Seeing deeply into cancer: early disease interception for improved outcomes.
How can we detect cancer early so that we can treat it more effectively?
A note about why I’m stepping down as Verily’s CSO after four years to become Chair of its Science Board, and my exciting new role at GRAIL, a startup focused on early cancer detection.
About four years ago, I stepped off the academic path and returned to industry, joining a then-secret project in Google[x] led by Andy Conrad. I remember fondly the day that Andy and Jeff Huber came to the Berkeley campus in a prototype self-driving car — at that time, such a novelty!
My reasons for originally coming to Google are as valid today as they were then. As scientists, even the questions we ask are circumscribed by the tools we use to answer them. That’s why many of the best scientists are tool builders; their work reveals unexpected ways of thinking about natural phenomena. I came to Google because many of the tools of data science, among the most important scientific instruments of my generation, were developed here. With observations derived from new clinical tools like wearable sensors and information-dense laboratory platforms in fields including genomics, immunology, and imaging, scientists are able to peer deeper into human biology than ever before. Verily’s scientists feel a duty and commitment to harness these data for the benefit of patients.
The related fields of personalized medicine and systems biology, on which the exercise of that duty depends, are just emerging from their intellectual infancy. It’s thrilling to see how far Verily has come in service of that long-term mission, and where the company is positioned to go. Starting from a single laboratory with a few people, we are now moving into a large complex of labs and core facilities with a formidable and multidisciplinary set of teams. We now benefit from a robust network of partners that greatly enhance our scope, scale, and impact, and Verily’s gifted scientists, engineers, and clinicians are poised to contribute in several areas of translational biomedical science and engineering.
As a co-founder and Verily’s Chief Scientific Officer, I’ve learned a great deal in working with Andy Conrad, now a friend and mentor, on a day-to-day basis to build this remarkable business. I’m now ready for a new challenge and have decided to focus on a field and an opportunity that has great personal resonance. I’ve accepted a position on Jeff Huber’s leadership team at GRAIL, where I will guide its translational science and personalized medicine portfolio.
GRAIL’s mission is to “detect cancer early, when it can be cured”. This quest is so personal for me, because my father, Parminder Bajaj, died of cancer last year. I’d like to tell you a little about him.
My parents’ story is typical of Indian immigrants of the first post-partition generation. Settling in Canada, they became servants of the public interest: my mother, as a talented and caring physician; and my father, as an executive in public and private education. They lived a measured life and planned, in retirement, to enjoy all the experiences they had elected to postpone.
Before his diagnosis, my dad was in excellent health and, except for some lingering hip pain, had no premonition of the spreading cancer that would soon consume him. In fact, by the time we discovered it, his cancer had metastasized well beyond the point where we could effectively treat it. I knew that the formidable arsenal of modern molecular methods available to us, so very powerful in the hands of a laboratory scientist, would not deliver the kind of actionable information that might meaningfully alter the course of his disease.
Unfortunately, this is a common story: cancer can be silent, signalling its presence only when it’s already too late. Personally and professionally, I wanted to do everything possible to address the outstanding need for early interception in this disease. That’s why I decided to join GRAIL.
GRAIL’s ambition to develop a pan-cancer blood test for early detection is bold and unprecedented. “Extraordinary claims,” as Carl Sagan often said, “require extraordinary evidence.” Given the tremendous set of challenges we must overcome to realize our ambition, we are resolved to approach them with humility and transparency.
To begin with, there is not one thing called “cancer.” Cancer, arguably an inescapable consequence of multicellularity, is a clinically and molecularly heterogeneous set of diseases. It evolves stochastically, but also in response to its environment and to the selection pressures exerted by the immune system and extrinsic therapeutic interventions. Some cancers eventually develop into tumors whose complexity mirrors that of many organs, and yet we don’t know enough about the steps in their early evolution. Finally, while an accumulating body of clinical and scientific evidence suggests that we can infer a great deal about the tumor from the material that it sheds into the greater circulation (particularly DNA and RNA), the precise mechanism and dynamics of that process remain unknown. Alex Aravanis and his outstanding team at GRAIL have been working hard to lay the groundwork for an approach to this set of complex problems.
The most important set of challenges GRAIL must overcome are clinical. We at GRAIL believe, above all else, that we must do no harm. We are therefore adopting a standard of clinical evidence that requires us to demonstrate (in terms of specificity, sensitivity, false discovery rate, etc., but also outcomes) that eligible patients will benefit from any test that we develop. We need to understand how to deploy these tests and how, where, and when to best intervene, guided by their results. All these questions argue for a creative clinical oncology program that’s equally unprecedented in its scope and focus on early detection of cancer. That’s our secret sauce. Mark Lee and his experienced clinical team at GRAIL are planning clinical studies and trials of the scale, efficiency, and quality needed to meet this high bar. You’ll hear more from them, including Anne-Renee Hartman, Amy Sehnert, Bill Novotny, Tara Maddala, Tina Clarke-Dur, and Matthew Purner, soon. For now, consider enrolling in our first large observational study, the Circulating Cell-Free Genome Atlas study (CCGA), if you are eligible. New sites are opening every few weeks.
Finally, we are pushing the operational and analytical envelope as well. Our anticipated compute requirements, both in terms of infrastructure and the analytical capabilities required to assemble genomic data and identify cancer-defining variants or other signals, are of a scale without parallel in modern genomic medicine. We are fortunate that Angela Lai, Cos Nicolaou, and Franz Och are spearheading that effort.
While I will miss working with my colleagues at Verily every day, I’m fortunate that we have become an extended and close family. I’ll stay deeply involved with Verily, serving as Chair of its Science Board, where we will continue to support its culture of scientific rigor and oversight through its quarterly research review committee process. Andy Conrad has been a proponent of GRAIL’s mission, and Google Ventures has made an investment in GRAIL. Finally, with several of my former Google colleagues and collaborators like Ken Drazan now united in our mission at GRAIL, I’m hopeful that we’ll make the kind of advances that could help patients like my father.