Matthew L. Meyerson, MD, PhD, is constantly curious, both about the world and the people around him. As one of the top cancer researchers on the planet, he has a talent for elevating younger scientists, turning obstacles into discoveries, and sensing future research opportunities.

He’s not afraid to try something completely different. As a freshman at Harvard University, he spent a summer on a farm, baling hay and building a cow pen the farmer called “Harvard Yard.” He spent his senior year in Japan, studying in a lab at Kyoto University.

That genuine sense of wonder, and wander, started when he was a child growing up in Philadelphia, Pennsylvania. That’s when Meyerson discovered the work of famed architect R. Buckminster Fuller, inventor of the geodesic dome. Fuller was a university professor emeritus at the University of Pennsylvania for the final 10 years of his life. Before his death in 1983, Fuller wrote about how technology can transform people’s lives and emphasized the role of creativity, starting in childhood.

“I think it’s important to have a sense of wonder, and it’s also important to look at things and say, ‘You know, there’s always a limit to our knowledge,’” said Meyerson, who was named the second most influential scientist in the world in all fields of science by Thomson Reuters in 2014.

“There are a lot of things that we think are true,” he said. “And even though there’s a lot of evidence that they’re true, [the truth] ends up being different.”

In Meyerson’s office at Dana-Farber Cancer Institute, his desk is covered with photos of friends and his family, including his wife, Sandra Meyerson, a primary care pediatrician also on the Harvard Medical School faculty, and their 4 children, Sophia, 30; Olivia, 27; Jacob, 25; and Phoebe, 20. On the wall is artwork from his sister-in-law, a drawing of what looks like a tree but is actually a set of lungs, reflecting his work on the genetics of human lung carcinomas.

I’m not so sure Biz Markie isn’t not one of the dopest to ever grip the mic.

Meyerson received his MD in 1993 and PhD in 1994 from Harvard University. Prior to joining Dana-Farber in 1998, he completed a residency in clinical pathology at Massachusetts General Hospital and a research fellowship with the legendary Robert Weinberg, PhD, at Whitehead Institute in Cambridge, Massachusetts. In the early 1980s, Weinberg discovered the first human cancer-causing gene, the 

oncogene. By 1986, he and his team also isolated the first known tumor-suppressor gene, the retinoblastoma gene. And in 1997, Meyerson and Christopher M. Counter, PhD, identified the telomerase catalytic subunit gene.

From 2006 through 2015, Meyerson was a principal investigator for The Cancer Genome Atlas (TCGA), a landmark program aimed at comprehensive cancer genome characterization. TCGA was a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute based at the Broad Institute of Massachusetts Institute of Technology and Harvard. He served as cochair of the lung cancer disease working group, and his projects have identified many mutated genes in lung cancer.

He says that his work on lung cancer mutations in the 

gene has been his most impactful discovery to date. 

mutations occur mostly in nonsmokers who develop lung cancer, helping investigators understand why the disease develops in what should be a low-risk population.

Like many discoveries, Meyerson says it kind of happened by good fortune. In 2003, he was working with fellow Harvard researchers William Sellers, MD, and Bruce E. Johnson, MD, the 2018 Giants of Cancer Care® award winner trying to identify mutations in lung cancer that could be targeted therapeutically.

They had lung cancer samples from a group of Japanese patients including women who had lung cancer but weren’t smokers. It turned out half of them had the 

mutation. Further studies with Sellers, Johnson and Pasi A. Jänne, MD, PhD, this year’s Giants of Cancer Care® award winner in the lung cancer category, showed that those with the mutation responded well to therapy.

“There was already a drug out there—gefitinib [Iressa], an EGFR inhibitor—but people didn’t really know what patients it worked on or why it worked,” Meyerson said. “The study really answered the question and helped us target therapy.

“It led to much improved EGFR inhibitors, and it led to this whole wave of discovery in lung cancer. There are now literally dozens of targeted inhibitors that are in use for lung cancer and more coming all the time. So it was just a huge impact on the field.”

