What is life?

Background

Many traditional biological concepts continue to be debated by biologists, scientists and philosophers of science. The specific objective of this brief reflection is to offer an alternative vision to the definition of life taking as a starting point the traits common to all living beings.

Results and Conclusions

Thus, I define life as a process that takes place in highly organized organic structures and is characterized by being preprogrammed, interactive, adaptative and evolutionary. If life is the process, living beings are the system in which this process takes place. I also wonder whether viruses can be considered living things or not. Taking as a starting point my definition of life and, of course, on what others have thought about it, I am in favor of considering viruses as living beings. I base this conclusion on the fact that viruses satisfy all the vital characteristics common to all living things and on the role they have played in the evolution of species. Finally, I argue that if there were life elsewhere in the universe, it would be very similar to what we know on this planet because the laws of physics and the composition of matter are universal and because of the principle of the inexorability of life.

     

A Novel Approach to Tradition: Torres Strait Islanders and Ion Idriess

This paper considers the significance of the novel Drums of Mer (1941) in contemporary Torres Strait Islanders' lives. Its use as narrative by many Islanders today constitutes one means by which men especially have come to know themselves, white others, and their past. In particular, I explore the ways in which this story appeals to and is appealed to by Yam Island people. Contrary to literary deconstructions of Idriess's representations of Aboriginal and Torres Strait Islander people, my paper argues that in seriously attending to Torres Strait readings of Drums of Mer we can see that for contemporary Islander readers, it is not themselves who are other but rather the white protagonists. I employ Said's (1994) notion of ‘cultural overlap’ and de Certeau's (1988) understandings of reading and writing as ‘everyday practices’ to frame my analysis of the differing impacts of the historical novel, Drums of Mer, and the Reports of the Cambridge Anthropological Expedition to Torres Straits. It is through story telling that Yam Island selves are placed in the past and the present, and in Idriess's memorable story a similar effect is achieved. In his novel approach, the past becomes his-story, a romanticised refraction of the Reports. Unlike the Reports, this novel is a sensual rendering of a Torres Strait past, and at this level it operates as a mnemonic device for Yam Island people, triggering memories and the imagination through the senses. This Torres Strait Islander detour by way of a past via a story, can be understood as a means by which Yam Island people continue to actively produce powerful images of themselves, for both themselves and for others.     

You are the most valuable reagent in the lab: mental health before and during the pandemic

No one maps out their tenure as a postdoc anticipating a life-altering tragedy. But mental health crises of all kinds affect academic trainees and staff at similar or higher levels than the general public. While the mental health resources available to trainees are often set by healthcare providers, all levels of university leadership can work to remove material and immaterial obstacles that render such resources out of reach. I describe how access to care via telemedicine helped me following a loss in my family.

Over the years, my siblings and close friends have sought mental health resources like therapy, psychoanalysis, or psychiatry, so I loosely understood their benefits. When I was a PhD student I went to therapy briefly, but my counselor and I decided I could do without it. Since I started my postdoc, stress manifested in some new ways but I managed it well with my usual coping strategies and support. That changed one bright December morning in 2019 while I was preparing for our weekly lab meeting. My phone rang indicating a call from my father, whom I had spoken to the night before to celebrate the news of my nephew’s birth. But the voice on the phone was that of a family friend, telling me that my father had died overnight of an undiagnosed heart condition. In the moment I couldn’t even understand what was happening, saying over and over, “but I talked to him last night.” Soon I was sitting at home, dazed, on a string of tearful calls with family and friends.I often read words like “lifted” or “buoyed” to describe the stabilizing support of a network of loved ones. In my case this network was tethering me to reality over the next few weeks, preventing me from spinning off the Earth’s surface in a storm of sorrow and anxiety. The trauma also took a strange physical form and convinced me that I was suffering from a cardiac condition of my own. I had a panic attack during which I went to urgent care convinced my own heart was about to give way. Night after night these physical symptoms prevented me from sleeping.Graced by many loving connections with my siblings, my boyfriend, and close friends, I was actually weathering the process as well as one can. My PI gave me a firm directive to take as much time off as I needed. These were two key elements early in my healing process: a supportive network and an understanding advisor. The third was getting professional help, which I soon realized I needed. Even if I felt OK one day, I didn’t trust that I’d be OK the next. My grief formed too thick and too broad a landscape for me to navigate without help.Deciding to seek mental health resources and realizing that one needs them are often the hardest parts. Connecting with those resources once the decision has been made should be as simple as possible. I called a mental health number, and a triage counselor noted my therapy needs and verified my insurance. She asked what times and locations I preferred and then searched for an open appointment with a therapist who accepted my insurance. She also informed me that my coverage allowed 12 sessions with no copay, which was a pleasant surprise. The therapist who agreed to see me had very few openings, in part because this all happened in December—the holidays are especially busy for therapists. I was aiming for a time after normal working hours, or in the morning before I would head to lab, but none of those times were available. I didn’t like interrupting my workday to trot off to therapy. Taking a long break once a week meant I couldn’t run experiments or mentor my student during that time. But I made the sacrifice because my highest priority was getting the help I needed. There was no shortcut. Prioritizing mental health over lab work is tough for researchers, and I would never have accepted that kind of weekly disruption before my dad’s passing. But as a wonderful mentor of mine used to say, “You are the most valuable reagent in the lab.” She wasn’t describing mental health at the time, but the phrase now provided a guiding principle for my recovery. My first few sessions were on Tuesdays at 2:00 pm.The afternoon break turned out to be less disruptive than I had feared, because I had recently come back to the lab and was working short days. Had she asked, I would have told my PI where I was on Tuesday afternoons, but she wasn’t normally abreast of my daily schedule, so I didn’t seek her approval beforehand. Coordinating experiments with lab members thankfully wasn’t an issue because my work was largely independent; I simply let lab members know that I’d would be out of the lab for a bit on those days.The weeks went by, and the benefits of therapy accrued, helping me in large and small ways as I grieved. In mid-March of 2020, my therapist followed public health guidelines and asked all her clients to transition to remote sessions. While this was easy and sensible, it was still a little disappointing. Therapists are professional empaths, among many other things, and doing away with the physical presence and exchange with her was a blow. Yet therapy via video felt less odd simply because most of my social interactions were now virtual. Thankfully I didn’t have to move out of state for the lockdown (as did many students living in campus housing), which meant I could stay with the same therapist without any insurance complications.A few weeks into lockdown, I asked my therapist whether we had reached the limit of my 12 sessions without a copay. She replied with the good news that my insurance provider had waived all copays for mental health costs due to the pandemic. By that time therapy had generated a platform and an outlet to explore areas of my grief beyond the trauma of my father’s passing. Without needing to weigh the costs and benefits of this resource, I saw my therapist for another 4 months. I slowly took stock of my upbringing in an unconventional family and the loss of my mother when I was 25 and waded through a series of difficult decisions regarding my father’s estate. My father’s death changed me at a depth that is untouched by any amount of therapy or treatment. I’m not “healed”: I feel aged, more brittle, and a little ground down compared with who I had been. But therapy guided me through the worst of my grief, past the acute trauma to help me grasp what I was going through.Since the pandemic began, the number of people reporting increased stress or mental health issues has steadily increased (information on the impact of COVID-19 measures on mental health: https://www.apa.org/workforce/publications/depression-anxiety-coronavirus.pdf) (also see Mental health resources for trainees). I am fortunate to have affordable health insurance and the support from my lab and my department. The ease of finding my institution’s phone number for mental health resources was itself an important benefit. I share these pieces of my story with humility and understanding that not everyone enjoys the privileges that I do and the knowledge that everyone weathers life’s tragedies in their own way. It is not lost on me that some benefits stemmed from a policy change made by a private insurance provider. The provider made the right decision to waive copays, freeing me from having to choose between cost and my mental health needs. Yet had I been a student who had to move out of state due to COVID-19, access to mental health resources might have been disrupted or cut off. The need for reduced out-of-pocket costs for healthcare is known and needs no repetition, but the benefits of telehealth should be a low-cost component of health plans offered to students and staff (information on telehealth recommendations: https://www.apaservices.org/advocacy/news/congress-patient-telehealth?_ga=2.231013471.1538013741.1619359426-1228006513.1619359425 and http://www.apaservices.org/practice/advocacy/state/leadership/telebehavioral-health-policies.pdf?_ga=2.3385904.1067518037.1620039082-1228006513.1619359425.I’m not a cloud of emotions attached to a pair of good pipetting hands, I’m a human who is choosing to spend my time doing research. This observation is easy to repeat, by trainees as much as by faculty and administrators, but much harder to act upon in the midst of conflicting priorities. Consider my story a success: Because I could access the resources I needed, I was able to prioritize my mental health in the midst of my ambitious research program even during the lockdown.MEET THE AUTHORI have been a postdoc in Stefani Spranger’s lab at MIT for 4 years. Supported by an Irvington Fellowship from the Cancer Research Institute, my work examines the behaviors of dendritic cells in tumors that contribute to productive or unproductive anti-tumor immune responses. My doctoral work examined modes of multicellular invasion controlled by the actin cytoskeleton with Margaret Gardel at the University of Chicago. Earlier I was a lab technician with Thea Tlsty at the University of California, San Francisco, which followed a bachelor’s degree in biology at the University of California, Santa Cruz. I serve on the Committee for Students and Postdocs at the American Society for Cell Biology, where I chair the Outreach Subcommittee.     

