Biologist Megan Hatlen worries that she’ll never make a breakthrough in her research.
Megan Hatlen is a biologist at Blueprint Medicines, a fantastic biotech located in Cambridge, MA. Recently transplanted from NYC, she earned her PhD from Cornell University and performed research in oncology at the Memorial Sloan Kettering Cancer Center prior to making the Boston/Cambridge life-science pilgrimage. Though nearly a decade has been spent on the East Coast, the West Coast will always have her heart. Megan is a California native; she was raised in Bakersfield and earned her bachelors in Bioengineering at the University of California – San Diego. When not running experiments, Megan can be found with her wife, Jess, holding their chubby Pomeranian back as he strives to attack anything and everything on the Minuteman Bikeway.
This story originally aired Oct. 27, 2017 in an episode titled “Pressure.”
Story Transcript
Science is 99 percent failure. Which is slightly horrifying especially if you're a scientist, which I am. I am six years into my PhD, which means I should be about to graduate except I am not even close to graduating because I haven't made my own discovery yet, which means I haven't published a significant first authored paper yet, which means I don't have what's required to obtain an awesome job yet. I am in limbo. I am studying this fusion protein that should normally never exist but that does exist in cancer. And strangely this fusion protein, it doesn't actually cause cancer on its own. It has to cooperate with another mutation and together they initiate disease. So what is this other mutation? Targeting the fusion protein is impossible. But if we knew what the other mutation was we could target that with one drug or another and offer patients some form of treatment besides the only thing they've got, which is chemotherapy. So what is the other mutation? From sequencing patients’ DNA, we know that these cancers harbor hundreds of mutations, any one of which could be mutation that cooperated with the fusion protein to cause the cancer. I'd spent years generating mouse models of this cancer by you know cherry-picking or strategically choosing mutations to pair with the fusion protein in a mouse. You know, like sidebar, I'm like probably that weird scientist that's trying to create cancer in order to like understand and cure it. A little weird.
But of all the mutations that I've chosen, only two actually cooperated with the fusion protein to cause cancer. And sadly we had no idea why these two, and not countless others, could cooperate. So we had no way of knowing how to predict which of these mutations was important. So, you know, here I am, six years in. My funding is spent. My boss has left the university and moved to Florida so I’m now working like an orphan out of another professor's lab. I'm no closer to understanding this cancer than I was when I started. And worse, I'm fielding questions from my wife, Jess, each night like, “When are you going to graduate? Where are we going to go? What are we going to do?” And questions that, like, don't even have answers, or have like built-in oxymorons like, “Are you going to be able to find a job in a place where we can live in one of those luxury condos that pay no association fees, and can we be steps from, like, restaurants and bars but have this massive backyard, and can we live, you know, within driving distance of her parents?” Which for me is, like, still way too close. You know. So I take all of this madness and I box it up and I like set it to the side.
But even I cannot ignore the fact that our lives together now hinge upon me making a discovery in a field that has a 99 percent failure rate. Jess is frustrated. “You know I'm a teacher, don't you? There are specific hiring periods for teachers, and I'm going to have to get newly certified if we work anywhere outside New York City. Are you thinking of this? Can we stay in New York? Are you thinking of me?”
I am very non-confrontational and when I get nervous I smile. Let me tell you, smiling during an intense discussion goes over horribly. Did Jess know that she was getting into this when she married me, to have her life stuck in limbo and dependent upon the actions of someone else? Does she believe in me? Do I believe in me? I don't know. I like to think of myself as the rock in our relationship. She gets nervous. I calm her down. She has questions, I have answers. She's got 99 problems. This bitch ain't one. What does it mean if I'm not the rock and if I need someone to believe in me when I can barely believe in myself? Dinners together become quiet and I smile a lot.
Eventually Jess asks, “Do you know how hard this is on me?”
“Yes, yes, I do.”
Silence. Then she reaches for my hand.
“Do you know that there is no one else that I would rather go through this with than you?”
I exhale and I smile for real. She does believe in me. She is my wife and now my rock and if she believes in me, I'd better believe in me.
So I get to work. I develop a hypothesis for why these two mutations and none of the rest could cooperate with the fusion protein to cause cancer. But for that hypothesis to be true I have to show that I can accurately predict a third mutation. I have to pair this third mutation with the fusion protein in a mouse and hope that cancer develops, a process that could take another year if it happens at all. So there is a high likelihood I could be another year out and in the exact same spot. But, you know, against many people's better judgment I accept this challenge and I pair another mutation with the fusion protein in a mouse and I sit one month later at a flow cytometer, which is like basically an advanced dishwasher analyzing samples of these mouse blood. Put a sample in, dots appear on the screen, sample out. Sample in, dots, sample out. At two a.m. in a lab that's even been abandoned by the cleaning staff. Sample in, flows cytometer clogs. I hit it. It works. Sample out.
How is this my life? Maybe, maybe Jess was wrong to believe in me. Maybe I'm not cut out for this. You know, maybe if I could just go back, I would make better choices -- and then I see it.
A dot appears in the upper-right-hand quadrant where no dots yet reside. And then another and then another and I'm sitting up now staring at the computer screen trying not to hope. And then another dot, and by the time the sample is finished, 50 percent of the dots on the screen reside in that upper-right-hand quadrant, that quadrant that has been gated to identify cancer cells. They are there, they are in the mouse, and they are dividing at a rate that I have never seen before. But it's only one mouse. You can't get too excited. Science is a cruel mistress and she will play these tricks on you.
So I run another mouse's sample. Dots and dots appear in the upper-right-hand quadrant, and another and another, and in the early morning in an abandoned building next to a glorified dishwasher, I know I have done something big. I have accurately predicted, out of hundreds of mutations, which one cooperated with the fusion protein to cause cancer. We'll be able to tell patients with this fusion protein exactly what drove their cancer and what drug they should take. Chemo will not be the only option.
I am going to graduate This is my eureka moment. My, like, stereotypical jump up and down in a lab coat with a beaker shouting, “Eureka!” You know, like they used to do back in the day, because in this moment science is moving my life forward and I have made a dent in science.
When I get home, Jess sees my face, and before I can even say anything, she knows. She jumps up, she tells me she's always known I was capable of having this eureka moment. She's always believed in me, and to prove it, she logs into Petfinder to show me all the dogs that she has flagged for us to adopt, knowing that at some point our lives would move out of limbo. And the rest is history. I do graduate. I go on the job hunt. I accept a position at an awesome company. Jess goes on to worry about other things, like our fat Pomeranian named Wally. She accepts a position at Cambridge Rindge and Latin and now I get to share my eureka moment with all of you. When will the next Eureka moment happen? I don't know, but science is always happening, which is what makes it so exciting. So the next eureka moment could happen at any time, even in an abandoned building at two a.m. Thank you.