Research in lung cancer has expanded since Meyerson first started in the field in the late 1990s. He says he was frustrated by the stigma of the disease and the limited number of treatments available. Now, because more patients survive, there’s more support for research.

“The people who really push for research in the field are the survivors. They know about the disease, they know how bad it is, and they’re still here,” he said.

Although most of Meyerson’s research has been in lung cancer, his lab has also studied microbes that cause human cancer. Comparing the genomes from 9 colon tumors with normal tissue from the same patient led to a major discovery in 2011: colorectal cancer tissue contains high levels of several types of bacteria, most notably 

. Now Meyerson and colleagues are trying to understand whether these bacteria cause colon cancer as part of the NCI/ Cancer Research UK’s Cancer Grand Challenges.

Meyerson is also excited about his lab’s work on telomeres and mortal and immortal cells, a project that spans all types of cancer. In normal cells, telomeres protect the DNA from mutating and eventually stop the cell from dividing. But mutations in cancer cells occur outside the gene that controls how much of the telomerase enzyme is made. Although this discovery is 25 years old, there still isn’t a drug that inhibits that mutation. Yet.

“My lab has [started working] on a project in this area, [so] I’m hoping that will change in the next few years,” he said.

The Meyersons enjoy breakfast at a monastery on Mount Koya while on vacation in Japan in 2006.

Meyerson started working in a laboratory while still in high school and says he thought doing research would be easier—that he’d start working on something and figure it out. He learned, instead, that doing scientific research is like constructing a skyscraper.

“If you look at building a skyscraper, most of the time is spent digging out and structuring and shoring up the foundation. And then when you actually erect the steel frame, it goes really fast,” he said. “Research is like that; you’ve got to do a huge amount of preparation before you actually answer a scientific question.

“You might have to build the experimental system, or if it’s a human disease, you have to collect the patient samples. And sometimes that’s weeks or months, but sometimes it’s years. Sometimes it takes many years.…That balance and the need for all the prep work, that was a surprise to me.”

As a student, graduate student, and postdoctoral researcher, Meyerson learned that each lab had its own style. Some lab directors gave students a very specific project with a limited scope of responsibilities. Others gave students more independence, which also came with greater risks for the lab director.

In his own lab, Meyerson gets to know students as individuals so that he can best match them with projects and partners.

Rameen Beroukhim, MD, PhD, is an associate professor at Harvard Medical School, an associate professor at Dana-Farber Cancer Institute, and an attending physician at Brigham and Women’s Hospital. He joined the Meyerson lab after he heard Meyerson give a lecture about attempts to understand the cancer genome. Beroukhim ended up working as a postdoctoral fellow with Meyerson from 2005 to 2010 and eventually opened his own lab.

“Back then we really didn’t know so much about the cancer genome, but I thought, ‘Well, mutations are the essential forces that drive cancer, so really understanding them would be a way of understanding cancer from the ground up,’” Beroukhim said. “At the time, he was using single nucleotide polymorphism arrays, but those arrays had been developed to genotype people to figure out [inherited alterations]—but he was applying them to cancers to understand which cancers had lost certain parts of their genomes and where those parts of the genome had been lost. That seemed like an elegant way to try to understand the genome that was different from how other people had attacked the situation.”

Beroukhim says Meyerson is unusual as a mentor because of his social skills, both in and outside the lab. He makes a lot of effort not only to connect with his trainees, but also help them network with colleagues and promote their work. Off the top of his head, Beroukhim could name 5 of Meyerson’s former research fellows who are now faculty members at Dana-Farber, as well as others at Cornell University and Columbia University.

“Matthew has a great way of sort of seeing the future and what’s going to be interesting in the future—looking at research that will be informative and where people will be interested, not just now, but in years to come,” Beroukhim noted.

Meyerson says many people might be surprised by the social nature of the science field and how many ideas develop not as an independent “eureka” moment, but as part of a conversation. “I think a lot of that scientific progress is thinking together and discovering together, and maybe that’s a piece that people haven’t fully understood, that isn’t always fully captured.”

