She defines herself as “very curious and very hyperactive.” Mara Dierssen (Santander, 1961) says that she owes who she is to the result of the combination of a painter mother and a neurosurgeon father. “Art and science are not two very different human activities.” He says that his approach to science is the same as that of an artist: “Both require creativity, the ability to see things with different eyes, and not to go overboard. The painter pays attention to the details, the scientist sees what others don’t see.”

The Cantabrian neurobiologist is one of the references in the field of brain research. That organ that refuses to reveal all the mysteries of its functioning. “We are taking steps forward in our understanding of brain mechanisms, but we have a long way to go.”

However, far from being pessimistic, he says that currently “neuroscience is going through a great moment.” And this is due to multidisciplinarity. Beyond neurologists, today one can find in this mission “electrophysiologists, anatomists, mathematicians, philosophers, cognitive neuroscientists, psychologists, neurocomputing engineers…”. He highlights the role that each one plays. “At this moment there are many people working on understanding diseases while others are working on finding treatments, obviously I am also dedicated to that.”

Dierssen stresses the first step: understanding the organ and its pathological processes, because this is what opens the door to “understanding the mechanisms of the brain’s functioning.” “And that is where I will never tire of supporting basic research,” he says.

For her, it is essential to lay the foundations for the advances that reach patients in the form of a cure or treatment in laboratories. Recent examples demonstrate this: without the work awarded this year with the Princess of Asturias Award for Research, the famous drugs against obesity and diabetes, Ozempic or Mounjaro, would not be possible today. Without the effort and tenacity of Katalin Karikó, Nobel Prize in Physiology or Medicine 2023, a pioneer in the development of mRNA vaccines, the outcome of the Covid-19 pandemic today would be different.

In the conversation with EL MUNDO, hours before participating in a new edition of Nobel Prize Conversations organized by Nobel Prize Outreach and the Ramón Areces Foundation this Thursday, in which Karikó participated, Dierssen provides a detailed review of many of the issues that pertain to his work, the challenges of his field and those intrinsic to the scientific profession.

The neurobiologist heads the Cellular and Systems Neurobiology group of the Systems and Synthetic Biology program at the Centre for Genomic Regulation (CRG) in Barcelona. Her main lines of research revolve around the mechanisms underlying cognition and behavior and its disturbance in mental disorders. He also dedicates great efforts to unraveling the neurological mechanisms of Down syndromea field in which he is a world reference.

What challenges keep you busy in the lab today?
We remain interested in How information is stored in the brain and how it is retrieved. At this moment we are working on a new line because techniques have been developed that allow you to specifically mark the neurons that are activated when you learn something; In addition, you can manipulate them so that you can reactivate them. It’s as if you can reactivate a specific memory. This allows us to understand how memories are stored in people, in our case, in animal models that have the human homologous trisomy 21.
Have they found anything significant?
One of the things we have discovered is that, unlike Alzheimer’s models in which the memory is there but cannot be recovered, in Down syndrome, what happens is that the memory is not formed correctly. So we are investigating what we can do to achieve, not only to activate the memory, but also to record it better. But in a much more specific way. Because the problem with pharmacological treatments is that they are very non-specific.

As?
What you do with a pharmacological treatment you transfer to the entire brain without actually choosing the region where you want to act; because it works as long as there is a receptor for that drug. So it’s pretty nonspecific. On the other hand, seeing therapy in a much more targeted and concrete way is providing us with very interesting advantages. But not only that, we are discovering that there are many elements involved, even those that were previously thought to be irrelevant. When the human genome was discovered, it was thought that what was called the dark genome was of no use. But today we know that this is almost more important than the genes that code for proteins, which at that time was thought to be the most relevant.
What does this progress translate into?
Well, now we know that those regulatory regions have a role. In fact, what we have seen is that medications that act on these elements, new designer drugs, could be very interesting for people with Down syndrome or other disabilities.
Regarding Down syndrome, is there little effort in the field of research in search of answers about therapeutic approaches?
Absolutely. In fact, this is not only the case for Down syndrome, but for most neurodevelopmental disorders. It is difficult to find a treatment, and even more so in the early stages, because they have a carry-over effect from childhood. There has been very little support for research into Down syndrome, as well as for treatment strategies.

