31.03.2020 – 10.26 – If we want to find the positive side of the arrival of the Coronavirus in our lives, one in particular stands out among all: the return to total confidence in the scientific world.
Unjustly mistreated by some in recent years, science is now the one and only one that can provide the answers that everyone is waiting for.
And it is precisely science we should listen to as we are waiting for the storm to pass. It is for this reason that Piero Carninci, one of the greatest experts in genomics in the world, has joined us on Skype, from Japan.
With regard to the current national framework, what are in your opinion the main critical points?
“Apart from the fact that there is currently no vaccine, which would clearly solve the problem, what is missing at the moment is the ability to test an extremely high number of people.
This problem is now partly due to the fact that the number of infected individuals is probably so high that it would be a particularly difficult undertaking: it would mean screening millions and millions of people“.
Would such a solution have been applicable if the virus had been detected in time in Italy?
“Realizing this in time, which is very difficult because Italy was the first European country to have encountered this problem, it would probably have been possible to isolate all the cases quickly enough.
An example of this is the Municipality of Vo‘, in Veneto, where also thanks to the small size of the territory, it was possible to ‘catch’ and map those who had been in contact with people who have been tested positive, doing the tests very quickly, isolating everyone, and managing to contain the epidemic.
Unfortunately, it is now too late for Italy: we will never have the capacity to do such a large amount of testing, especially in the situation in which the country now finds itself.
The test is also dangerous for those who carry it out, and this is the main problem: you have to have operating room equipment to be sure that there is no contamination of the people in charge”.
Testing everyone is therefore a solution that could work theoretically but is not very practical.
South Korea has done it and is doing it, how did they manage to do so?
“South Korea is doing it systematically.
The country had a biotech company that made kits for DNA or RNA sequence analysis and from the moment the alarm was raised about the spread of the contagion, that same
company in a month and a half managed to develop a kit that could do from fifty thousand to one hundred thousand tests a day, and even more, and this certainly helped a lot.
Why then could the same model not be applied to other countries?
“Technically, these are not extremely difficult tests. However, they are not tests that can be carried out on machines currently present in hospital laboratories. A technology called PCR, ‘Polymerase chain reaction‘, and in particular RT-PCR, ‘Reverse transcription polymerase chain reaction’, is required: few clinical laboratories have the availability of these machines, they are usually used in universities and research centers, and are used to look at the basic gene expression”.
What would the use of these technologies entail?
“One could organize oneself by ‘presetting’ the tools and working together with universities and research centers, where they are commonly used. However, the problem is organizational: it would not be a simple operation, it would imply a common effort that would go from the Ministry of Health to the Ministry of University and Research, and many others”.
Is this also a legislative and bureaucratic problem, then?
“There are laws that regulate in which laboratories certain diagnoses and researches can be made.
The difficulty is therefore mostly organizational because it is very difficult not to clash with these rules.
But they were written for ‘normal times’. Obviously, against the virus, we are now at ‘war’, so we should run much faster, with special laws and authorizations. In a world that moves in a logical way these things could be done.”
What about the development of a possible vaccine? How are we doing?
“Right now, there are a number of biotech industries and companies working night and day to create vaccines.
Two days ago, the first injection for phase one of a clinical trial for the first vaccine was carried out, it was developed by a company called Moderna, which works on RNA-based therapies.
This company has put a viral protein in a kind of complex that resembles the virus; this RNA is then injected, enters the cells, and contains only one protein, so it cannot replicate but can instead produce this protein which is a candidate for the constitution of antibodies”.
What are the next steps now?
“In step one you try to understand if the vaccine is toxic and you inject it to a sample of fifty to one hundred people.
If it does not turn out to be toxic, in the next step – we talk about weeks – we proceed to assess whether the vaccine is safe, and inject it to a higher number of people. The next step is to see if there is a percentage of people who have developed antibodies against the virus, and if they can neutralize it.
Then we move on to phase three, with even more people, and if this last phase is also passed, then we go on to production.
Clearly, for each phase there is the collection of data and a verification of the data is made,
followed by a commission that must give the green light to proceed”.
How long will it take for the vaccine to be available?
“Maybe a year, maybe a little less. Let’s hope that this vaccine will arrive; either from Moderna, or from the other thirty, forty, fifty companies that are working on it. There’s also an Australian company that claims to have a prototype available by May.”
Once the vaccine is created, what will be the next hurdles?
“A fundamental element that needs to be considered is that when we have the vaccine, we will need to produce a considerable amount of it. If, selfishly speaking, you decide to immunize North America, Europe and Japan, we are already talking about 800 or 900 million people. If we add China and India, the number will increase enormously. Unfortunately, looking at the situation globally, the number of victims will
probably be higher when this disease continues to spread in countries where there will not initially be a chance of having vaccines. Once we have the vaccine, we will of course be able to consider ourselves ‘safe’; at least until the next time, which we should prepare for, because it will come”.
“Viruses change, we see it with the flu virus that changes every year, develops in new forms, evolves.
