Barcelona Metropolis

Mara Dierssen is a neurobiologist and one of the country’s major communicators of popular science. She studies the human brain, and, more specifically, learning, memory and what happens when some of these cognitive abilities are affected by an intellectual disability. Much of her work is devoted to understanding the genetic architecture of Down syndrome, and her findings in this field have allowed these people to improve their cognitive performance and to contribute to research on diseases such as Alzheimer’s. Outside the laboratory, she is the lead singer in the rock band From Lost to The River, which raises money for research and a number of social causes, such as helping refugees. Her office is brimming with posters advocating for causes, from feminist declarations to others supporting animal research.

From a scientific point of view, animal testing has been crucial in finding treatments for many diseases. From cancer to Parkinson’s, and neurological diseases in between. Animals are essential to help us understand certain diseases and to come up with treatment. Unfortunately, cell models do not help us to evaluate the toxicity of a treatment, because they do not allow us to determine whether that drug is going to cause any damage, in systemic terms, throughout the organism. For this reason, animal testing must first be carried out, for which there is a very strict, I would say drastic, ethical regulation. An ethics committee and an animal welfare committee appraise the health, habitability and enrichment conditions of any research or practice to be carried out with animals. Everything is extremely controlled. And this applies to most laboratories.

Occasional problems have arisen, which is disgraceful and unfortunate, but when they do, they come to light in the press. What worries me is the lack of perspective: there is no mention of what is done to animals in the food sector and I think it is much worse. I respect every standpoint, but I believe we do not currently have an alternative to animal testing. We do not yet have prototypes that allow us to ensure that, if a drug is directly tested on a person, we will not cause irreversible harm and suffering.

Yes, because science, and society in general, cannot allow half of the population not to participate fully in an activity as important as knowledge acquisition and application. It makes no sense for us to lose out on a huge swathe of female talent. And that, unfortunately, happens both when we talk about horizontal and vertical segregation. On the one hand, we continue to have careers in which there are virtually no women and others in which there are only girls. On the other hand, we women come up against lots more problems when it comes to progressing in our scientific career. We are still considered to be less capable, that we will devote less time to researching because we have family obligations… As if family obligations only fell on women! We find ourselves in a situation where we have to produce twice as much to be considered equal.

In general, women are worse at negotiating promotions, receive less research funding, have poorer letters of recommendation, are interrupted more in interviews, are allowed to talk less, and are called into question a lot more. For all these reasons it is harder for us to reach any position of power. If we look at leadership positions, men predominantly hold them. How many female directors of research centres are there in Catalonia? How many female university deans? How many female hospital directors? We are always on the same page. Even in nursing, where the majority of professionals are women, men are the leaders. That just cannot be. And awards? Men are the recipients. Women in Spain receive only 18% of the prizes, and they are prizes with a lower monetary award.

I believe it is crucial certain correction factors be established, especially in appraisals for scientific positions and for obtaining funds. Saying, “As you have had three maternity leaves, I’ll extend the application period for this grant”, does not change this. It is a step forward, but I hope that it will be applied to men too, because it will mean they take parental leave too. What’s more, it must be borne in mind that maternity leave also reduces scientific productivity. Less importance should therefore be given to the number of publications or to their impact. Or the fact that you are the last author of the article, because women are poorer negotiators. Why don’t we attach a relative importance to these things? Evaluation panels need to be mindful of bias when hiring. If they know that bias exists, they will surely be more careful when making assessments.

I always explain that the human brain has 86,000 million neurons, but in the average human, which is a 50-year-old male weighing 70 kg. Women’s neurons aren’t counted. Then I make the joke that it’s because we’ve got more of them. But jokes aside, there are no neurobiological reasons for discrimination. The brain has now been found to be a continuum; there are no differences between a male and a female brain. It is not about weight or size. But in neuroscience there are so many biases... It’s amazing! And, indeed, it also poses a problem for metacognition: can the brain, with all its biases, be objective when studying itself?

Studying a cell is great, but it does not afford an idea of the system, of what the biological structure responsible for learning, memory, etc., ultimately is. It is not in a cell, it is in the circuit. Understanding how cells are connected; the topology of those connections; how these circuits, both anatomical and functional, are organised, and what alterations occur in people with intellectual disabilities or other cognitive disorders is really important. We are also interested in understanding which of the cells is responsible for each memory.