Last days in the old radiation laboratory (ORL), Berkeley,California, 1954

Govindjee, the founding editor of the Historical Corner of Photosynthesis Research, invited me 3 years ago to tell the story of why I left Melvin Calvin’s laboratory in the mid 1950s long before the 1961 Nobel Prize in Chemistry was awarded to Calvin for the path of carbon in photosynthesis. I have already written my scientific perspective on this topic (see Benson (Photosynth Res 73:29–49, 2002); also see Bassham (Photosynth Res 76:35–52, 2003) as he was also a major player in this research). Here, I present my recollections of my last days in the old radiation laboratory (ORL) at Berkeley, California. References have been added by Govindjee for the benefit of the readers.     

Academic motherhood – what happens when you can't make it happen?

We need more openness about age‐related infertility as it is a particular risk for many female scientists in academia who feel that they have to delay having children. Subject Categories: S&S: Careers & Training, Genetics, Gene Therapy & Genetic Disease

Balancing motherhood and a career in academic research is a formidable challenge, and there is substantial literature available on the many difficulties that scientists and mothers face (Kamerlin, 2016). Unsurprisingly, these challenges are very off‐putting for many female scientists, causing us to keep delaying motherhood while pursuing our hypercompetitive academic careers with arguments “I’ll wait until I have a faculty position”, “I’ll wait until I have tenure”, and “I’ll wait until I’m a full professor”. The problem is that we frequently end up postponing getting children based on this logic until the choice is no longer ours: Fertility unfortunately does decline rapidly over the age of 35, notwithstanding other potential causes of infertility.This column is therefore not about the challenges of motherhood itself, but rather another situation frequently faced by women in academia, and one that is still not discussed openly: What if you want to have children and cannot, either because biology is not on your side, or because you waited too long, or both? My inspiration for writing this article is a combination of my own experiences battling infertility in my path to motherhood, and an excellent piece by Dr. Arghavan Salles for Time Magazine, outlining the difficulties she faced having spent her most fertile years training to be a surgeon, just to find out that it might be too late for motherhood when she came out the other side of her training (Salles, 2019). Unfortunately, as academic work models remain unsupportive of parenthood, despite significant improvements, this is not a problem faced only by physicians, but also one faced by both myself and many other women I have spoken to.I want to start by sharing my own story, because it is a bit more unusual. I have a very rare (~ 1 in 125,000 in women (Laitinen et al, 2011)) congenital endocrine disorder, Kallmann syndrome (KS) (Boehm et al, 2015); as a result, my body is unable to produce its own sex hormones and I don’t have a natural cycle. It doesn’t take much background in science to realize that this has a major negative impact on my fertility—individuals with KS can typically only conceive with the help of fertility treatment. It took me a long time to get a correct diagnosis, but even before that, in my twenties, I was being told that it is extremely unlikely I will ever have biological children. I didn’t realize back then that KS in women is a very treatable form of infertility, and that fertility treatments are progressing forward in leaps and bounds. As I was also adamant that I didn’t even want to be a mother but rather focus on my career, this was not something that caused me too much consternation at the time.In parallel, like Dr. Salles, I spent my most fertile years chasing the academic career path and kept finding—in my mind—good reasons to postpone even trying for a child. There is really never a good time to have a baby in academia (I tell any of my junior colleagues who ask to not plan their families around “if only X…” because there will always be a new X). Like many, I naïvely believed that in vitro fertilization (IVF) would be the magic bullet that can solve all my fertility problems. I accordingly thought it safe to pursue first a faculty position, then tenure, then a full professorship, as I will have to have fertility treatment anyhow. In my late twenties, my doctors suggested that I consider fertility preservation, for example, through egg freezing. At the time, however, the technology was both extravagantly expensive and unreliable and I brushed it off as unnecessary: when the time comes, I would just do IVF. In reality, the IVF success rates for women in their mid‐to‐late 30s are typically only ~ 40% per egg retrieval, and this only gets worse with age, something many women are not aware of when planning parenthood and careers. It is also an extremely strenuous process both physically and emotionally, as one is exposed to massive doses of hormones, multiple daily injections, tremendous financial cost, and general worries about whether it will work or not.Then reality hit. What I believed would be an easy journey turned out to be extremely challenging, and took almost three years, seven rounds of treatment, and two late pregnancy losses. While the driving factor for my infertility remained my endocrine disorder, my age played an increasing role in problems responding to treatment, and it was very nearly too late for me, despite being younger than 40. Despite these challenges, we are among the lucky ones and there are many others who are not.I am generally a very open person, and as I started the IVF process, I talked freely about this with female colleagues. Because I was open about my own predicament, colleagues from across the world, who had never mentioned it to me before, opened up and told me their own children were conceived through IVF. However, many colleagues also shared stories of trying, and how they are for various—not infrequently age‐related—reasons unable to have children, even after fertility treatment. These experiences are so common in academia, much more than you could ever imagine, but because of the societal taboos that still surround infertility and pregnancy and infant loss, they are not discussed openly. This means that many academic women are unprepared for the challenges surrounding infertility, particularly with advanced age. In addition, the