Calum MacRae: The man behind the $75 million bid to wipe out coronary heart disease

BOSTON – During his first hour with this new patient – a woman who suffered a stroke in her 20s and now, in her 30s, grapples with debilitating migraines – Dr. Calum MacRae begins learning all about her.

He starts with typical questions, such as where it hurts and whether extreme heat or cold makes things better or worse. Then he broadens the conversation.

Has she ever lived near a chemical plant or been exposed to anything in the air at work? Can she roll her tongue or put an ankle behind her head? Ever had a pet cockatiel or snake?

They review her family tree, lingering on two uncles who had strokes in their 20s. Finally, the physical exam begins. MacRae is fascinated by her teeth, two of which recently broke while eating a salad, of all things. He’s so intrigued by the shape of her face that he takes a picture. He also photographs a birthmark on her hip.

“We think things are unrelated, but we never know,” he tells her. “So we’re trying to capture everything we can.”

While this exam was part of a study on undiagnosed diseases, it offered valuable insight into how MacRae approaches solving medical mysteries. Essentially, he believes in questioning anything and everything in and around a patient because you never know where you might find the clues that crack open the case. (link opens in new window)

And now, backed by a $75 million research grant, MacRae is bringing that approach to one of the world’s most deadly mysteries, coronary heart disease.

The funding is part of One Brave Idea(link opens in new window), a search for a completely new way to wipe out this disease, which is basically the buildup of plaque that causes heart attacks. The American Heart Association, Verily (formerly Google Life Sciences) and pharmaceutical company AstraZeneca are so eager to break the mold that each put up $25 million.

MacRae – the chief of Cardiovascular Medicine at Brigham and Women’s Hospital in Boston, one of the main training hospitals for Harvard Medical School, where he is also an associate professor – believes heart disease doesn’t necessarily begin in the heart. By finding the origin or earliest markers, researchers may be able to stop the disease before it starts causing problems.

“Science is so complicated that we’ve tended to only look at little pieces one at a time,” MacRae said. “With this, we’re embracing a problem in ALL of its complexity and saying, `We're going to shake it down and get to the bottom of it.’”

MacRae and a team of experts from a variety of fields will take all the tried-and-true methods of cardiovascular research and add explorations into areas researchers have rarely checked. They’ll use modern tools and techniques, as well as perhaps the oldest tool: the doctor-patient relationship.

After all, that’s a big part of how he got to this point.

***

MacRae was born and raised on Scotland’s Isle of Skye, one of the planet’s wettest and windiest places.

The elements have shaped its cliffs and valleys, and kept its rivers raging, creating an idyllic backdrop for many movies – and for the wall calendar his mom sends him every year.

“Just so I remember where I’m from,” he said, smiling and pointing to it during the first of two days of interviews with American Heart Association News.

About 7,000 people lived on the island in his youth. His elementary school had a total of 27 people; he was among three in his grade. Yet his education proved to be spectacular.

The island drew outdoorsy types, including many with doctoral degrees who became his teachers in Latin, biology, chemistry and calculus. They made such a profound impact that he still keeps in touch with many.

His love of learning also was stoked by his parents, Calum Og and Sarah. He recalls evenings when he and his five siblings – he’s the oldest – would each go to a separate spot in the house to read. Young Calum loved math and wanted to be an astrophysicist, right up until applying to college.

“I had a couple of astrophysics college slots at the top, all in pencil, and I had three medical schools at the bottom. At the last minute, I flipped everything,” he said. “The thing that made me really rethink it was one of my teachers telling me that medicine was basically a broader venue to think about physics and mathematics. You could bring over those core interests and skills into a different environment. And you're more likely to have a job.”

It also meant following his father’s footsteps.

***

As a small-town physician in a town 400 miles from the nearest hospital, Calum Og MacRae not only made house calls, he often brought along a cot. If a patient needed care overnight, MacRae would be a few feet away.

In addition to keeping his neighbors healthy and raising his growing family, MacRae also felt an obligation to shape the community’s direction. So he found time to be an active politician.

A local who appreciated the demands on MacRae chose not to bother him one Saturday night, instead enduring chest pains until the morning. When he finally called and described a likely heart attack, boy, did he get an earful for waiting.

Calum absorbed these lessons – the sense of community and responsibility, the selflessness and caring, the dedication to his people – as he set off for the University of Edinburgh.

“None of what my father did was unique,” he insisted. “But it did help shape my sense of what being a physician is.”

***

A medical school degree from Edinburgh can be earned in five years. Seeking a broader base of knowledge, MacRae spent three years earning an undergraduate degree in experimental physiology, then three years of medical school.

Next came training at one of the national research hospitals in London. He stayed there for cardiology training, then earned a prestigious Wellcome Trust Fellowship that brought him to Harvard.