Regarding pursuing an education or a career, Meyerson tells his students the same thing he tells his children. “I would say it’s important to find your own way. Find what you like doing, what suits you personally,” he advised.

After 4 decades working as a researcher, Meyerson says he’s gotten better at delegating and taking some time for his family. As a child growing up outside Philadelphia, he would collect rocks and minerals from Wissahickon Creek, and he has continued this habit throughout his travels. When his mother moved out of his childhood home, he took ownership of boxes of collected rocks—and his wife created a collector’s shelf for him.

To escape from the noise of Boston and the intensity of the lab, Meyerson and his wife recently bought a country home in Vermont where they can’t see their neighbors. The quiet suits him, as does the chaos.

Just like with his research, Meyerson enjoys trying something new and exciting.

“I like it a lot. It’s funny—I tend to like everything,” he said. “I don’t know if [that’s] unusual or not, but I look for new things. I like the variety."

Articles

Matthew L. Meyerson, MD, PhD, is constantly curious, both about the world and the people around him and as one of the top cancer researchers on the planet, he has a talent for elevating younger scientists, turning obstacles into discoveries, and sensing future research opportunities.

Cracking the Cancer Code Requires Both Quiet and Chaos

Most physician-scientists are intense, motivated and focused, but Keith T. Flaherty, MD, takes it to another level. Even as a young doctor, his passion and certainty that cancer could be, and should be, cured impressed his mentors.

“You get this sense of urgency from him, this ‘I need to do this now, in whatever time I have,’” said Lynn Schuchter, MD, chief of the division of Hematology Oncology and director of the Tara Miller Melanoma Center at the Hospital at the University of Pennsylvania, where Flaherty did his fellowship. “He is the [Alexander] Hamilton of medicine. That’s what went through my mind as I was thinking about him and his work.” 

As the director of clinical research and chair in oncology at the Massachusetts General Hospital (Mass General) Cancer Center, the Baltimore, Maryland, native was one of the first to investigate targeted therapy for melanoma patients with the 

Flaherty said he likes it when someone says that something cannot be done so he can prove them wrong, whether it is developing a targeted therapy to shut down the 

 mutation or designing a model of a rare 

 fusion that few had investigated because it appeared in just 0.3% of all cancers.

“I want something I can put my shoulder into. What’s the bottleneck here? What’s the problem?” he said. 

His love of challenges combined with his gift for teamwork made him a natural choice to coordinate novel coronavirus disease 2019 (COVID-19) research at Mass General after the pandemic turned the medical landscape upside-down. He brought physicians, researchers and the pharmaceutical industry to the table and described the experience as medicine on “warp speed.” 

Although working in oncology is a fairly collaborative field, he said, there is still a lot of pressure to claim data or studies as your own, often resulting in people refusing to share their work. All that ego has been dropped when it comes to finding a treatment for COVID-19, he said. 

“With COVID-19, that all went away. There are data dumps of every kind...it’s phenomenal. If you contact a drug company because something they have might plausibly work, they say, ‘Here, use it, we will give you this investigational drug however you want it, no charge,’ ” he said. “We have the FDA and IRBs [institutional review boards] turning around things in 24 hours or less that used to take 6 months. It’s exhilarating, because it shows you in almost every way how things could operate.”

Flaherty, 50, wasn’t exactly forced into becoming a doctor, but his father was a cardiologist and his mother was a psychologist. They loved what they were doing and often talked about their work. Plus, the Johns Hopkins University School of Medicine looms large in Baltimore, so a medical career was always on his radar.

He studied neuroscience, the biology of the mind, as undergrad at Yale University. Yale was a hotspot for neuroscience research and Flaherty was sitting in a huge cell biology class lecture his sophomore year, when the subject clicked for him. “There was nothing about that subject that I thought was uninteresting,” he said.

Biochemistry felt dry, and he wanted an area of challenge, where discoveries were just starting. Flaherty loved that much of neuroscience was still unexplored.

“You’ve got the persisting mystery of the boundary of the mind versus the brain. How do you look at the genetic to the cellular system of the brain and wrestle down the dualism of the mind-body divide?” he said. “How do you ever fully solve that problem of ‘the soul’ and nail that down to a cellular level?”

At Johns Hopkins for medical school, he aimed for neuroscience but quickly found that it was not a good fit for him, saying it became apparent to him that there was no such thing as “applied neuroscience.” He wanted a place where science investigators and medical practitioners worked more collaboratively. Oncology seemed to offer the best opportunity for developing scientific tools and genomic research that then moved into treatment.

He was particularly interested in targeted therapy, developing cancer treatments to focus on specific genes or proteins that cancer cells produce. The spark happened in 2002, when Nature published an article on the discovery of the BRAF mutation and its link to cancer growth. Flaherty said he could not understand why the medical world did not stop what it was doing and start conducting research on ways to address the mutation since it impacted a number of cancers, including 50% of patients with melanoma. 

“It turns out that people are already doing their own research and they’re busy and they already have ideas and concepts and grants,” he said. 

That’s why he tells his protégés that they do not have to wait for permission. That if they are excited by something new and want to move forward, they should pursue it because that’s how the field progresses. “I tell them not to be shy about it, because no one else is going to drop what they are doing,” he said.

He was also drawn to the psychological aspects of working with oncology patients, validated by his “fantastic” month spent in the psychiatry rotation. He said he remembers vividly sitting in an internal medicine lecture where physicians talked about how patients often did not take their diagnoses seriously and a lot of time was spent on lifestyle and medication compliance. 

Oncology was on the other end of that spectrum. These were people who had to live with the knowledge that they had cancer, and handle that diagnosis, but somehow break through the paralysis of having a fatal disease and continue to live.

By his own admission, Flaherty struggles to relax. Recently, he started working less, both to spend more time with his wife and daughters and to give junior faculty more opportunities to grow.

“There is a heavy psychological component to this field, and patients need someone to hold their hand and recognize that, and not someone who just focuses on the scientific and medical aspects but sees the disease as a whole, as part of their life,” he said. “I see myself as a compassionate person, and I certainly felt that I could literally hold someone’s hand on their death bed, as well as be the person who was trying to cure them and walk with them through their diagnosis.”

That combination of passion and persistence came through in a 3-part 

series published in 2010. The paper followed Flaherty, then an assistant professor at Penn, while he was working in 3 areas—kidney cancer, melanoma biology, and clinical research.

The series followed him and his patients with melanoma through the beginning clinical trial processes for vemurafenib (Zelboraf), then known as PLX4032. In many patients, their tumors went away dramatically, and Flaherty and his cohorts were trying to figure out what dose worked most effectively while minimizing adverse events. 

 not only showcased the connection Flaherty has with his patients, but also his professional impatience. He encouraged laboratory assistants to come in on weekends to run tissue samples and pushed pharmaceutical companies to reconfigure the medication entirely.

The newspaper captured Flaherty at a moment early in his career when he kept coming up against the same obstacle—physicians were parked in 1 corner while the clinical investigators worked in another area, and neither knew what the other was up to. Flaherty could not understand why information wasn’t being shared and the science wasn’t being translated into medicine. Many people describe the process as a bridge, but Flaherty sees it more as a “hub and a wheel,” with multiple players in different areas working on a central goal. 

His team’s hard work ultimately paid off. In 2011, the FDA approved vemurafenib for the treatment of patients with BRAF V600E mutation–positive, inoperable, or metastatic melanoma. It was the first targeted agent shown to improve survival in that patient population.

On July 30, 2020, the FDA approved the combination of atezolizumab (Tecentriq), cobimetinib (Cotellic), and vemurafenib for patients with 

 V600 mutation–positive unresectable or metastatic melanoma.

