Graduate in Strategic and Arms Control Studies, St. Petersburg University
<Fig 1> Pandemic representation
When the pandemic started, everything changed in the blink of an eye. A paradoxical situation was enough to cancel all the certainties on which we built our lives. When I think about my life, there is a pre-pandemic me and me after it began. At first, readapting my life was almost effortless. There were no more places to go but only surfing the internet, and my social life shifted to a computer screen. Readapting meant spending many hours in front of a screen participating in lectures and conferences. The voice of virologists and scientists has become the backing track of my life, and their advice was what I’d listen to more. I realized that my best friends were my computer and cellphone. Like in the movie Her[i], a sensitive tale of an individual who falls in love with an operating system, technology became the center of my life. Still, the more I dug in, the more I started to perceive something different within myself. I began to manifest heightened melancholy and depression.
The more I tried to stay focused, the more my brain tried to escape and refused to concentrate. This overwhelming situation made my daily tasks almost impossible to get done. My reaction has been to give an answer to all these new symptoms by doing online research. Indeed, I wasn’t the only one who felt this way. Certainly, children have been heavily conditioned by these restrictions and forcibly relegated despite themselves to daily life at home, strongly penalizing their socialization and development.
On top of that, problems of social inequality have emerged. Women and mothers have been burdened with responsibilities that have increased their daily tasks. There was no longer a line between private and professional life. So, for many of us, readapting our lives came with the cost of social anxiety, brain fog, depression, and other mental conditions.
Perhaps, human beings were never forced to stay isolated for so long throughout history. Nevertheless, social isolation is usually experienced by scientists in the Arctic and astronauts in space for long periods. My necessity to understand this situation resulted in asking myself questions like what are the effects of isolation on the brain? Do astronauts in space experience the same problems? Which are the effects of prolonged exposure to technology daily? How does the brain rule our lives? I asked these questions to two brilliant women-scientists: a neuroscientist and a medical engineer that wants to become an astronaut having done several simulations of Mars on the Earth.
This article is an interview with Ilaria Cinelli, Ph.D. in biomedical engineering and Fellow of the Aerospace Medical Association (FAsMA), and Catie Profaci, Ph.D., a neuroscientist.
<Fig 2> Ilaria Cinelli
In the last two years of the pandemic, 1,400 new satellites have already begun circling the Earth. The number of satellites will likely increase as the year goes on. Space has become so important that private companies have started to invest there. On the other hand, we often hear complaints about how funding for space experiments could be spent on Earth. In your paper, you explain how advances in space medicine can also be applied to epidemics and pandemics on Earth. In particular, during the 2021 CTBT: Science & Technology conference (SnT), you talked about the concept of “transferability”, meaning that what is studied in space can be applied on Earth. With climate change and new upcoming challenges, how important is this concept?
I think it is fundamental; everything done for space must then be applied to the Earth; in my opinion, this requirement is not very explicit in many sectors. I look more into health but in other contexts climate change, the prevention of diseases, and natural disasters – the link must be very strong. Unfortunately, it is thin and not so explicit nowadays, and this is bad news because, in 2021, we would like it to be stronger. Still, it is also good news because it gives job opportunities and research opportunities, especially to other people interested in the sector. Space is very important for the development of our society. Therefore the link between the Earth and space must not be vague but must be much stronger.
You are a mentor for the UNOOSA space4women program[iii]. During the SnT, you said that crews of mixed genders perform better than those composed of only one gender. How important is it to encourage diverse teams?
From the captain’s point of view, it is essential because I manage a crew better when the team is mixed; when there are crews only of women or men, you enter a competition context with different facets than when the crew is mixed-gender crews. It is difficult to understand who to send to Mars or the Moon and select the crew. But it is essential to have representatives (team members) of both genders. Most scientific research is based on data from essentially male astronauts, which is the target population. In statistics, when you go to validate and test something, you have to refer to the largest population, that of men. Women are a minority, and the number and data collected on women are less significant. This means that we have to include many more women in the simulated missions on the ground because we do not have the faintest idea of what could happen to the female body. So if we want to go to Mars and the Moon to stay there, we have to obtain data on the woman’s health and the equipment that the woman will use from the simulated missions on the ground. And it is fundamental because if we do not take this small step, we send a woman into space, knowing it’s riskier than for men. When a woman has to do a spacewalk, the suit has to be made according to the female body. It is difficult because we are in a moment of transition; initially, these spacesuits were a bit like vehicles, and there was one, and that’s it for economic reasons. But now you have to customize it and make it suitable for the female body. There is a balance between ingenuity and monetary resources, but it is essential. The inclusion of women is not only because we have nothing else to do, but there is a scientific motivation. What has not been done in the past must be taken up today and be simulated on the ground to make women safe in space.