In addition, we have seen that the flu virus often, due to its proximity, can take swine or avian sequences, going to change into something different.
But as it is no longer recognized by our system, it resumes its attack against humanity; in this case, if it has changed, it makes another world tour, with very low lethality rates and usually among the elderly and debilitated. However, in the case of the flu virus what works is that every year a vaccine is created in time, because we study where and how the virus is starting”.
And in the case of Covid-19?
“This virus most likely comes from bats: the virus sequence, if analyzed alongside the virus sequence that has been present in the bat itself for a long time, is extremely similar, except for a small region that has changed during the human infection.
The second closest animal is the pangolin, which also has a sequence very similar to that of the bat and the one that is infecting us at the moment. So, we can say that we have in these subjects a natural reservoir of viruses, and they could exchange their gene sequences in the future: if a bat was infected with the human virus, rather than a pangolin, we could have new combinations and a new variant that does not exist at the moment. At that point we would again have the problem of immunization, but with the experience we have had up to that point, we could also have a vaccine in much less time.
Is there any way to predict how the virus might evolve?
“You cannot predict how it might evolve; however, you can imagine it by seeing the sequences that are present in nature, studying more bats, pangolins and other similar mammals; in this way you might be able to understand what might happen. Usually these viruses infect the same cell, then the RNA parts exchange with each other and we have a hybrid molecule; so, the virus can take a gene from another virus and go on with a
The virus is already changing, but so far, it is still quite recognizable, because it is changing
in small positions”.
What about creating a drug?
“To develop a drug usually takes many years longer than the vaccine: it is a cycle that lasts almost ten years.
Take the case of HIV, for example: we now have effective drugs, but it took a long time. At the moment, the most promising drugs are those that interrupt the replication of viral RNA; now there is one, Avigan, which seems to have some effectiveness with influenza, but still has serious side effects, with the possibility of malformation of the fetus if given during pregnancy and with the risk of male sterility as it temporarily stops sperm production.
It is obviously not an aspirin, but drugs that could work if the disease becomes particularly critical and we don’t have alternatives to save the patient’s life”.
Apart from the time factor, what is the limit in this case?
“Here too, a clinical trial phase is required first. It has been used in a hospital in Japan, but still only on a few patients, so you have no way of knowing whether these people would be cured anyway.
You got to have a statistical number, and consequently also phases two and three of the clinical trial, so that you can reach a certain number.
The problem is, namely, statistics: if twenty patients are treated with a mortality rate of one percent, it cannot be said whether the drug actually saved them or not”.
Do you consider the containment measures applied in Italy to be effective?
“Isolation certainly helps to stop the contagion, and I know that in Trieste and in Friuli Venezia Giulia in particular this is working very well. Clearly, we need to have a little more discipline, but I would say that, not having any other cure, what is being done at the moment in this sense is essential”.
Is there anything you think could still be done?
“One thing: to make more swab tests. One thing that will become particularly important in the coming months will be to test recovered subjects: having the antibodies and no longer risking being infected for a long time, months or even years, you can go back to work and help those who are still sick.
Considering that most of the cases have been asymptomatic, I think we should start to do a sweep to intercept those who actually have the antibodies now, because all these people will be able to move freely, and as we go through this disease the number of these people will increase”.
So, once the “crisis” is over, could a reopening be considered starting from these very subjects?
“Yes, a reopening could start with those who have already recovered from the disease. And we will have to think about this: if we think about the number of cases in Italy, and if we consider the mortality rate, we most probably missed nine out of ten, passed among those who had the disease in a light form rather than with partial symptoms but who still decided to stay at home mistaking it for a flu. Then, probably, we will already have a million people in Italy who have gone through it, who could return to work, and who would play a fundamental role”.
Do you think the peak in Italy has been reached?
“Looking at the data of the Civil Protection, the number of daily increases of the currently positives seems to be rather stable, so we may have already reached the peak. We’ll have to wait a few more days to confirm it.”
In terms of social behavior, what do you think needs to be done to prevent contagion until normality returns?
“One experience that one should look towards, and which is what has worked so far in Japan, is the systematic, well done use of the right protective devices and careful social behavior: don’t talk to each other at close range, don’t shake hands, don’t take off your mask – which should be worn properly.
What could then lead us to a situation of greater ‘normality’ would be to be able to understand which social attitudes are harmful and which ones could be.
Clearly, if a person goes running alone in the Karst, the virus is not transmitted; if he or she goes running in a group, this is very likely to happen”.
[Piero Carninci was born and studied in Trieste, where he graduated in 1989 before moving later to the
Riken research Centre in Japan, starting, in 1995, an adventure that still lasts today. Author of more than 300
scientific publications and developer of techniques that analyze and ‘photograph’ the ways in which the
genome is transcribed, including the Cap Analysis Gene Expression or CAGE used in molecular biology.
Director from 2013 to 2018 of the Centre for Life Sciences Technologies and then Deputy Director of the
Centre for Integrated Medical Sciences at Riken itself].
Traduzione di Michael Guggenbichler