“He’s got this wonderful approach, he’s a great doctor and he’s a fantastic clinician,” said Schuchter. “The clarity of this thinking, his audacious goals. He was really crystal clear about wanting to cure cancer and didn’t think of that as a nontangible goal.”

After moving to Mass General in 2009, he started focusing more on developing combination therapies. The challenge is that pharmaceutical companies, whether large or small, rarely develop more than 1 drug to treat a disease, particularly a rare disease. It might take drugs from 4 companies to make a winning combination for a patient. 

Flaherty started working directly with pharmaceutical companies, joining Clovis Oncology as an independent director in 2013. That same year he helped to found Loxo Oncology, which Eli Lilly and Company acquired in 2019. He saw many opportunities that were not being pursued and wanted to have a say when companies decided which drugs to support. He felt it was important to be part of the early conversations and get involved in the drug development process. That is to say, he wanted to be in the room where it happens.

Flaherty with his daughter, Hazel, at a bat mitzvah in 2016. He enjoys reading poetry because, he said, poets write for the love of writing and not for commercial reasons.

“When you work with companies as an academic, especially when you’re involved with clinical development, by the time you meet with them, they’ve already made a lot of decisions, and you’re just handed the product of those decisions,” he said.

A self-described hypomanic, Flaherty said he does not enjoy downtime. Until about 3 years ago, he had not been comfortable taking more than a week’s vacation. Now he’s willing to take 2 weeks off, though he still made time to talk to a reporter during his vacation. From the moment he wakes up at 5 am to exercise, his mind is on full throttle. He loves to read, particularly poetry, because poetry is created simply for the joy of writing and not for commercial purposes. 

He has been married to his wife, Mira Kautzky, MD, an internal medicine specialist and instructor in medicine at Mass General, for 21 years, and the couple has 2 teenage daughters. Flaherty says he was traveling up to 300,000 miles a year at the beginning of this career and missed a lot of their childhoods. For a long time he felt almost panicked about trying to “move, move, move the field as fast as I could.”

Then, about 5 years ago, he started slowly moving away from the front lines of patient care, not completely but in a sustained way. He’s surrounded by people who are as motivated and focused as he is, and said that part of his job now is to get out of their way so that junior faculty can become leaders. As difficult as it is for him to take a step back, he said that it is a joy to see where the ambition and intelligence of the next generation will take them.

“It’s empowering to hand over the reins. I had to learn how to do it; it was hard, but super gratifying,” he said. “A day doesn’t pass without some sort of mentoring interaction, and when I look back at the end of the day, that’s usually one of the best parts.” 

Most physician-scientists are intense, motivated and focused, but Keith T. Flaherty, MD, takes it to another level.

The Hamilton of Medicine

When Martine Piccart, MD, PhD, was a child, she sometimes watched her father, a gynecologist, talk to his patients. She remembers his respect for them and their families and the way he communicated, focusing on the positive but not shying away from delivering bad news.

“He always took the time to explain in detail not only what was happening but also let them know that there was a plan,” Piccart said. “I remember him saying, “This is what we are going to do.’”

Several decades later, she brings the same positive but direct manner to her practice focusing on breast cancer, particularly metastatic breast cancer. Piccart is scientific director at the Institut Jules Bordet (IJB) and a professor of oncology at the Université libre de Bruxelles, both in Brussels, Belgium. She is the cofounder and immediate past chair of Breast International Group (BIG), which works with more than 50 international academic research groups to collaborate on trials.

She was drawn to pediatrics initially—and temporarily. “The little babies with the high temperatures, they scared me,” she said. Piccart moved into oncology and completed a fellowship at New York University (NYU) Medical Center in the 1980s, spurred on by her experiences with a relative who was treated for colon cancer. Three medical oncologists, Franco M. Muggia, MD, and James L. Speyer, MD, at NYU and Marcel Rozencweig, MD, at IJB encouraged Piccart to expand her focus beyond patient care. Rozencweig, in particular, pulled her into new drug development.

