Blog / / This is not going to last for short time
02/04/2020
This is not going to last for short time
Nemanja Despot Marjanović Boston University MIT doctoral student and a former Hemofarm Foundation scholarship owner
This is not going to last for short time
Impressive clarity of the power of science appears as the first image of the opening of the window (or maybe door?) of the captivating hope one feels when talking to Nemanja Despot Marjanović. He is going to defend his doctoral thesis at the prestigious Boston MIT, before the top scientists. His narrow specialization are lungs and he is also participating in the Human Cells Atlas project, which has lasted for several years already and which is going to last for several more. The aim of the Human Cells Atlas is to create a map of all the cells in the human body, as a basis for understanding human health as well as a basis for diagnostics and medical treatment.

It was hard not to notice the enchanting simplicity in explanation, straightforwardness in talking and intelligent humour Nemanja Despot Marjanović is endowed with, in spite of talking about very serious and difficult issues during this interview, conducted via e-mail and WhatsApp.

Taking into account that coronavirus, i.e. COVID-19, attacks lungs, it felt natural to ask him if a part of the cancer-related research could be applied to this virus and if the research could be helpful in fighting corona, which has become a global threat at the moment.

‘Exactly! I am working at the Human Cells Atlas project, the aim of which is to map all the cells in the human body, to assign the first name and the second name to all the cells, as well as to determine their job, to put it that way. As part of this project precisely, we study human lungs, both normal human lungs and lungs in different pathological conditions. The Human Cells Atlas, and the mapping of lung cells, as one of the subprojects of the Atlas, enables us in this situation to try to understand how COVID-19 enters the human cells, and which cells it enters.’ explained Nemanja Despot Marjanović for Novi Magazin.

Could you explain to us how the virus does that?

Maybe I need to explain the virus background first. Viruses are the smallest ‘living’ organisms, which are not capable of reproduction. In order to reproduce, viruses need a host. A host can be a bacterium or a cell of any other living organism. Since the virus needs a host to use for its replication, the virus first needs to find a host and occupy it.

The virus has certain receptors on its surface. You can imagine them as a kind of key, which is then searching for cells with appropriate keyholes. Once it finds it, the virus enters such a cell as a key would enter a keyhole and uses this cell to replicate, killing the cell in this process, in order to get out and continue spreading.

The very ‘killing’ of cells is one of the ways in which viruses harm an organism. The other way is that such a spread of viruses provokes our immune system. The response of our immune system resembles an army which is there to protect us from different pathogens: viruses, bacteria, parasites, etc. Defending our organism, our immune system can harm our body as well, but this is usually to a small degree and short-term.

If this fight of the immune system takes longer, the damage can be bigger and therefore bear more harmful consequences for us. What is interesting in this virus is that it provokes a forceful response of the immune system and it could therefore be one of the reasons of its higher morbidity in relation to the common flu virus, for example.

As I have already mentioned, the goal of the Human Cells Atlas is mapping of all the cells which in practice means that we wish to know, to comprehend what kind of different keyholes exist in each human cell. Once we have the information on what cells in our body have different keyholes, we will be able to learn which cells have the keyholes for entry of COVID-19. Consequently, we will be able to understand the way in which this virus causes the pathogenesis of the disease and what our targets are.

We have seen that most of those cells are lung cells. However, we also find cells with receptors in the digestive tract and even in some nerve cells. Of course, now we have to test all this in experiments.

Nemanja Marjanovic

How does cell mapping help scientists to understand the way in which the virus behaves in human body and can the research you participate in contribute to a faster invention of a vaccine/medicine to treat the virus and also for some other diseases?

Well, for example, we know the potential receptors this virus uses as a gateway for entering the human cell and reproducing itself, destroying the human cell in doing so. We can use the Human Cells Atlas to see which cells have such receptors. Once we comprehend that, we will be able to understand the pathogenesis of this virus better.

Once we understand the pathogenesis, we will be able to cure the disease.

There are speculations in the public that the process of finding a vaccine against COVID-19 will last between 12 and 18 months. Is this true?

