Using Genomics To Improve Patient Care: DNAnexus to Support Both Projects Selected by California Precision Medicine Initiative

dna-art2As Chief Medical Officer at DNAnexus, I’ve come to see my remit in very simple terms: I represent the voice of the patient-participant.

At least, that’s my aspiration. It’s been tremendously heartening to see the centrality of the patient-participant increasingly acknowledged (see here, here), especially in the context of the President’s Precision Medicine Initiative, for example (see here).

As a physician, there are few things more clarifying than the absolute commitment to do your best for the patient in front of you. Even as a resident, I was struck by how many seemingly intractable turf battles could be resolved simply by pausing to ask, “what’s in the best interest of this patient?”

When I set up the PASTEUR translational research training program with Denny Ausiello at Harvard about fifteen years ago, our focus was squarely on the patient; PASTEUR’s core philosophy – embedded in its motto – was: “Our patients as partners in discovery.”

Today — especially here in Silicon Valley – we are awash in data, and in folks who love, and have remarkable expertise collecting data, working with data, analyzing data.

The challenge, it has long seemed to me, is ensuring that we maintain our focus, and acknowledge data milestones (33 petaflops! One million genomes!) but reserve our greatest respect and joy for accomplishments that impact people – the conclusion of a diagnostic odyssey, the successful treatment of a patient – or even better, the prevention of disease in a high-risk participant.

Not only should technology be measured by its impact on people, but technology should also strive to leverage and bring out the best in the people hoping to use it – which in healthcare means researchers, providers, and participants.

During my training, I was especially moved by the words of pioneering pediatric surgeon Judah Folkman (see here), who preached the importance of inquisitive physicians and inquisitive researchers (and presumably, inquisitive participants) in driving medical progress.

This perspective perfectly captures how I view the DNAnexus platform – not as a magical solution (biology is still hard), but rather as a secure, cloud-based collaboration and analytics tool that can enable inquisitive clinicians, researchers (and increasingly, I hope, participants) to ask thoughtful questions of massive amounts of data, to collaborate easily, and to generate and share new insights that help patients and participants.

In this context, we feel especially honored to be supporting the two demonstration projects that were just selected by the California Initiative to Advance Precision Medicine (CIAPM), a public-private effort launched by Governor Edmund Brown, led by Dr. Atul Butte, and hosted by UCSF (see UCSF’s press release here). Both projects aim to yield quick results for patients.

The first project, led by Charles Chiu, an associate professor of laboratory medicine at UCSF, uses genetic sequencing to identify potentially treatable infections in acutely ill patients; Chiu’s approach was utilized, perhaps most famously, to save the life of Joshua Osborn, a 14-year old boy who had been placed in a medically-induced coma after falling critically ill and experiencing brain swelling for unknown reasons. Genetic testing, using a methodology developed by Chiu and colleagues, identified the causative pathogen, which led to the successful treatment of Joshua and his subsequent recovery.

The current project aims to expand the reach of this approach, initially to additional hospitals within the UC system, and eventually, I hope, to clinics across the nation (and globe). DNAnexus is committed to cloud-enabling the analytic pipeline, ultimately allowing samples and sequencing from a range of sites to be analyzed and securely shared using a common platform. Structurally, this approach of distributed sequencing and centralized analytics – which enables rapid scaling — is very similar to what DNAnexus has also enabled at Natera (see here).

Paul De Kruif’s classic Microbe Hunters (see here) played a critical role in spurring my earliest interest in the excitement and promise of medical research; consequently, it’s been especially gratifying to see the DNAnexus platform applied to accelerate the understanding of infectious disease. The platform has also supported the Ebola research of pioneering Broad Institute investigator Pardis Sabeti and her colleagues (work also supported by the Broad, Illumina and the CDC); see here for a summary, and here for the June 2015 paper in Cell.

The second project, led by David Hausler, a professor of biomedical engineering at UCSC and Ted Goldstein, a research associate at UCSC (and a former VP at Apple), seeks to identify precision treatments for pediatric cancer patients in California based on the genetic characteristics of their disease. This work builds on the UCSC Treehouse Childhood Cancer Project, which enables the combined analysis of cancer datasets.

DNAnexus is currently supporting oncology analysis pipelines at UCSF and Intermountain. I am particularly excited to contribute to the analysis and sharing of oncology data because the opportunity and the need seem especially great. It’s essential that the culture of medical research – including (some might say particularly in) oncology — evolve from one of hoarding data to one that recognizes the urgency – certainly from the patient’s perspective – of sharing data, and catalyzing knowledge turns (to borrow Andy Grove’s term), and accelerating the rate of progress.   We hope that our platform – and the analysis, collaboration, and insight it enables – can contribute impactfully to this process.

As excited as we are to be an industry partner of both teams selected by the CIAPM, we are, as always, focused on execution, and can’t wait to roll up our sleeves and get to work here.

We understand that for both demonstration projects, the ultimate measure of success is not the amount of DNA analyzed, or the amount of computation brought to bear. It’s also not the number of collaborators assembled nor the translational insights generated — though both are important intermediate markers.

Rather, our success metric is the difference we are able to make in the lives of patients and families. Our ambition is the relentless and unwavering pursuit of this goal. Our conscience is all those who continue to count on us and on science to fulfill our solemn commitment.

Dr. Shaywitz is Chief Medical Officer of DNAnexus. He also holds an adjunct appointment as Visiting Scientist in the Department of Biomedical Informatics at Harvard Medical School, and is co-host, with Lisa Suennen, of “Tech Tonics,” a podcast “focused on the people and passion at the intersection of technology and health,” available on iTunes (here).

