Scientist, advocate and entrepreneur Lucy Shapiro to receive Lasker-Koshland special achievement award

(Press-News.org) In 1959, Lucy Shapiro, a freshman honors student at Brooklyn College majoring in arts and literature, had signed up for a course in inorganic chemistry on a lark. It didn’t interest her, and she stopped attending. But at the end of the term, having failed to officially drop the class, she was notified she had to take the final exam.

“It was a multiple-choice test, so I just circled all the B's,” recalled Shapiro, PhD, professor emerita of developmental biology and director of Stanford Medicine’s Beckman Center recalled. She received a D.

Three years later, the budding artist met physical chemist and violinist Theodore Shedlovsky, PhD, at an art exhibition that included one of Shapiro’s paintings. “He had this thing of finding young people in the arts and, if he thought they were smart and creative, urging them to go into science,” Shapiro said. She fit the bill.

Shedlovsky convinced Shapiro to take a course in organic chemistry. But the only available class at the college was taught at an honors level.

“I went to the chemistry department office for permission to take the course,” Shapiro said. “The assistant to the chair asked about my chemistry course record, and I had to explain that I had none, and that furthermore the D in inorganic chemistry on my record was the result of circling all the B's.” As the assistant was about to throw Shapiro out, the department chair came out of his adjoining office. He stared silently at her awhile, then asked why she wanted to take his honors course.

“I assured him that I was quite smart,” Shapiro said. “He saw this as challenge, and I was in! At that time, girls studying chemistry were rare.”

She aced the class.

“That course changed the trajectory of my life,” Shapiro said.

An influential career It’s not an exaggeration to say that Shapiro’s extraordinary powers of persuasion also altered the field of biology. Shapiro has served as the first female department chair at three universities; launched Stanford Medicine’s department of  developmental biology; with her physicist husband Harley McAdams, PhD, a professor of developmental biology, emeritus, created the field of systems biology; served as an advisor on bioterrorism, antibiotic resistance and pandemic preparedness to two U.S. presidential administrations; addressed the U.S. Senate’s Armed Services Committee and the world’s leading economists on global health threats; founded companies that developed novel antibiotic and antifungal drugs; and been awarded a bevy of national and international awards including the National Medal of Science and Canada’s Gairdner International Award.

Next week, Shapiro will be awarded the Lasker-Koshland Award for Special Achievement in Medical Science. The Lasker Award, known as the “American Nobel,” is this country’s most distinguished honor for researchers in basic and clinical medical sciences. The Special Achievement award, which has been renamed in honor of the late biochemist Daniel Koshland Jr., is given only once every two years to commemorate a life of scientific contribution and service.

Shapiro will be the 18th recipient of the award and the third woman. In 2008, the late Stanley Falkow, PhD, a professor of microbiology and immunology at Stanford Medicine, received the same award for his work on the molecular basis of microbial pathogenesis. The 2025 awards were announced Sept. 11 by the Lasker Foundation and are to be presented at a ceremony Sept. 19 in New York City.

“Lucy has been described as a force of nature,” said Lloyd Minor, MD, the Carl and Elizabeth Naumann Professor for the Dean of the School of Medicine and vice president for medical affairs at Stanford University. “I wholeheartedly agree. In her 36 years at Stanford Medicine, she transformed the way biologists think of bacteria and developmental biology; she pioneered a truly interdisciplinary lab that brought together physicists, chemists and biologists; met with multiple heads of state; launched two extraordinarily successful biotech companies; and mentored dozens of students who now lead successful research projects around the world. And she does it with a smile on her face and an engagement with her colleagues that makes everyone feel valued. We are incredibly fortunate to have her as a member of the Stanford Medicine community.”

Shapiro is stunned by the recognition. “I don’t even know how to answer that,” she responded when asked how she felt when she first learned she would receive the award. “It was just so shocking. Many of the previous recipients are my heroes — people who I’ve looked up to my entire scientific career. It means more than I can possibly say to be part of that cadre. It is really the highest honor I can imagine.”

Since her graduate school days, Shapiro has focused on understanding how bacteria compartmentalize proteins and structures that generally lack the intracellular membranes and organelles that more advanced cells (from yeast to human) use for organization. Discoveries made in her lab in the late 1990s overturned the prevailing idea that bacteria were just a “bag of enzymes” by proving that proteins involved in the regulation of the cell cycle travel to the poles of the cell in a dynamic, regulated fashion prior to cell division. 

She did so by studying a unique bacterium called Caulobacter crescentus that divides asymmetrically to create one stationary, stalked cell and one mobile, flagellated cell that swims away to new locations. This type of cell division is the fundamental basis of stem cell function and the generation of diversity in the living world.