The vaccine has already been made – within 42 days, which is really a record. The testing of the vaccine will last up to 18 months and this part cannot be accelerated.

It is very important that people understand that such a method of testing is essential for any medicine which is to be released for sales. When a medicine is made, preclinical trials on model systems are conducted first, in order to show if the vaccine is effective. After that, tests are conducted on people and these clinical trials last long.

Let me explain why they take long. – Because the efficacy of medicines has to be tested against placebo, to demonstrate if medicines improve the condition of the diseased people. In addition, it is important to monitor if medicines are toxic or not. Patients have to be monitored for certain period of time, since we have a vaccine as a medicine here.

Is mapping of all human cells going to help in prevention of pandemics, like this coronavirus one, in the future?

Of course, it is. However, it is important to realise that numerous comprehensive and much larger-scale research studies and trials are necessary as well as much more investment in biological research, which is not an area in which we should be penny-pinching. Research should be reinforced globally.

What is the difference between the COVID-19 virus in relation to plague or ‘Spanish flu’, SARS-1, SARS-2, Ebola, and other viruses which have been remembered in human civilisation as viral pandemics?

COVID-19 belongs to another group of viruses, except for the SARS, which is the same group. I am going to explain what it means: the other group of viruses means that a virus from the other group has a different way of entering the cell, i.e. it uses a different keyhole than the other viruses, and as such it can have other host cells. Apart from this, COVID-10 also has a different method of reproduction, not counting SARS. There are a few interesting things about this virus: in comparison to the flu virus, this virus is transmitted more easily. On the other hand, it has lower mortality rate in comparison with SARS, for example, which gives it the so-called ‘sweet spot’, as they call it here, which would mean it has found the right button to press. It is capable of creating the appropriate balance between the speed of spreading and the point of action in an organism and this is exactly why it is dangerous.

I am not an expert in this field, but it seems to me that COVID-19 spreads faster than all the other viruses. How is it possible?

What we are witnessing now, is that COVID-19 is spreading faster than a flu virus. It is more contagious, so to say. Understanding infectiveness of a pathogen depends on different factors. One of the reasons is certainly that fact that asymptomatic people – people who have the virus but have not developed symptoms, can spread it easily. Next, COVID-19 can remain in the air for three hours, as demonstrated by the latest research. It can remain for up to three hours in the air in the form of small drops called aerosols.

Moreover, its infectiveness is probably related to how easily the virus finds the keyholes, i.e. cells of a host and how easily its key enters the keyholes. The more easily the key finds and enters a keyhole, the higher the chance of its fast spreading.

Can you share your thoughts of the ongoing pandemics? Why is it happening to us and when can we expect it to end globally?

I sincerely believe that this is not going to last for a short time. Its duration also depends on our individual contribution, on how responsible we are in listening to epidemiologists’ advice, not only of those from our native countries but also relying on the global experience and how hard we try to slow the spread of the pandemics.

What is your assessment of the situation in Serbia and can you give us a scientific estimation of the virus development as of September? Are we going to go back to the quarantine after September or are we going to acquire ‘collective immunity’ by then?

I am of the opinion that the measures which are introduced now with the aim of social isolation are very good. In addition, the preparation of ‘hospital centres’ for people when they get infected is commendable. I think it is very important to ensure as comprehensive mass testing of Serbian population as possible.

I believe there is a good chance for acquiring a certain degree of collective immunity by September. However, I am not sure if this is going to be enough. What is your view regarding the measures taken by the authorities and the healthcare and scientific community in Serbia?

The measures are currently really appropriate. I would like to point out again that what we can do is social isolation, i.e. social distance. In addition, the preparation of hospitals, such as the one at the Fair, is a good step. The only thing I am not certain about is whether the number of tested citizens is sufficient. The capability of testing a large number of people is of key importance.

As this situation imposed, most of the questions were related to the pandemics. However, it would be interesting, not only for the Serbian public but also for the entire mankind, to hear from you how far has the creation of the Human Cells Atlas progressed? How long has the work on this project been in progress and how much more labour is going to be necessary until new knowledge and new ways of treatment of cancer have been mastered?