As his airplane landed in the United States, he fell in love with the place, smitten by the contrast of wooden homes near the Boston airport and gleaming downtown buildings taller than any he’d ever seen.

“There was a dynamism here that was really attractive,” he said. “I visited for two days and I knew I wanted probably to stay the rest of my life.”

While working in the renowned genetics lab of Jon and Christine Seidman, MacRae met his wife. They married in 1995, and a year later it was time to launch his career. However, there was a problem: While he could conduct research in the U.S., he’d have to repeat clinical training to see patients.

MacRae treasured that interaction so much to him that he signed up for four more years of school. As with his dad schlepping a cot, he insists it’s no big deal, saying many foreign-trained colleagues do it.

He spent two years at Brigham and Women’s, then two at Massachusetts General Hospital, where he worked in another renowned lab, that of Mark Fishman, studying zebrafish, which have genetics similar to humans. He eventually started his own lab, then returned to Brigham and Women’s in 2009. He became chief of cardiology in 2014.

Along the way, MacRae keenly observed his profession. He didn’t always like what he saw.

***

Back in the days of William Osler, the father of modern medicine, checking the pulse and blood pressure during an office visit were industry standards. A century later, they still are, which irks MacRae.

He doesn’t understand why doctors settle for that one snapshot in time when simple devices can provide readings taken over hours, days, weeks and months. Using – or creating – other devices to track other things in a patient’s body would make checkups more efficient, more valuable.

“Your bank knows every transaction you’ve made for years but we can only take your blood pressure once or twice a year? I can look on Waze to know which route I should take home but I don’t know what I was exposed to today?” MacRae said. “The tools are already available. We just haven’t put them together around health care.”

Despite working in one of the top research institutions – much of what we know about cardiovascular medicine came from his colleagues and predecessors – MacRae also questions why studies are often done in small teams at one site. This bothered him enough that a few years ago he considered leaving for private industry.

Then, last November, he was in Orlando for Scientific Sessions, the AHA's flagship gathering of cardiovascular thought leaders, when he wandered into a hall to hear from several prominent speakers.

***

MacRae arrived as AHA Chief Executive Nancy Brown and Dr. Andy Conrad, CEO of Verily, were on stage discussing a new project based on upending traditional scientific research.

He could hardly believe it. He’d been concocting his new approach and now these organizations wanted that very thing?

“Wow,” MacRae said to himself.

When the One Brave Idea application went online, its bare-bones approach – simple questions requiring answers of 250 words or less – served as further proof that this was truly novel.

“My entire being lit up,” he said. “Honestly. I thought, `Finally there’s an opportunity to break down the barriers that have held us back.’”

MacRae was among 349 applicants. He actually was a team member on two others, including another in the final 10. He was to have used zebrafish on those projects.

Dr. Robert Harrington, a member of the One Brave Idea selection committee, said a winning attribute of MacRae’s bid was the man himself.

“His ability to stand in front of the room and articulate a vision and to create a story that's highly compelling I thought was pretty extraordinary,” said Harrington, chair of the Department of Medicine at the Stanford University School of Medicine and an AHA board member. “Maybe most extraordinary is his grasp of very, very different sorts of science and the type of expertise that he saw as needing to bring to the table.”

That gets back to the core of MacRae’s brave idea – engaging teams of researchers from a wide variety of specialties and asking new questions.

And, of course, looping in patients and their relatives.

***

The walk from MacRae’s basement office to his clinic takes about 10 minutes and weaves through a maze of corridors, stairs and a skyway.

Along the way, he greets everyone from esteemed colleagues to cafeteria cashiers by their first name.

In the exam area, he’s not sure where to find his patient. While some doctors demand the same rooms, he goes wherever is convenient for everyone else.

It’s all part of the way MacRae sees himself – traces, perhaps, of being his father’s son. While he’s proud to be chief of cardiology and a $75 million researcher, he doesn’t put himself above others.

Especially not patients.

***

When MacRae finishes with the migraine-suffering stroke survivor, he sees her mother, then a younger sister.

He notices that the mom has a different birthmark and doesn’t have extreme headaches. Yet the sister has a similar birthmark. And migraines.

Maybe something in the skin connects to something in the blood vessels that leads to the problems in the brain, triggering first the headaches and then, ultimately, a stroke. Or maybe not. To MacRae, it’s worth looking into.

“This is a detective story, like `CSI: Migraine,’” MacRae said. “Patients don’t necessarily see the link, they just see their own birthmark. But in the clinic we can see connections.

“That’s what this study will try to do. Let's try and find the point at which a disease first arrives and ask, `What could we have done differently? How could we make this better? And more importantly, how can we predict what might happen and stop it from ever happening?’”

It’s all about the questions. Powered by One Brave Idea, MacRae could find revolutionary answers.