silence surrounding this issue means that women lose out on what would have otherwise been a natural support network when facing a challenging situation, which can make you feel tremendously alone.There is no right or wrong in family planning decisions, and having children young, delaying having children or deciding to not have children at all are all equally valid choices. However, we do need more openness about the challenges of infertility, and we need to bring this discussion out of the shadows. My goal with this essay is to contribute to breaking the silence, so that academics of both genders can make informed choices, whether about the timing of when to build a family or about exploring fertility preservation—which in itself is not a guaranteed insurance policy—as relevant to their personal choices. Ultimately, we need an academic system that is supportive of all forms of family choices, and one that creates an environment compatible with parenthood so that so many academics do not feel pressured to delay parenthood until it might be too late.     

A preliminary report on my life in science

I describe my wanderings from the United States to East Germany and back. I hope this gives a glimpse of science in East Germany and encourages people who do science under less than favorable conditions. Although elements of my story are unique, the main points are general: don't be afraid to start something new; it pays to be persistent; and science is a passion--if it feels like fun, you've probably got it right.     

Report on the 2nd Workshop on Fluorescence Chemosensors and Bioimaging,Dalian, China: one participant’s view

Abstract

I was invited to this Workshop, because I have published papers on the mechanisms of action of small molecule fluorescent probes used with living cells. The Workshop provided an opportunity to interact with some significant figures in the chemosensor and bioimaging field from across the planet; to spend time with a large, friendly and active group of local investigators and their graduate students; and to take a brief look at a vibrant modern city. Many scientific connections were made and collaborations planned for the Biological Stain Commission and for my own future work.     

New perspectives on the declining significance of race: a rejoinder

In sharp contrast to many earlier studies, the articles in this symposium encompass a careful discussion of the two major underlying themes of my book, The Declining Significance of Race: (1) the effect of fundamental economic and political shifts on the changing relative importance of race and class in black occupational mobility and job placement; and (2) the swing in the concentration of racial conflict from the economic sector to the sociopolitical order. In my rejoinder I reflect on their arguments, including those that relate these themes to more recent developments in American race and ethnic relations featuring other groups, including whites and Latinos.     

Amphotericin B Lipid Complex (Ablc™): A Molecular Rationale for the Attenuation of Amphotericin B Related Toxicities

Abstract

When the idea of putting together a Forum on the subject of polymer and glycan coated liposomes came across my mind, I thought that this would be an unique opportunity for those of us who argue fiercefully in meetings to do the same in writing. The idea was well received when I contacted my colleagues about a year ago. After some minor arm-twisting by phone and FAX, here is the first Forum published in JLR.     

50 years a biomedical engineer remembering a long and fascinating journey

Looking back at one point of life appears as a nice exercise to round out and summarize. However, the objective should not be simply to tell a story; it must transmit a message to the young. To start with, two concepts are useful: Respect for others begins when you learn to laugh at yourself and, taken from an old saying, I did not want to be poor ... but money wouldn't make me rich. After elementary and high schools, during times of turmoil, I describe my engineering school years at the University of Buenos Aires and a working experience in an international telecommunications company. Significant events taught me a concept, rooted in another motto: Isn't this house nice? It is my house, and I love it very much. In 1960, I began my activities in the USA. A couple of bad decisions resulted in significant events for me teaching me an important truth: "Beware of golden promises; time is the most precious asset". Finally, in 1972, settled down in Tucumán until retirement in 2001, a long period of productive activity came about, not without difficulties and also stained by a dark political interval. Crises seem to characterize our generations in Argentina. Non-the-less, there were some real accomplishments: an undergraduate program in BME and a National BME Society (SABI) plus an archive of specialized published material. After spending time following retirement in Peru and Italy, my current activity came as unexpected dessert at the University of Buenos Aires, with a small research group, so offering the opportunity of transmitting what I still have available.     

Looking back on a life of unacknowledged privilege and a call to action

The year 2020 provided a wake-up call about the role systemic racism plays in shaping our nation and shaping science. While hard work and great mentors helped bring me a long way from a farm in Minnesota, it’s become much clearer that the privilege of being white and male and the accumulated advantages that began there played powerful roles. It’s time for white scientists like me to listen, think, and take action.

We all have personal stories that we use to describe our trajectory in life and science. For the past five decades the narrative I told myself was a simple one of good luck, hard work, support from my community, and mentors at pivotal times. However, in many important ways, this was just a small part of the truth, ignoring the role unperceived privilege played. The many underlying injustices that were laid bare in our nation this past year began to open my eyes, prompting me to look back at the roles hidden privilege played in my career and the power that these have given me. This challenged me to use the power of that privilege to speak and act to try to change the system in which engrained advantages benefit some but not all. I am telling my story in hopes it will encourage my white colleagues to examine their own.     