This is the largest project in biomedicine from the moment of sequencing the human genome. I believe this project is going to last for at least 10 years.

We have all learnt at school: cell is the main structural and functional unit of each organism. Human body contains approximately 37.2 trillion cells. What the Human Cells Atlas is trying to do is to perform mapping of all these cells. We know the main types of cells, but we are far from having absolutely classified all the human cells. Once we understand the cell identity, for example, what proteins it has available, we can also understand the function of the cell better. Consequently, we will be able to understand better the pathogenesis of different diseases in which such a cell plays an important role.

Simply said, as much as a cell is the main structural and functional unit of each organism, so is a human being the main unit of a society. So, if we want to simplify it and view human beings as cells and our world as one organism, what we are trying to do is to determine and understand what makes his/her identity, who his/her parents are, and what they do. Thus, we are creating, to put it that way, a Facebook for all cell types, which will contain all their principal data.

Really alarming warnings have reached us on the consequences of COVID-19 in Boston, Washington and New York. Was the American society late in joining the fight against the pandemics? Do you think the American public was not warned on time and that necessary preventive measures were not taken on time?

Coming up with such opinions is very unrewarding. Not because I wish to avoid blaming people but more for the fact that there is a large number of factors here – the method of healthcare organisation, the structure of healthcare, etc. In general, my motto in life is ‘Don't put off until tomorrow what you can do today’, so I think those who stuck by the ‘Early bird catches the worm’ maxim managed to fight coronavirus better. It is best illustrated by the example of South Korea which tackled this problem at a very early stage and managed to slow down the spreading through aggressive testing.

Nemanja Marjanovic

Too Early for End of Pandemics Prediction

I am aware that it is unrewarding to make predictions, but could you convey the opinion of the scientific community to us on how the pandemics is going to unfold in the USA? How many infected people are expected, what protocols have been established and when the crisis is expected to end?

It is really very hard to come out with any kind of forecast. The general public must understand that we, the scientists, are also learning through this situation that is going on. Unfortunately, we are not ready to such things. The key thing at this moment is to introduce certain measures in order to prevent the spreading of the COVID-19 virus, both at the individual level and at the level of the society.

As regards the individual aspect, it is crucial for each of us to wash our hands as frequent as possible, to avoid touching the face and to cherish sleeping and resting as well as everything else which could strengthen our immune system. Last but not the least, we should practice social distancing whenever possible. At the global level, what the USA is doing is increasing the number of tests. I mean, it is of crucial importance to have a possibility of testing as many people as possible, including those who are asymptomatic.

Then, combine this with ‘contact tracing’, in order to isolate the people who have been infected. It is early to talk about the end of the crisis. I hope we could expect a return to normal life in the mid-summer. However, this will only depend on the degree in which the individual and the social measures have been established and put into practice. Therefore, the message is: the more effort we ourselves invest in practicing the above-mentioned measures, the higher the chances of sooner returning to normal life will be.

CV

Nemanja Despot Marjanović was born in Bosnia and Herzegovina and he grew up in Serbia. Due to the breakup of Yugoslavia, he came to Inđija, Vojvodina. Here also, he was an excellent student and one of Hemofarm Foundation scholarship owners. He is a doctoral student at the Broad Institute of MIT and Harvard, major in engineering science at a multidisciplinary study programme in which doctoral students are ‘trained’ in the fields of programming, engineering and biology. The idea is to educate young people to become multidisciplinary scientists, to be able to apply engineering and programming (data science) in resolving important biomedical problems.
He is going to defend his doctoral thesis in July this year, mentored by Aviv Regev (applied and theoretical maths), who is presiding over the Human Cells Atlas project, as well as by Tyler Jacks, Director of Koch Institute (KI) at MIT and President of American Association of Cancer Research (KI is a unique institute in which engineering is applied order to get better understanding of cancer).

Source: Novi magazin
Interviewer: Nadežda Gaće
AUTHOR
Nemanja Despot Marjanović
Boston University MIT doctoral student and a former Hemofarm Foundation scholarship owner