March 15, 2018 (Vol. 38, No. 6)

Visionary Researcher Leroy Hood Advocates “Scientific Wellness”

Few scientists earn a repeat invitation to keynote the Molecular Medicine Tri-Con (TRICON) event, especially not after a gap of 23 years. But Leroy Hood, M.D., Ph.D., is an exception. Kicking off the 25th anniversary edition of TRICON in San Francisco, Dr. Hood reflected on his mission to promote “P4 medicine,” a synthesis of personalized, predictive, preventive, and participatory medical approaches. He also reviewed how P4 medicine and systems biology approaches are impacting 21st century healthcare.

Dr. Hood’s reputation hardly needs 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,” Dr. Hood said. “Invent [whatever technologies] you want, but unless you can apply them … they’ll sit idle.”

Briefly reviewing the progress biology has made in handling complexity, Dr. Hood emphasized seven paradigm-changing developments:

1. Bringing engineering to biology. In the 1970s, the use of sequencers and synthesizers led to high-throughput data acquisition—the forerunner of big data.

2. Implementing automated sequencing. In 1990, the Human Genome Project was launched. It was embraced by those eager to take advantage of automated DNA sequencing, but 80% of biologists were opposed to the project on the grounds that it was “big science,” Dr. Hood said. Ironically, the strongest opposition was the NIH, but the institution “came around at the end.”

3. Instituting cross-disciplinary biology (part I). In 1992, Dr. Hood tried to persuade the California Institute of Technology to invest in this approach, but the biologists there vetoed the idea. Then, Bill Gates recruited Dr. Hood to the University of Washington. This setting proved to be less than ideal, so Dr. Hood began considering other possibilities for a systems biology infrastructure.

4. Instituting cross-disciplinary biology (part II). In 2000, Dr. Hood launched the ISB, the first institute for the study of systems biology.

5. Crystallizing ideas. Between 2004 and 2014, Dr. Hood consolidated his ideas about P4 healthcare and scientific wellness.

6. Forging a new direction in wellness. In 2014, the ISB launched a pilot study called the Hundred Person Wellness Project (HPWP).

7. Partnering with Providence St. Joseph Health System. In 2016, Dr. Hood was approached by the Providence CEO, who invited 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, medicine will, Dr. Hood believes, embrace systems approaches to understanding wellness. With these approaches, medicine becomes individualized (Predict It, Prevent It, Personalize It).

Dr. Hood suggested that systems approaches will rest on data clouds that are personal, dense, and dynamic (longitudinal). “These are exactly what we need to study,” he insisted. “They’re the essence of what precision medicine should be.”

Leroy Hood [Courtesy Institute for Systems Biology]

Network Biology

During his presentation, Dr. Hood cited many applications of network or systems biology, including an example relevant to lung cancer. He highlighted the sorry statistic that half of surgeries on patients with lung nodules turn out to be benign. One way to do better, he suggested, would be to use a mass spectrometry assay developed by Integrated Diagnostics, a company Dr. Hood co-founded.

This assay, which can simultaneously measure multiple circulating proteins associated with lung cancer, is designed to distinguish benign lung nodules from their neoplastic counterparts. It has the potential to save the U.S. healthcare system some $3.5 billion in unnecessary surgeries.

Another assay that Dr. Hood mentioned measures the levels of proteins associated with preterm births. According to a preliminary study, protein levels at 19 weeks’ gestation can be used to predict which pregnancies will end in preterm birth.

Examples such as these led Dr. Hood to propose that P4 medicine represents the convergence of “five thrusts—systems biology, scientific wellness, digital health, big data/analytics, and social networks.”

P4 medicine, he stated, could succeed today’s “imprecision medicine,” which depends on clinical trial biomarkers that usually fail to distinguish responders from nonresponders.  

Scientific Wellness

In 2014, Dr. Hood and colleague Nathan Price, Ph.D., launched a pivotal 108-person “scientific wellness project” that involved blood work, whole-genome sequencing, and microbiome analysis. “Every person had a long list of ‘actionable possibilities,’” Dr. Hood recalled. “They weren’t nearly as well as they thought they were!”

In this project, the actionable possibilities were delivered to each volunteer “pioneer” by a scientific wellness coach. Overall, 91% of volunteers had nutrient abnormalities; 68%, inflammation; 54%, an elevated risk of developing diabetes; and 59%, an elevated risk of developing cardiovascular problems. Detailed results appeared last August in Nature Biotechnology. Looking at the audience, Dr. Hood said, “Most of you would find yourself at the bottom of this staircase of wellness.”

The results of that study prompted Dr. Hood to launch Arivale, a company that now has about 3,500 pioneers and hopes to grow to about 50,000 in three years. The company’s mission, Dr. Hood noted, is to “turn data into action.” Dr. 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.

Dr. Hood also touted advances in measuring genetic risk based on genome-wide association studies (GWASs) for some six 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,” Dr. Hood explained.

Dr. 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, adding that 1,000 Providence employees have been enrolled in Arivale.

In closing, Dr. Hood asserted that the vision he has espoused for nearly two decades is finally being realized. The democratization of P4, healthcare, and the creation of a scientific wellness industry, he predicted, will transform the diagnostic company ecosystem.

“When the cost of assays comes down, we’ll be able to democratize P4 healthcare,” he declared. “We’ll reverse the ever-escalating costs of healthcare.”

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