Breaking Through

By Katalin Karik'o (Crown, 2023).

Overview

Very touching book!

Preface

• Thank you to educators everywhere. You are planting seeds.

Prologue

• Sometimes a complex and satisfying life—or the complexity of life itself—can look, to others, like nothing at all.

Part I: A Butcher’s Daughter

• p. 5: It’s our job, though, to fill the insert container with sawdust every morning. This is hard work, and it must be done carefully. Like many of the things we do, it isn’t a chore—at least not in the sense that people use the word now. It’s not something that our parents ask us to do, not a favor we’re doing for the family. It’s simply what must be done. If we don’t do it, our family will freeze.

• p. 7: Everything is like that: Nothing goes to waste. We shake walnuts from trees, eat the nuts, and burn the leftover shells as fuel. It will be years before plastic becomes a part of my life, years before I understand the concept of garbage, the idea that some things are so useless they can simply be thrown away.

  Communist Hungary sounds so familiar. Are all communist countries the same?

• p. 12: Intelligence and education are not the same thing. A person may lack prestige or a diploma but nevertheless have a swift mind.

• p. 13: But is all of this really work? Or is this just life? … And of all my early lessons that prepared me to be a scientist, that one, I think, is the most important of all: that work and play can bleed into each other, become one and the same, until the very idea of their distinction feels meaningless.

• p. 35: This was a virus; it had no ideology, no political agenda. If we weren’t careful, it would spread. Then we would all suffer. Those were just the facts. That’s how viruses work.

• p. 38: Sometimes, I think, that is the best we can do: to learn from the world we’ve been handed and then try to leave things a little bit better for the next generation.

• p. 45: I like that Mr. Toth doesn’t merely teach us facts. Nor does he try to tell us what he thinks about these facts. Instead, he wants to know what we, his students, think about them. Perhaps more important: He wants us to know what we think.

• p. 48: Not is it simply that Selye was an outsider when he began his inquiry—no sense of how things are supposed to be done, no preconceived notions. (Sometimes, he seems to be saying, the most important questions are asked by outsiders.) It is also that Selye somehow understands how I want to think, the way I want to define a big question, then begin zeroing in, systematically and logically, on clear and specific answers. Early in the book, Selye notes that nature “rarely replies to questions unless they are put to her in the form of experiments, to which she can say yes or no.”

• p. 49: Only those blessed with the understanding that comes from a sincere and profound love of Nature will…succeed in constructing a blueprint of the many questions that need to be asked to get even an approximate answer… Only those cursed with a consuming, uncontrollable curiosity for Nature’s secrets will be able to—because they have to—spend their lives working out patiently, one by one, the innumerable technical problems in performing each of the countless experiments required.

  stress isn’t merely a negative physiologic experience; it has positive forms, too—such as excitement, anticipation, and motivation. While negative stress can be harmful—it can, in fact, kill you—positive stress is necessary for a fulfilling life. And with the right attitude, we can transform negative stress into positive stress. How? By focusing on the things we can control, instead of the things we can’t. For example, as Selye seems to suggest, we cannot control anyone’s reactions but our own. Therefore, we shouldn’t work to please others or to gain their approval; we must, instead, set our own goals and work to satisfy those. When faced with setbacks or failures, we mustn’t blame others; assigning blame keeps us focused on thins over which we have no power. Instead, we can respond to misfortune by learning more, working harder, and being more creative.

• p. 52: Scientific investigation can be tedious. It generates a lot of data, and sometimes the bulk of that data appears to point in one direction. It can be tempting to look for the data that fit one’s existing narrative, and when you find that data—which you will—to feel you’ve done your job. But you must do your experiments correctly. You ask one question at a time. Then you change just one variable and ask again. And then you change the next variable. And then the next. Just one more thing. There’s almost always just one more thing. You must stay patient, examine everything, every tiny detail. You have to set aside the mountain of information that appears to confirm what you expect and deliberately seek out that one thing that doesn’t. Because that thing—that tiny, nagging piece that, for whatever reason, does not fit—may, if you pay attention, point you toward truth.

• p. 61: I’d learned some important things: Not everyone is rooting for me. Not everyone wants good things for me. Not everyone wants my contributions. Some people may even choose to hate me. Ok, then. Noted.

