AMED Research Program on Emerging and Re-emerging Infectious Disesses.
Study of antitoxins/antivenoms and their replacement by humanized monoclonal antibodies.[Ato Group]

Conversation

Attitudes Toward Serum Therapy Research and Ideal Human Resource Development: Be passionate and be sincere

CROSS TALK

Attitudes Toward Serum Therapy Research and Ideal Human Resource Development: Be passionate and be sincere

Akihiko Yamamoto×Toru Hifumi×Hidero Kitasato

The Shibasaburo Kitazato Museum in Aso-gun, Kumamoto. The museum exhibits a number of documents that celebrate the achievements of Dr. Shibasaburo Kitazato, who pioneered serum therapy and is known as the “father of modern Japanese medicine.” This time, I visited it together with Dr. Akihiko Yamamoto of the National Institute of Infectious Diseases.

Dr. Hidero Kitasato, the museum director and Dr. Shibasaburo Kitazato’s great-grandson, gave us a guided tour. Dr. Hidero Kitasato is also serving as a Professor Emeritus at Kitasato University, specializing in microbiology. We spoke to him about Dr. Shibasaburo Kitazato’s work at the institute and his attitude toward research.

Lastly, we had a conversation with Dr. Kitazato about the human resources development efforts that should be passed on going forward.

Dr. Donner at the Institute

01 Dr. Donner at the Institute

Hifumi:As you can see in the exhibit, Dr. Kitazato was the director of the first private infectious disease research institute in Japan. What kind of person was he at the institute?

Kitasato:He was more enthusiastic about his research than anyone else. At that time, the institute was a gathering of talented people from all over the country, but even so, regarding research, he would scold them without mercy. Therefore, because of his personality, he was affectionately nicknamed “Donner,” which means “thunder” in German.

Yamamoto:Wow, Donner. He must have been scary.

Kitasato:He was. But it wasn’t that they were just afraid of him. When something went wrong at the research institute, he would insist that it was all his fault. Instead of blaming his subordinates, he would find the strengths of each of them and promote them to appropriate roles and positions.

Hifumi:That’s wonderful.

Strong Sense of Responsibility as Director

02 Strong Sense of Responsibility as Director

Kitasato:There are two points in Shibasaburo’s human resource development. One is about Shigella.

Hifumi:Kiyoshi Shiga, who was in Dr. Kitazato’s laboratory, discovered Shigella.

Yamamoto:It is well known that the official name Shigella comes from Kiyoshi Shiga.

Kitasato:Shibasaburo had been studying Shigella before he went to Germany to study. However, he appointed Kiyoshi Shiga, who had just entered the Infectious Disease Research Institute at that time, to search for the pathogens of dysentery, and directly instructed him in the research. Kiyoshi Shiga made a bed in the laboratory, worked hard as though he were under siege, and succeeded in discovering Shigella in about a month. It is said that at the time, Shibasaburo told Kiyoshi Shiga that his name (Shibasaburo) did not need to be mentioned.

Hifumi:I didn’t know that. I see.

Yamamoto:It seems that there was an attitude of, “I don’t care about my name, but let’s preserve the names of my disciples.”

Kitasato:It shows a strong sense of responsibility as the head of the center. I think there was a sense of taking all the bad things upon himself.

True Learning, Not Research for the Sake of Research

03 True Learning, Not Research for the Sake of Research

Kitasato:The second point is the story of the plague.

Hifumi:Dr. Kitazato found the Bacillus pestis in Hong Kong, didn’t he?

Yamamoto:I’ve heard that they found it as quickly as two days after arriving.

Kitasato:Because Shibasaburo had been training at Koch’s lab, he noticed that the symptoms were similar to anthrax, and examined blood before anything else. He immediately identified it, but there was either a problem with the Gram-stain solution he had, or he mistook the gram-negative and gram-positive. After that, a paper was published saying that, “the Kitazato bacillus is not the true Bacillus pestis,” and Shibasaburo admitted his mistake. It is said that in the end, he did not claim to have discovered the Bacillus pestis.

Hifumi:He didn’t?

Yamamoto:Honestly, it’s a very difficult thing to say, right?

03 True Learning, Not Research for the Sake of Research

Kitasato:I agree. He gracefully admitted that he was wrong about the Gram stain. Now, the kit is complete, but at that time, they made three kinds, so depending on how they made it, it kind of looked like all of them. As you know, the condition of the bacteria also affected the results.

