«We are particularly interested in people who do not get the coronavirus at all. We decided to conduct research among families, e.g. in the parents plus child model, where two people, preferably a child, and one of the parents, suffered the disease, and the third person who lives with them under the same roof remained healthy »- says Dr. Paweł Zawadzki, participant of international genetic research aimed at determining which genes are responsible for the course of COVID-19.
- Dr. Paweł Zawadzki is a doctor of biotechnology and the founder of MNM Diagnostics – a company that uses new technologies to read information contained in the genomes of patients and thus support their fight against the disease
- Together with the Central Clinical Hospital of the Ministry of the Interior and Administration, the company joined an international initiative aimed at explaining how our genes affect how we pass COVID-19
- «We are different from Finns or Spaniards. Research on our population will answer a number of questions: do the same variants in the Spanish population, the same variants in the Polish population, cause the same effect in the course of COVID-19? Does the genetic background, or what makes us more “Polish” or “Spanish”, affect how we go through the disease? »Says Zawadzki
- One of the goals of the project is also to find genetic variants that make some people come into contact with patients or even live with them under one roof, but do not become infected themselves
Karlinska Gierblińska, Medexpress.pl: The time of the epidemic undoubtedly makes it clear to us that all hope for a better tomorrow lies in science. In 2003, the sequence of the human genome was fully read, but the world of science did not fully understand what it meant. How long, then, is it still to wait, with the fresh experience of the epidemic, for the effects of this world-changing medical revolution?
Paweł Zawadzki: Admittedly, the current epidemic shows us a number of aspects that should change if we really want to have a better future. And some things will probably change for good. One of them will be that agencies that regulate access to drugs, new technologies will start to accelerate this process. We already have proof of this. COVID-19 drugs, vaccines and tests are introduced within weeks, not several or several years.
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In the context of widely understood treatment, the epidemic allows us to ask whether there is a solution that can help us and if so, despite the fact that it is not yet a standard, can we introduce it to this standard? Genetic diagnostics is in this category of thinking – for patients, scientists and doctors alike.
For 17 years, we have been able to read our genome, and I know two hospitals that have introduced whole-genome diagnostics as a standard. I dare say this revolution is around the corner. It will take two or three years and will not be anything we just talk about but start experiencing. The more that we have the appropriate technology, and the costs of carrying out this revolution are not so high anymore.
Genome-wide testing can be crucial in developing a variety of therapeutic strategies. In what processes exactly can this knowledge play such a role, and what does it mean for patients?
Here I would mention two basic areas. The first is rare diseases (1-3 percent of people are born with a certain genetic defect). Until now, diagnostics had dealt with this task so that the patient was sent to one study that failed, then a second study … and it often took years for the diagnosis to be made.
The European average for diagnosing a child with a rare disease is almost seven years. Whole genome diagnostics reduces this time to three months.
Until now, the logic was that we did one small test and then more until we finally did all the tests that existed. A genome-wide test, by definition, is one test that includes all possible genetic tests, and the shortening of the diagnostic process is of great benefit to patients. One genome is 20 genes plus a whole host of regulatory elements and non-gene sequences that are not normally considered for diagnosis. For the system, it seems that a cheaper solution is to send the patient for one test, if there is no response – another one, but when they are summed up, their cost is higher than one expensive whole genome test, additionally saving time, which is invaluable for the patient.
Is the entire genome or individual genes tested more often in patients?
The entire genome is standard in only a few places in the world. The UK has introduced very extensive genome-wide testing. Last year, the genome sequencing project in approximately 100 patients, mainly with rare diseases, was completed there. The United States is introducing a similar program, but today the technology is available virtually everywhere. Also in Poland.
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So if Jan Kowalski wanted to have such a study, what would his path look like?
Jan Kowalski cannot decide about it himself. He may ask his doctor whether it is appropriate to use whole-genome diagnostics in his case. And it is the doctor who makes this decision, because he has the competence to assess whether this method is justified in the case of Kowalski. And then the doctor contacts us, and we conduct the entire further process in consultation with the attending physician.
Let’s go back to the second area where genome-wide diagnostics brings such important results …
This is, of course, oncology. Advanced diagnostics of the whole genome is a process that is still developing too slowly in this area. Perhaps the pandemic will open our eyes and some solutions will be implemented faster.
