Few scientists earn a repeat invitation to keynote the Molecular Medicine Tri-Con (TRICON) event, especially not 23 years apart. But Lee Hood is an exception.
Kicking off the 25th anniversary edition of TRICON in San Francisco earlier this week, Hood reflected on his mission to promote “P4 medicine”, illustrating with real-world examples ways that systems biology is being integrated into modern 21st century healthcare.
Hood’s reputation needs little restating: his group pioneered the development of automated technologies for synthesizing and sequencing proteins and DNA, in the process transforming biomedical research and the biotechnology industry. “Technology development is empty unless its driven by first-rate biology,” Hood said. “Invent what you want but unless you can apply them… they’ll sit idle for long periods of time.”
In 2000, Hood established the Institute of Systems Biology (ISB), and evangelized the promise of what he calls P4 medicine – personalized, predictive, preventive and participatory. In 2016, the ISB became the research arm of the Providence St Joseph health system. (Hood is now Senior vice president and CSO of Providence St Joseph Health, Seattle.)
Hood briefly reviewed his seven paradigm changes in biology dealing with complexity:
- Engineering to biology (‘70s) – sequencers and synthesizers leading to high-throughput data acquisition — the forerunner of Big Data.
- Human Genome Project (1990) – the automated DNA sequencer. 80% biologists were opposed to the Genome Project on the grounds it was “big science”, Hood said. The strongest opposition was ironically the NIH, but “they came around at the end.”
- Cross-disciplinary biology (1992) – Hood tried to persuade Caltech to invest but the biologists vetoed the idea. Bill Gates recruited Hood to the University of Washington. UW. State university wasn’t ideal setting so…
- Systems biology (2000) – focused on disease.
- Crystallization of ideas – P4 healthcare and scientific wellness (2004-14)
- Pilot project for Scientific Wellness (2014)
- Providence St Joseph Health (2016) – Hood was approached by the Providence CEO inviting the ISB to become a partner to bring P4 medicine into the healthcare system.
In the 20th century, the approach to medicine was trying to understand disease (Find It, Fix It). In the 21st century, Hood believes systems approaches will be the key to understanding wellness, by studying disease in the context of the individual (Predict It, Prevent It, Personalize It).
Hood is an advocate for “personal, dense, dynamic (longitudinal) data clouds… These are exactly what we need to study… they’re the essence of what precision medicine should be,” he said.
Most of Hood’s presentation was devoted to discussing recent examples of applications of network or systems biology. For example, take lung cancer. Hood highlighted the sorry statistic that half of surgeries on patients with lung nodules turn out to be benign. Using a mass spectrometry assay, Integrated Diagnostics – a company Hood co-founded — has marked 12/13 proteins that fall into lung cancer disease-perturbed networks – saving the US healthcare system some $3.5 billion in unnecessary surgeries. More recently, this assay has been refined to a 2-protein blood panel that identifies more than 50% benign lung nodules.
In a related example, a different pair of proteins has been identified as a marker for pre-term births: a preliminary study suggests that tests at 19 weeks’ gestation can distinguish mothers destined to have a preterm birth.
Hood said P4 medicine, then, was the convergence off “five thrusts – systems biology, scientific wellness, digital health, Big Data/analytics, and social networks.” This would replace “imprecision medicine” – the current state of affairs – where most ordinary clinical trial biomarkers will not distinguish responders vs non-responders.
In 2014, Hood and colleague Nathan Price launched a pivotal 108-person “Scientific Wellness Project”, involving whole-genome sequencing, blood work, and microbiome analysis. “Every person had a long list of actionable possibilities,” Hood said. “They weren’t nearly as well as they thought they were!” “Actionable possibilities” were delivered by a scientific wellness coach for each volunteer “pioneer.”
Among the actionable recommendations from blood results: 91% volunteers had nutrient abnormalities, 68% inflammation, 54% diabetes risk, and 59% cardiovascular. The results were published last August in Nature Biotechnology (Price et al. August 2017 Nat Biotech). Looking at the audience, Hood said: “Most of you would find yourself at the bottom of this staircase of wellness.”
The results of that study prompted Hood to launch a company called Arivale, which now has about 3500 pioneers, and hopes to grow to about 50,000 in three years. The company’s mission is to “Turn data into action.” Hood is a firm believer in Personal Data Clouds, which he likened to the Hubble Space Telescope. These would reveal statistical correlations, such as the association between cholesterol and vitamin E, and a negative association with endogenous thyroxine.
Hood also touted advances in measuring genetic risk based on genome-wide association studies (GWAS) for some 6- diseases, including Alzheimer’s, type 2 diabetes, breast cancer and obesity. “We take GWAS variants, change [the relative risks] into probabilities, then compare them against 2,000 controls,” Hood explained.
Hood said that the opportunity to join Providence Healthcare, which operates 50 hospitals across seven states with 7,500 physicians, was too good to pass up. “We’ve created translational pillars – clinical trials driven by systems biology,” he said. 1,000 Providence employees have been enrolled in Arivale.
In closing, Hood predicted that the vision he has espoused for nearly two decades was finally being realized: “the democratization of P4, healthcare, and the creation of a scientific wellness Industry.” This, in turn, would transform the diagnostic company ecosystem.
“When the cost of assays comes down, we’ll be able to democratize P4 healthcare,” he said, and “reverse the ever-escalating costs of healthcare.”