ORALS

SESSION: MedicineWedPM1-R1	2nd Intl. Symp. on Technological Innovations in Medicine for Sustainable Development
Wed. 29 Nov. 2023 / Room: Dreams 1
Session Chairs: Hans Leuenberger; Gregory Knipp; Session Monitor: TBA

14:05: [MedicineWedPM105] OS Plenary
THE ORGANIC SUPERCOMPUTER ABLE TO REPLICATE AS VIRTUAL PATIENT
Hans Leuenberger¹ ; ¹University of Basel, Basel, Switzerland;
Paper Id: 63 [Abstract]

In 1869 Friedrich Miescher, Basel, first identified "nuclein" inside the nuclei of human white blood cells. This term was later changed to “deoxyribonucleic acid” (DNA) [1]. Erwin Schrödinger published in 1944 “What is Life?” by predicting the role of DNA [1] as genetic code [2]. Based on the work of Nobel Laureate Ilya Prigogine, Hans Leuenberger wrote “What is Life? A new Human Model of Life, Disease and Death – A Challenge for Artificial Intelligence and Bioelectric Medicine Specialists” [3] for the 40th anniversary of SWISS PHARMA. Later he presented “Virtual Patient & in-silico Design of Solid Dosage Forms”[4]. The current model of a Virtual Patient is described by 4 pillars of the Center of Pharmacometrics & Systems Pharmacology, CPSP, at the University of Florida [5] consisting of Population Pharmacokinetic and Pharmacodynamic Modeling, Real World Outcomes, Artificial Intelligence and Mechanistic Modeling. The goal of CPSP is to create a rigorous and integrative academic translational science program in quantitative clinical pharmacology with a focus on bio-simulation. The common denominator is modeling. The first two pillars are linked to many patients. Artificial Intelligence tries to mimic a human being in 4 steps, Machine Learning, Deep Learning, Theory of Mind, and Self Awareness. Mechanistic Modeling is inspired by Physiologically‐Based Pharmacokinetic Modeling and Simulations that need to be complemented by cardio-vascular and nervous wiring system etc. In other words, the holistic VIRTUAL PATIENT can be described as an organic supercomputer able to replicate, consisting of approximately 40 1012 cells as microprocessors [3, 4]. This healthy being corresponds to stage 4 of Artificial Intelligence. The computer operating system of the VIRTUAL PATIENT is, as we know, sensitive to single drugs, to a combination of drugs (HIV treatment), to the combination of Syrosigopine, and Metformin as an anti-cancer agent [6]. Thus, the combination of low dose generic drugs opens a new research avenue in drug discovery [7] avoiding preclinical trials. Since Paracelsus, University of Basel, we know that the toxicity of a substance depends on the dose. Unfortunately, the early dose of a discovered drug is usually high for showing a significant effect. Our system is sensivitive to food, such as grapefruit, which is interacting with drugs, to parasites such as worms, to bugs and to viruses, etc. If our body (computer hardware) is severely damaged by a car accident can it be rebooted as a supercomputer, respectively reanimated as human being in an emergency room? As conclusions, it is proposed 1) to systematically evaluate combinations of n drugs, with n = 2, 3...m low dose generic drugs. In an optimal case new safe therapies of n drugs showing less side effects can be registered. 2) The pharmaceutical industry should adopt the workflow of the automotive industry by first evaluating in-silico the tablet formulations before manufacturing the drug delivery systems [8]. Thus, time to market can be reduced. 3) The sensitivity of the VIRTUAL PATIENT = DIGITAL TWIN can be explored on the basis of Clinical Phase I – III studies using a combination of n low dose generic drugs [7].

References:
[1] Pray, L. (2008) Discovery of DNA structure and function: Watson and Crick. Nature Education 1(1):100 [2] Erwin Schrödinger, WHAT IS LIFE? First published 1944 Reprinted 1945, 1948, 1951, 1955, 1962, Canto edition with Autobiographical Sketches and © Cambridge University Press 1992 Foreword to What is Life? by Roger Penrose, 14th printing 2013. [3] Hans Leuenberger, “What is Life? A new Human Model of Life, Disease and Death, SWISS PHARMA, 41 (2019) Nr. 1, 20 – 36; & PHARM TECH JAPAN, 35, 14 (2019) 55(2765)-61(2771) in Japanese. [4] H. Leuenberger, invited lecture, Virtual Patient & In-Silico Design of Solid Dosage Forms at the 12th PBP World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology (11.05 - 14.05.2021). [5] Stephan Schmidt et al, Requirements, expectations, challenges and opportunities associated with training the next generation of pharmacometricians, open access, May 2, 2023, https://doi.org/10.1002/psp4.12970. [6] Benjamin et al, Syrosingopine sensitizes cancer cells to killing by metformin. Sci. Adv. 2, e1601756 (2016). [7] H. Leuenberger, invited Keynote Lecture, Gala Technology 2013, May 8, Artificial Intelligence, Digital Revolution & New Research Avenues, Shinagawa Prince Hotel, Tokyo. [8] D. Maneerojpakdee et al. An attempt to adopt the workflow of the automotive and aircraft industry for the design of drug delivery vehicles , Pharm. Tech. Japan, 33,11 (2017) 145-156.

SESSION: MedicineWedPM2-R1	2nd Intl. Symp. on Technological Innovations in Medicine for Sustainable Development
Wed. 29 Nov. 2023 / Room: Dreams 1
Session Chairs: Hans Leuenberger; Gregory Knipp; Session Monitor: TBA

16:00: [MedicineWedPM209] OS Keynote
BLOCKAGE OF THE FIRST EXCITED STATE OF 198HG
Angelo Comunetti¹ ; Hans Leuenberger² ; ¹Gempenstrasse 13, CH-4104, Oberwil, Switzerland; ²University of Basel, Basel, Switzerland;
Paper Id: 333 [Abstract]

A 197Au solution with bi-distilled water was prepared using a single gold electrode, connected to a special oscillator with a sinewave voltage of 50 Hz at 160 V. It was known that it was not possible to detect gold in such a solution by chemical analysis at room temperature. Thus, neutron activation analysis (NAA) by creating 198Au seemed to be the method of choice for detecting the missing gold. 198Au is a b emitter that decays to an exited state of 198Hg nucleus, subsequently emitting a g photon of 411.8 keV, that can easily be detected. For this purpose, three solutions were prepared: Sample 0: 100 ml of water as zero-reference in case of impurities. For samples I and II, 200 ml of the same water were treated by a single electrode for 16 hours. Immediately after the treatment, the 200 ml were split into two samples perfectly mixed: sample II, i. e. 100 ml of the treated water was heated above 60°C, sample 0, had been heated before, and sample I, i. e. 100 ml of the treated but not heated water. All 3 samples together were exposed to a flux of thermal neutrons. Result: only the treated and warmed sample II showed the typical peak of g photons with the energy 411.8 keV. Samples 0 and I did not show any trace of gold. