Special Interview
Interview with Dr. Yasuharu Tokuda, Director of Muribushi Okinawa Center for Teaching Hospitals,
Okinawa, JapanThe Outlook for the Pandemic
By Japan SPOTLIGHT
There is still a high-degree of uncertainty around the outlook for the pandemic at the beginning of March
2021 in spite of the significant increase in vaccinations. We are not sure yet if these vaccines will beeffective for all the variants that have rapidly occurred in 2021. It is also unclear how quickly the vaccines
can be made available around the world including developing nations.
We do not yet know when we can find effective therapeutics for the pandemic. What we do know at thisstage is that the best policy to restore malfunctioning economies due to the pandemic is to contain thevirus. For the good of the economy, we need medical experts’ views on the outlook for the pandemic.
We interviewed Dr. Yasuharu Tokuda, a general practitioner, clinician-educator, and distinguished expert
on clinical epidemiology on this issue.
(Interviewed on March 2, 2021)

Introduction
JS: First, could you please

introduce yourself briefly? Youhave been working on a wide
range of healthcare issues
including local medical care andmedical education, as well as
public health policies as a memberof a think tank named the Healthand Global Policy Institute.

Assessment of Public Health
Policies to Counter thePandemic
JS: How do you assess eachnation’s policies to deal with the
pandemic so far?

Tokuda: A relevant assessment would needcomparisons among nations. In this case, I
believe that selecting nations properly to becompared would be important. The
Tokuda: I was born in Okinawa and have been
pandemic’s impact on the human body isworking as a general practitioner, tutoringsignificantly different depending upon the
medical residents and working on medical
infected people’s genetic background andresearch since graduating from thealso their living climate and environment.
Department of Medicine at Ryukyu University
Therefore, it would be appropriate to compare
Dr. Yasuharu Tokuda
in Okinawa 32 years ago (https://sites.google.
policy performance among nations ethnically
com/view/cv-yasuharu-tokuda-md-mph/close (meaning genetically close) to eachhome). I am currently working for Muribushi Okinawa, an allianceother and also close geographically. In the case of Japan, thus I
network of teaching hospitals in Okinawa, as its director. There arebelieve that we should compare the situation of infections withsome hospitals accepting medical residents on junior residency
countries in Asia and the West Pacific area and not with either
programs. Our alliance consists of 28 hospitals among which eight
Europe or the United States. In comparison with Europe and the US,
are core hospitals, and 20 are cooperative hospitals or clinics. As
Japan has much fewer infection cases and less mortality. But indirector of the Alliance, my main responsibility in Okinawa is medical
comparison with Asian or West Pacific nations, the situation in Japan
education.
is not necessarily good.
In addition, I am doing outpatient consultation as a generalpractitioner and doing research on clinical epidemiology. I used toJS: The number of PCR tests in Japan was notenough to contain the pandemic at the beginning.
live in the Kanto district of Japan for 11 years and then worked for
Tsukuba University for five years. Even now, I am a visiting professor
Tokuda: I think our target setting was not well placed. That wouldof Tsukuba and frequently participate in education and research
have a more negative impact upon performance than insufficient
there.
https://www.jef.or.jp/journal/

Japan SPOTLIGHT • July / August 2021

45

PCR tests. Experts and policy makers in Japan thought at thebeginning that it would be possible to achieve a growing economy
with virus infections remaining flat, or not increasing much. Like theEuropeans and Americans, Japan had a strategy for co-existence
between economic activity and the pandemic. But I found that theywere wrong. After having suffered significant increases of infectionsa few times, I found co-existence of our economy and the pandemic
would be difficult.
JS: Containing the virus would be the first priority torestore our economy, since another big rise ininfections and another possible lockdown policy
could result in its destruction.

Tokuda: Yes. I would like to emphasize that pursuing zero infections
would be a better strategy. All nations successful in containing thepandemic have been taking such strategies so far, such as China,Taiwan, and Asia-Pacific nations like Australia and New Zealand. On
the other hand, the Philippines and Indonesia could not control
significant increases in infections and mortality with the strategy ofco-existence of the economy and the pandemic. New Zealand has
been successful in having largely contained the pandemic with a zero
infection strategy based on science and the prime minister’sleadership. The economies of those nations with zero infection
strategies have not been seriously damaged. For the economy’s own
sake, we would need to try to contain infections first. The WHOannounced in March 2020 that it would be possible to fully containthe pandemic (https://www.npr.org/sections/goatsandso
da/2020/03/02/811271217/coronavirus-update-we-are-inunchartered-territory-who-says). We should have set this as our goalat the beginning.