Support for a career in science

I am so very honored to receive the Women in Cell Biology Sandra K. Masur Senior Leadership Award from the American Society for Cell Biology (ASCB), particularly because many of the previous awardees have served as mentors and sources of inspiration throughout my own career. I also thank the ASCB for always striving to be maximally inclusive, in terms of both the scientists it supports and its broad vision of what constitutes cell biology. As a graduate student I gave one of my first talks at an ASCB meeting, and I am proud to have been an ASCB member for almost 30 years. In this essay, I describe my own career to illustrate the support that I believe is needed to achieve a career in science.

S. L. Wolin     

A year since George Floyd

The murder of George Floyd sparked an awakening, long overdue, which reverberated throughout society. As science begins to acknowledge its role in perpetuating systematic racism, the voices of Black scientists, which have largely been absent, are now being called on. As we rightly begin to make space for diverse voices and perspectives in science, we all must think about what it is we are asking minoritized individuals to do.

It has been roughly 1 year since the murder of George Floyd, an unarmed Black man, who was killed over an alleged counterfeit 20 dollar bill in Minneapolis, Minnesota (Hill et al. 2020; Kaul, 2020; Levenson, 2021). In many ways, his murder was no different than the murders of thousands of other murders of Black people in this country (Thompson, 2020; Lett et al., 2021; Tate et al., 2021). However, what distinguishes George Floyd’s murder from many other high profile cases is that it was unambiguously captured on video (Alexander, 1994), an act of bravery by Darnella Frazier, a 17-year-old Black woman (Izadi, 2021), at a time when the world was mostly housebound by a raging global pandemic. As a result, his murder reverberated through society in a way that has not happened in my lifetime. While there have been other high profile cases of murders carried out by police (Treyvon Martin, Walter Scott, Breonna Taylor, and Philando Castile, among many others), these cases failed to fully sustain the attention of a national and international audience (Chan et al., 2020; Chughtai, 2021). The murder of George Floyd was fundamentally different, and for once, more than just Black people were paying attention. His murder sparked protests across the nation led by the Black Lives Matter (BLM) movement (Day, 2015; Taylor, 2016; Banks, 2018; Taylor, 2021), and the demands for change were so loud people could not help but hear.As a Black, gay man who is also a scientist, I was thrown into despair. All of my life I have thought if I just worked hard enough, if I am kind and unthreatening, if I play the game and keep my head down, maybe I can make it in academia. Maybe then I will be seen and accepted, not just by society, but by the scientific community. George Floyd’s murder reminded me, and many of my Black colleagues, that our degrees can’t protect us, that our privileged middle-class upbringing (if we had one) was not a shield. Our lives were not worth more than a counterfeit 20 dollar bill.Science, which has always been a product of society, was not impervious to these reverberations. By late June my inbox began to slowly fill with invitations to speak at several institutions for their seminar series, retreats, or special symposia. It felt as if the scientific community, for the first time, realized that there were Black scientists among them. In the throes of my own despair, and the feeling that I needed to be doing something for my community, I began to say “yes.” I was not going to participate in the nightly protests that occurred in my newly adopted hometown of Portland, Oregon. Aside from fearing I could be next to lose my life at the hands of the police (Edwards et al., 2019), these protests were happening in the backdrop of a global pandemic. I came to the conclusion that by accepting these invitations to speak, this could be my activism, my way of sparking change, increasing visibility, and being seen not only for my own sake but also for other Black scientists.Before I write anything else, I want to be clear: I am extremely thankful to all the institutions and organizations that invited me and gave me a platform. I am extremely proud of my students’ work and of the research we produce. I am sharing my experiences with the hope that they can be instructive to the greater scientific community, but if I am being frank, there is a bit of anger.I received over 15 invitations and gave an additional three or four interviews over the course of the year. Most of these came with the expectation that I would also talk about my work in Diversity, Equity, and Inclusion. But here’s the lowdown: prior to this year, I did not view myself as someone who did Diversity, Equity, and Inclusion work. I am co-chair of the LGBTQ+ committee of the American Society of Cell Biology and a member of the Diversity, Equity, and Inclusion committee of the Genetics Society of America. I volunteer for both of these committees because they speak to something I care deeply about, the advocacy for minoritized ¹ scientists. I also embody both of these axes of diversity; so, in some way, I am only looking out for myself. This is far from being a scholar or doing “Diversity work.” I fully recognize that there are individuals who have dedicated their lives to this type of work with entire academic fields populated with accomplished scholars. So, I started this year of talks being invited because I am a Black, gay scientist at a time when science was grappling with its own systematic racism, under the guise of my nonexistent Diversity, Equity, and Inclusion work.What has this year actually taught me? The first thing it taught me is that I have been missing out. Prior to George Floyd’s murder, I had only received three seminar invitations from major research institutions and unfortunately all within a year of being posttenure. That is after nearly 6 years in my current position.In giving these talks I got the opportunity to meet with some of the giants in my field, people I have looked up to for years. I received reagents, offers to collaborate, and a litany of great ideas that will help drive my research program for years to come. I left some of these meetings truly inspired and excited to start experiments. These opportunities would have been invaluable to me, pretenure. One could argue, I did not need it. I made it even without this networking and the advantages these visits bring. Before you applaud my ability to persist and be resilient, we should take a deep look at the systems that have forced people who look like me to be doubly resilient. If George Floyd had not been murdered, would any of these invitations have happened? If the previous 6 years are any indication of a trend, I would have to say most certainly not. Why did it take a murder and the reignition of a Civil Rights movement for me to have the type of interactions I now know many of my straight, white counterparts have had from the very beginning of their independent careers? Let me be clear: this is a form of systematic racism, plain and simple.As I began to make the rounds, I was often asked to either share a bit of my journey or include my Diversity, Equity, and Inclusion work in my talks. This sometimes came at the expense of sharing my lab’s work. While I was very happy to do so, this was very much implicit in the invitations I received. At times it did feel that my inclusion was only checking a box, placating the graduate students so that they could see that their department or institution was responding to their demands. This also had the consequence of making me feel as though my science was merely performative. I was being invited to do the Diversity work institutions did not want to do. This is the tension I, and many other minoritized scientists, face. I want to share my experiences with the hopes that the next generation will have it better; but, my scholarly work is not in Diversity, Equity, and Inclusion. I fully recognize that it is my embodied diversity that is bringing me to the table; but, it is the science I want to share.On the first invitation to give a seminar, I promised myself that I was going to be honest. This meant that I would tell the truth about my experience and bare my soul over and over again. What I had not counted on was the emotional toll this would take on me. Reliving my own trauma, on a regular basis, left me emotionally drained after these visits. In one of my “stops” (I use quotes here because these “visits” were all virtual), I met with the queer, person of color (POC), graduate students. This session quickly turned into an emotional support group where I heard stories of mistreatment, racism, and discrimination. It was nearly impossible to maintain my composure. Diversity, Equity, and Inclusion work is clearly extremely important, but, maybe, we could just start by listening to the needs of the students and having a bit of humanity.The trial of Derek Chauvin has come and passed, and much to my surprise, and to the surprise of many other Black people nationwide, he was found guilty and was sentenced to prison (Arango, 2021; Cooper and Fiegel, 2021). This, of course, is not justice, not even close. Justice would mean that George Floyd is still alive and would get to live out his life in the way he chose. We are also at the beginning of the end of the pandemic. In 6 months or less, we may all be returning to life, more or less, as it was before George Floyd, before COVID-19. Does this mean we stop fighting? Does this mean that I, and many other Black scientists, suddenly disappear? For George Floyd, for countless other faceless Black people before him, I sincerely hope not. We need to continue to give Black scientists a platform. We need to ensure that they, too, are given the opportunity to network, collaborate, and interact with the larger scientific community. This means the invitations cannot stop. To further this, we need to ensure that Black scientists are included in every grant review panel, are included on speaker lists at every national and international meeting, are funded, and are in the room where funding, tenure, and other critical decisions are being made. We need to recognize that systematic racism has not gone away with Derek Chauvin’s conviction and sentencing. We need to continue to push forward. And, for all of you young, minoritized scientists (and allies) reading this, demand change and do not take "no" for an answer. I am truly sorry this has fallen on your shoulders, but enough is enough. The next generation of minoritized scientists should be recognized for their science without the additional burden of creating their own space.About the AuthorI am currently an Associate Professor of Biology at Reed College (https://www.reed.edu/biology/applewhite/index.html), which is located in Portland, Oregon. I arrived at Reed in 2014; prior to that, I was a postdoctoral fellow at the University of North Carolina, Chapel Hill. I received my PhD from Northwestern University in Cellular and Molecular Biology and a BS in Biology from the University of Michigan where I was also a 4-year letter winner in track and field. My research focuses on the cytoskeleton where I study cell motility and morphogenesis using Drosophila and Drosophila derived in tissue culture cells to explore actin, microtubules, and molecular motors. My current lab is composed of fierce, determined undergraduate students. I am a member of the American Society of Cell Biology (ASCB) and the current chair of the LGBTQ+ Committee (https://www.ascb.org/committee/lgbtq/). I am also a member of the Diversity, Equity, and Inclusion Committee for the Genetics Society of America (https://genetics-gsa.org/committees/). I also serve as an editor for MBoC’s Voices series.     

