My opening speech for the Insigneo Showcase 2017

Dear members of Insigneo, dear students and research associates, honoured guests, representatives of our academic, industrial and clinical partners, of the research funders, and of the management of the University and the Trust, I warmly welcome you to the Insigneo showcase 2017.

Today, through the presentations of 16 members of Insigneo, we will provide you sample, hopefully representative, of the extraordinary research and technological innovation work that this institute has undertook in the last 12 months.  The four sessions of the programme well represent our objectives:

We believe in silico technologies can transform fundamental biomedical research, and the session "In silico Science”, Chaired by Damien Lacroix, will provide you a small but representative sample of this important work.

At the core of Insigneo there are radical technological innovations that enable all we do; the session "In silico Technologies”, chaired by Andrew Narracott, will give you a taster of some of them.

After lunch we will focus on the clinical and industrial applications.  The session "In silico Medicine: Predictive Medicine” chaired by Paul Morris, will offer some examples of how in silico medicine is transforming clinical research; the last session, "In silico Medicine for Industrial Exploitation” chaired by Gwen Reilly, will instead offer a sample of the translation toward new biomedical products and technologies.

During the breaks please visit our poster area, where you can catch a much broader view of what we are doing, and stop at the booths where we and our industrial partners show some exciting ideas.

At the end, after Damien conclusions, please try to stay a bit longer if you can, for our drink reception, where we can relax, socialise, and network.

In October 2011, a bit less than six years ago, I started to work at the University of Sheffield, with the mandate to setup a research institute on in silico medicine.  The few of you who were into this adventure from the very beginning know with how much trepidation I started.  After 25 years working in the same institution in Italy, it was a big change, most was unknown.

but I got lucky.  Here I found Rod, I found Pat, Wendy and Richard, Paul and Simon, Damien joined us soon after, and slowly I started to be confident we would make it. And we did: in May 2012 the Insigneo institute opened its membership, and today we celebrate five years of uninterrupted success.

But this is not the end, it is just the beginning.

I want you to picture Insigneo today as one of those 5-year old boys, who runs around constantly, and cannot keep calm for all the gold in the world. It is like there is too much energy bottled up in that little body, can you see it?

OK that what I want Insigneo to be in the next five years.  a restless, over energetic kid, that enthusiastically explore every possible direction of development and improvement.

I want to see Insigneo Ltd, to commercialise our services; I want to see Insigneo international, to fight the effect of the Brexit.  I want to see large clinical trials fully augmented with in silico technologies, and more and more hospital specialists taking clinical decisions with the support of our subject-specific models.  I want to see the next generation of specialist trained in our new master spreading through the world, and make the vision of the Virtual Physiological Human a global reality; I even want to see a module of computational medicine in the standard curriculum of our medicine and nursing students, some time soon.

We do live interesting times. I am sure you have heard of the story of the wolves.  The grandpa tells the grandson that are two wolves constantly fighting inside each of us: one is anger the other is hope; which one will win, ask the grandson? The one you feed, answer the old man.

Well, in Insigneo we plan to feed only the wolf of hope, tolerance, and social justice.  Please dream with us of better futures.

The role of in silico medicine within biomedical research

The publication in 1823 of the first issue of Lancet symbolically marks the 19th century revolution of biomedical research. Out of this expansion, modern biomedical research organise itself around three fairly different paradigms, each trying to cope with impossible complexity of human body:

• Cellular and molecular biological research, driven by an aggressively reductionist agenda, which focus on small sub-units of the system;
• Clinical research, which largely treats the human body as a black box, and vastly relies on the statistical modelling of empirical observations;
• Physiological research, which tries to investigate the human body following the approach typical of physical and engineering sciences.

The third approach, undermined by the dramatic limitations of 19^th-early 20^th century calculus and instrumentation, has been the least successful of the three, and its importance has been progressively decreasing.

Two events we believe are changing this scenario: the first is the dramatic progress that physical and engineering sciences drove around biomedical instrumentation. Using x-ray, magnetic fields, ultrasounds, we can now imagine the inside of the human body with amazing accuracy; automated chemical analysers, spectroscopes, sequencers are offering a high-throughput biochemistry that open entirely new scenarios; the amazing capabilities of modern electrophysiology give us details on the working of the heart, the muscles, the brain; motion capture, dynamometry and wearable sensors offer a detailed view of the biomechanics of human movement.  In short, today we can collect a deluge of quantitative data on each individual patient that describe in full detail their anatomy, physiology, biochemistry, metabolism, etc.

The second is the amazing development of calculus, thanks to the advancements of mathematics, computational science and engineering, and of the raw computational power that modern hardware and software can offer to modelling and simulation.  This development is essential, because for the first time in history we can solve the enormous number of complex mathematical equations that can quantitatively describe many physiological and pathological processes; we can finally handle the complexity, and we do have the means to measure pretty much all we want to measure in each individual patient. 

The problem with complex living organisms is that they are dramatically entangled, so the functioning of each of their parts can hardly be assumed independent from the others; while large part of biological research ditch this problem with reductionism, and clinical research bypass it entirely by renouncing to the search for detailed mechanistic explanations, a biomedical research agenda based on the methods of physical and engineering sciences must face this complexity; and this is possible only if we use mathematical and computational methods to formulate our theories and quantitatively compare their predictions to experimental observations as primary mean of their tentative falsification.  

At the same time, once a theory resist extensive falsification, the predictive model that embodies it can be used to solve clinically relevant problems, as many of the grand challenges of modern medicine (prevention, personalisation, participation) would be easily addressed by an increased ability to accurately predict the course of a disease or the effect of different treatment option for each individual patient. 

Therefore, we believe in silico medicine is the main road through which the great physiologists of the past generation will be ultimately proven right, and a biomedical science based on the methods of physical and engineering science will become more and more successful.

In this sense, we believe in silico medicine is not only a new family of technologies we can use to investigate the human body, but it may enable a paradigm shift in the sense proposed by philosopher Thomas Kuhn, “a fundamental change in the basic concepts and experimental practices of a scientific discipline”.