PCR Tests as Primary Means to Control
Infections
JS: To contain the pandemic then, do you think

and Prevention (CDC), around 50% of infected people get infectedfrom those without any symptoms.
So far, the policy of isolating infected people in past ordinary
pandemic cases has been based on those people with obvious
symptoms, but in the case of Covid-19 it is not valid anymore. We
need to find who is infected before they start to have symptoms oreven if they have no symptoms, and then isolate them. It would be
difficult to do so without PCR tests. We did not have this test at thetime of the so-called Spanish Flu over 100 years ago. We have it
now. Thus we should have had more PCR tests at the beginning of
the pandemic as well as other countermeasures, like requesting
people to wash their hands, keep a social distance and wear a mask.
A PCR test is a technology developed over the recent decades thathas enabled us to find infections clearly. We should use thisinvaluable technology.
Science journals such as Nature, Science and The New England
Journal of Medicine recommended large scale PCR tests, while theJapanese Ministry of Health, Labour and Welfare (MHLW) as well assome experts in the advisory group to the Japanese government
were skeptical about its accuracy, which may still mislead people’s
understanding about it in my view. It is said that 1% of those tested
would show false positive in PCR tests. But this is wrong. Because,PCR is originally a test to discover nucleic acid molecules with aspecific nucleotide sequence, and in the case of Covid-19, this is an
RNA (Ribonucleic Acid) virus and we try to discover RNA in theRT-PCR test. This RNA has an extremely specific nucleotide
sequence, namely four kinds of bases – adenine, uracil, cytosine andguanine. SARS-CoV-2 has around 30,000 bases. A PCR test canidentify very specific nucleotide sequences out of these bases. It isso specific that we cannot get the wrong result unless there is crosscontamination in which a different sample is mixed with theauthentic one by human error. There should not be as much as 1%of false positive results in total.

Recently Developed Vaccines

enlarging PCR test capacity would be mostimportant?

JS: What do you think about the effect of theTokuda: The WHO also mentioned the importance of PCR tests as ameans to isolate as many infected people as possible to prevent
widespread infections a year ago when they found that an infected
person even before symptoms emerged could infect another andalso an infected person without any symptoms could infect another.
According to the latest data of the US Centers for Disease Control

Tokuda: Vaccines seem to be more effective than we assumed. But
we have to add “at this moment” as a reservation. We have now four
new-type vaccines developed – Pfizer, Moderna, AstraZeneca, andJohnson and Johnson. Among these, Pfizer is available now in Japan.
Its clinical tests show rather positive outcomes, namely the preventive
effect for symptomatic infection is more than 90%. In Israel, where46 Japan SPOTLIGHT • July / August 2021

currently available vaccines?

vaccine injections are most rapidly under progress, it has resulted in asignificant decrease in infections. This truly shows the wonderfulprogress of medical science, as in the case of PCR tests.

Tokuda: Yes, certainly it is. From now on, most likely, how quickly
we can achieve vaccinations against possible evolutions of the virus
will be a key to containing the pandemic. We will need to repeat
injections of vaccines in response to emerging variants. This wasoriginally assumed, because RNA is a single helix and its bases arenot protected as in DNA (Deoxyribonucleic Acid) with a double helix,
where bases are preserved in a double helix structure. Intranscription, errors in copy are unusual in DNA, but there could be
errors often in RNA. Most of the variants are failed ones and uselessfor the survival of the virus and in many cases those viruses die on
their own. However, there are some cases of survival of the fittest,
the outcome of evolution. Such mutations could happen when thepandemic is spreading. At this moment, we have seen these variantsof concern with strengthened functions in nations such as the UnitedKingdom, South Africa, Brazil and the US. In order to contain theepidemic, it is said that we would most likely need to give a booster
injection of vaccines structurally adjusted to the variations of themolecular structure of a virus once a year or so, as in the case of flu.

such as Ivermectin. However, appropriate clinical trials for thesehave not been done so far in Japan. We should have done suchclinical trials properly designed and played a leading role in thedesign of those tests under the leadership of the MHLW and theNational Institute of Infectious Diseases.
As for PCR tests in Japan, collaboration between the MHLW andthe Ministry of Education, Culture, Sports, Science and Technology
should have achieved to ramp up capacity for PCR testing, since
medical research organizations have more capacity. But except for
departments of medicine at universities with their own hospitals
which actively did PCR tests to prevent cluster infections at theiruniversity hospitals, the medical research organizations’ capacity for
PCR testing was not actively utilized – and this was very different
from the US case.
On therapeutics as well, Japanese university hospitals have notsucceeded in developing them so far. I think this is because
collaboration between the two ministries I mentioned did not work
well either. Therapeutics are possible only when clinical trial doctors
for patients at hospitals and basic research scientists on virus
structures at laboratories are well coordinated. I wish at least there
had been a conclusion on the effectiveness of Ivermectin by clinical
trials during this past year. We should have had a randomized
controlled trial (RCT) for Ivermectin, simply comparing it with aplacebo. It is actually used in Africa, but without an RCT, and though
it looks effective that would not be enough evidence.
Anyway, laboratory researchers are working hard on developing
therapeutics, so I believe it is possible for us to have more effective
therapeutics than Dexamethasone, but we do not know yet exactlywhen.

Current Status of Therapeutics

Pandemic Making Us Innovative

JS: Vaccines are effective at this moment, but they

may not last long and there is a concern that they
may not work well against emerging variants. Asmost infections from now on will come from thevariants, it is increasingly difficult to predict how thepandemic will develop.