In search of evolutionary developmental mechanisms: the 30-year gap between 1944 and 1974

The approach I have elected in this retrospective of how I became a student of evo-devo is both biographical and historical, a case study along the lines of Waddington's The Evolution of an Evolutionist ('75), although in my case it is the Evolution of an Evo-devoist. What were the major events that brought me to developmental biology and from there to evo-devo? They were, of course, specific to my generation, to the state of knowledge at the time, and to my own particular circumstances. Although exposed to evolution and embryology as an undergraduate in the 1960s, my PhD and post-PhD research programme lay within developmental biology until the early 1970s. An important formative influence on my studies as an undergraduate was the work of Conrad Hal Waddington (1905-1975), whose writings made me aware of genetic assimilation and gave me an epigenetic approach to my developmental studies. The switch to evo-devo (and my discovery of the existence of the neural crest), I owe to an ASZ (now SICB) symposium held in 1973.     

Borrowed robes

Should scientists indulge their fantasies by writing fiction? Subject Categories: Careers, Economics, Law & Politics, History & Philosophy of Science

Like a substantial fraction of the literate population, I have a collection of unpublished novels in the drawer. Six of them in fact. Some of them were composed in barely more than a week, and others I have been struggling to complete for over 10 years: so maybe it is more accurate to say five and a half. Anyhow, most of them are good to go, give or take a bit of editorial redlining. Or, as my helpful EMBO editor would say, the removal of thousands of unnecessary adverbs and dubiously positioned commas.What do I write about and why? My style is not unique but rather particular. I write fiction in the style of non‐fiction. My subject matter is somewhere in the general realms of science fiction, alternate history and political drama. Putting these ingredients together, and taking account of my purported day job as a serious scientist, it is easy to see why my fictional work is potentially subversive—which is one reason why I have been rather reluctant thus far to let it out of the drawer. At the very least, I should take pains to conceal my identity, lest it corrupts perceptions of my scientific work. Even if I regularly tell my students not to believe everything they read, it would impose far too great a burden on them if they came to question my peer‐reviewed articles purely on the basis of untrue statements published in my name, spoken by jaded politicians, washed‐up academics or over‐credulous journalists. Even if they are imaginary. Real journalists are theoretically bound by strict rules of conduct. But imaginary ones can do whatever they like.Today, I noticed a passage in one of these unpublished works that is clearly written in the style of a young William Shakespeare, dealing with a subject matter that fits neatly into one of his most famous plays. In fact, the illusion was such that I was sure I must have lifted the passage from the play in question and set about searching for the quote, which I then could and should cite. Yet, all Internet searches failed to find any match. The character in whose mouth I placed the words was depicted as being in a delirious state where the boundaries of fact and fiction in his life were already blurred; borrowed identities being one of the themes of the entire novel and arguably of my entire oeuvre. But am I guilty here of plagiarism or poetry, in adopting the borrowed identity of my national playwright?In another work, I lay great emphasis on the damaging role of mitochondrial reactive oxygen species (ROS) as the cause of biological ageing. I have even grafted this explanation onto a thinly disguised version of one of my most valued colleagues. Although there is some support for such a hypothesis from real science, including some papers that I have myself co‐authored, it is also a dangerously broad generalization that leads easily into wrong turnings and misconstructions—let alone questionable policies and diet advice. But, by advancing this misleading and overly simplistic idea in print, have I potentially damaged not only my own reputation, but that of other scientists whom I respect? Even if the author’s identity remains hidden.In one novel, I fantasize that nuclear weapons, whilst they do undoubtedly exist, have in fact been engineered by their inventors so as never actually to work, thus preventing their possible misuse by vainglorious or lunatic politicians unconcerned with the loss of millions of lives and planetary ruin. But if any insane national leader—of which there are unfortunately far too many—would actually come to believe that my fiction in the style of non‐fiction were true, they might indeed risk the outbreak of nuclear war by starting a conventional one in order to secure their strategic goals.Elsewhere, I vindicate one author of published claims that were manifestly based on falsified data, asserting him to have instead been the victim of a conspiracy launched to protect the family of an otherwise much respected American President. None of which is remotely true. Or at least there is no actual evidence supporting my ridiculous account.I have great fun writing fiction of this kind. It is both liberating and relaxing to be able to ignore facts and the results of real experiments and just invent or distort them to suit an imaginary scenario. In an age when the media and real politicians have no qualms about propagating equally outrageous “alternative facts”, I can at least plead innocent by pointing out that my lies are deliberate and labelled as such, even if people might choose to believe them.In a further twist, the blurb I have written to describe my latest work characterizes it as the “semi‐fictionalized” biography of a real person, who was, in fact, a distant relative of mine. But if it is semi‐fictionalized, which bits are true and which are made up? Maybe almost the whole thing is invented? Or maybe 99% of it is based on demonstrable facts? Maybe the subject himself concocted his own life story and somehow planted it in falsified documents and newspaper articles to give it an air of truth. Or maybe the assertion that the story is semi‐fictionalized is itself a fictional device, that is, a lie. Perhaps the central character never existed at all.It is true (sic) that the most powerful fiction is grounded in fact—if something is plausible, it is all the more demanding of our attention. And, it can point the way to truths that are not revealed by a simple catalogue of factual information, such as in a scientific report.But I have already said too much: if any of my novels ever do find their way into print, and should you chance to read them, I will be instantly unmasked. So maybe I’ll have to slot in something else in place of my pseudo‐Shakespearean verse, mitochondrial ROS hypothesis, defunct weapons of mass destruction and manipulated data manipulation.     