Ilaria, you have been a mission leader of several simulations of missions to Mars. You have had the opportunity to experience isolation and its consequences. Also, in an interview, you talked about the brain’s neuroplasticity and how it increases in space. Can you explain how these Earth simulations can help produce scientific studies on brain isolation and behavior?
There are studies about it from people in Antarctica who do research. They stay in isolation for many months, so it’s forced isolation. They don’t simulate anything that has to do with the space; the context and the environment force them into isolation. They lead a very similar life to what you can have in simulation. The great thing about the neural aspect is that the brain adapts to anything. It’s beautiful because we take it for granted that there is a process of growth, adaptation, and aging in the human body. Still, in reality, the brain is so active. Every day, it compresses and deforms to send electrical signals, and according to the environment in which we are, the brain adapts. And I believe that the environment may be the following medicine.
Because now we take drugs and administer them, there are components that induce a reaction inside and have external manifestations and, therefore, benefits. But I believe that the environment in which the person is can be a complementary part of what the pharmaceutical prescription is, so you cannot think that a person can improve if he is always confined to the same environment. For example, prisoners, for whatever reason, cannot improve. It is stupid to expect [them] to improve because they are forced into isolation, rules, and deprived of many things, even affection. Hence, the brain has no stimulus to maintain plasticity to improve its life.
So, on the one hand, it is also paradoxical to expect these people to improve from the moment they are reintegrated into society. This cannot happen, and I believe it cannot occur because of how people are managed inside prisons. But also, from an anatomical point of view, if you force a person into isolation, they will never be the same as before. There are anatomical aspects that change and can be more or less permanent based on the individual’s medical history; if this changes, that person cannot improve. The same for other contexts of pathologies, so you can trust anyone, a person can choose to do it for work or reasons of society, as in the case of prisons but environment is fundamental. Therefore, the medical prescription is not enough. Still, the medical prescription must accompany a life directed in a place with specific characteristics because environmental factors impact human health. And this is very clear in space but not evident in society. So if we want a better society, we must realize the impact that specific structures have on our health, which also concerns schools. If you put kids in a gray classroom in a decadent place, they’ll never get the urge. The brain needs different stimuli based on different ages. Some concepts can be transferable and applicable to society. Others, however, must be matured and supported by terrestrial infrastructures and other aspects.
Numerous private and public funds have been invested in shortening the distance between Mars and us, but there are still several unknowns. How will astronauts withstand so much radiation, and what will the infrastructure need to be to protect them?
When we send a person into space, the human body adapts, this has been seen in the literature. When he returns to the ground, he crosses the path that is rehabilitation, in which he tries to recover to restore the physical and health conditions he had before. We expect the person to return to the ground to maintain the same performance as initially. We do not accept that the human body’s change and, therefore, the human body’s adaptability can be a permanent component. As we see it now, it has to be a temporary component, as it ensures that we send the same person into space multiple times. And this suits us to be able to do more research. In missions, however, such as those of Mars, which last longer, I believe we must accept that there will be consequences in the human circle that we cannot recover from. If we accept it, we agree that we can go to Mars even now, being aware that we cannot shield any type of radiation and that we are okay with it, both for us on Earth and for those who will do the mission. I’m sorry to say that – but the initial missions will be a bit suicidal, in the sense that there are so many risks that it is difficult to understand, and so much insecurity because missions to Mars require so much collaboration between nations. It is not only financial, but it is also scientific. If a country has more infrastructures, maybe it can understand more, but it does not mean that it will have an extended version of all the risks on Mars.
Mars is tough. The aspect that I like the most is Mars’s importance compared to the Moon. Many of the United Nations Sustainable Development Goals will be implemented for the mission to Mars. The UN has launched the goals that nations have to implement by following all directions, and there is a deadline. But if we want to make it truly viable and transferable to the Earth, space is the key. Because if we guarantee the testing of the use of water, of gender equality, of all these objectives in space, we can transfer them much faster than on Earth. So, I believe that space is an accelerator for implementing the sustainable development goals of the United Nations.
