The document discusses the history of prediction throughout time from magical thinking to complex rational thinking. Early humans used magical thinking and symbols to predict the future, believing they could control outcomes. Rational thinking developed methods using data and logic. However, predictions face limitations, as some phenomena are probabilistic or chaotic. Modern predictive models aim to move from group to individual predictions to tailor treatments to patients.

1. Making Predictions throughout History Riccardo Valdagni ESO Prostate Cancer Programme Coordinator European School of Oncology, Milan (IT)

2. Why Talk about Prediction throughout History? I first heard about predictive models (building the first formula to predict positive nodes for pelvic radiation) when I was in Stanford 25 years ago. And during the Nineties I was fascinated by the possibilities of trying to anticipate clinical outcomes in the single patient. But it was only in 2007, while I was holding our first nomograms on radiotoxicity, that suddenly I asked myself: why this interest? Are predictive models only related to my profession ? Did they start and gain popularity with Partin and Kattan ? Are they confined to very limited fields? Or …

3. … Or ... … are they deeply rooted in our everyday life though camouflaged?

6. “ The fact that humans have self-awareness as well as instincts also forms the basis for free will, and implies that humans experience not only the benefits but also the responsibility and the weight of freedom of choice ” U. Galimberti, philosopher, “Myths of our times”, 2009 M. C. Escher, Drawing Hands , 1948

7. Throughout history methods and instruments for predicting the future have been conditioned and modified by the type of thinking: Magical Thinking, Symbolic Thinking, Positivist Thinking, Complex Rational Thinking

8. Lascaux Drawings, 15.000 – 13.000 BC Magical thinking According to magical thinking, humans can not only predict but also shape the future

9. Magical thinking If the moon is full, the hunt will be abundant. If I drink that potion, I will win the fight. If I fall from that cliff and survive, I will be the chief.

10. Symbolic thinking According to symbolic thinking, the symbol is a material or abstract entity which refers to a meta-physical entity An example of symbolic thinking is astrology which dates back to Babylonian cultures but has so many fans nowadays! Enuma Anu Enlil, earliest extant Babylonian astrology text, 1600 BC, describing astronomical omens and their application to national and political affairs.

11. Antother example of symbolic thinking is divination which took on many forms. One of the most interesting is Haruspicy: examining the entrails (particularly the liver and intestines) of sacrificed animals it was possible to understand divine signs or how to behave in certain circumstances or if the war could be won. Giovanni Caselli, Divination by an haruspex. Haruspexes wore fringed cloaks and tall conical hats and used a special wand with a spiral-shaped end known as a lituus. The figure of the wizard is thought to have derived from this type of clothing. The Piacenza Liver , I-II century BC , bronze sculpture marked with the regions and names of the gods, used to compare the liver of sacrificed animals.

12. In the 15th century people began to collect data on the natural world systematically but were not able to use this data as part of a scientific paradigm. Magical-symbolic prophecy began to lose importance. Astronomy and alchemy became the new focuses of interest. Modern thinking

13. Rational thinking began to progress in the 16th century. The French astrologer, writer and apothecary Nostradamus was the first who systematically studied possible correlations in historical events and set up the first ever concept of a “database”. Nostradamus (Michel de Notre-Dame), 1503-1566 According to his supporters, examining “historical courses and recourses”, Nostradamus, one of the most important prophecy writers in history, predicted future events such as the French revolution, the advent of Hitler, and the atomic bomb. Rational thinking

14. In the Renaissance, man was placed at the center of the world, feeling in a position to understand the secret analogies which lay within this infinitely complex reality. Leonardo’s famous drawings of the Vitruvian proportions of a man’s body inscribed in a square and then in a circle provides an excellent early example of the way in which his studies of proportion fuse artistic and scientific objectives. 1490, Gallerie dell’Accademia, Venice

15. Rationalism Reason is the source of knowledge. Visible phenomena can be measured with tested instruments. The measurements can be correlated with mathematical formulae and according to linear logic. And applying linear logic … experience, deduction and logic enable us to predict the future. Renè Descartes (1596-1650) Isaac Newton (1642-1727) Baruch Spinoza (1632-1677)

16. Late 18th - early 19th centuries, Malthus, the father of modern futurology, came up with the concept of preventive control. Robert Malthus (1776-1834) Based on precise observations and calculi, he correlated demographic growth with food production, and production and storage capacities with consumption. His aim was to “predict” when food supply would run out. Rationalism

17. A spectacular success was, in 1705, the prediction of the apparition of Halley's Comet in 1759. Another great achievement was in the field of chemistry. In 1870 Mendeleev predicted and described properties of a number of elements yet to be discovered (gallium, scandium and germanium) . Dmitrij Ivanovič Mendeleev(1834-1907) Rationalism