Advice to a young scientist (by someone who doesn’t know how to give it)

While trying to extract original and general advice from the details of my career, I realized this might not be possible. My path, like those of so many others, had too many idiosyncratic twists and turns that had to work out just the way they did to be mined for generally useful strategies. So I abandon the conceit of advice and simply give you my story. There are many like it, but this one is mine. Take what you wish from it.     

Discovering the Mechanisms of Neurodegeneration in Prion Diseases

The purpose of my chapter in this issue of Neuroscience Reviews dedicated to Dr. Lawrence Eng is to summarize my contributions to understanding the mechanisms of neurodegeneration in prion diseases. I explain that I was able to advance the field of prion disease neuropathology largely because of the foundation of neurochemistry and immunohistochemistry that I learned while working 5 years in Dr. Engs laboratory. In my review, I relate how my Neuropathology Research Laboratory began as a collaboration with Dr. Stanley Prusiner 20 years ago that led from immunohistochemical staining of amyloid plaques in rodent and human brains using prion protein-specific antibodies to molecular evidence that the abnormal prion protein, PrP^Sc, is the cause of the clinically relevant neuropathological changes in animal and human prion diseases.Special issue dedicated to Dr. Lawrence F. Eng.     

Decoding the genetics of rare disease: an interview with Monkol Lek

Monkol Lek, Assistant Professor at Yale University School of Medicine, and Associate Editor at Disease Models & Mechanisms, dedicates his research to finding a genetic diagnosis and improving treatments for rare disease patients. As he originally studied computer engineering at the University of New South Wales in Sydney, Australia, he now utilises computational methods to optimise large-scale genetic studies, provide globally accessible resources for genetic research communities and, importantly, resolve diagnostic odysseys for rare disease patients. Monkol completed his PhD in Prof. Kathryn North''s lab at the University of Sydney, studying the genetics of muscle strength and performance, and then continued his investigation of muscle disease in Prof. Daniel MacArthur''s lab at Massachusetts General Hospital and the Broad Institute. During his postdoc, he led several large-scale studies aimed at distinguishing pathogenic from benign variants, including the Exome Aggregation Consortium (ExAC) project ( Lek et al., 2016). Monkol established his own lab at Yale University School of Medicine, which continues to improve the diagnosis and treatment of rare muscle disease, and also focuses on underserved populations, whose genetic mutations are not as well characterised as those of European ancestry. In this interview, Monkol discusses how his own diagnosis with limb girdle muscular dystrophy has shaped his career and what he envisions for the future of genetic research in rare disease.

