When the cures come out of Dr. Sean J. Morrison’s lab—and he’s certain they will—almost no one will remember when the place used to be just a couple of empty concrete boxes.
The floors were bare. The walls were unfinished. There were no centrifuges, no dissection microscopes, no imaging flow cytometers.
But in 2011, when Morrison, as the newly minted founding director of the brand-new Children’s Medical Center Research Institute, first walked into those empty concrete boxes on the top two floors of a building at UT Southwestern in Dallas, he already knew how they would look when they were filled in. He could envision what the equipment would be and where it would go. He could picture the team of top-flight scientists working there. And he could see the treatments they’d create. Treatments that would help sick kids. Treatments that might cure rare diseases. Treatments that even held the promise of curing cancer.
To make that happen, all Morrison needed to do was, well, everything. “When they actually offered me the job in 2011, even though the groundwork for the institute itself had been laid, and the institutions behind it—Children’s Medical Center Dallas and UT Southwestern—were committed, there was nothing physically here,” the blonde-haired, 46-year-old Morrison says from his office at the institute off Harry Hines Boulevard. “We had been allocated two floors, but there was just bare floor here. And no one else worked here. It was just me.”
The opportunity to fill in the blank concrete boxes with whatever he wanted was exactly what had lured Morrison away from the founding directorship of the Center for Stem Cell Biology, which he’d held at the University of Michigan since 1999. Before the dawn of the new millennium, Morrison had already become one of the world’s top stem cell researchers. He’d made breakthrough after breakthrough, discovery after discovery, about the human body’s most crucial cells. That’s why he was the leading choice—perhaps really the only choice—to lead the new institute, for which Children’s Medical Center had pledged to spend no less than $150 million to fund through 2026. “There aren’t very many opportunities in academia to create a new institute from scratch,” Morrison says. “But here I had an opportunity to create a culture that would be optimized for discovery and innovation.”
Read those words again: “Optimized for discovery and innovation.” That sounds more like executive-speak than something you’d hear from a guy who spends his days staring into a microscope.
The staff, which will eventually number 150, has mostly been recruited from the world’s top universities. “The best of the best,” Morrison calls them, echoing any number of tech execs who say they recruit for the same type of worker. Like many of those tech execs, Morrison has lofty goals for his organization. He wants CRI to have a “transformational” impact on our understanding of human cells. In fact, he wants nothing less than for CRI to contribute to a cure for cancer.
“You don’t create a new institute to make incremental advances in treatments,” Morrison says. “You create a new institute to try to have a transformative effect. That’s why we want everybody in this new institute swinging for the fences. What’s exciting about this business, about this institute, is that we have an opportunity to change the world.”
FERTILE BEGINNINGS
Fertilizer could have made Morrison filthy rich. In 1986, as a high-school senior in Halifax, Nova Scotia, the Canadian-born student had figured out an efficient way to hydroponically cultivate something called mycorrhiza fungi—a natural plant fertilizer. His breakthrough was big. So big that even before he graduated, he’d started his own fungus-growing company. The Canadian government awarded him grant money to develop his breakthrough. Dalhousie University in Halifax, where he enrolled, gave him—gratis—his own laboratory to work on it. “I hired a handful of staff to work full-time in the lab,” Morrison says. “I’d run back and forth between class and the lab, supervising what was going on.”
“Throughout my career, I’ve been
attracted to the idea of studying things that no one has ever studied before.”
Then came the ironic twist. To grow the fungus-growing business, Morrison needed cash—business fertilizer. And in the years immediately following the 1987 U.S. stock market crash, cash was a commodity in short supply. “I remember regularly having to clean out my bank account to make payroll,” he says. “There were times when I had just $50 left to my name.”
So he did something Hughes and Ford and Carnegie never would have—he quit the business. Morrison wasn’t a CEO at heart. He was a scientist. And money wasn’t his motivation. What he really wanted to do was solve problems. “I realized,” he says, “that if I was going to invest years of my life in trying to solve a problem, I really wanted people to care about the solution. People feel much more strongly about investing in a cure for cancer than investing in a method for increasing soybean yields. So I intentionally made the transition to medical research.”
Twenty-five years after that transition, Morrison is making breakthroughs that won’t make him a tycoon, but that may save a lot of lives. Morrison spent the past two and a half decades in academia and medicine focusing on some of the most complex issues in human biology. Twenty years ago, while getting his Ph.D. at Stanford, he decided to work on stem cells, mostly because little was known about stem cells at the time. Where were they to be found in the body? How did they reproduce? What was their function? Morrison wanted to answer those questions.
“Part of what is involved in good science is not only looking more carefully at things that people have studied in the past, but looking at things people haven’t looked at before,” he says. “Throughout my career, I’ve been attracted to the idea of studying things that no one has ever studied before.”
At Stanford, Morrison focused on researching blood-forming stem cells. Once he had his doctorate in hand and was doing post-doctoral work at Caltech, he turned his attention to stem cells that were part of the nervous system. There again, almost nothing was known about Morrison’s research subject. His work was groundbreaking—eventually.
Morrison spent most of his first year at Caltech trying to purify central nervous system stem cells. Months into the project he discovered that the cells he’d been working with were not actually neural stem cells, meaning he’d been wasting everyone’s time studying the wrong kind of cells. “I thought I had no future in science,” he says.
But months later, Morrison had righted his research. He began making breakthrough discoveries about stem cells in the peripheral nervous system. That attracted the attention of the University of Michigan, which offered Morrison his first faculty position in 1998.
At Michigan, Morrison turned again to learning about what was still unknown about stem cells. He knew that stem cells replicated and that they were key to sustaining life. He knew, among other things, that stem cells in the skin made new skin cells every day; that stem cells in bone marrow made new blood cells every day. What he didn’t know was how stem cells replicated. No one did.
“Fifteen years ago, there was nothing known at the molecular level about how stem cells replicate,” Morrison says. “And I really felt it was a fundamental question in biology to understand. It was a question that was central to a lot of important issues, because the ability of stem cells to self-renew is critical to form your tissues throughout development, to maintain your tissues throughout adulthood.”
Because Morrison was looking at that kind of fundamental question while at the helm of the Center for Stem Cell Biology, the University of Michigan quickly became the leading spot in academia for the study of stem cells. At the same time, the state of Michigan had some of the most restrictive laws in the country related to stem cell research. For instance, Michigan had made it a crime to use stem cells from human embryos in the lab. “It was a felony to do certain kinds of stem cell research in Michigan—the same kind of research that was being allowed and being funded by other states like California and New York,” says Morrison, who has testified twice before the U.S. Congress on the issue of stem cell research.
In 2006, Morrison was drafted into a movement to change Michigan’s stem cell research laws. He helped to campaign, and regularly met with the state’s lawmakers to explain the science behind stem cells. At the time, the issue was hotly controversial nationwide, and had been since 2001 when President George W. Bush curtailed federal funding for research on stem cells that had been taken from human embryos. President Barack Obama overturned that decision in 2009, in part because so many scientists—including Morrison—had lobbied state and federal lawmakers to change policies that restricted stem cell research. Michigan, too, changed. In 2008, voters overwhelmingly voted in favor of a statewide referendum calling for a change to restrictive stem cell laws—the same referendum Morrison had spent several months campaigning for.
“One of the amazing enemies of effective policy is misunderstanding,” he says. “Several years ago, when debates about stem cell policy were raging in certain states like Michigan and at the federal level, one of the problems was that there was a lot of misinformation that was being put out for ideological or political reasons. That misinformation misrepresented the science. It tried to trick people into adopting positions inconsistent with facts. For those of us who worked in the scientific field and really understood the issues, it was important for us to be able to explain those issues to the public so people could make an educated assessment. As a result of that process, I think it is fair to say that all the states that went though that policy process now have much more effective policies.”
That Morrison was so effective in explaining the science of stem cells to lawmakers in Michigan and in Washington, D.C., came as no surprise to his peers. “Dr. Morrison is not only willing to reach out to the public and to governing officials, but he has been at the forefront in communicating critical ideas and concepts related to stem cells,” says Yosif Ganat, a post-doctoral researcher at Memorial Sloan Kettering Cancer Center and a producer of the Stem Cell Podcast, which Morrison appeared on last year. “Besides that, Dr. Morrison is also a prolific and brilliant scientist.”
Two of CRI’s top individual financial backers—Ric and Debbie Scripps—certainly agree with Ganat. “Sean can very easily speak in eight-syllable words,” says Ric Scripps. “But,” Debbie Scripps adds, “Sean is also able to relate to non-medical people—people like us. He can describe the science in terms we can easily understand. The first day we met him, we came away with a clear understanding of what Sean was trying to accomplish. That’s why we wanted to put our investment in him.”