Along the way, Shapiro sought out and cultivated interdisciplinary collaborators at Stanford Medicine and beyond, including McAdams, a former department head of systems engineering at Bell Labs who moved with her to Stanford in 1989 when Shapiro was recruited to be the founding chair of the new Department of Developmental Biology. Together, first in a spare bedroom in their house on the Stanford University campus and then in side-by-side laboratories when McAdams became a faculty member, biologists, geneticists, physicists and electrical engineers rubbed shoulders and drew parallels between genetic feedback networks and electrical circuits. “This revolutionized our understanding of the complex genetic and molecular interactions that govern how cells grow and divide,” Shapiro said.

“Lucy’s emotional intensity and focus, along with her willingness and desire to solve any problem, is inspirational” said W.E. Moerner, PhD, the Harry S. Mosher Professor, a professor of chemistry at Stanford University and the 2014 recipient of the Nobel Prize in chemistry for the development of a type of microscopy that enabled the detection of single molecules within a living cell. Shapiro and Moerner used the technique to track the movement of proteins associated with the cell cycle in Caulobacter — cementing the idea that bacteria actively regulate the location of proteins and DNA during cell division.

“People didn’t believe it at first,” Shapiro said. “I had to fight to get those papers published in Science.”

Never one to shrink from unconventional ideas, Shapiro leveraged what she’d learned about bacterial biology in a collaboration with  Steve Benkovic, PhD, a chemist at Pennsylvania State University, to explore whether replacing a carbon molecule in the active site of potential antibacterial and antifungal drugs with a boron molecule could lessen toxicity while maintaining efficacy.

“The boron-based molecules killed the pathogens, while sparing human cells,” Shapiro said.

She and Benkovic obtained the license to this new class of anti-infectives and launched a company called Anacor Inc. Anacor developed the first new antifungal in 50 years and an anti-inflammatory drug effective against eczema — both of which were approved by the Food and Drug Administration. In 2016, Anacor was sold to Pfizer for $5.2 billion. Shapiro co-founded Boragen, which subsequently merged with AgriMetis to form the agricultural company 5Metis that is designing boron-containing antifungals to protect bananas and rice crops worldwide. She has served on the boards of multiple biotech companies.

Lunching with a purpose For decades, Shapiro participated in monthly lunches hosted by former U.S. Secretary of State George Shultz. During these meetings, Shultz would ask Shapiro, then-Stanford-provost Condoleezza Rice and nuclear nonproliferation expert Sid Drell what they had accomplished (or failed to accomplish) during the previous month, as well as what concerned them the most.

“Being forced to articulate, and be aware of, existential threats in my area of expertise expanded my concerns from how a cell goes about its business of being a living entity to ones of national policy,” Shapiro said. “I developed a new vision of an integrated world system — or circuit, if you will — in which the components were the economy, political national interests and technological developments that were rapidly changing our understanding of global dynamics. Underlying these issues was the specter of climate change that was clearly the elephant in the room.”

The lunches, which began in the mid-1990s, caused Shapiro to contemplate how to respond to challenges facing human health. As a result, she embarked on a three-pronged mission: speak publicly about the rising threats to global health, gain the political visibility and influence to champion the support of basic research, and design and obtain regulatory approval for new anti-infective drugs.

In true Shapiro fashion, she was remarkably successful. Over the years, she spoke with Soviet Union leader Mikhail Gorbachev about emerging infectious disease threats; met with then National Security Advisor Condoleezza Rice during the George W. Bush administration; briefed President Bill Clinton about how the threat of bioterrorism is similar to the threat of the natural emergence of dangerous pathogens; and, in 2019, addressed the Senate Armed Services Committee about the looming threat of a global pandemic. She met with Mark Zuckerberg and his wife, Priscilla Chan, to encourage the collaboration between Stanford University and the University of California, San Francisco, that would become the Chan Zuckerberg Initiative, and she counseled former California governor Jerry Brown about antibiotic resistance and SARS-CoV-2 and Microsoft founder Bill Gates about boron-containing anti-infectives.

“If Lucy sees something that is not right, she is not going to sit around and do nothing,” said Peter Kim, PhD, the Virginia and D.K. Ludwig Professor in Biochemistry and former president of Merck Research Laboratories. “Her role as a government adviser on bioterrorism and antimicrobial resistance has been remarkable. And the overall breadth of her accomplishments, along with her ability to influence so many different parts of society in such positive ways, is astounding.”

“She’s a true citizen scientist who feels responsible for the broader community,” said scientific colleague Jeremy Nathans, MD, PhD, professor of molecular biology and genetics at the Johns Hopkins School of Medicine. “Not just for her own lab, or department, or university but much more broadly. And she understands the consequences of large-scale public misunderstanding of science and how incredibly damaging that is.”

Early days Shapiro graduated from Brooklyn College in 1962 with a bachelor’s in fine arts and a minor in biology. She launched into graduate school under the auspices of Shedlovsky and biochemist Jerry Hurwitz, PhD, first at New York University where she became part of the “jungle biochemists,” then at Albert Einstein College of Medicine. “They were rough, competitive, demanding and exquisitely able chemists. And now I was one of them,” Shapiro recalled in an unpublished reflection.