You have a very unique career path – could you tell us a little bit about that? My first degree was in computer engineering. When I first went to university, I studied the hardware and software of computers. I really liked the software aspect of the degree, and so I worked for IBM as a software developer when I finished university. However, during the last few years of university, I noticed that my muscles were getting weaker. My university was on a big hill, with classes at the bottom and top of the hill, and I had to stand up for about 3 h a day while commuting on public transport. It started becoming obvious that I had something wrong with my muscles because I felt totally exhausted at the end of the day. It was frustrating, because I felt that my performance at university was impacted by something that had nothing to do with my ability to think. So, I went from doctor to doctor to try to find out what was wrong with me. As a lot of doctors are not trained in rare diseases, they didn''t consider a rare disease diagnosis. Then one doctor did a blood test for creatine kinase (CK), which is leaked into the bloodstream when muscle is damaged. In healthy people, high levels of CK are detected in the bloodstream after they''ve done intensive exercise, like a marathon. If someone hasn''t done something like that, but they have high levels of circulating CK, it could be an indication that there''s something wrong with their muscles. As I had high levels of CK in my bloodstream, I then went to a neurologist, which was when I got a clinical diagnosis. At that point, they didn’t know the root cause of the problem, but they knew that I have a muscle disease based on several tests, including a nerve conduction test.I received this clinical diagnosis during my time in IBM, and that''s when I became dissatisfied with my job, because I felt that I was using all my talents to make a very big, international company richer. I was also becoming frustrated when visiting the neurologist every 6 months, as all they would tell me was that my muscles were getting weaker, which I already knew. I began to think that not much was happening in the neuromuscular disease field if that''s the best they could offer me. I wanted to know what the root cause of my disease was and if there were any treatment options. I came to the conclusion that no one would care about my disease more than I would, because I''m the one that has lived with it every day of my life.That''s when I decided to leave IBM and pursue a career in researching muscle disease. It didn''t go down well with my parents and friends, because I was leaving a well-paid job to go back to university to get paid nothing for an unknown number of years. If I had known my chances of success – completing a meaningful PhD, doing a meaningful postdoc and landing a faculty position – I wouldn''t have gone on this journey. I have been very fortunate, but I wasn''t always in the right place at the right time.When I finished my undergraduate degree in bioinformatics and physiology at the University of New South Wales, I started a PhD in Melbourne, but it didn''t work out, because not all supervisors are perfect. My wife and I then returned to Sydney, where my wife bumped into one of the professors from our undergraduate degree. She explained that we''d had a bad experience in Melbourne with our PhDs, but our passion was still to do muscle research. The professor''s daughter was researching muscle disease in Kathryn North''s lab at the University of Sydney, and she invited us to visit the lab. I was offered an opportunity to do my PhD in Kathryn''s lab, but I was initially reluctant as it was a diagnostic lab, and I was more interested in developing therapies for people with muscle disease. However, I thought I could still learn a lot about muscle physiology and, in the long term, I''m glad that I received training and mentorship from Kathy''s lab. Also, if I hadn''t done my PhD there, I wouldn''t have met Daniel MacArthur, my future boss. He was a very talented student in Kathy''s lab, who taught me a lot about scientific communication among other things, and I taught him some coding skills. He left to work on the 1000 Genomes Project in Cambridge, UK, but I kept in contact with him to get his advice on my project.When I was finishing my PhD, Daniel asked if I wanted to join the lab he was setting up in Massachusetts General Hospital and the Broad Institute. His lab was going to study common loss-of-function mutations in human populations using large datasets from the 1000 Genomes Project, but he offered me a project investigating neuromuscular diseases. As soon as I submitted my PhD thesis, I started working in his lab. This was perfect timing, because it was 2012, when exome sequencing had recently been published in the context of rare diseases (Ng et al., 2010) and, more importantly, it was becoming affordable, in terms of research. I waited over 10 years for a genetic diagnosis, so my goal was that no one should have to wait that long in the future.Through collaboration with our former PhD lab, Daniel and I used samples from undiagnosed patients to find answers for Australian families. The first family had two affected girls with undiagnosed nemaline myopathy, who had been on a diagnostic odyssey for about 9 years. It was amazing how quickly we progressed from receiving the samples to identifying the novel gene, LMOD3, associated with their disease (Yuen et al., 2014). This was part of my main project during my postdoc – working on gene discovery in neuromuscular diseases and finding answers for patients that have been waiting years and years to get a genetic diagnosis (Ghaoui et al., 2015; O''Grady et al., 2016).The project that most people know me for is the ExAC project, which was initially my ‘side’ project during my postdoc. The idea was to create a big database of all rare variants that we see in the general population, so we can better interpret the rare variants that we see in rare disease patients. When we were creating it, we thought that it may be useful to other researchers around the world. Therefore, we tried to ensure, through data-use agreements and consent processes, that we could share as many of our findings as possible. I''m happy to say my side project was quite successful. After that, I led other projects, including an analysis group in the Centre for Mendelian Genomics, to expand that framework and idea across all rare diseases, not just neuromuscular diseases (Baxter et al., 2022).I was having a lot of fun at the Broad Institute, and I was co-author on a lot of high-impact papers. However, the reason I left the Broad Institute was that I wanted to be involved in the full journey for the patients. Sometimes scientists don''t understand that getting a genetic diagnosis is not the end of the journey for a patient. After the diagnosis they want to know what treatment options are available. Yale gave me the opportunity to continue doing the gene discovery and analytical work that I was doing at the Broad Institute, plus the capability of doing experiments with mouse models to investigate gene replacement therapies and other therapeutic approaches.

“I waited over 10 years for a genetic diagnosis, so my goal was that no one should have to wait that long in the future.”

How has being both a researcher and a patient affected your career? When I was first diagnosed, there was a neurologist who discouraged me from researching my own disease and this became the basis of my TEDx talk, because I thought it was very condescending. I thought, “Just because I have this disease, it doesn''t mean that I have a low IQ”. However, this experience motivated me more. I discussed it with Kathy before starting my PhD, and her encouragement and enthusiasm was refreshing. At the time, in the early 2000s, people hadn''t accepted the idea of patients researching their own disease. Things have changed since then, mainly because there are more examples of it now (Branca, 2019), but at the time, it was really hard for me to progress in science. I always thought that people were looking at me with sympathy, and I felt like I had to achieve twice as much to get the same respect as someone else who wasn''t as talented or didn''t work as hard as me. It was frustrating, but in everyday life people still correlate physical disability with intellectual disability. For example, if my wife is pushing me in the wheelchair in public, no one ever directs a question to me because they assume that the physical disability comes with mental disabilities. There are well-known examples of scientists with physical disabilities, like Stephen Hawking, but it is still challenging in academia when you have a physical disability and people make certain assumptions about you.On the other hand, just before starting at Yale, my collaborators at the University of Massachusetts took a skin biopsy from me. With this skin biopsy, they created induced pluripotent stem cells, and, using CRISPR, they corrected my disease-associated gene variant in the cultured cells. They then published this in a Nature article, in which fig. 1 is the experiment in which they corrected my mutation (Iyer et al., 2019). Are there specific skills or knowledge you learned while working in computer engineering that have helped shape and develop your research today? When I started my PhD, there was an increase in how much genetics research, and biological research in general, relied upon big data. It can be very challenging to work with big data if you''re a biologist without a background in computer science. You can go online to teach yourself to an extent, but it gives you an advantage to learn the theory behind a lot of algorithms and other aspects of software engineering, in a formal setting. It makes the difference between building tools that take a week to analyse a set of data and building tools that take a few minutes to analyse the same data. If you can analyse the data more quickly, you can explore different possibilities and ideas much more quickly. You can''t learn everything online, and having a firm foundation of knowledge can enable you to work with big data in an efficient way.The other thing that you learn from computer science is a certain mindset when approaching problem solving. This is because you have to debug code frequently and, due to this fast pace, you learn quickly. This helped me to troubleshoot problems in biological research quickly.

“Getting a genetic diagnosis is not the end of the journey for a patient. After the diagnosis they want to know what treatment options are available.”

