Sanjiv Sam Gambhir, pioneer in molecular imaging, dies at 57
The professor and chair of radiology at Stanford was a global leader in advancing techniques for molecular imaging and early cancer detection.
The Virginia and D.K. Ludwig Professor of Cancer Research, Gambhir dedicated his career to developing methods of early disease detection, ushering in a new era of molecular imaging to flag signals of disease in its nascent stages. He was director of the Canary Center at Stanford for Cancer Early Detection, director of the Precision Health and Integrated Diagnostics Center at Stanford and director of the Molecular Imaging Program at Stanford.
“Sam was a true visionary and a scientist of the highest caliber. His research and innovations have, with no uncertainty, founded modern medicine’s approach to early disease diagnostics and will continue to guide the future of precision health,” said Lloyd Minor, MD, dean of the School of Medicine. “Sam’s contributions to Stanford, to human health, to the science of diagnostics and to the many lives he has touched and impacted throughout his career have been immeasurable.”
Within the field of radiology, Gambhir was known for the development of positron emission tomography reporter genes, which can flag molecular activity that signals something’s gone awry in the body.
To colleagues far and wide, he was known as a leader and scientist with sprawling expertise and a work ethic to aspire to. More than that, colleagues said he was a kind and generous friend, a nurturing mentor and a catalyst for collaboration.
On the eve before his death, he was awarded the Dean’s Medal, the School of Medicine’s highest honor, for his “revolutionary contributions to biomedicine and to human health.” In tandem with the honor, Minor announced that a new professorship, the Sanjiv Sam Gambhir Professorship in Translational Medicine, would stand as a tribute to Gambhir’s remarkable career “to further recognize his unwavering leadership, compassion and commitment to science and medicine.”
Part physicist, part physician
From the earliest days of his career, Gambhir’s efforts focused on bringing his unusual background — a physicist-mathematician turned physician-scientist — to bear on improving patient health by developing technologies that could reveal early signs of disease, especially cancer. Of his many research efforts, the creation of PET reporter gene expression imaging was among the most impactful, earning him a reputation as a founding father of molecular imaging.
Positron emission tomography is a radiological technique that can detect changes in tissues and organs with the help of radioactive particles, which emit signals that are transformed into an image. Often the technique is used to reveal the location of tumors in the body. Gambhir took PET imaging to the next level through PET reporters. These particles can latch onto certain tissues based on their genetic activity, enabling PET scans to not only show where the cancer is growing but reveal the molecular details driving the disease. Such information can be used to tailor treatments to an individual or predict whether a patient may respond well to a certain type of drug.
Alongside his work on PET reporters, Gambhir is also credited as one of the individuals who helped ensure government insurance programs would reimburse medical providers for PET imaging, thereby establishing its foundation in the clinic, a crucial step in expanding PET as a go-to method for cancer diagnostics.
Sam worked so hard to try to save his son. It was both inspiring and tragic.
Gambhir’s quest to hunt down molecular traces extended beyond PET reporters. He pioneered a technique that used microbubbles, tiny gas-filled bubbles that are detectable through ultrasound, for use in cancer detection; the bubbles would latch onto tumors. Alongside that work, he also developed a novel technique in an area known as immunodiagnostics, which repurposes the body’s immune cells to report on the presence of disease. For this particular research, Gambhir re-engineered immune cells to release a biomarker upon contact with damaged cells or cells with hallmarks of cancer; the biomarkers would then be excreted through the urine, where they could be detected. Gambhir was among the first to successfully demonstrate this research, and by extension the concept of immunodiagnostics, in animals.
Precision health champion
In 2013, tragedy befell the Gambhir family. Milan, the teenage son of Gambhir and his wife, Aruna, was diagnosed with a type of highly aggressive brain cancer known as glioblastoma multiforme — the exact tumor type Gambhir had been studying in his lab.
“I will never forget the morning that Sam called me to tell me that Milan had been diagnosed with a brain tumor,” said Garry Gold, MD, professor of radiology and vice chair for research and organization in the Department of Radiology. “Sam worked so hard to try to save his son. It was both inspiring and tragic.” Gambhir and teams of multidisciplinary specialists both within and beyond Stanford fought for his son’s life for 21 months but, in the end, Milan could not be saved. He died on May 2, 2015.
“I saw how difficult it was when Sam and Aruna lost him. And yet to see Sam returned and reengaged in his work, knowing that he could still help people around the world was just awe-inspiring,” Gold said. “If anything, Sam worked harder on his efforts in early cancer detection because of it.”
Gambhir, who understood for decades that the focus on late-stage disease resulted in suboptimal health outcomes, worked diligently to shift the paradigm to focus on early cancer detection through his efforts at the Canary Center. His efforts have led to major investments globally by public and private sectors in the field of early cancer detection.
Another component of the paradigm shift meant bringing precision health to the forefront of his research and to the field of medicine more broadly. In a precision health-focused talk he gave to a group of conference attendees, Gambhir remarked on the tragedy of his son.
“What motivates me is knowing if he’d been born 100 years from now, the tools of precision health could [have] possibly allowed him to live much, much longer,” he said. “I remain optimistic that the fundamental basic science that we all continue to do [will] lead to new technologies that will help reengineer our own bodies so that we can detect disease early.”