Obama’s Precision Medicine Initiative: DNAnexus is There

David Shaywitz_White HouseLast week, President Obama held a meeting unveiling details about the Precision Medicine Initiative, an audacious research effort to revolutionize how we practice medicine and ultimately improve human health. At the center of this bold new initiative lies a huge new biobank containing electronic medical records and genetic information on more than a million Americans. Our very own Chief Medical Officer, David Shaywitz, joined the other personalized medicine stakeholders at the White House to weigh in as President Obama made the historic announcement. You can read David’s own first hand account of his visit to the White House here.

Developing cures for complex diseases is incredibly complicated, and the President’s initiative requires long-term vision. Already, the underlying sentiment seems to be that the reality of genomic medicine is here today, in the case of cancer, and targeted therapies are becoming increasingly common. But the realization of a more complete understanding of human genetics, one that will drive discovery and improve human health, requires deep, accurate, and accessible integration of genomic and phenotypic data from millions of people.

The development of a US biobank will require three distinct executional elements: creating, integrating, and analyzing complex data sets. Each of these elements presents unique and difficult challenges, but experience tells us that none are impossible. President Obama’s Precision Medicine Initiative calls for national implementation of solutions very similar to those developed by DNAnexus in collaboration with Regeneron Genetics Center and Geisinger Health System, and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), Baylor College of Medicine’s Human Genome Sequencing Center (HGSC), and other partners.

Robert Plenge, Heidi Rehm, David Ledbetter, Robert Nussbaum, waiting to enter White House (Photo: D. Shaywitz)
Robert Plenge, Heidi Rehm, David Ledbetter, Robert Nussbaum, waiting to enter White House (Photo: D. Shaywitz)

A cloud-based genome informatics and data management platform like DNAnexus combines state-of-the-art security with fluid data sharing among researchers, providing a collaborative environment that facilitates and promotes insight and discovery. And that’s exactly what the White House is betting on. These are exciting times, and we are thrilled to be participating, alongside our partners, at the front lines of innovation and policy.

Xconomy Forum: Healthcare’s Punctuated Equilibrium

Xconomy Innovation at Biotech's EpicenterLast week we had the pleasure of speaking at the Xconomy Forum: Innovation at Biotech’s Epicenter. It was only fitting that this meeting be hosted in the burgeoning biotech neighborhood of San Francisco’s Mission Bay, the latest urban biotech core to spring up in the Bay Area, the birthplace of modern biotechnology.

The opening Keynote was presented by UCSF’s Chancellor, Sam Hawgood, who argued that the collision between technological sciences and the advancement in big data and medicine has positioned healthcare for a new era in punctuated equilibrium. Hawgood argued that in order to take advantage of this exciting era, the life science and healthcare community must capitalize on partnerships, both public and private, openly sharing data and collaborating on projects. We were humbled that DNAnexus was mentioned by the Chancellor for our contribution to clinical cancer care with UCSF.  As we look to 2015, we are prepared for this disruptive change, with collaborative and scalable technologies that enable researchers to work together, share ideas and data, and tackle some of the most exciting opportunities in human health.

Our CMO, Dr. David Shaywitz, played moderator and panelist for the forum’s discussion on big data for big (and small) biopharma, stacked with a very talented and seasoned group of industry leaders: Gini Deshpande, CEO for NuMedii, Dongliang Ge, Director of Bioinformatics for Gilead Sciences, and Rick Morrison, CEO for Comprehend Systems. This group took on challenging questions, like “What is the key blocker to getting pharma to adopt an agile Silicon Valley mindset?” Deshpande noted that applying genomics to drug discovery seemed a bit aspirational to some skeptics at the moment. Morrison argued that it’s hard to break old habits: The Silicon Valley philosophy of “move fast and break things” doesn’t work in medicine — it’s people’s lives at stake if “things break,” he noted.

As expected, there was considerable enthusiasm expressed for leveraging large data sets and smart algorithms to generate verifiable novel insights and new therapies. A thoughtful audience member asked whether the field has gotten out over its skis, and wondered whether drug development has truly been impacted by big data.  Shaywitz cited the example of PCSK9-based therapies as one example of  where big data – and specifically “happy genomics”, which he has written extensively about here and here – may lead.  Right now there are lipid-lowering drugs in late-stage development by Amgen and Regeneron/Sanofi, which came about through genomic studies of the gene PCSK9.

Ge, of Gilead Sciences, also offered another example: Dr. Lukas Wartman, a cancer researcher at Washington University in Saint Louis  fell ill to the very disease he was studying. When standard chemotherapy treatments failed him, Wartman and colleagues sequenced his genome, and discovered a gene called FLT3 was being expressed at a much higher level than in healthy individuals. Using a drug-gene interaction database, they found a drug, Sutenet, normally used to in kidney cancer that targets a “hyperactive” FLT3 gene.

The story of Dr. Lukas Wartman really speaks to us at DNAnexus. Eventually we envision a world where it’s routine to sequence the tumor and genome of every patient and produce a clinical report indicating what drugs best target the cancer. Or better yet, a routine non-invasive blood test will catch cancer in its earliest stages, and clinicians will prescribe effective, individualized therapies right away to knock the cancer out. But for now, we are deeply engaged in the discussion around genomics in the clinic and providing the technological backbone that enables various research partnerships through sharing and management of data and tools around large volumes of sequencing data to discover novel insights. By making it easier, and in many cases feasible, to work with genomic data, pharmaceutical companies and their collaborators (both medical centers and, critically, the patients themselves) can benefit from the power of genomics and use this knowledge to drive drug discovery and deliver new medicines to benefit patients.