����������ý�Ļ���Ʒ

Some might say the cards were stacked against Leslie Leinwand.

At age five, the precocious kindergartner was plucked from her Manhattan home and transplanted to the one-stoplight town of York, South Carolina, after the sudden death of her father, an internal medicine doctor. Her mother remarried a man who told young Leinwand repeatedly that, “girls didn’t need to go to college.” Then, when she was 13, tragedy took her mother and she was sent to live with extended family.

Leinwand persisted, landing at a small college in North Carolina where an astute professor noticed her interest in science and insisted she take a summer organic chemistry course at Cornell University.

“That’s when my somewhat sad story changed,” she recalls, now seated in her spacious office at the glistening, $210-million biotech facility she helped bring to life. “All because I had this fantastic professor.”

Today, Leinwand is a distinguished professor of molecular, cellular and developmental biology and the chief scientific officer of the BioFrontiers Institute at ����������ý�Ļ���Ʒ. She has achieved what many scientists only dream about: turning a seed of scientific inquiry into a multibillion-dollar company that saves lives — more than once.

Leinwand stayed at Cornell and helped pay her way through by working as a fraternity house waitress. She later earned her PhD in genetics from Yale and served on the faculty at Albert Einstein College of Medicine for 15 years before landing in Boulder in 1995.

Throughout this time, one fundamental question drove her research: What genes and proteins are responsible for making the heart function properly, and what causes this complex machine to break down in some people? 

“She is very special. When she discovers things in her lab, she doesn’t stop there,” said Nobel laureate and Distinguished Professor of Biochemistry Tom Cech, who has known Leinwand for three decades. “She works tirelessly, doing whatever it takes, to make something happen that will impact patients.”

Healing a big, sick heart

Much of Leinwand’s work has centered on hypertrophic cardiomyopathy (HCM), which she describes simply as a “big, sick heart.” 

It is the most common genetic heart disease in the United States, impacting roughly one in 500 people, as well as the most common cause of sudden death among athletes — who often don’t know they have it and push their hearts too hard, with lethal results. 

HCM first made headlines in 1990 when Hank Gathers, an all-American college basketball star, collapsed and died while on the court during a game at the age of 23. Since then, a long list has followed, including Reggie Lewis of the Boston Celtics, who died on a basketball court shortly after Gathers in 1993. 

In patients with HCM, their hearts — the walls thickened by disease — squeeze too hard and don’t fully relax, which burns through energy, leaves them breathless, causes the heart to race and depletes their energy.

HCM gets worse over time — and, until recently, there was no medication to treat it.

Leinwand’s interest in the disease dates back to 1985, when she first began studying a protein called myosin, which converts chemical energy into mechanical energy to move muscles, including the heart. Early on, she suspected that glitches in this ubiquitous protein might contribute to heart troubles and that studying them could ultimately lead to new therapies.

“It was an idea before its time,” she recalls. “We didn’t have the technology back then that we did later.”

First, she and her students had to develop a way to manufacture myosin in the lab so they could study it. That alone took years. 

In 1996, Leinwand and other CU colleagues took what they had learned about myosin and founded Myogen, a startup that developed two novel drugs for treating hypertension, which sold to pharma giant Gilead Sciences for $2.6 billion in 2006.

Ultimately, Leinwand’s team determined that faulty myosin was a key culprit in HCM.

In 2012, she joined Harvard’s Christine and Jonathan Seidman, who study the genetic mechanisms of heart disease, and Stanford biochemist James Spudich, who studies how muscles contract, to create the biomedical company MyoKardia.

MyoKardia developed a drug that attaches to the faulty protein, effectively cranking down the heart’s overactive motor. The drug was tested in clinical trials and mavacamten (brand name Camzyos) was born.

Bristol Myers Squibb bought MyoKardia for $13 billion in 2020 and, in April of 2022, the Food and Drug Administration approved mavacamten as the first and only cardiac myosin inhibitor approved in the United States for treating HCM.

“We had hoped that the best outcome could be that the disease progression was slowed, but what cardiologists are telling us is that they are actually seeing a reversal in some patients,” says Leinwand. 

Leinwand is not one to get emotional in public. But she can’t help but choke up a bit when asked how this makes her feel.

“It has been the most amazing thing to hear patients say things like, ‘I can now walk up a flight of steps again. I am no longer bedridden. I can get out of my house.’ It feels great.” 

Paying it forward

Leinwand has no plans to retire anytime soon. The BioFrontiers Institute, which she and her colleagues dreamed up in the early 2000s, is now a thriving intellectual melting pot, bringing hundreds of physicists, engineers, biologists, chemists, geneticists and computer scientists from around the world together under one roof to improve human health. 

Today, her Python Project, another way-outside-the-box idea she came up with in 2006, persists, enabling undergraduate researchers to study Burmese pythons as a means of better understanding what healthy versus unhealthy heart growth looks like. 

Pythons can go 6–12 months without eating and then swallow animals as big as they are in one bite, prompting their heart to balloon 40 percent in just 48 hours. In the python’s case, this growth is healthy, much like a well-trained athlete’s heart that grows larger with conditioning.

By understanding how pythons can grow and reverse a larger healthy heart so quickly, Leinwand and her team hope to someday develop therapies that could help people strengthen or shrink their heart muscle, according to need. 

Dedicated to her research, she was undeterred when told that the reptile breeder in Oklahoma City could not ship live pythons to Colorado due to interstate shipping guidelines. Instead, every year, her students drive 20 hours roundtrip to buy them and bring them to her lab on campus. 

Leinwand continues to mentor students and travel the country giving lectures on leadership, paying forward the gift she got from the professor in North Carolina who encouraged her pursuit of science. She prioritizes her own health too, carving out time to pedal 12 miles each night on her indoor recumbent bicycle while watching cooking shows to inspire the gourmet meals she prepares for friends.

When asked how she gets it all done (a question she hears a lot), she offers this singular piece of advice: 

“Pick your battles, and don’t pick battles you cannot win,” says Leinwand. “I know how to get stuff done,” she adds with a modest shrug. “I’m happiest when I’m doing five things at once.”

  Submit feedback to the editor

Illustration by Sol Cotti