As we know, a cancer arises because a specific mutation in a gene has occurred. Targeted therapies help us fight specific cancers, but they only work in people who have known mutations in certain genes.
Five years ago, there were so few targeted therapies that it was enough to check three genes and you could adjust the treatment. Today, there are many more of these therapies and some of them require in-depth research, because the information on whether the drug should be used is found outside the gene regions, i.e. in the genome, but it is not entirely clear where.
In addition, the situation is worse than in the case of rare diseases, namely, genetic tests are often not performed at all before starting the oncological treatment process. This is often due to the inability to perform the test, often due to the lack of reimbursement and sometimes due to the lack of knowledge about the latest global recommendations. We are on the verge of a technological leap, which will result in the fact that without examining the tumor genome, it will not be possible to make a therapeutic decision.
Slowly, there is no point in studying single genes. We develop genome-wide tests and on the one hand we combine therapies with what is in the genome, and on the other hand, we want to introduce solutions that will lead to a single test that will answer all possible questions.
My hope with the epidemic is that this process of introducing new solutions will accelerate. I think people after this experience will realize that if there is a valid solution, there is no reason not to introduce it sooner than has been done so far.
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Jacek Dukaj says in a similar way, who wrote in his last column that “[…] the coronavirus means acceleration. In economic strategies. In technological trends. […] I estimate that the virus accelerated us on average in 10 years. After emerging from its shadow, we will be in a place where we would be around 2030 without the virus. “
I strongly agree with that. For medicine, pharmacy, diagnostics and biotechnology, it is a huge impulse that accelerates development. We can see that research teams are starting to work more intensively, there is much more focus and a better definition of the problem that is being addressed.
And going directly to the coronavirus, what suggests that genes are responsible for how a given patient goes through COVID-19? It is generally accepted that this disease is the greatest risk for elderly people with comorbidities. Is this classification not sufficient to identify people who may be at risk?
When we look at human history in terms of how people deal with viruses, or rather viruses with people, we will notice a certain repeatable feature. There is always a certain social group that is most at risk, whether because of age or lifestyle.
It also turns out that there are always genetic factors that make some people very severely ill and some people not at all. One such example is the HIV virus. When the research on it was deepened, it turned out that there was a group of people who had contact with the virus, theoretically should have become infected with it, and never had symptoms, because the infection did not occur.
This has led to a series of discoveries of certain genetic variants that are responsible for the failure of the virus to enter the cell. There are also variants that will make the virus very easily attack a person and he will be infected in a severe way. Therefore, it can be argued that such variants also exist for SARS-CoV-2.
It is true that age and co-morbidities are the two biggest determinants of mortality in coronavirus, but we see that the hospital also includes patients who are young, have no comorbidities and are suffering from COVID-19 very hard.
We hear about stories of families living together where the older person with comorbidities does not get the virus and the younger one does. We are faced with the task of finding these variants in the appropriate genes.
And it is carried out jointly with the Central Clinical Hospital of the Ministry of Interior and Administration in Warsaw, which during the epidemic was transformed into a homonymous hospital …
Yes, together with the hospital, we joined an international research initiative to search for these genetic variants. This research consortium was initiated by New York’s Rockefeller University and several scientists who work with viruses in the SARS family. At the moment, the consortium associates over 150 institutions, incl. Yale University or King’s College in London. The idea behind the consortium is that scientists from around the world share their experiences and research results. If 150 isolated centers conduct research, it can be assumed that each of them will start to make the same mistakes at some point. Joint activity avoids this.
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Why is it important for Poland to take part in this project? Well, we are different from the Finns or the Spaniards. Research on our population will answer a number of questions: do the same variants in the Spanish population, the same variants in the Polish population, cause the same effect in the course of COVID-19? Does the genetic background – what makes us more “Polish” or “Spanish” affect how we pass COVID-19? It is a great merit of the Ministry of Interior and Administration hospital and director Zbigniew Król that he decided to launch this project.
And what, when will the task be completed and genetic variants found?
When we find them, the first thing we can do is test all medical personnel to see who can work with the virus because it will be naturally protected, or who absolutely shouldn’t work because they are more vulnerable. Ultimately, we can test all of us to be able to estimate the risk of infection. An additional aspect will be that there is already talk of a possible second wave of the epidemic due to the likelihood that SARS-CoV-2 will mutate (this happens quite often in this type of virus). The new version of the virus can infect the same people again. By having the genetic data of the patients and knowing how they passed through the infection, we will be able to model how the mutant virus will spread and how dangerous the new version will be.