In 2017, Gambhir determined that with recent advancements in biology and technology, he could formalize his approach more broadly, and he helped launch the Precision Health and Integrated Diagnostics Center at Stanford, a program that harnesses cross-disciplinary collaboration to prevent or stop disease early, ideally before it can substantially harm one’s health. To this end, Gambhir was particularly keen on something called passive monitoring. The basic idea is to make measurements of one’s health in a consistent yet minimally intrusive manner, and in this way collect enough data to not only inform what an individual’s health looks like on a day-to-day basis, but what it looks like when things deviate.
Perhaps Gambhir’s most famous, and recent, example of this idea is the smart toilet, an invention that monitors molecular and physical details of a user’s stool and urine in an effort to detect early signs of disease, such as blood in the urine. To some it seemed a little out there, but it provided the world with a glimpse into Gambhir’s vision for the future of health care: proactive, not reactive.
Born in India, raised in Arizona
Gambhir was born in India and moved to Arizona with his family in 1969. As a teenager, he attended Arizona State University, graduating in 1983, when he was 20. With a bachelor’s degree in physics, Gambhir was accepted to the medical scientist training program at University of California, Los Angeles, where eventually he completed a PhD program in biomathematics and also earned a medical degree. It was during this program that Gambhir began to develop a vision — one that drew from physics to power medicine.
He was the most gracious and thoughtful person to anyone he would meet.
In 1994, shortly after the completion of his MD-PhD program, Gambhir was recruited onto the UCLA faculty by Michael Phelps, PhD, a pioneer of PET imaging and director of the Crump Institute for Molecular Imaging at UCLA.
“He was a young assistant professor, and he came to me one day and told me he did not believe that people would be interested in his bringing physics and math and nuclear medicine together, that they would not have any interest in his work,” Phelps said in a video shown during the online Dean’s Medal ceremony for Gambhir. “I said, ‘Sam Gambhir, you are bright, exciting, smart and extremely hard working. And you have a vision of the world that you see. They will not only be interested in what you create, you will change our field.’”
By 2001, Gambhir was leading the Crump Institute at UCLA and was serving as the vice chair of the Department of Molecular and Medical Pharmacology. Two years later, he, Aruna and Milan left Southern California and moved north after Gambhir accepted a position at the Stanford School of Medicine as the head of the Nuclear Medicine Division.
Over his 17 years at Stanford, Gambhir chaired the Department of Radiology, established and directed the Precision Health and Integrated Diagnostics Center, directed the Molecular Imaging Program at Stanford and directed the Canary Center at Stanford for Cancer Early Detection. In 2019, Gambhir co-led the team that created the Innovative Medicines Accelerator, a program that arose as part of Stanford’s Long-Range Vision and was conceived as way to accelerate the translation of scientific discovery into tangible clinical progress.
By any measure, his research developments, career accomplishments and inventions were prolific. He co-authored nearly 700 peer-reviewed papers, and his research led to 40 patents and the establishment of several companies. He believed that basic research findings should be swiftly translated to the clinic if it could benefit patients. Under his leadership of the Radiology Department, faculty founded 21 companies. Beyond Stanford, Gambhir had leadership roles on a number of advisory boards and committees, including the Advisory Council of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health, the editorial boards of several scientific journals, and the advisory boards of many biotechnology companies and scientific organizations.
What fueled such a fruitful career was something deep and fundamental, his colleagues said. “He does what he loves to do with those he loves to do it with,” Phelps said in the video. So much so, Phelps recalled, that when Gambhir was still at UCLA, he would even sleep on the PET scanner some nights. “He’s just relentless.”
Gambhir’s intense scrutiny of the molecular traces of disease and his efforts to design and iterate on detection technology always came back to one thing: his desire to make a tangible impact on patients.
“He would often start lab meetings by saying, ‘I want you to all remember why we’re here, and if anyone has forgotten, I want you to let me know and come over to the clinic with me, because … there are real people on the other side of this that we’re trying to help,’” Michelle James, PhD, assistant professor of radiology and one of Gambhir’s former lab members, recalled in the video.
I’ve never had a mentor like him.
Gambhir’s unique expertise in disparate areas and his willingness to reach across departments — and schools — was an integral part of what made him such a prolific scholar and effective leader. “Seeing the way he approaches questions and problems made me also approach my science and the questions I care about differently,” James said in the video. “I’ve never had a mentor like him … somebody who clearly cares so deeply about all of his people in the lab. All of his students are like his children, basically. And we all felt like that, and still do, to this day.”
One of Gambhir’s most unique and endearing qualities was his ability to connect with children of all ages, Aruna said. He could engage with kids at their level, figure out how to motivate, challenge and reward them with candy, money or tickles. His genuine love for children from a young age left an indelible mark on the kids who had the privilege to interact with him, she said.
Gambhir mentored more than 150 postdoctoral scholars and graduate students throughout his career.
“Here was somebody who was clearly brilliant — I mean, absolutely off-the-charts brilliant scientifically — who was producing world-class science every day in his lab. And at the same time, he was the most gracious and thoughtful person to anyone he would meet, anyone who would come into his office, anyone who he could help,” Gold said. “The world will miss Sam’s scientific achievements. But for those of us who felt Sam’s impact on a personal level — and it’s so many — we will miss his friendship, his support and his mentorship the most.”
Gambhir is survived by his wife, Aruna Gambhir.
In lieu of flowers, donations may be made to the Precision Health and Integrated Diagnostics Center, the Canary Center for Cancer Early Detection at Stanford, the Ben and Catherine Ivy Foundation, or the Sanjiv Sam Gambhir Professorship in Translational Medicine.
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