Yamamoto:It’s a simple kit, but even now, a little bit of staining can make it a surprisingly dubious color. It says that normal bacteria are gram-positive, but they can also be stained red.

Kitasato:However, as the book I just gave you describes, two researchers in California have since claimed that Shibasaburo definitely discovered the Bacillus pestis.

Yamamoto:But it is terrible they left out his name when pointing that out.

Kitasato:Still, I think that Shibasaburo was more proud of the fact that he had identified the infection route and created the Open Port Quarantine Act to prevent a pandemic from spreading to Japan.

Yamamoto:He didn’t receive any honor for his scientific discoveries.

Kitasato:He put emphasis on how to prevent the plague from spreading, not on research for the sake of research, and he actually did his best to save people. Shibasaburo was pragmatic.

The Thoughts of Dr. Shibasaburo Kitazato That We Would Like to Pass On

04 The Thoughts of Dr. Shibasaburo Kitazato That We Would Like to Pass On

Kitasato:Let me tell you a story. The institute was originally under the jurisdiction of the Home Ministry, but in 1914, it was suddenly transferred to the jurisdiction of the Ministry of Education, Science, Sports and Culture. However, this important decision was not known to Shibasaburo, the head of the institute. Shibasaburo got very angry and left the office after throwing in his resignation letter. But then, two-thirds of the employees resigned one after another and followed him.

Hifumi:Two-thirds… That’s amazing. They came together in admiration of Dr. Kitazato.

Yamamoto:You can see from these things that he was respected by his subordinates.

Kitasato:No one will follow you if you only get angry with them. However, Shibasaburo himself was surprised, seemingly thinking that everyone was just afraid of him. He then made a vow to build a new institute for the employees who followed him. This is how the Kitasato Institute was completed.

Hifumi:The Kitasato Institute is one of the world’s three largest research institutes, isn’t it? A world-class research institute comparable to the Robert Koch Institute in Germany and the Institute Pasteur in France.

Yamamoto:This passion for medicine has been passed down to this day.

Kitasato:Shibasaburo probably couldn’t forgive that the institute was to become a research center attached to the University of Tokyo without being consulted. I think there were various conflicts in his mind.

Yamamoto:It was a research institute of infectious diseases built with Yukichi Fukuzawa’s help, but a transfer to the University of Tokyo would change its purpose.

Kitasato:I think that research for the sake of research was unbearable for Shibasaburo. Shibasaburo had always believed that preventing disease before it occurs is the duty of a doctor.

Hifumi:These ideas may have driven his passion for research. Today, in seeing many of Dr. Kitazato’s exhibits I felt that I received a lot of energy and drive from his passion and will put into my own research.

Yamamoto:This spirit must be passed on to modern research.

Hifumi:Thank you for your time today. This has been a worthwhile conversation. It made me think about human resource development while looking back on half of Dr. Shibasaburo Kitazato’s life.

Yamamoto:I enjoyed myself very much, too. Thank you very much.

Kitasato:Thank you very much.

PROFILE

PROFILE

Shibasato Kitazato Museum, Director/Kitasato University, Professor Emeritus

Hidero Kitasato

The great-grandson of Shibasaburo Kitasato, the bacteriologist immortalized in the history of medicine by establishing serum therapy. Having experience as an overseas researcher himself, after becoming professor and head of the School of Allied Health Sciences at Kitasato University, he retired to the Kitazato Memorial Museum in July 2022, where he remains to date.

St. Luke’s International Hospital, Department of Emergency and Critical Care Medicine, Chief of staff of CCM, HCU

Toru Hifumi

The only person nationwide involved practice and research of serum therapy, bringing Dr. Shibasaburo Kitasato’s serum therapy into the present. While active as an on-site emergency physician of critical care, day and night, he dedicates himself to the research of venomous creatures. For 24 hours a day, 365 days a week, he is in charge of severe cases throughout Japan as a part of clinical research that uses Yamakagashi antivenom. His areas of expertise are serum therapy, neurological intensive care, trauma, sepsis, and airway management.

National Institute of Infectious Diseases

Akihiko Yamamoto

In the National Institute of Infectious Diseases, the Second Bacterial Section is responsible for the research and quality control of tetanus bacteria and antitoxins. They are involved not only in the study of venomous snakebites from snakes like Mamushi, Habu, and Yamakagashi but also in epidemiological investigations of government-owned antitoxins such as diphtheria antitoxin, gas gangrene antitoxin, and botulinum antitoxin. They are leading experts in the field of basic research on antitoxins.