Building a Basis for Precision Medicine in Japan

Every living creature on earth carries in their DNA the instructions to make each one unique. Yet despite the diversity we see, all human beings are remarkably similar at the genetic level— up to 99.9 percent according to the Human Genome Project1. However, the remaining 0.1 percent makes a world of difference, and is responsible for variation that can include one’s predisposition to certain diseases or how they respond to treatment.

Traditionally, medical treatment has been based on a “one-size-fits-all approach,” which prescribes standardised treatments to all patients based on clinical history and symptoms. However, studies have established that patients will experience varied benefits or side effects to treatment, depending on their genetic makeup2.

A precision medicine approach considers these individual genetic variations along with environmental and lifestyle factors to ensure more accurate medical treatments, and so requires large amounts of data. In the earthquake-stricken Tohoku region of Japan, the Tohoku Medical Megabank (TMM) Project was established to help restore and improve healthcare and at the same time, collect a large biobank of biological specimens from the region’s residents.

As one of TMM’s founders, Professor Masayuki Yamamoto has dedicated the past decade of his research career to establishing precision medicine in Japan. Here, he shares his motivations for spearheading the Tohoku Medical Megabank Organization (ToMMo) and for championing the use of precision medicine to improve healthcare where it is needed most.

1. Can you tell us a bit about yourself and your work in precision medicine?

I graduated from Tohoku University School of Medicine in 1979 with an M.D. and Graduate School of Medicine in 1983 with a Ph.D. I worked as a postdoctoral fellow at Northwestern University in the United States of America under Professor Doug Engel for more than four years. When I revisited the Engel laboratory in 1989, we collaborated on a project in which we identified the GATA family of transcription factors, some of the most important transcription factors regulating gene expression.

In 1991, I returned to Japan and continued studying the GATA1 and GATA2 genes. Since then, I have worked on various projects addressing critical questions related to gene expression regulations. My current research interests include transcription factors, oxidative stress response, hematopoietic differentiation and genetically modified mice.

Currently, our focus is on translating some of our research findings in animal models from over the years to human health with precision medicine in mind. On that note, we have been working to establish a biobank that recruits large population cohorts and establish precision medicine in Japan.

2. You established the TMM as part of the Tohoku Medical Megabank Organization. Why is the biobank important to you?

The Great East Japan Earthquake of March 2011 caused unprecedented damage, with nearly 18,000 casualties. At the time, I was the Dean of the School of Medicine at Tohoku University. We decided to work on an immediate rescue project to help rebuild the community and spent months reconstructing the tsunami-devastated area with the help of the government.

We conceptualised the Tohoku Medical Megabank (TMM) biobank as a cutting-edge project to deliver the most advanced medicine to earthquake and tsunami survivors, and launched it in February 2012. Through the TMM biobank, we aim to establish an advanced medical system to foster the reconstruction of the tsunami-devastated area. We envisage personalised medicine and healthcare to be the most advanced medicine we could provide.

3. What are some of the benefits of the TMM biobank?

The biobank has become a mutually beneficial project. Through this project, we helped reconstruct the community’s health and welfare by rebuilding the Tohoku area’s medical system while the residents living and working in that area participated in the TMM cohort studies.

Since then, the organisation has assembled a large biobank that combines medical and genome information. The information from the biobank has created an advanced medical system that supports the establishment of precision medicine in Japan. Based on its magnitude, the TMM now attracts medical practitioners and experts from all over the country, promoting industry-academic partnerships and creating employment in related fields.

4. What excites you about precision medicine and its potential in clinical applications?

Some of our work has shown that genetic and environmental factors, such as air pollutants, activate the genetic mechanism resulting in atopic dermatitis in mice. Using the TMM Birth and Three-Generation Cohort Study, research is now underway to investigate the connection between environmental factors such as traffic smoke and atopic dermatitis.

The work to see how the findings from mouse studies will translate into a better understanding and treatment of human diseases is truly exciting, because analyses of genetic and environmental factors are critical for clarifying disease progression and treatment options.

References:

1. Collins, F., Mansoura, M. The Human Genome Project. Cancer 91, 221-225 (2001).

2. Crews, K. R., Hicks, J. K., Relling, M. V., Evans, W. E. Pharmacogenomics and Individualized Medicine: Translating Science Into Practice. Clinical Pharmacology & Therapeutics 92, 467-475 (2012).