Before we analysed the entire structure of the hippocampus, a brain region responsible for the acquisition of new memories, to study memory and learning. The brain recognises new information and commits it to memory, based on biological significance. We used to study it as if that were something that happened throughout the hippocampus. Now we study the engram cells [those that encode memory details and that are found in the hippocampus and other parts of the brain] to identify which of them are activated in a special way when we learn something. What happens to those cells? Why are they able to keep that memory? We don’t really know the answer, but we do know that if I manipulate just those cells – and it can be between ten and fifteen cells, depending on the brain region – I can erase a memory or implant a false memory, simply by activating or deactivating those cells with techniques known as chemogenetics or optogenetics. These techniques allow cell reactivation using light or a drug that acts on genetically modified receptors, designer receptors, which open up some incredible possibilities for us. We are studying what the activation of these engram cells is like in animal models of Down syndrome, because it can open new doors for us.

We are engaged in a European project in which we compare patients with depression, some of whom are resistant to treatment and others who respond well to therapy. We have a multiomics analysis, which we can group with clinical and neuroimaging data, thanks to the help of Ferran Sanz’s group [director of the Research Programme on Biomedical Informatics at the Institut Hospital del Mar d’Investigacions Mèdiques and the Pompeu Fabra University]. We hope that this research can help us build a computational model of resistance to depression treatment to ascertain, from the outset and using peripheral markers, whether a patient will be able to respond or not to treatment. Just achieving that would already be a huge help, because many of these patients suffer from depression symptoms for extended periods of time because we do not find the treatment that is effective for them.

From my point of view, Down syndrome is extremely interesting. It is the most common intellectual disability of genetic origin: it affects more than six million people in the world. Secondly, its prevalence has not decreased. Although there are more voluntary terminations of pregnancy in many countries, lots more people wish to continue with the pregnancy too. There are also many older mothers, so Down syndrome is more common. And thirdly, life expectancy has grown dramatically. For all these reasons, Down syndrome continues to be a major health issue.

In most cases, congenital disorders that cause intellectual disability are due to a mutation in specific genes that later have a more complex phenotypic effect. Down syndrome is a scientific challenge, because we have an entire chromosome [chromosome 21] in three copies. That means we have transcriptional dysregulation in the genome. More than 300 proteins that are produced in excess. That is what made us think for many years that nothing could be done about it. But we believe the opposite is true: we think that it is a manageable challenge. And the proof lies in the increasing number of researchers dedicated to Down syndrome. Furthermore, it presents other very interesting aspects, such as the fact that people with Down syndrome have an increased risk of developing some medical conditions, but, in turn, are more resistant to developing others, such as solid tumours or hypertension. This means that there is a protective factor in chromosome 21.

Ninety per cent of people over the age of 60 with Down syndrome develop dementia, which is usually more severe and appears earlier. Down syndrome is especially linked to Alzheimer’s disease. These people have a trisomy [three copies of the same chromosome] of certain factors, such as the protein that produces amyloid, which is found in excess throughout their lives. Therefore, 100% of people with Down syndrome show neuropathological hallmarks of Alzheimer’s disease. Understanding the factors that lead to the development of dementia in people with Down syndrome cannot only help these people, but there are common components with Alzheimer’s that we see in the general population, in sporadic cases, or even in some of the genetic cases. Aside from helping that population to age better, our findings also help to gain a better understanding of Alzheimer’s itself.

It was great how online research emerged at the outset of the pandemic. At that time, I had just left the presidency of the Trisomy 21 Research Society (T21RS) and families had expressed their concern to me over the possible greater susceptibility or vulnerability of people with Down syndrome to Covid-19. I conveyed this concern to the executive committee of T21RS, which considered it to be a vitally important issue. It was clear to them that our society had to do something. I spoke with Agustín Matías, managing director of Down Spain, who informed me that similar work had begun in Madrid, Santander, Barcelona, etc. We held a joint meeting to agree on the same survey to attain lots more cases for the study. We submitted the proposal to the executive committee, which went on to cover not only Spain, but also almost the entire world. We have cases almost all over the world, in Brazil, India, Europe, the United States, Canada, Africa...

There are several genetic factors that make people with Down syndrome more vulnerable to Covid-19. On the one hand, Down’s people have three copies of the protein that is responsible for allowing the virus to enter the cell, so the virus has more entry points to the body. On the other hand, its intracellular signalling pathways are favourable to how the virus acts, compromising the cell’s DNA and genetic systems. And then, in symptomatic terms, people with Down syndrome have immunological alterations that make the whole cytokine storm triggered by Covid-19 more serious. Thus, not only do they have a higher potential risk of contracting the disease, but also when they contract it, it can be more severe. Experience has shown us that people with Down syndrome spend more time in the ICU, take longer to be discharged and have a higher risk of dying when severe Covid occurs.

From the get-go, it’s hard to define creativity. The next obstacle is how to objectively and experimentally measure and address this aspect of our brain. How can we determine whether someone is creative or not? The brain of artists has been compared to that of non-artists, but this method provides a partial response to what creativity is. Why will artistic creativity be the only kind to exist? Scientists are also creative and have innovative and original ideas. If we wish to ascertain which areas of the brain are activated in a creative process, how do we situate a person in a creative moment? Perhaps that moment is not the only one contributing to creativity: what happened prior to that moment of inspiration? What has to be activated for it to come about? If we could have systems to conduct what is known as longitudinal monitoring of brain activity in the future, we could endeavour to investigate creativity, if the person told us at what point in time an idea came to them. Ideas do not come to us when we are working hard on something but when we stop thinking about it, when having a beer or taking a shower.

We know that the brain’s attention span, especially in young people, does not exceed about 30 or 40 minutes. So what’s the point of giving one-hour classes? We also know that the brain is very visual. Therefore, in master classes, the use of images and not just the spoken word is important. We also know that the brain likes to be told stories. If you can turn a class into a story or learn by experience, get out of the classroom, do things… that knowledge is better recorded. Unfortunately, very little research into neuroeducation has been carried out. However, we are fortunate to have a chair of neuroeducation at the University of Barcelona to study how the learning process takes place in the classroom with a view to improving it. In any event, in science, the most complicated part is always the transfer, that is, transferring the findings in neuroscience to the teacher’s day-to-day work.

There is a common tendency to demonise screens, but I think they have a positive and a negative side. On the one hand, new technologies have democratised knowledge and have made it much more accessible to one and all. On the other hand, it is true that studying solely with screens affects the way of learning. Now you go into Google and there is no need to relate a concept to other things, since Google already makes all the suggestions for you. What’s more, your attention tends to be very divided: you are looking at one thing and suddenly an alert pops up and you switch screen... It has been proven that we skim more on the internet, in other words, we spend less time on each page and read it more superficially. Screens affect attention and concentration more than memory and learning itself. Then there is the importance of multisensory experiences that technology does not provide. For example, when reading a book, you hold it in your hand, smell it, turn the page, and feel its thickness. In this case, the experience is much richer and helps you focus more.

Sleep plays an important role in the consolidation of memory. People suffering from fragmented sleep or sleep problems generally have more trouble learning and retaining information. That’s because the hippocampus, a very important part of the brain for memory, replays the things we’ve learned at night. This memory consolidation process is critical for memories to be retained in longer-term memory.

Firstly, advances in understanding the brain are applicable, and are in fact being applied with greater or lesser success, and in a relatively professional manner, to many fields. The field of decision-making plays a large part in economics and marketing, for example. Advances in understanding mental illness are helping to reduce the impact of mental disorders and to improve the quality of life of those suffering from them. One in three Europeans will suffer from a disorder of this kind at some point in their lives. Rehabilitation has also been improved thanks to neurotechnology methods, robotic rehabilitation therapies, and so on. Using different sensors we can help people who cannot speak by reading their brain waves so that they can communicate.

Neuroscience is currently one of the foremost disciplines in scientific terms. Unfortunately, it has been granted very little importance from the point of view of funding, especially at European level. Most funding has been earmarked to study cancer and that has led to spectacular breakthroughs in research, but we forget that brain disorders are highly prevalent and also bear an enormous economic, social and personal cost. The time has come to support mental illness. Between us all, we would have to speak out for this to happen.