Part II: An Extremely Brief Interlude on Science

• p. 66: The history of science, it turns out, is filled with stories of very smart people laughing at good ideas.

Part III: A Sense of Purpose

• p. 79: If I have any superpower, it has always been this: a willingness to work hard and methodically, and refuse to stop.

  It felt so difficult to retain all this information, as if filling my brain with new information might squeeze out things I had previously learned. I was often up until two in the morning. I’d sleep for just three or four hours before waking to do a bit more homework before classes. If I grew tired, I opened a window. The truth is, I was always tired, so the window was always open, even when it was snowing. (I still do this now, even in winter, to keep myself awake.)

• p. 80: …small handful of my classmates packed the bulk of their studying into the last few weeks of the semester. They’d cram for final exams, absorbing like sponges hundreds of pages of material at the last minute. Then they’d take their exam and head to the bar for a celebratory beer. Whether they retained the material or not beyond the exam, I cannot say. I know only that this approach would not, could not, have worked for me.

  Sounds so familiar…

• p. 81: Do not believe that hard work and happiness are in opposition. Do not believe that one must embrace leisure to know joy.

  True, very true.

• p.86: “You should know about things fellow scientists are doing and have something to say.”—Janos Ludwig

• p. 88: The lower the temperature at which a fat goes from liquid to solid, the healthier that fat is.

  Seems like a typo: probably meant the opposite.

• p. 90: You find an excuse only if you don’t want to accomplish something. If you genuinely want to do it, you find a way. You sit down, get to work, learn how to transform what you have into what you need.

  Well said.

• p. 109: I’ve read nearly nine thousand scientific articles that seemed to me worth tracking (I’ve read plenty more that I didn’t care to track). When I read a scientific paper, I usually read everything—not merely the abstract, or the conclusion but also the background, the experimental methods, every figure and table. I read the references, too, often using them as jumping-off points for new papers I want to read. My life has been journal after journal, day after day, week after week, year after year, decade after decade. … It was science, science, science, science, nothing but science. Everything felt essential to me. Everything felt relevant. Even if it wasn’t yet relevant, it might be someday. I didn’t want to miss a thing.

  Aha, that makes two of us :)

• p. 113: “you work with scientists from many different countries around the world. It’s possible some of them could be…foreign agents. If they are, they might try to steal discoveries made by our own Hungarian researchers… We need to watch out. We must prevent theft. Protect our values.”—secret police

• p. 116: this overwhelming sense of urgency flooding me. I cannot let this happen, I thought. I cannot stop working. I cannot settle for less. No one, I suddenly understood, was waiting for the work I hadn’t yet done. Sure, my colleagues would notice my absence. Then they’d hire someone else and go right on with their work. … In this path, I simply lowered the bar for myself. It would happen gradually—a little at a time, and always for some reason. Those reasons would be real: illness or family obligations, or any of the other countless obstacles life might eventually throw into my path. Each of those obstacles would always be more tangible than contributions I hadn’t yet made. Obstacles have shape and structure; you can see them. One’s future impact, by contrast, remains invisible, hypothetical, at least until the future finally arrives.

  WOW!

• p. 124: Sometimes today people ask me what it takes for a woman to be a mother and a successful scientist. The answer is simple, obvious: One needs high-quality and affordable childcare. … If we want more women in science, if we want more women in anything, this is something we must address. The sooner the better. An affordable system of quality childcare is an investment for a nation, and it is one, I think, that comes back a millionfold.

Part IV: An Outsider Inside the System

• p. 147: I reminded myself that I hadn’t come here for money, that I didn’t need much. I’d never needed much. I reminded myself that I was grateful to be here, grateful to be able to perform my experiments. Sure, things might be tight, but I could live like this. Forever if I needed to.

• p. 159: Monday morning: I’d rise at three in Philadelphia. I’d get in my maroon Celebrity—then drive three hours through the dark. I’d carry a bag with me, inside of which was five days’ worth of broccoli and sausage. I also had half a gallon of milk and a bag of bread. That was it. Every week, the same groceries, in the same quantities. … I worked day and night. I never went out. I kept a sleeping bag in my car and a key to the apartment of a Hungarian colleague who offered up a place to sleep, as immigrants so often do for one another.

• p.170: Elliot’s philosophy as a PI and mentor was simple: Hire smart people who have good chemistry with one another. Listen to them. Give them mentoring and support where they need it, then get out of their way. Encourage them to outgrow you, to move beyond you … and celebrate them when they do.

• p. 172: It was infuriating. I had important work to do, and here I was, being held back by a couple of kids who had zero long-term investment in the work. I tried to remain calm—I’ve never been someone who yells—but I also told them the truth. “This is shit,” I said. I couldn’t pretend otherwise. We were going to have to start over. “It’s useless, garbage.”

• p. 178: Experiments never err, only your expectations do.—Leonardo da Vinci

• p. 183: In my quest for knowledge, I’d set exacting standards for myself and for my study design. By living up to these standards day after day, I’d become a very good scientist. But I was learning that succeeding at a research institution like Penn required skills that had little to do with science. You needed the ability to sell yourself and your work. You needed to attract funding. You needed the kind of interpersonal savvy that got you invited to speak at conferences or made people eager to mentor and support you. You needed to know how to do things in which I have never had any interest (flattering people, schmoozing, being agreeable when you disagree, even when you are 100 percent certain that you are correct). You needed to know how to climb a political ladder, to value a hierarchy that had always seemed, at best, wholly uninteresting (and at worst, antithetical to good science). I wasn’t interested in those skills. I didn’t want to play political games. Nor did I think I should have to. Nobody had ever taught me those skills, and frankly I wasn’t interested in them anyway.

  Yeah, why do we have such high and unrealistic expectations in academia?

• p. 192: This science giant, who had once been at the forefront of the field, hadn’t kept up with his reading. Listening to his talk felt like opening a time capsule from decades past. In the years since he’d made his breakthrough, new molecules had been discovered, new mechanisms of action described and articulated, new lat techniques developed that expanded the possibilities of what we could know. But there he was, clearly stuck in time. It wouldn’t be the last time this happened, and every time it did, I made a note to myself: Whatever happens, I must never stop reading. I must never. If I no longer can keep up with my reading, I will not give a talk.

  Never.

• p. 193: two mutually exclusive responses to stress in human relations: revenge and gratitude. Revenge is an attempt to relieve stress. It is a very human response to a threat to one’s security. But revenge has no virtue whatever, and can only hurt both the giver and the receiver of its fruits. Revenge brings only more revenge, in an endless cycle. Gratitude is also cumulative. Like revenge, it brings ever more of itself. But the place where it leads is entirely different. Gratitude amplifies those things on which a successful life depends: peace of mind, security, fulfillment.

• p. 194: People forget. They forget the specifics of how things were, the whole messy story of what they did, or how those things might have affected someone else. … I was ready to move forward. Not for his sake, but for mine.

• p. 195: I wrote at least one grant application a month. For two years I did this. I submitted research proposals to private and government agencies and the University Research Foundation. Not one came through. … Anyway, I never got a dime for my mRNA projects. As you might imagine, this didn’t go over so well at Penn.

• p. 197: I was learning every day. I was contributing to a body of knowledge. I was pursuing something that I was certain would be useful … someday, to someone, even if it was only in a small way, even if it didn’t happen in my lifetime. I was content to stay here for as long as I could.

  Salut.

• p. 210: I think it matters, having your own personal cheerleader. I think everyone deserves to know, Here is someone who believes in me. Here is someone who believes I can do great things, and who will never, ever quit rooting for me.

• p. 216: There were so many researchers who worked beautifully within the system of academic medical research. They got along with their colleagues, they joined committees, earned every gold star. By nearly every measure, they were successful. But they were so incurious. They had grants that funded their work and seemed happy enough to live off those. They wanted a nice life, and had one, and that was enough. I suppose there was nothing wrong with that. But David and I were hungry. We wanted to learn everything, examine closely, leaving no stone unturned, make a difference. For better or for worse, we were both cursed with what Hans Selye had described as “a consuming, uncontrollable curiosity.” Together, we chased one more thing, and one more thing, and then still one more thing after that. Sometimes I complained to David about the strange lack of curiosity I saw among people who were, in theory, at the top of the scientific hierarchy.

• p. 220: I wondered if having lots of options might be its own sort of burden. If many doors are open to you, but you can walk through only a handful in one lifetime, do you live forever haunted by what-ifs?