Do we now have a tendency to make this syndrome invisible at a social level?
I don’t so agree with this statement. People with Down syndrome now live much longer. Therefore, what we are finding now is that there are other problems associated with it because most cases develop Alzheimer’s disease. I think society has started to see the value of these people. Perhaps they may have learning, memory, or intellectual problems, but on the other hand, on an emotional level, on a level of solidarity, they are individuals who contribute a lot within families.
So there is less stigma?
I think we are beginning to change that mentality a little, although it is true, and I am completely right about that, that on a social level we still have that stigma. The problem is that our model is based a lot on productivity, on competitiveness… “I have to be the first, I have to do everything better than anyone else…”. And what does that translate into? Relegate people who are different.
But our society is diverse…
Exact. In the studies that have been done on this, it is seen that the region of fear and aversion is activated a little when we see someone who is not the same as us. So, that generates a series of stereotypes. But the same thing happens with older people. Before, the elders were the wisest of the tribe. Our society greatly lacks diversity and we see this in all areas. Simply with gender: how is it possible that half of the population, half of the talent is not encouraged and is not fully incorporated? In the scientific system, in the political system, in the business system… It’s incredible!

Dierssen is demanding in all areas. Also in the scientific one, in which she promotes from the Trisomy 21 Research Society – which he initiated together with other researchers and chaired – that people with Down syndrome, “who we know have amyloid deposits from a very young age”, can access clinical trials with drugs from which they could benefit.

There are also critics of how science is done today. Many of them involve the “publish or perish” approach, which explains the continuous demand for scientists to have a kind of fast food scientific. «The other day I read that 42% of papers The ones that are published are not cited. But you don’t have time to read everything that comes out.” Regarding the time needed for research and changes in direction, he says that “if I have found something that is super interesting, why do I have to verify the hypothesis? Scientists need freedom of thought, we need to be able to decide on what we see.”

“There has been very little support for research into Down syndrome, as well as for treatment strategies”

Demand diversity in clinical trials, where biases condition access. “The only studies that really imitate society, that is, the clinical situation that you are going to find yourself in are those called Real World: take every patient that comes through the door,” he clarifies. The problem, as he explains, is that you cannot then have “statistical results” because the response of the therapy will be different in each patient.

Here, Dierssen, as part of the Spanish Brain Councilhas a series of proposals that will be collected in the future Spanish Brain Plan. «In neuroscience, we have to do the same thing as in cancer with the studies basketball and umbrella: where one drug has different diseases or there are several drugs for a single disease.

What is the goal of the Spanish Brain Plan?
We are very vocal about brain disease and brain health. Why? Because we are facing a pandemic of brain disease. This includes neurological, psychiatric and neurodevelopmental diseases, obviously. There is an increasing incidence of each of them and because others, such as long-term Covid, have also had a very significant impact. They are a source of absenteeism at work.
What actions do you have underway?
We have carried out a very important campaign with the MEPs through the European Brain Council to really put brain health on the table and as a cross-cutting priority. We have had a very good reception. We have received a lot of replies from MEPs expressing their interest and we are very pleased because there are also all political colours; that seems to us to be very good news. Health and science do not have a political color. The idea is to also involve patients and scientists and train them so that both benefit from the processes. We also want records: there is no data, only estimates of neurological diseases in Spain. We need to work with the administration, because in Spain the postal code influences access to treatments.

However, brain pathologies ‘have come out of the closet’ and now there is more talk about them. Mention brain health, does technology help us maintain it?
It is complicated if we outsource our brain functions to machinesmemory or calculation, that is a mistake. There are studies on taxi drivers, waiters and even musicians that show how there are regions of the brain that are enhanced by the skills of their work.
So, what do you think of it being said that artificial intelligence will be able to replace a human brain?
I don’t think it will be possible. Something that you don’t know how it works cannot have a substitute. As a friend of mine used to say, it is neither intelligence nor artificial, that is, what AI does is look for patterns. It seems strange to want artificial intelligence to help us understand how our brain works and then replace it…
One of the maxims is to live longer, but with quality of life. Is the brain prepared to live 100 years?
It’s an interesting question. We have a chronological age and a biological age. As we get older, there are more errors in genetic transcription. And these accumulate over time. The brain is a very plastic organ And it is precisely the most plastic regions that are most sensitive to this process. If a good cognitive and cerebral reserve is generated, that is, we have maintained good brain health, we have kept it active, it will arrive in better condition, yes. That is apart from illnesses, of course. But, if it is not used, it is outsourced, nothing at all: no cognitive reserve, no cerebral reserve.

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