19. In the social sciences “prediction” is reduced to an “analysis of possibilities”. We can analyze the problems which a society may face but because there are various strings of solutions to choose from, the actual outcome of events is never (and never will be) predictable by nature M. C. Escher, Tower of Babel, 1928 M. C. Escher, Three Spheres II, 1946 Rationalism : not only a success

20. Prediction showed several limitations also in understanding and predicting the outcomes of very complex phenomena such as the universe, diseases and the unconscious . Rationalism : not only a success

21. In 1903 Poincaré theorized the concept of Deterministic Chaos and promoted the analysis of the behavior of dynamic systems that are highly sensitive to initial conditions. Small differences in initial conditions may cause widely diverging outcomes for chaotic systems, rendering long-term prediction impossible in general ( Butterfly effect* ). * E. Lorenz, metereologist Predictability: Does the Flap of a Butterfly’s Wings in Brazil set off a Tornado in Texas? American Association for the Advancement of Science, 1972 M. C. Escher, Butterflies,1950

22. Two segments of the three-dimensional evolution of two trajectories (one in blue, the other in yellow) for the same period of time in the Lorenz attractor starting at two initial points that differ only by 10−5 in the x-coordinate. Initially, the two trajectories seem coincident, as indicated by the small difference between the z coordinate of the blue and yellow trajectories, but for t > 23 the difference is as large as the value of the trajectory. The final position of the cones indicates that the two trajectories are no longer coincident at t=30 The flapping wings of a butterfly represents a small change in the initial condition of the system, which causes a chain of events leading to large-scale phenomena. Had the butterfly not flapped its wings, the trajectory of the system might have been vastly different.

25. Predictive systems began to use the logics of complex thinking based on Cybernetics and Systems theory. A complex system is made up of a large number of elements. These interact in such a way that the dynamics produced are different from those governing each individual element. Understanding how a bird flies … … does not mean we understand how the flock flies! Complex thinking

26. Magical-symbolic thinking Rational thinking Complex thinking Thinking involving abstraction and use of universal paradigms: complex aspects are handled as a sum of minor issues to be solved separately Deep knowledge of initial conditions is regained. Correlation among separated issues is highlighted Historical evolution of human predictive thinking Causal reasoning that looks for correlation between acts, symbols or utterances and certain events

27. 20% 6% 24% 15% 10% 30% 35% Predictive Medicine If we apply these historical passages to the history of predictive medicine, we may say that we are trying to move from group prediction to individualized prediction…

28. to “tailor-made” treatments designed to suit the individual patient The Tailor , GB Moroni, c. 1570, National Gallery, London Prediction in medicine That is… from standard, pre-packaged treatments with patients fitting into stages or risk classes

29. So, to end this long discourse, from Magical Thinking to Symbolic Thinking to Positivist Thinking and to Complex Rational Thinking, considering the limits of reason, not forgetting the chaos and the relativity, balancing the pros and cons of probability thinking …. Courtesy by S. Wheeler How about a short story to answer the question many of you would like to ask: shall we use predictive models then?

31. “ Look, thank God, oops, thank Zeus you have no kids. If ever a son should come from your marriage bed, remember: the boy would kill you, his father, and marry Jocasta, his mother. And this is just the beginning, my friend. Misfortune and disgrace will follow to ruin your house and your kingdom” The Sphynx and Oedipus, J.A. D. Ingres, 1808 Without telling his wife, he travelled to Delphi in Greece and fixed an appointment with the world famous and esteemed oracle. And the oracle said: Laius was frightened to death. “What shall I do to save my life? I’m in danger, man”. So after some thinking he made his decision. He went back to Thebes and without a word of explanation he rejected his wife.

32. Laius was desperate and scared as hell and tried to get rid of the kid. The problem for Laius was the child was saved and taken to the court of the king of Corinth. There he was given the name Oedipus. Apollo’s Temple , Delphi, VII century BC Oedipus tried as hard as he could to escape the prophecy and kept at a distance from his mother and father. Unfortunately he ended up killing Laius and marrying Jocasta, without realizing that they were his parents. Jocasta was really mad at him for having thrown her out of the house. So, one night, she managed to get him drunk and lie with him. And she got pregnant too!

34. And this is my prediction for our conference: Thank you for your attention As Prostate Cancer Programme Coordinator of the European School of Oncology and as Co-Chair of the conference Considering the esteemed faculty Peter Scardino, Louis Denis, Karim Touijer and I managed to have in the program I am quite sure I can predict a successful, interesting, debated and stimulating conference!