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Our genome is not our destiny



14 March 2016 – EMBO Associate Member Leroy Hood is president of the Institute for Systems Biology (ISB) in Seattle, United States, and senior editor of EMBO’s open access journal Molecular Systems Biology. At the first joint EMBL | Stanford Personalised Health Conference he presented his vision for P4 Medicine – predictive, preventive, personalized, and participatory. In a keynote speech, he described the 100K Wellness Project he launched last year as president of the Institute for Systems Biology. The study aims to track the biometrics of 100,000 participants over 20 years. The pilot study involving 108 participants was concluded in 2014. In an interview with Thomas Lemberger, chief editor of Molecular Systems Biology, Hood talks about how he defines wellness and his objective to provide actionable information to the participants of the study. 



Why do you focus on wellness?

In classic healthcare, physicians wait until the patient exhibits visible symptoms of a disease. This however generally happens only long after the initial transition from a healthy state to disease. And after this long period following the intitial transition the disease often becomes irreversibly altered. I think that wellness is the fundamental key to health in the future. The reason for this is really twofold.  Firstly, one needs to optimize the wellness of the individual to maximize their human potential – feeling well both mentally and physically. Secondly, we need to be able to follow the wellness to disease progression to identify the very earliest point of change. Analyzing this critical earliest disease phase will allow one to develop diagnostic and therapeutic approaches that can revert back to wellness immediately. In a sense, this is “preventive” medicine:  We want to take all the common diseases, figure out what the earliest transitions are and develop approaches to revert them back to wellness immediately.


What is the Hundred Person Wellness Project?

Two years ago we invited 108 volunteers to be intensely monitored for a ten-month-study. The aim of the study was to identify actionable possibilities that could improve their wellness or assist them avoiding disease. The study collected data at daily and three-month intervals. Each participant had their whole genome sequenced at the beginning and every three months provided samples of blood, saliva, urine, and stool for clinical parameters analyses, metabolite, proteomics measurements and microbiome profiling. We also used wearable devices to gather quantitative longitudinal data on physical activity, pulse and quality of sleep.


What did this pilot study reveal?

It turned out that every single one of the 108 individuals had multiple actionable possibilities during the course of the study. For example, we found that 53 of them were pre-diabetic and five per cent of them actually had chronic diseases without being aware of it.
One participant was a poster-child example of having an unknown chronic disease. He displayed a gradually increasing degree of arthritis that prevented him from hiking with his wife.  His genome sequence revealed that he was homozygous for the genetic defect of hemochromatosis.  Only about 30 per cent of these homozygous individuals go on to get the actual disease. Two observations suggested this individual had active hemochromatosis. First, blood tests revealed that his iron levels were very high. Second, arthritis can be one early finding of this disease.  Moreover, hemochromatosis can progress to a serious chronic disease as it can attack the pancreas (diabetes), the liver (fibrosis) and the heart (decompensation).  Thus, his health coach advised him to go to a doctor. Hemachromatosis is actionable and can be managed by bringing down the blood iron levels by removing a unit of blood every month until normal iron levels are achieved. After these treatments, his arthritis disappeared and his hemochromatosis was under control. He is one of a number of examples we achieved in reversing disease transitions.


What was the participants’ feedback?

Most individuals felt that this was a really transforming experience because they understood that their genome is not their destiny. Indeed, many learned that changes in lifestyle could control the consequences of many genetic defects.  They realize with enough information that they could take control of their own health. I feel that this is an important step in bringing down the costs of healthcare. They also began to realize that the journey of scientific wellness is probably going to be life-long journey and not just for a month or a year. Indeed, as more and more data are accumulated, new kinds of actionable possibilities are being uncovered, opening up new opportunities for each individual to further optimize their own wellness. Most people were so enthusiastic that the vast majority of them have gone on to the next stage of this programme.


The next stage is the creation of a consumer-facing scientific wellness company that utilizes the scientific wellness strategy described above.  We easily raised about 40 million US dollars to fund this company.  In just six months we have recruited more 1000 people and now we have a long waiting list. It is very likely that within 18 months we will have 10,000 individuals with dense and dynamic personalized data clouds – meaning that we will have more than hundred times as much data as we have today available for analysis.


Are there clear boundaries between wellness and disease?

No, the boundaries are not clear. If you look at definitions of wellness they are all psychiatric or psychologically-oriented definitions. What we found is that by identifying actionable possibilities from each individual’s dense and dynamic data cloud, you can deal with wellness in a more objective manner – specific for each individual. Moreover, in analysing individuals that transition from wellness to greater wellness, we can begin to identify blood biomarkers for wellness that will provide a quantitative assessment of wellness – eventually both physical and mental.


How did the participants’ physicians react to the study?

A third of the physicians were absolutely enthusiastic and wanted to learn all about it. A third were indifferent – they were too busy to think about it.  And a third of them had concerns about the project. I think for the latter group it was mostly a defensive reaction to something they did not understand. A key task we have ahead of us is to educate physicians as to the benefits of scientific wellness.


How does your approach fit with the role of the FDA?

The FDA has a responsibility to prevent direct-to-consumer companies, such as Arivale, from practicing medicine. Hence Arivale has been very careful to avoid any hint of practicing medicine. We have MD’s analyse the individual data and talk with the coaches about what are appropriate actionable possibilities. We obviously learn a great deal about individuals that we cannot communicate to them because this would be view as practicing medicine (e.g. pharmacogenomics variants that provide insights about how individuals react to common drugs).


What will it take to bring the scientific wellness approach to clinics?

We need to convince the payers (insurance companies) that the scientific wellness approach is really going to save healthcare dollars. I am confident that if we can develop ten thousand dense and dynamic data clouds we will have enough examples to begin to set up compelling economic and social arguments for this approach. In fact, we are beginning to approach healthcare systems to convince them to become payers directly in order to benefit from savings that come from scientific wellness.


Which technological developments are you particularly interested in for longitudinal personal phenotyping?

In wellness, one of the things you want to do is to measure complex traits that integrate many different types of physiological information. A great example is heart rate variability: it beautifully integrates parasympaphetic and sympathetic nervous system activity. A restricted heart rate variability is unhealthy and often reflects some type of disease.


Facial features represent complex phenotypes and potentially are a rich source of systems-integrated information. What computer facial recognition software can achieve these days is incredible. Leveraging this technology to explore how dynamical facial measurements relate to disease transition is going to be fascinating.


We are also working on a protein chip to get 2500 organ-specific proteins: fifty proteins from each of 50 different organs. From a drop of blood once a month these assays will allow you to follow wellness to disease transitions for all of your major organ systems. Once you set such assay systems up they are infinitely stable.


There are two areas we consider really important in the future. One is the immune response, which is involved in every disease and many aspects of wellness. The other thing I want to do deep phenotyping on is the brain. I would like to be able to map specific changes in different regions of brain. Those are the areas of opportunity that I really see coming: Obtaining and measuring more complex phenotypes and going deeply into systems that are really critical for humans. The immune system is one of them and the brain another one.


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Tilmann KießlingTilmann Kießling
Head, Communications
T. + 49 160 9019 3839