On which groups will this clinical trial be conducted, and why will the medical history of the patients involved be important?
We have several such groups. We know that people with respiratory and cardiovascular diseases often have a hard time COVID-19. Some cases of diseases of these two systems are of genetic origin. We want to combine the genetics of the disease with genetic changes that can affect whether and how COVID-19 develops. Nevertheless, the basic group of patients for us are relatively young patients, who do not have any comorbidities and are very seriously infected. This is the group where the genetic factor will most likely very strongly determine that these people get sick.
And the last group, especially interesting to us, are those who do not get infected at all. We decided to conduct research among families, e.g. in the parents plus child model, where two people, preferably a child, and one parent, underwent the disease, and the third person who lives with them under the same roof remained healthy.
Finding genetic variants in this third person that protect him against infection will allow us to include the variant later in the test, which is to be the result of our project.
And this “family” method is in fact the uniqueness of the research that scientists from Poland will carry out as part of an international consortium?
Yes, this is our unique approach in this study. Most research centers chose to test as many patients as possible from different groups. We assumed that it is worth being a little more clever. Anyway, one of the leading Danish universities also has a similar idea of work, which strengthens our belief that this is the right strategy.
Are there any downsides to this method that you can see at this stage?
Two. The first is that IT specialists and programmers will have twice as much work to do, and the second is that the person coordinating this project … will also have a lot more work to do. The co-ordinator will have to call the survivor, ask him if he agrees that we should talk to family members and convince those who did not get sick to donate a milliliter of blood. We are a bit afraid that people may approach it in such a way that it is a nuisance and it will be a waste of time for it.
What will it be like to work on a quick and cheap diagnostic test to help predict how a person will pass COVID-19?
The project implementation is divided into several stages. The first is collecting samples, the second is the construction of the entire analytical infrastructure, then sequencing of genomes and their analysis in order to select genetic variants that will determine how we will undergo COVID-19. The next step will be to validate the test on a certain group of patients about whom we know how they underwent this disease. We are able to do this “test” of the test in two months and we assume that after this time we will have a tested and developed tool that any diagnostic laboratory will be able to carry out. The test will probably cost around PLN 100 and will take two days.
Artificial intelligence is also to be used in the project. What exactly will it be like?
When we do a simple genetic test, we can read 500 to 800 letters from our genome. The challenge of genomic analysis is that we get over three billion instead of 500 letters from the test. It’s like reading information from 500 books, each of which has 500 pages. A classic genetic test is a tiny piece of a page from one book. Artificial intelligence and machine learning, programmed by us, will support human work in searching for specific information.
What benefit will the health care system itself benefit from conducting such research, from collecting databases of patients who may, for example, develop some disease complications after contracting COVID-19?
Today, we do not know yet whether there are complications after contracting COVID-19, but we have a number of reports that the respiratory system can be severely affected after the virus has passed through. There is a very good chance that in a few months we will have a lot of information that there is a group of patients with very serious complications. We should be preparing for that by now. Here, too, the genetics bows, who are often responsible for complications appearing in Kowalski, not Nowak.
Part of our project is that we will monitor what happens to the patients whose genomes we have sequenced. When post-morbid complications appear, we will be able to use a ready-made database. Thanks to this, we will be able to influence the mortality observed as a result of the pandemic, we will be able to provide patients with appropriate care, even before symptoms resulting from complications from infection appear, for example.
Why did you decide to connect your life with this field of study? What spoke for such a choice?
My father struggled with cancer for many years and lost this battle. I was already working in research at Oxford at that time, dealing with DNA repair and genomics. And as I realized how deplorable genetic diagnosis is when it comes to treating people, and how advanced science is, I felt I wanted to change that. When I went to the hospital, it turned out that not only did the doctors not know that genetic testing could be done, but the technologies that were used in genetic diagnostics were already very insufficient for me, a scientist, because they were used in science. 20 years ago. It was the moment when I realized that I had enough understanding of genetics that I was able to implement a technology that is already very mature in the clinic.
What is MNM Diagnostics for?
Mutations No More, which means that mutations will no longer be only harmful to us. It is thanks to the fact that we can read and interpret them that we can better use them to fight many diseases.
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