The Scrippses are not alone in having that level of confidence. A half-dozen people and private foundations are now members of the Scripps Society, named for Ric and Debbie, which honors those who have given $1 million or more to CRI. “Sean Morrison is a fundraiser’s dream,” says Pete Kline, past president of the Children’s Medical Center Foundation. “He’s a world-class scientist who can get up in front of any audience and explain his very complex research to non-scientists, in terms that are both understandable and exciting.”
Here’s what Kline is talking about: If you ask Morrison to explain just how his stem cell research might cure cancer, he explains it in three sentences. “Cancer is a disease of regulated self renewal,” Morrison says. “Cancer cells make tumors by hijacking the mechanisms that stem cells normally use to maintain normal tissues. So as we identify some of these molecular mechanisms in the lab, we not only learn something about how adult tissues regenerate themselves, but also how that process of regeneration goes wrong in diseases like cancer.”
That sounds strikingly simple. To cure cancer, you just have to identify cancerous cells and make them stop regenerating. If only it were as easy to do as it is to say.
A CULTURE OF INNOVATION
They have names like Ralph DeBerardinis, Woo-Ping Ge, Jian Xu, and Hao Zhu. These are some of the “best of the best” that Morrison has recruited to lead labs at CRI. The researchers he’s hired are mostly in their late twenties and early thirties. Morrison has a picture of many of the researchers assembled in front of a window in what used to be that blank concrete box at UT Southwestern. If someone told you the group of denim-clad, T-shirt-sporting scientists was actually a team of programmers behind the latest, greatest tech startup, you’d believe them.
CRI is now staffed with 74 people working in five different labs. Eventually there will be 150 in 15 labs.
That’s why Morrison created a cultural blueprint for CRI that was reflected in the blueprints the architects who designed the space came up with—one with few walls and free-flowing workspaces.
“As director,” Morrison says, “there are a lot of subtle things that you do to create the kind of culture you want. The space is one of those things. Back in 2011 when I stood here on the bare cement floor with very few walls around me, I thought, ‘What do I want this to look like in the end?’ I wanted it to be the kind of place where everybody is excited to work together. I wanted laboratories with very different expertise working side-by-side. I wanted a place where there were ideas bouncing back and forth, where no one would be worried about who gets credit for the idea, where everyone is just focused on figuring out the biggest thing, the biggest idea we can work on together. The more productive collisions you can have between people—the better they know each other—the more likely they are to come up with an idea together that nobody would have had individually.”
To foster that collaboration, Morrison takes everyone in the institute out to a bar on the first Friday of every month. If you’ve been in a swillery where you’ve overheard a couple dozen people talking about distinguishing long-term, self-renewing hematopoietic stem cells from transiently reconstituting multipotent progenitors, then that was probably Morrison’s group.
“The First Friday outings serve to lubricate the scientific collaborations,” Morrison says, chuckling. “We’re living together a little more than other people in other fields might be. There are people here every Friday at 10 p.m. still hard at work, for instance. So it’s important that people who are around each other so much get to know each other on a social level.”
What the scientists at CRI are doing at 10 p.m. most Fridays is trying to make discoveries about stem cell biology, cancer, and metabolism, and then apply those scientific discoveries to the treatment of human patients—mostly kids. Morrison expected a 10-year timeline for making discoveries that would move from the lab to the clinic. Instead, it only took three for the first lab-to-clinic program to become active.
The project is called the Genetic and Metabolic Disease Program. Today, a child who comes to Children’s Medical Center with what’s called an “inborn error of metabolism” that can’t be diagnosed with existing tests will have their genomes sequenced to aid in diagnostics. This process is expensive, and rarely offered other than to newborns and a handful of older pediatric patients with extremely rare conditions. The objective at CRI is to learn the specific genetic defects that are, in layman’s terms, mucking up a child’s metabolic pathways. If they can pinpoint the corrupted pathways—the defects leading to disease—technicians could make it much easier for doctors to diagnose even rare conditions. That could lead to treatment breakthroughs.
“We hope to learn from these kids,” Morrison says. “A subset of these kids will have genetic defects that will tell us how metabolism works.”
