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A Passion to Develop and Commercialize Anti-Cancer Drugs Made in Japan, by Japan

Driving the forefront of vaccine treatment

Professor Nakamura performs clinical research geared toward the practical application of new cancer medicine, including cancer vaccines. He is known around the world for his Cancer Genome/Personalized Treatment Research. In April of 2012, he was invited by the University of Chicago's School of Medicine as a professor of surgery and internal medicine. Prof. Nakamura told us, "Japan has a slow approval process for new drugs, so after considering the offer for some time, I decided to study in the United States." Currently, Prof. Nakamura comes back to Japan about 5~6 times a year for about 6 days and 4 nights to appear in lectures requested by academic societies with which he is associated.

Now, in the field of cancer therapy, after surgery, chemotherapy, and radiation therapy, immunotherapy is taking root as a 4th type of cancer therapy. Immunotherapy raises the immunity of the patient and inhibits the growth of cancer cells through treatment such as cancer-specific vaccines. This advanced treatment is gathering attention from all over the world due to its ease of scientific verification as well as its low number of side effects. Last fall, Professor Nakamura's discovery of a chemical compound, a prime candidate for molecular-targeted drugs to kill cancer cells, was published in the "Science Translational Medicine (USA). Clinical trials are set to begin next year, with inquiries already being received from all over the world.

The right treatment at the right time

Professor Nakamura has long proposed the idea of "custom-made treatment," which more safely and effectively provides medicine to patients. "Currently, this treatment is often called 'precision medicine.' It's probably not a very familiar term, but the intent is the same as custom-made treatment. Rather than the uniform treatment of the past, precision medicine attempts to establish prevention and treatment that takes into consideration the genome characteristics of each individual. As shown in the announcement of details of 'Precision Medicine Initiative' in President Obama's State of the Union address, medicine that delivers the right treatment at the right time is beginning in the United States."

Some patients do not respond to anti-cancer drugs, even if the drugs are the latest ones, so precision medicine may be the most appropriate approach to treating cancer. But, "Japan lags behind other nations in the use of precision medicine in cancer treatment," says Professor Nakamura.

I want to provide patients with hope until the very end

There is a huge gap between medical treatment in Japan and the United States. "The biggest different is how far you can provide hope to cancer patients.

For example, at the University of Chicago, clinical trials begin on some 200 kinds of cancers each year, which provide patients with a number of treatment options. But in Japan, patients can receive only standardized treatment, limiting their access to new treatment methods.

On top of that, cancer treatment is performed following a manual, and when the medicine covered by your insurance is used up, the doctor simply tells you how long you have left to live.  To me, that sort of practice is not legitimate medical treatment. As a physician, I want to provide hope to patients until the very end. Even if their life has ended, I want the families of individuals to be convinced that he or she received the world's most advanced treatment, and to understand that we did absolutely all that we could. We must create a medical system in which there are no regrets."

Getting the media to understand the risks

Media and the public's perspective and reception of medicine are quite different between Japan and the US. "Treating refractory diseases carries a significant risk. But if you don’t try any treatment, the patient faces certain death. The media criticizes these attempts to respond to the earnest hope of patients and their families by appealing to the sentiment of the public without evaluating client progress in treatment. As long as society and the media cannot understand and accept methods that have a certain amount of evidence but have not yet been established, no new treatment methods will come out of Japan.”

Prof. Nakamura also feels a striking difference in the enthusiasm and attitude between researchers in Japan and the USA. In his laboratory at the University of Chicago, there are researchers from 10 different countries, but he says, “The Japanese researchers are clearly lacking in drive. Researchers from countries outside of Japan have a strong desire to contribute to their home country in the future or stay in the United States and contribute to society. But most Japanese researchers have a guaranteed position waiting for them when they return to Japan, so I don’t feel as though there’s that fighting spirit that fuels the need to survive in the US.” Prof. Nakamura continued his candid opinions, saying, "I think it's necessary to make a proper evaluation system to motivate young researchers, one in which an individual can get a good position if he/she works hard overseas, even if the individual has few personal connections."

A long journey with a heavy burden

Currently, Prof. Nakamura’s research is focused on genetics and oncology, but he originally worked in surgery at Osaka University Hospital. As for why he wanted to become a physician: “When I was in my second year of junior high school, I broke three bones in my leg (femur, tibia, and fibula) while skiing and had to stay in the hospital for 3 months. The doctor that treated me was like a hero to me. Around the same time, I lost my grandfather and uncle to cancer, which affirmed my intent to enter medical school.”

Afterwards, he traded in his scalpel for a test tube and began on his path as a medical researcher. Said Prof. Nakamura, “I’ve liked surgery since I was young, so I never imaged myself as the researcher type.

However, when I was working as a surgeon at a municipal hospital in Sakai, I watched young cancer patients die one after another.

At that time, physicians didn't tell patients that they had cancer. Physicians avoided providing true information by creating a tacit understanding that neither the patient nor the physician would bring up the topic. But as the symptoms gradually worsened, the patient couldn’t bear the pain, grabbing my gown and shouting to take out the mass in his stomach. I was speechless. Through this experience, I found an interest in genetic intestinal cancer, a young person’s cancer, so I went to become a researcher at the Howard Hughes Medical Institute at the University of Utah, USA. I had good name recognition during the subsequent five years or so. I thought I would be able to be beneficial to cancer patients, so I put down the scalpel.”

Prof. Nakamura sees himself as a person like “Oda Nobunaga,” a powerful feudal lord in the late 16th century who attempted to unify Japan.

In fact, there have been episodes in which he has displayed his hot-blooded personality.

While working at a prefectural hospital in Osaka, over the treatment of a member of a motorcyle gang with stab wounds transported by ambulance, Prof. Nakamura got into a bit of a shouting match in the outpatient lobby with a leader of the gang who rushed to the hospital on his bike, making quite a lot of noise.

But he admits with a laugh, “I’ve calmed down a bit lately.”

He's also felt the pressure of expectation from cancer patients for his research as well, so he empathizes with a famous saying by Tokugawa Ieyasu, the founder and first shogun of the Tokugawa shogunate of Japan: “Life is like a long journey with a heavy burden.”

Fighting back at cancer

There is an event that weighs heavily on the shoulders of Prof. Nakamura as a researcher. A gallstone patient on whom Prof. Nakamura performed an operation ended up brain-dead, although he took all steps around the clock after the surgery.

“The wife of the patient said calmly, ‘You did your best for my husband.' Not accusing me, although presumably bitterly disappointed, she offered an encouraging word to me, 'I hope you will become a great doctor.'

I can never forget her words,” said Prof. Nakamura, gritting his teeth slightly as he spoke.

In addition, losing his mother to colon cancer has been a driving force in his life as a researcher.

 “My mother knew that I had produced results in my research on colon cancer, so she apologized to me when she learned she had colon cancer herself, saying, ‘I’m sorry that I embarrassed you.’ These words really hit me hard. And when I saw her face struggling against the pain and her leg swelling up with edemas, I really felt the powerlessness of my research, which changed my outlook on life. I felt even more strongly that research that is not beneficial to patients does not make sense to perform.

From then on, my urge to take revenge on this disease, which takes the lives of 1 in 3 Japanese, has been my driving force. My life’s goal will not be fulfilled until I can see patients returning to their lives after taking medicine that I created to cure their cancer.”

Regarding his attitude moving forward, Prof. Nakamura said, “I love Japan and if there is something that I can do for Japan, I want to return there to be of service. But, I also feel my role of introducing what I’ve learned at the University of Chicago to Japan is an important duty of mine. What I feel is the most important is doing my work in a place where I can be the most useful to patients.”

“Treatment is practical science”: what can be done for patients

While a student, Prof. Nakamura was inspired after hearing lectures from Prof. Yuichi YAMAMURA and Prof. Hisao MANABE, thinking that he, too, wanted to “become that kind of doctor.” From then on, he built his career as a physician surrounded by outstanding mentors. On the other hand, he also feels the difficulty of developing young students and researchers.

To current medical students, Prof. Nakamura said, “I want them to not perform aimless research, but to become doctors that can really grasp what is ailing the patient and what treatment they need in the everyday medical setting.

Treatment is ‘practical science.’ The most critical challenge you’ll face as a physician is having a point of view like OGATA Koan* in which you ask yourself what you can do for the patient and how you can save him or her. I want students to pursue academia for better treatment while asking themselves whether or not their treatment is the best that they could do and if there is anything more they can do."

He continued, “I want you to think of your results as the prize for your research and to not become a researcher who is in it just for the fame.” Prof. Nakamura had one final message for the younger generation that, while harsh, is also encouraging: “I feel like the vision of the young generation is very narrow. I want this generation to have pride in Japan and think about what Japan, as well as they themselves, can do in the world."

*Note: OGATA Koan was a physician and scholar of Western learning in late Edo period Japan, noted for establishing Tekijuku, a place of learning,  which later developed into Osaka University.

• Yusuke NAKAMURA

A 1977 graduate of the Osaka University Faculty of Medicine, Yusuke NAKAMURA worked in the surgical department at Osaka University Hospital and related facilities, and from 1984 to 1989, he served as a research associate at the Howard Hughes Medical Institute, University of Utah, and as a research assistant professor in the Department of Human Genetics, School of Medicine, University of Utah. From 1989 to 1995, Prof. Nakamura served as the Head of the Department of Biochemistry at the Cancer Institute of JFCR. In 1994, he became a professor at the Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, and served as Director at the Human Genome Center at the same institute from 1995-2011. He also simultaneously served as Director of the Center for Genomic Medicine, RIKEN, from 2005-2010. In 2011, he became Secretary General in the Office of Medical Innovation in Cabinet Secretariat, Government of Japan and began at his current position in April 2012.

President Nishio -- After the talk

Prof. Nakamura and I just happened to serve on the same government committee in the past, with his seat right next to mine, as the seats were arranged in Japanese phonetic order. It had been a while since we last met, but by curious coincidence, I was given the opportunity to award the title of Global Alumni Fellow to Prof. Nakamura. His open-mindedness with unconventional foresight was just as present as it ever was. I couldn’t help but once again admire his sincere passion for medicine and treatment, especially his strong will to give hope to suffering patients.

His suggestions, such as making the all-Osaka medical system by using research institutes and hospitals concentrated in the Osaka area, including Osaka University, and promoting cooperation between OU’s world class medicine and medical information and its data engineering and analysis technology, which is my field of expertise, showed his wide point of view. I want to take another serious look at what I can do as President.

I want Prof. Nakamura to both continue his worldwide success and also offer words of support to his alma mater, Osaka University. I’m very grateful that I was able to have this fruitful discussion and I pray for Prof. Nakamura’s continued success.

Osaka University Global Alumni Fellow

As part of global network building in education and research, Osaka University created the title of “Osaka University Global Alumni Fellow” for Osaka University alumni and former faculty and staff members who have found success at overseas universities and research institutes.

Seventeen individuals have been awarded this title as of December 2015.

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