Making the Key Fit

"The natural history of heart valve disease had not changed in hundreds of years—until Dr. Starr stepped in."   In September 1960, Albert Starr performed the first successful valve-replacement surgery on a human patient. He placed a mechanical valve in the patient's heart that he and his collaborator, Lowell Edwards, developed. The patient survived for 10 years. Building on Starr's success, Alain Carpentier developed a method to use heart valves from pigs. Patients with mechanical valves need to take anticoagulants (blood thinners) for the rest of their lives. Carpentier's use of natural valves eliminated that need. Starr and Carpentier became good friends and colleagues. They shared the 2007 Lasker Award for the development of prosthetic heart valves; Edwards passed away before the Award was given.

"By the time we finished walking across this great lawn, we had decided on this exciting experiment." —Elizabeth Blackburn on meeting her collaborator, Jack Szostak at a research conference. Elizabeth Blackburn, Carol Greider, and Jack Szostak won the 2006 Lasker Award for the prediction and discovery of telomerase, the enzyme that maintains the ends of chromosomes (telomeres). Blackburn and Szostak predicted the existence of such an enzyme, based on experiments they did in yeast and tetrahymena. Blackburn and Greider showed that this enzyme, telomerase, really does exist. The research of these three scientists broke open a new field and forever changed science and medicine.  

Roderick MacKinnon won the 1999 Lasker Award for elucidating the structure of potassium channels. His work provided the first molecular description of an ion selective channel and helped knock down what he called "psychological barriers" in the field. After MacKinnon, the structure of transmembrane ion channels went from being seen as unsolvable to solvable. In this 1999 interview with Chris Miller, Professor of Biochemistry at Brandeis University, MacKinnon shares anecdotes from his early career, discusses how the field reacted to his groundbreaking work, and talks about what motivates him scientifically. This interview has been edited for clarity and brevity. Find the full 55-minute interview here: https://laskerfoundation.org/winners/function-and-structure-of-ion-channels/  

Lasker Laureate Daniel Koshland's work changed our understanding of how enzymes interact with their substrates. In this 1998 interview with Robert Tjian, a fellow professor at Berkeley, Koshland talks about how the scientific community reacted to his "induced fit" model of enzyme-substrate interaction, and discusses his decades-long career, which spanned work as a scientist, an administrator, and a journal editor. Read about the 1998 Albert Lasker Special Achievement Award in Medical Science: https://laskerfoundation.org/winners/science-communication-and-education/

"It wasn't enough to sit at the table," said Nancy Brinker, founder of the Susan G. Komen Foundation, "we wanted to be the table." Brinker, a 2005 Lasker Laureate, tells the story of how a small startup nonprofit came to lead the effort to increase funding for breast cancer research. When Nancy Brinker's sister, Suzy, was diagnosed with breast cancer in 1977, people did not talk about cancer, which could make receiving a diagnosis especially isolating and frightening. After Suzy passed away, Brinker started the Susan G. Komen Breast Cancer Foundation. Her goal was to spark a cultural and a clinical change by bringing the disease into the open, jumpstarting research, and improving patient care. In this 2005 interview, Brinker talks about her sister, about the early struggles of getting the Foundation off the ground, and about the hard-won success of what is now the world's largest nonprofit funding source for the fight against breast cancer.

In May of 1995, a man was thrown from his horse during an equestrian competition and broke his neck, becoming paralyzed from the shoulders down. This would be a life-altering injury for anyone, but this man was Christopher Reeve, the actor who played Superman from 1978 to 1987. After his accident, Reeve used his celebrity to advocate for federal funding of medical research. In this 2003 interview, recorded in celebration of Reeve receiving the 2003 Public Service Lasker Award, he discusses his activism.

Lasker Laureate Alec Jeffreys developed DNA fingerprinting, a technology that revolutionized human genetics and forensics diagnostics. He thought that it would take years to see his technique used outside of the lab. "But," he says, "I could not have been more wrong." Listen to Jeffreys tell the origin story of DNA fingerprinting and hear about the first real-world case that it helped solve.

"The idea of spending your time digging into mysteries…I thought that would be a wonderful way to spend your life." Evelyn Witkin did spend her life digging into mysteries, and she was recognized with the 2015 Lasker Award for her work that solved one—how some bacteria survived 100x the radiation that killed other cells. Witkin discovered the DNA-damage response, a genetically regulated emergency system that protects the genomes of all living organisms. In an interview with Emmy-nominated writer/director/podcaster Flora Lichtman, Witkin talks about what it was like to be at Cold Spring Harbor in the 1950s, when many major discoveries in molecular biology were made, and tells us a little bit about her hobby in retirement: Victorian poetry.

The venom of the Brazilian pit viper Bothrops jararaca causes a sudden and catastrophic drop in blood pressure. Armed with this knowledge, David Cushman and Miguel Ondetti set out to isolate the active component. In this 1999 interview with Princeton University professor Leon Rosenberg, Cushman tells the story of their Lasker Award-winning work that resulted in ACE inhibitors for the treatment of hypertension. Cushman and Ondetti were recognized not only for their development of a life-saving medication, but also for their innovative approach to drug design. Listen to the incredible story of captopril, one of the first drugs developed through rational design. This interview has been edited for brevity and clarity. The transcript of the entire 43-minute interview, along with the transcript for a 54-minute interview with Ondetti, can be found here: http://ow.ly/wGL750Oo4uQ

Oliver Smithies freely admits that he did not find a solution to the problem he set out to solve, but he was able to turn his initial failure into a success that forever changed biomedical research. The gene targeting method that Smithies developed made it possible to generate knockout mice as models for human disease. In this 2001 interview with Raju Kucherlapati, Smithies talks about his education, his Award-winning work, and why research is a bit like flying an airplane.     This interview has been edited for brevity and clarity. Find the entire interview here: https://vimeo.com/146792245