JS: Another key to containment of the pandemic is

JS: The pandemic has promoted medical innovation

Tokuda: So far, what has been known in the past year is that
Dexamethasone could certainly lower mortality. Remdesivir used in
the US could work well depending on the timing of the therapy or
specific group of those infected. The cocktail therapy of monoclonal
antibodies that former US President Donald Trump received would
be effective at the early stage of the disease. However, bothRemdesivir and monoclonal antibodies are so expensive and neither
is recommended by the WHO. The WHO recommends only
Dexamethasone. There have been many candidates for therapeutics

Tokuda: Yes, it is. In the US, this vaccine development was achievedat so-called “warp speed” and what would take six years usually wasdone in six months. New types of vaccines were developed one after
another such as a vaccine with a messenger RNA (mRNA) and theAdenovirus vector vaccine, as well as the ordinary inactivatedvaccines developed by China. It is often said that mRNA would be aneffective cure for a variety of diseases and at this moment it isconsidered to work well for preventing and curing tuberculosis andcancer. Though there is a BCG vaccine for tuberculosis, prevention oftherapeutics. How do you assess the current
situation of the development of therapeutics?

in a sense. For example, an RNA vaccine is anextremely remarkable innovation, isn’t it?

Japan SPOTLIGHT • July / August 2021

47

it is difficult. Treatment for it is also difficult, in particular in the caseof a tuberculosis virus with resistance. Thus it is still one of the threelargest infectious diseases in the world.
Cancer is the primary cause of Japanese mortality, but also achallenge for the whole world. There is a treatment for it byeliminating cancer cells by an immune force called immune therapy
developed by Prof. Tasuku Honjo, winner of the Nobel Prize inPhysiology or Medicine. An mRNA vaccine could strengthen
immunity and create immune cells specifically attacking cancer cells
in large numbers within a patient’s body. This is how this vaccine
would have an extremely positive impact upon treatments for otherdiseases. That would lead to an unprecedentedly wonderful world
which we have never dreamed about.
This vaccine would be ready to prevent possible new pandemics inthe future, including the current one’s variants that some experts
even refer to as new infectious diseases, because new effectivemRNA vaccines could be easily prepared only by changing bases. It
would not take a long time to make them. Also, while in the case of a
vaccine for flu we cannot make it without a chicken egg, an mRNA
vaccine does not need a chicken egg as it is mechanically created ina factory like a laboratory. Thus massive production is easily done.

The Pandemic & Public Health Policy
JS: Have we Japanese learned a lot about publichealth policy to counteract the pandemic?

Tokuda: Japanese people have learned about their own weakness inpublic health policy. A virus is invisible, different from bacteria. We
cannot find it even by an optical microscope. Therefore, without
turning the invisible into the visible by PCR tests, we cannot have apublic health policy intervention. In this regard, we should not havegiven up PCR tests at the initial stage.
There are only three public health policy interventions against
infectious diseases – namely, countermeasures against infection
sources; measures against routes of infection; and measures toenhance immunity among hosts. A vaccine is to enhance immunity
and thus it is in the third category. Keeping a social distance, wearing
a mask, keeping adequate ventilation in closed spaces, and washinghands are in the second category. Another important
countermeasure against infections is to discover the sources ofinfection at an early stage and protect and isolate them.
Experts and policy makers of Japan should learn that thesemeasures in the first category must have been exhausted on a large
scale.
48 Japan SPOTLIGHT • July / August 2021

JS: We should examine and analyze the outcome ofour public health policies on this occasion by anevidence-based approach and find out how we canimprove our policies.

Tokuda: Yes, experts and policy makers of Japan should learn fromthe best practice cases such as in New Zealand, Taiwan and someSoutheast Asian nations. Inside Japan, Wakayama Prefecture’s casecould be considered a successful one.

The Future of the Pandemic
JS: It is difficult to predict the future of this pandemic

as we still see growing uncertainly around it. But
predictions about the future of the pandemic arevital for economic forecasts. Most economists seemto see the end of this pandemic at the end of 2022.
When do you think the pandemic will be contained?

Tokuda: The key question is to what extent effective vaccines prevail
all over the world. Assuming the current speed of vaccinations goeson as it is now, it will be after 2022 when developing nations will
have enough vaccine injections to contain the pandemic. That means
the pandemic will not be contained until after 2023. It is also
noteworthy that variants are evolving to make vaccines less effective
even as vaccine injections are increasing.
According to the latest opinion poll organized by the sciencemagazine Nature, a majority of experts worldwide think it will bedifficult to eliminate this virus completely from the earth and assume
this pandemic will become endemic.
For example, the Middle East Respiratory Syndrome (MERS) issimilar to Covid-19 and is still now endemic in the Middle East with
infections through camels. Covid-19 could infect an animal as well,though it is still unknown from what animal the infection comes.
Since it is almost impossible to eradicate this virus completely, it
would be endemic. The question is where this endemic will be. I
hope it will not be in Japan or any countries in the world.

Written by Naoyuki Haraoka, editor-in-chief of Japan SPOTLIGHT, with theassistance of TapeRewrite Corporation.