Part V: Susan’s Mom

• p. 263: Drew and I first submitted our finding to Nature. We heard back within twenty-four hours. Their editors rejected our paper outright as merely an “incremental contribution.” … In the place where we’d expected attention, acclaim, there was only silence. This groundbreaking discovery had been met by a collective shrug. Our breakthrough had apparently failed to break through to, well, anyone. … Well, I might be destined for a life of obscurity, but Susan was dead set on greatness.

• p. 269: Dollars per net square footage again. As if that’s what mattered, as if the system in which we operated was above all what must be maintained. The fact was, I barely cost this department anything. I didn’t get paid much; my salary was laughable compared with those of the neurosurgeons who surrounded me. I was now in my fifties, and I still did all my experiments by myself. I had no staff, no postdocs. All these years, ever by myself. I had no staff, no postdocs. All these years, ever since my demotion by Judy Swain, I’d been attending faculty meetings when I wasn’t even a faculty member! In front of me now, Sean was still talking. Not about science, not about all the ways mRNA might help the world, but rather, as always about budgets. Funding. “…I hope you’ll work with me to find a solution,” Sean said, “because if not—” “Sean,” I said. “I need to get back to work.”

• p. 271: Susan had told us the team to beat was Romania; they’d taken the gold in the women’s eight category for the last three Olympics.

• p. 272: Another way rowing and science are similar: You just have to keep going back to square one, starting anew—a new goal, a new experiment, a new chance to prove oneself, a new set of unknowns. Even after winning the gold, Susan was, upon her return, just another rower competing for eight slots in the next Olympics. You get no extra credit for having been at the top of the world once. The only question that mattered after Beijing was whether Susan could help bring home the gold in 2012.

• p. 273: Before 2008, when other rowers beat Susan in competition, it had been expected. Suddenly, she had new expectations for herself. If she lost a race, she had to beat back self-doubt: Why are they beating me? Why can’t I do this anymore? What if I’ve peaked?

  Repeat is difficult.

Part VI: A Changed World

• p. 288: money mattered in academic research, too. But there, so many people pretended it didn’t. They papered over the influence of money with symbols of prestige: publication records, citations, committees, fellowships, alma maters, “influences.”

  Wait: didn’t we just despise Dollars per net square footage?

• p. 311: May immigrants keep coming. May they continue aspiring to more, going wherever they must to get the opportunities they deserve. May they keep making their way, and in the process remake our world.

  All this attention. I didn’t need it, I hadn’t asked for any of it. I’d decided early in my career not to place any value on recognition, to value only the work itself—to do my work well and trust in where it might lead, even if it got there long after my own lifetime.

• p. 315: we might create a clearer distinction between markers of prestige—titles, publication records, number of citations, grant funding, committee appointments, etiquette, dollars per net square footage—and those of quality science. Too often, we conflate the two, as if they’re one and the same. But a person isn’t a better scientist because she publishes more, or first. Perhaps she’s holding back from publication because she wants to be absolutely certain of her data. Similarly, the number of citations might have little to do with the value of the paper and more to do with external events.

  Unfortunately, this is easier said than done. I mean, how do you tell?

  We can also expand the criteria by which we measure our scientists. Most institutions define a scientist’s value, first and foremost, by their funding. But most grants require a researcher to define at a very high level of detail what work they will do, what discoveries they might make. I’d argue that science, at its best, is about asking questions, trying things, and going wherever that inquiry takes you. It requires walking into the unknown—the unknown is the very point!

  Finally, we can also be more up-front about the influence of money on academic researchers and its implications. Money mattered in the university setting, just as it mattered in industry. But in my experience, academia, uniquely, had the luxury of ignoring a good idea.

Epilogue

• p. 319: I had a flash of insight: No one would ever miss the contribution I didn’t make. No one would knock on my door and beg me to continue working. If I stopped, or if I pulled back my efforts one bit at a time until I was giving less than my full potential, the loss would go entirely unnoticed. A world that’s missing an important contribution looks ordinary. It is the definition of the status quo.

  Ok, this is scary and real.

  Your future contribution might still be hypothetical. Please treat it like it’s real. It matters. It matters even if you don’t get to see the impact. That’s not the part any of us gets to control. Just keep going with your one more thing, and your one more thing, and your one more thing after that.

  Something I know for sure is this: Every seed gives rise to new life. This life in turn produces new seeds, which in turn give rise to still more. On and on it goes.