That kind of integrated work, where the scientists meet the doctors, is—like the open-plan office—rare. But it’s exactly why Children’s Medical Center and UT Southwestern teamed up to create CRI in the first place. Both institutions wanted doctors and researchers working together. “Historically, science and medicine have been done in different silos,” Morrison says. “Communication between the silos is inefficient, so progress forward is inefficient. But we want something different, something that is interdisciplinary. We’re doing science in the ordinary course of healthcare—trying to understand what’s going on with these kids, trying to better treat them, and then bringing that information back into the laboratory to try and better understand how human metabolism works.”
That part of CRI’s goal—to put its science into clinics as quickly as possible—was what sold Debbie Scripps on investing in Morrison’s concept back in 2011. And, yes, she, like Morrison himself, calls it “investing,” not “donating.”
“One of the things that convinced us to make our investment was that Sean’s goal was to take the research from the lab to the bedside as quickly as they could,” she says. “So we knew we’d see a return on our investment. And we’re already seeing a bang for our buck. The first time we went into the institute, it was just Sean there unpacking boxes by himself. And now it’s buzzing over there. It’s like an ant farm with all the activity.”
CRI is now staffed with 74 people working in five different labs. Eventually there will be 150 in 15 labs. But Morrison doesn’t know when he’ll have a complete staff, in part because he’s very deliberate with hiring. He interviews only eight to 10 scientists per year, and new hires have to be people who are judged to be in the top 1 percent of early-career scientists in the job market. “When I was interviewing for the position here, I said, ‘If I take the job, I’m only going to want to hire A-pluses, and there aren’t more than a few of those people on the job market each year,’” Morrison says. “‘So I’m only going to hire one or two new faculty a year. That means it might take me 10 years to fill up the institute.
“In most places, they would have said to me, ‘Don’t call us, we’ll call you,’ but instead, they were already thinking the same thing.”
Still, 74 people, even if they are some of the country’s top thinkers, are a lot to manage. Morrison has to oversee their research, meet regularly with donors, and try to secure grants, like the multimillion-dollar infusions CRI has gotten from the Cancer Prevention and Research Institute of Texas, the Howard Hughes Medical Institute, and the National Institutes of Health. This year he’s also serving as president-elect of the International Society for Stem Cell Research, and will become president in June.
With all of that, you have to wonder, does a man who’s spent 25 years as one of the top researchers in the field of stem cells still have time to look into a microscope?
“One of the things that can go wrong in organizations like this, is that the value system gets flipped over, and it starts to seem like the scientists are there to raise the money to run the institute instead of the institute existing to fuel the science,” Morrison says. “But it’s the science that creates real value. So the director of your institute should be spending most of his or her time trying to create value, not trying to keep the trains running on time. That’s our value system. And that’s why I still spend 80 percent of my time on science, and 20 percent trying to build the institute.”
That leaves Morrison with not as much time as he’d like to pursue one of his true passions—golf. He gave up competitive hockey more than two decades ago because he was afraid he’d gotten so slow that he’d be an embarrassment to his two, now-teenage daughters, Alix and Annika. But he had no such worries about golf. “But this job is really hard on the golf game,” he says. “My 3 handicap has gotten pretty dicey.”
That might be good news, though, to some—particularly those who may benefit from the cures Morrison expects the CRI to develop. In one of the institute’s first breakthroughs, Morrison’s researchers found a novel combination of existing drugs that were effective in treating melanoma in mice. So last year, doctors began testing that combination in a clinical trial with human patients—late-stage melanoma patients who are either not candidates or have already failed the other treatments. “It’s an incredibly motivating thing to have the opportunity to help someone,” Morrison says. “We don’t know if this new treatment is going to cure people or not. But if not, then there will be another attempt and another attempt and another attempt, until people stop dying of melanoma.”
But there’s the rub. Morrison’s team thinks they’ll save lives. But they know they’re going to fail in some of their research. Repeatedly. So how do you keep people motivated when they may spend months on a project only to see it fall apart in the end? “I’ve been doing this for more than 20 years now,” Morrison says. “And for every idea I have, I think it will be the best thing since sliced bread and I believe it will work. But one of the characteristics of good scientists is that they critically test their ideas. And the people in my laboratory disprove nine out of every 10 ideas I have—nine out of 10 ideas I was sure would work. But the one idea that turns out to be true is always worth the ones that weren’t.
“Trying to treat diseases more effectively is really hard. The easy stuff has been cured already,” he says. “But that’s also why we want to solve the hard problems. Because we believe we can. The ultimate hope of every single person who works in this institute is to cure someone who otherwise would not be cured. That’s what we all live for.”
