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In 1970, the first studies were laid that laid the foundations for immunotherapy, an innovative cancer treatment based on making the immune system attack tumor cells. But it was not until 1992 when the Japanese researcher Tasuku Honjo and his team discovered a mechanism to enhance the natural defenses of patients for this purpose.
The work of this immunologist, born in Kyoto in 1942, has been fundamental in the identification on the surface of T lymphocytes of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), which control the immune system as a switch, activating or inhibiting the cells of the immune system, so that they are unable to recognize the tumor as foreign and eliminate it. By releasing those reins, using a medication called nivolumab, the immune system itself viciously attacks the tumor cells.
One of the first successful cases is engraved in Honjo’s mind, that of a 60-year-old woman with ovarian cancer. After a year of treatment, it was clean. The strategy – effective for around 25% of patients, according to the Spanish newspaper El País – has been approved since 2014 for some types of skin, lung, kidney and liver cancer. And the indications do not stop growing. There are 2,000 clinical trials underway. Nivolumab sales exceed 4,300 million euros per year.
These findings earned Honjo the 2018 Nobel Prize in Medicine (along with American James P. Allison) “for his discovery of cancer therapy by inhibiting negative immune regulation.” “I think cancer may be a chronic disease someday … I think cancer will not threaten our lives,” said Honjo. And in the Nobel conference he put a date to that milestone: 2050.
But today Honjo, considered one of the “parents” of immunotherapeutic treatment and one of the main culprits of the “paradigm shift” in cancer treatment, is concerned about the Covid-19 pandemic. In a television show, he said Japan needs to increase PCR (Polymerase Chain Reaction) tests to detect Sars-CoV-2 coronavirus outbreaks to more than 10,000 per day, compared to the current peak of about 7,000 in the mid of April. As part of his emergency proposals, he urged residents of Tokyo, Osaka and Nagoya to impose “full self-containment of exits” for a month.
And it is that, in the opinion of the professor of the Department of Immunology and Genomic Medicine, in the Faculty of Medicine of the University of Kyoto, “this is a fight against an invisible ninja”. “The battlefield is at home and abroad, and it is necessary to know where and to what extent the enemy exists around us,” he graphs, as Japan records 12,829 cases and 345 deaths from the Covid-19.
In this interview with ThirdHonjo delivers his vision of the pandemic. Along with questioning the reaction of the Japanese authorities to the outbreak, he warns of the little information that exists today about the degree of immunity of those recovered from Covid-19 and the risks of initiatives such as the immunity passport. “This is dangerous,” he emphasizes.
What do you think about the current Sars-CoV-2 coronavirus pandemic?
This is an extraordinary emergency and a great challenge for Japan. Many lives have been lost and the world economy has suffered a tremendous blow. The key is how we can minimize the impact. It is as if we are trapped in the mud, so we must think hard about how we can escape from it. It will be a competition from countries that can quickly end the crisis, and to do that, we need to control contagion. We want to avoid an increase in patients and the resulting collapse of the healthcare system. People panic because they could die. We need a treatment to reduce the losses, therefore, we must take advantage of the research data, including those reported from China, and actively use the drugs recommended for the virus. The government should take extralegal measures to ensure that insurance covers such treatments.
You have said that the Covid-19 pandemic “is a fight against an invisible ninja.” In your opinion, how serious is the threat of this new coronavirus? Can it be as deadly as the Spanish flu of 1918?
Yes, I think this is a very serious problem. It is obvious, because we have many dead people in Europe and the United States. It is very difficult to compare it with the Spanish flu, because the medical situation was totally different at that time, almost 100 years ago. The death rate at this stage has not yet been established, because the number of people infected is still questionable. This is because not so many PCR tests are done to make those data reliable and the test itself is not 100 percent reliable, but assuming the death rate is 5%, this is a very serious disease. .
How do you assess how the Japanese authorities have dealt with the Covid-19 crisis? What mistakes have been made?
I think his movements were too slow. They should have made a quicker request to stop people from leaving their homes. Financial compensation is not my specialty and this argument is very difficult. But I totally agree: the government should help people who suffered with this stay-at-home policy. However, I cannot give a correct answer on how much or how and to whom this policy should be addressed. Definitely, they should be quick and sufficient support for those suffering from this pandemic.
