activity recording was done with huge sheets of paper on a pen-and-ink recorder. All calculations were done by hand with a calculator, and therefore data had to be checked and rechecked. Although NM could be suspicious of technology, his lab was one of the first to use computers in chronobiological recording. When DataQuest software became available, NM’s lab worked out the bugs and, by close attention to detail, discovered a 10-minute delay in the storage of data (Mrosovsky, 1992).

I think if we had T-shirts made for our lab they would say “Check Your Data” across them. . . . Everything Nicholas published had to be beyond reproach and he expected no less from any member of his lab. For some, that expectation could be trying at times, but eventually they came to appreciate his scientific fastidiousness. Every detail, whether it was stereotaxic surgery or weekly cage changes, was an integral part of the study and had to be taken into account and reported on.

At times he could be quite infuriating when he dug in his heels over some arcane detail. Which tests to use for post-hoc comparisons after an ANOVA brought out our attitudinal differences, and separately he took me to task for log-transforming data in order to apply parametric stats. It is very likely that he was correct, and even now I am wary of Dunnett’s test.

Meticulous Writing

NM was an excellent writer and was also willing to write outside the confines of scientific papers, authoring five books and many editorials and commentaries that were marvels of clear writing. NM’s collaborators describe coauthoring a paper with him as “unique” and “an interesting experience.” According to legend, NM once retracted a paper from JBR because he disagreed with Marty Zatz about the punctuation of the title.

I always found that writing papers with him was first about the content. The data had to be checked, re-checked and then cross-checked. When that was all in the clear, he wrote much like a poet writes a poem; weighing every word and even punctuation. . . . N. Mrosovsky was his “nom de plume”. He always published abbreviating his first name, illustrating how he would scrutinize only the content of a paper but never the author.

I had the special opportunity to co-author with Nicholas only once, on a paper we wrote together with Kim Edelstein and Horacio de la Iglesia. His involvement was certainly memorable, with an intensity and erudition that were unmatched. OK, OK, so it might have been a bit exasperating, but he truly was an artisan of the written word—and he was right.

Who complains about getting your name on a paper in Nature? NM did, for several reasons: for the stingy space allotted to methods, which to NM were critically important to understanding a paper and which prompted an editorial on the subject (Mrosovsky, 2006); for the tiny size of the figures, which needed a magnifying glass to inspect the actograms; and especially for the need to over-hype the results to catch an editor’s attention.

Meticulous Reading

It’s a common complaint that no one reads beyond the title and abstract of papers anymore. NM’s journal clubs taught the opposite: every detail of the methods was picked over, every figure was dissected, and we weren’t allowed to move on until NM was satisfied we had squeezed all the juice from each section of the paper. NM would then write a letter to the first author, listing the questions that had been raised and requesting explanations.

Kim Edelstein knew what it felt like to be on the receiving end, when NM approached her at a conference carrying a copy of one of her papers, covered in red ink:

It was already published and he had a million questions, and comments, and suggestions. What I learned later when I came to the lab is that he would do this every week in the journal clubs. Nobody read papers like Nicholas did, so carefully, so attentively and so interested in what the researchers were trying to do.

Mentorship

He was a good supervisor. I found that he gave me just the right balance between independence and supervision. He would let me do my thing during the week and then at the end of the week, Friday afternoon, he would come down to my office and sit down, lean back in the chair and ask me, “So Stéphan, what have you found this week?” and I would show him my actograms and we would discuss the results and we would chat about things in general. I thought that was great.

Nicholas would often come out with maxims to sum up a situation that became sort of mantras for the lab—a number I repeat to this day to my own lab group (and family!). From the mundane, “Duct tape—always useful in the field” and “Nobody ever drowned in his own sweat” to quotes to ponder like, “Most people say that it is the intellect which makes a great scientist. They are wrong: it is character” (Albert Einstein). He was wise: “One swallow does not make a summer” (Aristotle). Nicholas stressed the utter necessity of building up a case—not being satisfied with your one or two experiments (or anyone else’s)—ruthlessly repeat and build on past work. He was a hard worker: “It seems the harder I work, the more luck I have” (Thomas Jefferson); and “Write a page a day and in a year you have a book.”

Life Outside the Lab

NM was a family man, married for 47 years to Sara Shettleworth, and father of Lara and Sebastian. He was a keen sportsman, a swimmer, a runner, a tennis player, and an excellent squash player. Stéphan Reebs recalls playing squash with NM when Stéphan was a PhD student, and although he has an unfair advantage at 6 foot 9 inches and can span the squash court from side to side, NM always managed to beat him (and NM was in his 50s). The arts were another passion of his: He was a lover of opera and an accomplished painter. Those who visited NM’s home remember the almost photo-realistic painting of, yes, a sea turtle on a beach (not a hamster in a wheel—another piece of evidence for the place the turtles occupied in his affection).

Dry Wit

“Revolutionary science: An improved running wheel for hamsters”; “Nonphotic phase shifting in the old and the cold”; “Animal anorexias: Anorexia yes, Nervosa no.” NM was unafraid of using humor to catch the reader’s attention and get a point across, and he enjoyed a good joke. Although the intensity of his focus could sometimes make his manner appear a bit brusque, if you were patient the warmth and the humor would come through.

Nicholas quoted Ovid: “A field that has rested gives a bountiful crop.” Contrary to the image many people I meet had of Nicholas—he was not always so serious. He was a believer in distraction from the lab—whether it was a game of squash, or a gathering at his home or lake cottage with a glass of wine (in that crazy angled glass he had . . .). He was intense, but also could laugh at himself.

Nicholas’ journal club evenings at his home would be clearly marked by the timing of the cookies arrival. Before the cookies, we discussed the journal articles methodically and critically. After the cookies, we enjoyed gentle gossip and sly jokes. I can’t decide which activity was more enjoyable! I miss him a lot.

Intellectual Legacy

. . . he has rarely shied away from asking challenging questions concerning thorny issues. . . . While some may not agree with his ideas, few could say that they have not been influenced by him or his writings.

The influence of this rare scientific intellect will be hugely missed by our field, and of course all of those who consider that knowledge and scientific truth take precedence over politics and hierarchy. Nicholas was uncompromising in his view that truth will always triumph.