What do you think are the key challenges for rare disease research and diagnosis moving forward? I now have a greater appreciation of the challenges because I see it from two points of view: one as a researcher in a group and one as a PI, who leads the research. The diagnosis rate for rare disease is about 50%, so there are still 50% of patients with a disease that has an unknown genetic cause. The gold standard requirement for associating a new disease gene with a novel phenotype is that it presents in multiple unrelated families (MacArthur et al., 2014). However, when you work with rare diseases, there is the issue of small sample numbers. One challenge for basic scientists is creating good collaborations with physician scientists across the world to enable you to create a large enough dataset.The other challenge is the cost of research for these diseases with unknown genetic cause. The 50% of cases for which we know the genetic cause are no longer considered an area of research, as clinical genetic services can now diagnose these patients. To diagnose the remaining patients, you have to use more expensive technologies, such as long-read sequencing.The last thing is the interpretation of rare variants. Although the ExAC project helped with this, there is still a challenge. For example, if a patient has a rare genetic variant, this doesn''t necessarily mean it is the cause of their rare disease. This is because even healthy people have rare variants. So, we have a massive interpretation challenge in rare disease genetics, which can be overcome by creating a laboratory model system with that genetic variant to investigate it further. However, if you had 1000 variants to consider, it''s not going to scale as an animal model. So, an important question is how can we interpret these variants in a scalable manner? This is one of the main driving forces behind the new Subject Focus, ‘Genetic variance in human disease: decoding diversity to advance modern medicine’, that we are launching in DMM. You have led and coordinated several studies involving very large cohorts. From your experience what are the key components of a successful study? I think the key to a successful large cohort study with unsolved rare disease patients, is the amount of structured phenotype data you can collect. This requires a good collaborator, who has the time to prepare that data in a meaningful way, which makes it easier to find other families with the same rare disease. The other thing is to have the ability to recontact patients and collect different samples from them, because we''re moving to a more multi-omics world. Therefore, we need the ability to go beyond just collecting DNA samples. Also, we''re in a world where we''re starting to link data to electronic health records, which allows the collection of deeper and richer phenotype data that enable associations to be made between families.In addition, you can''t work in isolation. In order for us to make a meaningful impact, we need to work with groups that have specialties outside of our own. For instance, we collaborate with groups that specialise in the interpretation of non-coding variants. This is important as variants in these regions could hold the answers for some of those unsolved cases.Another key aspect to a successful study is collaboration with statistical geneticists because some of the more complicated questions are best asked by them. Some of these questions go beyond monogenic diseases. We are seeing convergence between genome-wide association studies, looking for many variants, each with very small contributions to a disease, and studies of Mendelian disease that are looking for one gene that causes disease. The field has to start looking at diseases in the middle of this spectrum, which requires statistical geneticists. This is because you need to make sure that your conclusions are correct. For instance, if you''re asking whether a rare disease is caused by a combination of two genes, then you must have a robust statistical model to show that these variants aren''t presenting together by chance. You have to prove that those two variants are acting in concert, instead of independently, to cause this disease. My colleagues at Yale published a great paper that demonstrated this concept (Timberlake et al., 2016).Lastly, it is important to forge meaningful collaborations beyond academia. A lot of my colleagues are being funded by industry collaboration, and a lot of these companies have access to more samples than we do in academia. You can also collaborate with large biobanks, such as the UK Biobank, which has a rich set of phenotype data and also the ability to recontact patients (Glynn and Greenland, 2020). The FinnGen project is a recent public–private collaboration that combines genetic data with electronic health records from Finnish biobank participants to improve disease diagnosis and treatment (Kurki et al., 2022 preprint). So, working with biobanks and industry is another way of increasing sample numbers, which is the biggest challenge in rare disease research.

“We don''t want to create disparity in terms of health, especially in the context of genetics, which will continue to become more prominent in modern medicine.”

You dedicate a lot of your research towards patients in underserved populations, such as East Asian populations, whose genetic mutations are not as well characterised as those of European ancestry. Can you explain the importance of this? One of the reasons that it took over 10 years for me to get a genetic diagnosis was because the gene that causes my disease was first reported as not commonly associated with disease in populations of European ancestry. The problem with biomedical research is that when people read that, they think it applies to everyone, even patients who have non-European ancestry. Although the gene that causes my disease aligned with my muscle disease phenotype, it wasn''t sequenced because of this assumption. They only decided to sequence this gene once they did linkage analysis of my family, and this was the only gene associated with neuromuscular disease in the linkage region they identified. This is the reason why we need to have good data on all populations. The ExAC and gnomAD studies that I worked on acknowledged that we need good allele frequency data for populations of East Asian, South Asian, Latino and African ancestry, because we don''t want to create disparity in terms of health, especially in the context of genetics, which will continue to become more prominent in modern medicine.If you want to deliver the best healthcare, you have to realise that some variants and diseases are more common in certain populations, such as Tay-Sachs disease, which is common amongst the Jewish community, and sickle cell anaemia, which is more prevalent in populations of African ancestry. By understanding these differences, we can actually find a genetic diagnosis a lot quicker. If it''s not a de novo variant, and is instead a variant inherited in the population, and if you''ve made the discovery in East Asians, there is a better chance of identifying more incidences of this variant in the population in which it was first discovered.I think it''s also good for validation of data, because if you had discovered a potential disease-causing variant and you find that this variant has a frequency of 1% or higher in a non-European population, then it''s impossible for it to be the cause of a rare disease, regardless of its frequency in a European population (Lek et al., 2016).     

The story continues: recent advances on the life and death of the Pleistocene cave bear

ABSTRACT

In this issue, we cover an exceptional topic in Vertebrate Paleobiology that has been an enjoyable challenge for scientists and the popular media alike: the life and death of the Pleistocene cave bear (Ursus spelaeus). As an icon of the ice-age, the cave bear inhabited the glacial ecosystems of Eurasia, and it was the inspiration of a popular book written in 1976 by Björn Kurtén, entitled The cave bear story: life and death of a vanished animal. Although ‘The life and death’ was a summary of the knowledge acquired on cave bear biology at that time, four decades later, many aspects of its palaeoecology, extinction and evolution are still a matter of debate. With this volume, we aim to bring together the most recent research on cave bear biology in order to provide an update on the palaeoecology, biogeography, systematics, and phylogeny of this recently extinct ursine bear. We thus organised a symposium on the 1st of August 2017 as part of the three-day Annual Meeting of the European Association of Vertebrate Palaeontologists (EAVP) in Munich, Germany, that was an additional opportunity to announce the volume and to discuss this exciting subject face-to-face among specialists.