Human Technopole, man at the centre

This text is part of the Italian Tech album “In search of a better future”, on newsstands with Repubblica on May 4th.

The infinitely small. With a microscope worth 5 million euros, 3 meters high, in the Science and Technology Park of Milan human cells are divided into particles invisible to the human eye, atoms and molecules, after freezing them at -180 °C. The purpose is decipher every aspect of the genome, genes and proteins.
It is the last frontier of science: understanding the functioning of the human machine helps to seek remedies for the most serious diseases, from tumors to neurological pathologies. Thus, in the shadow of the Tree of Life, in the place which in 2015 with the Expo marked the beginning of a rebirth of Milan, a unique scientific adventure in Europe has now started, the Campus Human Technopole, the research institute for life sciences in the heart of the Mind Milano Innovation District, a sort of Silicon Valley of medical and biological sciences.
A completely Italian centre, but an international place. Able to bring back home so many researchers emigrated abroad experts in advanced research. A force of attraction that convinced even the scientist who is now the director to return, Marino Zerial. Italian by birth, but German by adoption, until recently head of the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden.
Its staff includes researchers in their early thirties (one of the department leaders is 38) with at least ten years of experience abroad. They come from thirty different countries, most of them are Italian but have spent half their years in European, Asian and American centers of excellence. The official language? English, the language of science.

They arrive early in the morning by subway and enter the Human Technopole, in what was the Italian pavilion during Expo, a white spaceship of 35,000 square meters that has been completely repurposed. Watching them chat while having a coffee, they look like students from any university, but once inside the laboratories you see them for what they are: scientists capable of sequencing even one hundred strands of DNA in 48 hours. We are entrusting them with research to prevent and fight the big killers of our century. The challenges abound.

The Technopole looks like an American campus, with the Decumanus, the street overlooked by the pavilions of the States, transformed into a cycle path. However, far from the silences and white coats of traditional research centres. It took four years to build. From scratch. When the lockdown began, 19 people worked there, today there are 380 between scientists, administrators and technicians. At the beginning of the recruitment they hired, with international tenders, about one scientist a week.

In one year, 8.5 million funds were raised, mainly European.
To give an idea of ​​how much the Italian research world focuses on Human, it is enough to indicate the fixed annual funding allocated by governments: 120 million euros on average. For ten years. Objective: the dual mission of creating a pole of excellence in scientific research and a support center for laboratories throughout Italy through the creation of the National Platforms.

It feels like entering a spaceship with blue lights. There there are five microscopes: Titan Krios, Spectra, Glacios, Talos and Aquilos. The Titan Krios is housed in the North Pavillon, one of the buildings inherited from the Expo. Where once there was a restaurant, there is now a place where even the smallest fluctuation is recorded. Let’s forget the image of the classic microscope we are used to, here we are talking about electronic cryo-microscopes. Machines based on the studies of the 2017 Nobel Prize winners in Chemistry Jacques Dubochet, Joachin Frank and Richard Henderson.

“I am among the most complex in the world – explains Alessandro Vannini, head of the Structural Biology center, the first department to be inaugurated – . We study the molecular mechanisms of proteins in detail and with this technology we can look down to the level of the atom. We study both the shape and function of genes and the proteins that play a key role in gene regulation. These mechanisms are involved in numerous pathologies and provide valuable information for the study of human pathologies, such as neurodegenerative pathologies and tumors”.

The trial, hearing it from Professor Vannini, eight years spent in the United Kingdom as Principal Investigator and Deputy Head of Division at the Institute of Cancer Research in London, seems like a leap into the future. The cell samples are first “cut” into even thinner sections and frozen in liquid nitrogen at -180 degrees. Placed inside the machine, the nano particle is then hit by electron beams which allow it to be analysed. The images will arrive on a computer screen in a couple of days. The super microscopes, which also analyze viruses and bacteria, never turn off.
In the Milan spaceship that is bringing home the brain drain there is also the building of the genomics where DNA sequencing is studied. Seeing it from here, the road to large-scale personalized therapies to prevent hereditary diseases, or the battle against certain types of cancer no longer seem like a chimera.

“Of course, science needs its time – warns the professor Nicole Soranzo, for years professor of genetics at the University of Cambridge, now head of the research center of medical and population genomics – and we cannot expect to have the results in a few years. It will take 10-15 years.”

Meanwhile, however, the collaboration with the European Cancer Institute in Milan is a certainty and now the large hospital is sending the slides with the diseased tissue samples to the Human Technopole. And here, looking down to the infinitesimal part of the cells, as the researchers led by Professor Sottoriva are doing, one can observe the evolution of the disease, understand where the mechanism of the protein is jammed, one can decrypt information on why there is a drug resistance and arrive at that increasingly personalized precision medicine that will be the therapeutic approach of the future.
The group approaches cancer as a complex system. Studies are also carried out on organoids, matter that traces the primordial stage of the cells on which drugs are tested, we observe how they react to toxic agents, the impact that risk factors have.

A sort of time machine that shows us where something goes wrong. Merge lab data with mathematical models will give way to build new treatment strategies. It also means that we are approaching the time when DNA sequencing will be similar to blood tests and this could pave the way for the prevention of hereditary diseases.
But what are the diseases to which Italians are more predisposed? Professor Nicole Soranzo, included in 2016 among the most influential researchers and scientists in Italy, is trying to give an answer to this question. You have been studying the role of the genetic component in the development of metabolic and cardiometabolic diseases for some time.

“Because – as he explains – there is not only one genome that applies to everyone – Northern Europeans, Southern Europeans, Asians, Africans – but many genomes that have small variations between them. Important for some ways in which diseases develop”.
In Italy he is working on the creating a database, starting from the analysis of 25,000 DNA, to find out if and how there could be a correlation between a certain genetic variation and the risk of getting sick. It’s about the Moli-sani project, conducted by Soranzo and Professor Pietro Carninci, one of the most important scholars of DNA and RNA, deputy director of the Riken research center in Japan and now advisor to the genomics centre.
Twenty-five thousand people in Molise have offered their DNA for scientific purposes. They have been undergoing tests and withdrawals for years. “We don’t want to sound too optimistic, but we have DNA sequencing programs for half a million people. It will take time. Our aim is to create an infrastructure similar to the Biobank of Britain, which wants to reach 5 million, to explore variegated genetics of our country”.

The amount of data will be deciphered by Iorio, the Center for Computational Biology. Falling behind in building this map of human genomes on the Italian population is not possible, given that most of these studies are done in the countries that invest the most in genome sequencing. Studying genomes as broadly as possible means understanding whether certain diseases are caused by specific variants of a certain population. And then try to prevent them and know how to deal with them.
Lights, super microscopes, technologies. The spacecraft landed on the outskirts of Milan never shuts down. For a part of the Italian academic community, however, they are still aliens.

It certainly makes us reflect on the fact that scientists such as Professor Soranzo, or Professor Vannini and Carninci have decided to return to their homeland, leaving behind prestigious careers. “I had ruled out going back but the opportunity to open a research center from scratch was a unique opportunity – says Vannini – , this time I’m sure: it’s different”.
“I returned to Milan with the same conviction – nods Professor Soranzo -. Each of us has left behind laboratories of excellence but then we said to each other: ‘It’s time to create a high-level research center in Italy too’“.
Since then a sort of scientific community has been created, ready to board the Human Technopole spaceship, the great research center for the life sciences. But not only. For our health and well-being in the future.