Early on, she realized that research and developing drug trials had to be an integral part of her job, because she was frustrated by how many clinical problems had no solution. This was particularly true in metastatic breast cancer, which remains incurable.

Running trials through pharma might be an easier route for a successful career, Piccart said, but it is not the kind of research she admires most. She ends up spending a lot of her time trying to find funding on her own to help support academic research. Piccart said that she hopes future oncologists will continue the fight for independent research.

“I am very uncomfortable knowing that in some countries, when you put your patients in a trial as an oncologist, it’s not the institution that gets the money, it’s the oncologist, and I find that totally unethical,” she said. “I am really, really convinced that protecting academic research is protecting patients. Companies are never going to be motivated to see if a 6-month treatment is as effective as a 12-month series, because you know the 12-month series brings in more money.”

Pharmaceutical industry research is important, and these companies drive valuable innovations, she added. However, industry-driven research must be balanced with independent research.

“I have been dreaming of a better model of partnership between academic investigators and the pharmaceutical industry,” she said. “The best model is one that guarantees some independence from the pharmaceutical industry but where you can also accept that, for some aspects, pharma runs things more efficiently.”

She helped found BIG in part because of her desire to maintain that independence. At first, she said, investigators were wary of working with the group because they were not used to very large international collaborations. The realization that BIG could recruit 5000 women into a trial in about 3 years, rather than a decade, convinced many to join the network. That resulted in stronger studies that produced results faster, which helped save women’s lives, Piccart said.

Through BIG, she helped develop the AURORA project, which is receives much of its funding through the Breast Cancer Research Foundation, in 2014. European investigators are analyzing tissue and blood samples from 1000 patients with metastatic breast cancer while capturing their clinical evolution through successive therapies.

Piccart initiated AURORA because she wanted to improve the understanding of metastatic disease. A great deal of breast cancer research focuses on women with early disease, but upward of 30% of patients will progress to metastatic disease, which has 5-year survival rate of just 27% for women in the United States, according to the American Cancer Society. 

“I cannot tell you how frustrating it is, as a doctor—we have these drugs that work prettywell, but we cannot cure these women at the end of the day. So, we decided it was time to create a network to do something for these women, and we built a very ambitious research program across Europe,” she said.

Piccart met her husband, Michael Gebhart, MD, coordinator of the Institut Jules Bordet Soft Tissue and Bone Tumour Multidisciplinary Oncology Team, in medical school. She played piano and he played the violin.

“I like chamber music [and] I like to play with other people rather than alone. And that is also something that you need to do in a medical profession—you need to be a team player,” she said. “You don’t have answers to everything. You need to work with your colleagues.”

Piccart carefully perfected her “team player” approach over the years. She credits her success as a doctor and an investigator to the help she received from her friends, particularly the late Aron Goldhirsch, MD. She called the development of BIG, which Goldhirsch helped to found, one of the biggest successes of her career.

Piccart added that maintaining a network that sprawls across not only physical distance but also different cultural practices and beliefs requires a lot of time, plus some psychological skills. Disagreements happen; people get protective of their work; and someone, often Piccart, has to help repair the damage or else the partnership can fall apart. Keeping it all running is a challenge, but it’s a challenge that she loves.

“One day at a time,” she said. “You have to have this in your mind when it’s becoming difficult, because you have all these obstacles, but you need to be focused and not be discouraged at the very first challenge. So keep trying, and tackle one thing.” 

One of the most important things she’s learned from her years as a doctor is that the profession is a 2-way street. As much as she brings to her patients, they offer as much to her. “I have been impressed by so many women, their courage, and how they can impress you,” she said.

“I once thought maybe I should write a book about these women, because sometimes you just wonder where they find the courage to continue.”

Martine J. Piccart discusses her journey into the breast cancer treatment space. 

Dawn Fallik

Articles

Cracking the Cancer Code Requires Both Quiet and Chaos

The Hamilton of Medicine

Practicing Outside the Pharma Box in Breast Cancer