<Fig 3> Catie Profaci
During the last two years of the pandemic, we have experienced lockdowns and isolation. Which consequences does isolation have on the brain? What would the long-term effects on the brain be?
This is a kind of social experiment that we live through right now. We’ve evolved to be social creatures. The earliest humans had to rely on each other and work in teams to survive. We were heads to sort of hardwired into our brains that we needed to be social. There are definitely some negative consequences. Isolation can undoubtedly increase the sense of depression, anxiety, and aggression, which is interesting. I don’t know to which extent this is true throughout the world, but we actually use singular confinement in prisons in the US. The worst punishment has to be being alone, which makes sense because it is a horrible punishment. But honestly, if we are trying to punish someone for aggression, it makes no sense because it can actually increase aggression. Through the pandemic, we have seen increased violence in the US.
One interesting work about it was done by Moriel Zelikowsky;[iv] a few years ago, it showed the same things in mice. Social phenotypes start developing if you leave them in a cage alone for two weeks. It’s more likely to attack another mouse; if you put another mouse in a cage, it’s more scared that things are a threat. They found that this molecule, this peptide called tachykinin2, was super involved in all of those responses to social isolation. With a drug that blocked the receptor for this peptide, they were able to stop the effects of social isolation. There might be a drug that would help mitigate some of the adverse effects of social isolation at some point. I think that we might see more people suffering from depression and anxiety in the long term. Even when you can’t see each other in person, zoom does help really; obviously, physical touch is also essential, but socialization in any way is better than nothing. We are all tired of zoom, but it’s necessary to see each other.
Your studies have analyzed the close relationship between blood vessels and the brain. Could you please tell us why the blood-brain barrier is important and why you have dedicated your research to it?
I just finished my PhD in a lab studying the blood-brain barrier (BBB). I had training in neuroscience before I got into that lab. The BBB is something that many neuroscientists don’t necessarily think about; a lot of neuroscientists think about neurons, which are the cells that fire action potentials to one another. But you have blood vessels throughout your brain. The purpose of blood vessels is to bring blood with oxygen and nutrients to keep your cells alive, and in the rest of the body, the blood vessels are permeable. They are tubes with tiny holes, it’s not real tight tubes, so things from the blood can move into different organs and then move back into the blood, and that’s not true for the blood vessels in the brain. Also, the spinal cord and retinal are the same. In those organs, the blood vessels walls form this tight seal, and it’s complicated for things in the blood to get into the brain. Hence, for nutrients and elements that the brain needs like glucose, they have these specialized transporters to transport them across. The blood barrier is not just one thing; it’s all the qualities of the blood vessels in the brain that make them able to prevent them from moving. It’s important because your brain cells can’t really regenerate; conversely, a lot of the cells in your body can. In particular, neurons, don’t regenerate very well, and so if they die, you won’t get them back. To function correctly, they need a particular chemical environment in the brain. The barrier protects them and also helps them work properly. It can be a problem for treating if you inject medicine or take it by mouth, and it gets into your bloodstream; the blood barrier can, unfortunately, prevent [medication/it] from getting into your brain, which is why we have trouble treating a lot of neuro diseases because it’s hard to get the medicine into your brain. It’s important but it’s also a problem for drug delivery.
For many years and even centuries, it was believed that women were different from men, negatively. We often hear about differences between man and women’s brains; however, is it true? And how important is it to study women’s bodies and brains to have more homogeneous and complete studies?
There are indeed some structural differences between males and females. It’s not absolute though, it happens continuously, so yes, men are more likely to have slightly bigger brains. It has nothing to do with intelligence. There are some brainy genes; the hippocampus is marginally bigger in females. Again, sexes are going to happen in a spectrum. There are so many different brain areas that might be slightly different depending on the hormones that are going through your body or depending on the chromosomes you were born with. Because there are so many factors, you can combine all the factors and look at the brain and maybe guess whether the brain comes from a male or female. Still, it’s almost impossible based on someone’s sex to describe their brain. It varies so much from individual to individual. It can be more in a spectrum. In terms of your second question, I think because there’s this a horrible tradition of only studying male bodies and not even in just humans, it’s probably even less of a problem in humans, but traditionally in animal studies which you often have to do in order to get a drug that’s safe to put into a human. We’ve only been working with male animals, specifically with mice; a lot of people cite that female behavior is more variable depending on what time in their cycle they are and so because it’s ‘the date is more variable’ then we chose to study male instead. For some things, males and females react the same to certain drugs and illnesses, but for other things, they react differently and so we are just starting. The NIH, which funds a lot of research in the US, now mandates that you have to study an equal number of female and male mice to have funding. But this is very recent. Hopefully, now people will start looking more closely at how whatever they are studying affects males and females.