As a graduate student, Shapiro was challenged to determine how a bacterial virus that used RNA as its sole genetic material was able to hijack an infected bacterial cell and make numerous copies of itself. Her PhD thesis was the discovery of an RNA-dependent RNA polymerase encoded by a virus that infects the bacterium E. coli. Learning that RNA could be stable enough to serve as a primary genetic code, rather than just a messenger to carry instructions from DNA to the cell’s protein-making machinery, was a key step in the development of today’s mRNA vaccines.

“I had no way of knowing then that the test tubes and cold rooms with which I quickly became familiar would yield information that would be absolutely critical to battle a pandemic nearly six decades later,” Shapiro said.

Within 10 years of graduating, Shapiro rose to lead the department of molecular biology at Albert Einstein — the first woman to hold a department chair at the school. 

“Lucy burst like a bolt of lightning upon the scientific scene,” said colleague Carol Gross, PhD, professor of cell and tissue biology at UCSF. “Although her PhD thesis was purely biochemistry and almost all her coursework was in chemistry or physical chemistry, when faced with starting her own laboratory, Lucy determined that the most significant question she could address was in developmental biology.” 

Caulobacter crescentus was an obscure, understudied bacterium in a time when the vast majority of biologists were using E. coli — a common gut bacterium that divides symmetrically — as a model system. But Caulobacter was ideal for the questions Shapiro wanted to address — namely, how a linear DNA genome gives rise to a three-dimensional cell with specific architecture and function. The topic was incredibly daunting, but Shapiro had confidence in her “hydrogen atom” (the simplest possible unit of study that, when understood, could shed light on much more complex systems).

“At scientific meetings, where every session focused on E. coli, Lucy and I took to calling ourselves the ‘un-colis’ as a nod to the popular ad for 7 Up as the ‘un-cola,'” said Richard Losick, PhD, a professor of biology at Harvard University and a Howard Hughes Medical Institute investigator. Losick was also studying a little-known bacteria called Bacillus subtilis.

“For a long time our work was largely ignored. But her remarkable charisma convinced the planet to pay attention to her as she developed Caulobacter into an excellent model for research. And I came along for the ride,” Losick said. “It seems like she can do anything she sets her mind to. It’s amazing. This award is the crowning recognition for Lucy’s career. It’s a category that recognizes broad contributions to science and the world. It is a perfect fit for her.”

After 19 years at Albert Einstein, Shapiro moved to Columbia University as professor and chair of microbiology and immunology. She lasted three years before yielding to Stanford Medicine’s repeated offers to chair its new Department of Developmental Biology. The opportunity to recruit the best of the best to the new department was too appealing to turn down. At Stanford Medicine, Shapiro set about assembling a cadre of researchers studying similar questions in model organisms from bacteria to mammals.

A woman in science Once again the first woman to chair a department at a school of medicine, Shapiro was used to the experience. Jarring moments during her early career — being heckled during scientific presentations and ostracized in classes — had made it clear that women face particular challenges when entering male-dominated fields.

“More than any other woman of her time, Lucy showed that women could compete in all aspects of the scientific enterprise at the level of their male counterparts, even without a male scientist partner to pave the way for her,” Gross said. “At a time when very few women were scientists, much less in leadership positions, Lucy’s brilliance, foresight and determination showed what is possible, paving the way for others to follow.”

Her determination included helping young scientists facing similar hurdles.

“Lucy is not just a brilliant scientist, but also a very caring mentor,” said Christine Jacobs-Wagner, PhD, a professor of biology and of microbiology and immunology as well as a former postdoctoral student in Shapiro’s lab. “When I first arrived, I had won an award and needed to attend a very fancy reception in Sweden where you had to have a cocktail dress. And Lucy, who is very stylish, just looked at me and said, ‘Let’s go to Stanford Mall together on Saturday and we’ll pick up a dress.’ And this is what we did. Once you are part of her lab, you are part of her family.”

Many of Shapiro’s former protégés, including Jacobs-Wagner, have launched highly successful laboratories of their own.

“She is the kind of mentor who helps you feel independent and empowered, while also giving you the structure to really thrive in such a seamless way that you think you’re coming up with all these great ideas yourself,” Jacobs-Wagner said. “She knows what you need before you know you need it.”

“The important thing about winning this award is that people realize that buried within a career is a full life, which includes a family,” said Shapiro, who raised three children with McAdams. “That isn’t often mentioned. We talk all about that company and this science, but raising my children and my grandchildren has been such an important part of my life. The same was true for Marie Curie and her daughters. We are all human. That tends to get lost when you start talking about the ‘American Nobel.’ It shouldn’t be lost.”

Now, 65 years after Shapiro talked her way into the course that would change her life, she has a message for the young scientists following in her footsteps.

“If you are confident in what you are talking about, and your science is excellent, there is no need to be intimidated by anyone.”

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