Leroy (Lee) Hood

At the beginning of the interview, Lee Hood gave us a presentation about his current work.

Here is what we learned:


Research, the Human Genome Project, and Visions

Dr. Hood began his career at Caltech as an assistant professor. At that time, he decided to focus on two things: 1) molecular immunology and 2) using technology to make new instruments to synthesize molecules. Humans are very complex. At the time, they didn’t have tools to effectively take lots of measurements on humans. The way to deal with biological complexity is by analyzing the entire system (all parts, pieces and interactions) with enormous detail. Dr. Hood wanted to study humans, but didn’t have the tools to measure DNA, proteins, or other important macromolecules. In 1970, he set up a lab initially for automated protein and DNA synthesis. Instruments were the foundation of modern biology and gave them the ability to generate enormous amounts of information, such as how the genome is 3 billion letters and can be divided into 23 pairs of chromosomes. 

In 1985, Dr. Hood was invited to the first meeting about the Human Genome Project. The project allowed them to see the variability of human genomes – it was very difficult, but possible.  They were split as to whether it was a good or bad idea. Those who opposed, opposed because they were worried it was big science and would take the money away from traditional science. However, the opposite happened, big and small science became synergistic. 

Dr. Hood believed the ideal approach was to create a new cross-disciplinary science, with subjects such as biology, chemistry, math, and computer science. He proposed this to Caltech in the 1980s, but it was difficult to invent new science in a university, so he resigned and started the Institute for Systems Biology (ISB) in 2000. The Institute applies a global and holistic perspective towards the complexity of biology and using this framework Dr. Hood and his team began thinking about medicine from a systems point of view. In the following years, Dr. Hood developed technologies that allowed them to create a population of health studies. They took many measurements and are using this data to analyze genomes and phenomes so they can begin to optimize wellness. Arivale was a company whose clients had their whole genome sequenced in an effort to promote wellness. It allowed Dr. Hood and his team to analyze a whole list of what they called “actionable possibilities” to improve wellness. Per Dr. Hood, by 2019 this model failed for two interesting reasons: it was way too expensive and there weren’t enough physicians. In addition, it couldn’t deliver actionable possibilities to the patient. When Dr. Hood became the CSO of a large hospital, he was able to scale up from 5,000 patients to a million because he received funding from the government. He believes this new kind of wellness is going to pay for itself.


Beyond the Human Genome

Beyond the Human Phenome Initiative (HPI) builds on the first Human Genome Project (HGP), which generated one human genome sequence over 13 years. HPI proposes to generate whole-genome sequences and longitudinal phenomes for one million people over 10 years. It gives the opportunity to convert individual data into actionable possibilities for individuals to improve the health of both their body and brain. Dr. Hood and his team want to learn how to bring wellness to all types of individuals. HPI measures genetics, the social determinants of health, patient reported outcomes, electronic health records, self-tracking, blood, the brain, and the microbiome. In the short term, they will use data-rich approaches to study a few major diseases that use most of the healthcare dollars. Four out of the five conditions responsible for 60-70% of healthcare dollars are cardiovascular diseases, cancer, diabetes, and degenerative nerve diseases.  In the long term, it will be a million-dollar project paid for by the government. The project will prove the power of a data driven assessment for the optimization of the health trajectory of individuals and invent the science of wellness and prevention through a million-person project. Phemone Health, a nonprofit, has a powerful team and partners that will help Dr. Hood execute this challenging project. In addition, Arivale already has 5000+ individuals who have had genome and longitudinal phenome analyses over the course of 4 years.

To Implement HPI, there are 7 major partnerships:

  • Guardian Research Network will help acquire and consent patients along their electronic health records.
  • Posit Science, which has 40 digital measurements for 25 cognitive assessments of healthy and diseased brains, will carry out brain health assays and generate standardized data. They have the ability to restore cognitive function to even 80 year olds and more than 10000 diseased patients beyond 25 clinical trials.
  • Technicity will help build the necessary computational platforms for data management/analysis.
  • ISB will help with technology and computation (digital twins and systems thinking)
  • BioAnalytica will generate the genome and phenome data.
  • Deloitte will provide industrial partnering, administrative functions, and project management.
  • Google will connect everyone to teams within Fitbit, Search, Platforms, Cloud and hyperscale AI via DeepMind.