You have shifted your research to other issues; what is your last study about?
I started to study microglia, which are the brain’s immune cells, to understand if they have a role in the blood-brain barrier; the short answer is that it seems they really don’t. So we depleted microglia, there’s a drug that you can use to kill off microglia in the brains of mice, and then we looked closely at the structure and function, and gene expression of the blood vessels, and it seemed pretty normal. But then, the drug I was using to deplete the microglia I found had a fascinating effect on the blood vessels. It sort of increased the enzymes; they started making more enzymes than cholesterol. A lot of people have a negative connotation of cholesterol associated with food. But actually, we have a lot of cholesterol in our brain so it’s not associated with the food we eat. You’re not going to increase the cholesterol in your brain if you eat more cholesterol. They are totally separated tools, and the brain makes its own cholesterol. It’s used as isolation for neurons to send signals to each other, so it’s important and it’s not studied in blood vessels much. I found that neuroactivity can increase endophilin so the cells in the blood vessels walls increase their production of cholesterol and I think this can be a mechanism. If you increase the cholesterol in the blood vessels there are deficits in neurovascular coupling. When your neurons are active, they need a lot of extra oxygen and nutrients and so, there’s this phenomenon that when a part of your brain is active, there’s instantly more blood flow to that area of the brain to bring extra oxygen and nutrients. That process of increased blood flood and neuro activity was deficient in the mice whose blood vessels were making more cholesterol. We may find negative feedback for mechanisms increasing blood flood in response to neuroactivity. An excellent and frustrating thing about science is that you start with one question, and then an expected result can bring you in a different direction.
You have recently become a doctor of philosophy, what is your advice for women pursuing a PhD?
My most extensive advice is to choose the lab and the mentors carefully. There are so many setbacks for women in science that just exist as part of the system. Still, having a mentor and advisor who can advocate for you and nominate you awards and introduce you to people at conferences really helps put your career forward. It makes all the difference. It is essential, particularly for women and anyone, to have a happy lab environment and supportive people around them. It makes 100% of the difference. In my grad program, the people who had a toxic environment don’t want to do science anymore, which makes total sense. Especially for women in science, we must ensure that they are supported and advocated for.
What will the future look like?
I’d like to express my gratitude for what Ilaria and Catie taught me. I’m also grateful to have interviewed women working in STEM fields, which used to be predominately male ones. Their voices are necessary for building a more sustainable future in which all genders are equally represented. The past year taught me the importance of science, listening to experts, and the necessity to inform ourselves about scientific issues. It is difficult to ask ourselves these questions when our lives run so chaotically fast. When we study biology in school and learn that the brain is the most crucial part of our body, we do not precisely know why. Nor do we honestly ask ourselves how our brain behaves in certain situations. The fun part is that we rely every day on the functions of our brain; we could say that we are our brains.
On the other hand, technology has become an integral part of our lives. Without it, we couldn’t have readapted to a remote lifestyle. Doing this interview, I realized that I did not know what astronauts go through when in space. We are likely to hear complaints about how money should be spent on Earth and not in Space. However, we never imagine that space is a valuable tool to understand how women’s bodies work and to produce research. Many questions remain unsolved, and it would be unrealistic to have an answer for all of them. Indeed, the situation we face will likely bring long-term effects that are tough to analyze in the short run. So what will be the lessons I will remember when all of this is finally over? Perhaps, now I know that our brain is something we should take care of, whether with the help of a specialist or not; our brain can play some tricks on us or help us survive the toughest challenges. But, what is valuable is the experience of people that already been through it; what can I learn from them? How are they able to survive the tough environments? I now know that our bodies and minds are probably more substantial than we think. Being grateful for that is the first step toward building new consciousness.
[i] Her, directed by Spike Jonza, is a 2013 American science-fiction romantic comedy film. It’s the story of Theodore Twombly, a man who develops a relationship with Samantha, an artificially intelligent virtual assistant.
[iii] 「UNOOSA space4women program」, space4women.unoosa.org
[iv] Zelikowsky M, Hui M, Karigo T, Choe A, Yang B, Blanco MR, Beadle K, Gradinaru V, Deverman BE, Anderson DJ (2018) “The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress”