Transcript from an interview with Tasuku Honjo

Interview with Tasuku Honjo on 6 December 2018, during the Nobel Week in Stockholm, Sweden.

How did you receive the news that you had been awarded the Nobel Prize?

Tasuku Honjo: The first message I received from another foundation was by a telephone call. It was around 5 p.m. of October 1st. Actually people told me that something happened maybe before 4 o’clock se we are completely free out of these things. We were concentrating with my colleague about our paper in the manuscript editing and suddenly my secretary came with some stiff face and knocked and opened the door and: “You have to take the phone!”, so I was not so sure what was going on, something bad or good. I took the phone and the person calling was Dr Perlmann so I made it to catch the point and then I had a very nice and pleasant conversation. But often I heard there is a fake call. And so of course he also mentioned I asked him to send an e-mail to just confirm. Once I received the e-mail, it was real and so we told everybody in the lab and of course my family and other kind of the good exciting celebration – I mean the nice picture. The picture we took then was posted on the website of the Nobel Foundation so it was a very exciting and pleasant and unforgettable incidence in my life.

Why did you decide to become a scientist?

Tasuku Honjo: There are several reasons, first I had to decide whether go to medical school or the law school or several other choices. Of course I went to medical school strongly influenced by my father, I mean the family reason, and secondly I read the biography of Hideyo Noguchi who was the very interesting doctor, who went to the United States in his 20s and become professor in the Rockefeller Institute. He found the syphilis as a cause of the paralysis. He died in Ghana during his study on the yellow fever pathogen so that was very striking, and I went to medical school. And the other reason I had a friend, only a father and a son and he died of this stomach cancer, very acute and I was very sad and I thought can I do anything for this type of disease.

Can you describe the main impact of your discovery?

Tasuku Honjo: Cancer immunotherapy has been, I mean the idea, has been around many decades before Jim Allison and myself demonstrated in the above system. The reason why many people failed one after another is they didn’t realise that the immune system is already suppressed by the tumor growth. If we push the accelerator of the immune system while the immune system is under the strong brake, there is no way they can drive the immune system forward. And only the people find the major immune negative regulator means a break, that was CTLA-4 and PD-1. Jim Allison first showed say CTLA-4 blockade can cure the cancer in animal model and soon after we found a PD-1, I mean we found the PD-1 before, but we demonstrated the PD-1 blockade can also cure the cancer. Unfortunately, the PD-1 one is less toxic, PD-1 blockade I mean, and has chronic and now it is used in a wide spectrum of tumor starting from melanoma, lung cancer, renal cancer, stomach cancer, many. That is slightly advantage of the PD-1 over CTLA-4. CTLA-4 has a very strong activity and sometimes too strong, also a bit side effect is strong.

How does it feel to do work that saves lives?

Tasuku Honjo: I received many prizes of course before the Nobel Prize and this is probably the last prize I get. But I felt when I see the patient and saying they were saved by the therapy we developed, that is the most moving, and also the time I feel my life has some meaning. So that was the very very, you know, unforgettable and also very touching. And I feel awarded.

Can you tell us about some of the cancer patients you’ve met?

Tasuku Honjo: I am not a clinician but I have been involved in some clinical trials and the one lady who had a big tumour, this is a ovarian tumour, and doctor of course thought hopeless but she recovered and that was almost five years ago and treatment lasted one year and she is still tumourfree and enjoying her life. One time I saw she was playing golf so it was really amazing. A similar story; I play golf myself and I have a friend who told me: “This is my last round in my life because I have lung cancer”. But about half a year or so later he came back and had just started the treatment we developed, and he was just completely cured. It was fantastic.

Do you have a message for those who are fighting cancer today?

Tasuku Honjo: Unfortunately our treatment is still not complete, only 20-30% are responders and we have a long way to go, but now this is just the beginning and many many scientists and the industry jumped in. I hope this therapy will be widely used and reach almost everybody in the world hopefully by the end of the century just like the infectious diseases almost completely eradicated during the last century. I hope this century will be remembered as the century of the cancer treatment. That’s my hope.

Do you think that diversity is important for fruitful research?

Tasuku Honjo: Yes, I think so. Always, especially in the life science. We don’t exactly where is the best target. Nobody knows which mountain we should climb. We have to try many things, so for that purpose everybody has to think different ideas and have to discuss, so diversity is including everything; gender, nationality, different culture, maybe age. You have some brave young people, very brave, that’s good and aged people has more experience and that’s very important.

What qualities do you need to be a successful scientist?

Tasuku Honjo: To make yourself a good scientist I would say first, you have to have curiosity. If you don’t have any curiosity you better choose something else. To be good scientists we have to solve something new. Something new usually is not easy because it is difficult, that is why it remains unknown. You need enough courage to tackle this difficult problems and you need courage and that is a challenge. Challenge with courage. I call this three primary C’s. And then once you decide to tackle, you have to concentrate and continue and eventually you build up confidence. So this is another three C’s. That is what I tell my students.

How have you maintained your curiosity?

Tasuku Honjo: I never tried to keep my curiosity, it comes from inside. When I learn something new I always: Oh, this is quite interesting but why? Curiosity is just endless; it just comes from inside.

Who has most inspired you?

Tasuku Honjo: There are several levels. As general science the first incident I was enchanted or charmed by the natural science is the very tiny tiny ring around the Saturn which I watched through the telescope at the elementary school. That was the first. I got very much interested, I wanted to be an astronomer and I read many books. But then later switched to medicine because I read the biography of Hideyo Noguchi. And the second very critical moment, maybe the time to come back to Japan, so it was another big choice in my life whether I stay in United Stated, keep going and many people advised to stay, but I decide to go back to Japan. That was -74, another type of turning point. Both cases I was fortunate that my decision was correct or correct because I made something, retrospective.

Was there a specific moment that sparked your interest in science?

Tasuku Honjo: For my science I have so many important mentors or advisors. The first mentor was Osamu Hayaishi, who discovered oxygen, gas oxygen directing cooperation into the organic compounds, gave my solid background in science and also international theory. Science has to be international, it is not a local thing. And the next person who opened my eye to the molecular immunology is Donald Brown of Carnegie Institution of Washington. Without him I never go into this particular field and then I went to Philip Leder’s laboratory where I actually started this antibody diversification. So those three are very important during my scientific career.

How did you stay focused on your research for all these years?

Tasuku Honjo: I didn’t have any resistance, fortunately my parents very supportive, psychologically and financially they supported and my family, wife and children – I was kind of workaholic. I don’t spend much time with my family, I feel sorry for them, but they just allowed me to concentrate on my research, so I am very fortunate.

You’re a keen golfer – do you do your best thinking on the golf course?

Tasuku Honjo: Playing golf I completely forget about science and I concentrate. But the reason why I like golf game it’s not the competition, it is kind of the fight against yourself. For example if you hit a bad shot you get angry but you get angry against yourself and always you have to think very carefully because every time you hit, the ball run into different conditions sometimes grass thick sometimes different weather and you always have to think. But it is a different type of challenge. I can completely forget about my science. It is also very enjoyable.

What do you consider to be your greatest achievement?

Tasuku Honjo: For scientific career I think I made two major contributions. One is I found the molecular mechanism for the antibody diversity, namely antigen induced antibody diversity class switch recombination and somatic mutation and this PD-1 break discovery and its application to cancer immunotherapy. But these days, I am still working, I am very much pleased that my two lines are now coming very close. Because cancer immunotherapy depends lots on your gut microbiota. And gut microbiota regulation depends on IgA secretion and the molecule I discovered for antigen induced memory, AID, I found another important molecule. And the two molecules collaborate to maintain our gut microbiota and this is important for homeostasis and also anti-tumour immunity. So that is my scientific contribution, but for the personal life I have a family and two children, fortunately both are doing well. Our son is the medical doctor, physician, and daughter is the embryologist working in science field and what’s rest? I also served at the administration in the medical school and I also served as the scientific advisor to the Prime Minister almost ten years ago. And I don’t know whether I made something through this type of administrative work but at least I tried to improve scientific environment.

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