They are exploring federal partnerships and are backed by an outstanding advisory board of 12 leaders in science, tech, and health. Efforts have been made to present to the House Committee on Energy and Commerce. Dr. Hood and his team are determined to persuade an academic healthcare system to join them to revolutionize family practice. This will generate actionable possibilities by the analysis and integration of this data, which then can be delivered to physicians. Dr. Hood and his team strive to promote the transformation from a disease-based healthcare model to one focused on wellness and prevention.


Aging in Humans

Healthy aging is a major component of the science of prevention. Aging is the most important predictive factor for all chronic diseases. There is a blood analyte metric for biological age that also provides therapeutic options for healthy aging. Fundamental high level aging control mechanisms are highly conserved across evolution from single celled yeast to humans. Hence experiments in model organisms will generally apply to humans. One can enhance their health span due to aging by attacking all chronic diseases simultaneously, rather than one at a time. A slowdown in aging that increases life expectancy by 1 year is worth 38 trillion dollars and an increase by 10 years is worth 367 trillion dollars.

Improving education for 21st century medicine

The goal is to integrate new thinking into K-16 science curricula. As part of this, they’re creating a year-long course on Systems and P4 medicine for high school students. They are working on a textbook on systems biology and systems medicine, along with a popular book on 21st century medicine. Dr. Hood has been working on a 90-minute documentary film about wellness over the last 23 years titled, The Phenome Age: A Quest for Wellness. He has also partnered with Scientific American to make a special issue on wellness.

Then, we had time to ask a few questions:

When you were younger, what did you envision your path would be, and how does that compare to your path in retrospect? What would you do differently?

I first got into biology when my high school chemistry teacher asked me if I wanted to help teach biology to sophomores. One of the lesson plans I developed was about the structure of DNA. It was simple, it was elegant, to think it was the basis of life was staggering, and I thought gee, that’s where I’d like to be. I’d say, my career has very closely followed DNA. The ability to sequence and analyze it, and to change healthcare by understanding some of the things it does. But I will say when I decided I wanted to go into biology, my chemistry teacher persuaded me that Caltech was the best way to go and gave me the tools to become a terrific scientist. At the time, I wasn’t thinking that far ahead. I kind of thought I’d like to be a researcher and wanted to learn enough biology to do that. After Caltech, I decided to go to medical school. I wanted to learn human biology, partially because I had a younger brother that had Down syndrome. I was just struck by the fact that doctors couldn’t tell me why that happened. That was one of those big why questions. Later it was discovered it was trisomy in chromosome 21. I don’t think I articulated that I wanted to be a researcher until maybe graduate school. But choosing biology was really fortunate for me. I’ve had a career as exciting as I ever could’ve hoped for.


When you first founded ISB, what were your hopes and dreams for the institution? How does that compare to what is being done at ISB now?

We founded ISB to create an institution that would practice systems thinking and apply it both to biology and medicine. We founded it with the idea that, intrinsic to looking at a systems approach to medicine was the need to develop technology and computational tools that could help generate and analyze a lot of information. In that context, ISB has been everything and more. I am a little disappointed it didn’t grow bigger than we are now, but we’re intimate. All the faculty like each other. At Caltech we had roughly 32 faculty members who never talked to each other. At Caltech you had so many resources. You were king or queen in your castle. You did your own thing. Here it’s enormously interactive. We have lots of different expertise and we need each of them to solve the hard problem we are tackling. 

So, I think that another big part of ISB that I felt really strongly about is creating a group that focuses on K-12 education. I think our educational group is unique, outstanding and is really transforming education in this part of the world. You all are a reflection of the commitment to diversify experiences for various levels of K-12.


What are some of the biggest challenges you have encountered throughout your career?

I’ve always tried to be on the leading edge and argue for things that weren’t quite here yet. Some of the biggest challenges I’ve encountered are called paradigm changes. That was true in instrumentation. When I was developing those four instruments at Caltech, a lot of the senior faculty were opposed to having an engineer in biology. They were annoyed by engineers in biology. You know, biology has a lot of needs and most of the engineers aren’t well adept in what those needs are in detail. Engineers focus on precisely the right kinds of technology or computational tools. I always argued that domain expertise like that is really critical. That was true when I tried to set up ISB and there was skepticism about data-driven wellness. That’s why we have the million person project, which hopefully we can save 1-2$ trillion dollars in the next 15 years in healthcare. I think the biggest disappointment is that you really have to have determined optimism to deal with criticism and lack of funding. However, in the end it is really gratifying.