What challenges does Japan specifically face?
Responding to an outbreak is a bit like war. You must take control of social systems in an emergency and respond with firm authority. Experts need to make policy recommendations before a disaster strikes, and the government needs to implement them, but Japan does not do this. There needs to be an organization like the Centers for Disease Control in the USA. to constantly monitor the situation and link research and policy. It is not ideal that we do not have a defense force for medical emergencies. The current outbreak has shown how far behind we are in our information technology strategy and how socially unprepared we are. Taiwan’s response is a good example for us. Each citizen has a unique identification number that is also linked to their medical information. Online classes also help students feel that they are receiving personalized attention from their teachers and are better than being isolated in a classroom of 40 students. We should be promoting online learning.
What is your opinion on the usefulness of quarantine and social isolation measures? What is the minimum time that must be maintained to be effective? Is there a risk of a second wave of contagion if these restrictions are lifted?
I think this is the basic strategy to fight epidemics. First, the infected persons must be identified and isolated. A large place of isolation, totally free and separated from the infirmary. But the minimum is to stay at home. On whether there is a risk of a second wave of contagion if these measures are lifted, yes, I can clearly see that it is a possibility, a significant possibility. I believe that it is important to determine the treatment of the disease and the establishment of the detection of antibodies of the individuals.
In some countries, such as South Korea, cases have been reported of patients recovered from Covid-19 who are now reinfected. How can this situation be explained?
My direct answer is that the PCR test could be a false positive. The other possibility is that the defense power of immunity is variable between individuals. So, then, there are people who were infected once and then recovered who now have very strong protective antibodies or not. They have to verify it. There are many variations between individuals.
You said on a television show that Japan needs to increase PCR tests to detect virus outbreaks to more than 10,000 per day, compared to the current peak of approximately 7,000 tests in mid-April. What is the recommended daily test rate to adequately control the spread of the new coronavirus?
Yes, I think it is very important to increase the tests to as many as possible. But now it’s also important to set your accuracy. I think the blood antibody test is more reliable and faster.
What is known about the degree of immunity acquired by people who have become ill with Covid-19? How long does this immunity last?
Nobody knows.
When is it considered that a patient recovered from Covid-19 can no longer infect other people? Which test is more reliable to certify this condition: a PCR or an antibody test?
The antibody test is definitely more reliable and robust here. It registers positive only when the person is still producing viruses in his body and once he has fully recovered there will be no virus that can be detected by the PCR method.
Some countries are considering granting immunity passports to people who recovered from Covid-19. Do you consider that its implementation today is a correct measure? Why?
I don’t think so. This is dangerous.
So far, no effective therapy has been found against Covid-19, although some researchers have insisted on the benefits of using hydroxychloroquine or plasma transfusions. What is your opinion about this?
Well, this is a very important question and I strongly urge the government to invest a lot of money to find out if there are any drugs that can be useful against Covid-19. Hydroxychloroquine is undoubtedly one of them, but there are many other medications used for influenza, Ebola, or HIV, so these medications are potentially useful against Covid-19.
Do you think the only solution to the pandemic is to find a vaccine? When could it be ready? Can the urge to develop a vaccine carry risks?
I think that generating vaccines against this type of virus that contains RNA (ribonucleic acid) genome is not easy. We already know about influenza or HIV vaccines that have so far not been very successful. And it actually takes a long time to develop a good vaccine. I would focus more on treatment, in the initial phase, with the use of drugs used for other viruses, and in the later stage, to avoid cytokine storm, I would recommend treatment with an antibody that is already known and works against to the interleukin-6 receptor (IL-6R) to stop the Covid-19 induced cytokine storm.
What will the post-coronavirus world be like?
We cannot stop people’s movements forever just because of the new coronavirus pandemic. I do not expect the outbreak to reverse the tide of globalization. China will have a big role to play. The disease originated in China, but the country will also be the first to recover from it. I cannot say whether this will increase Chinese influence or whether the world will avoid China, but there is a possibility that the global order will change with the outbreak.
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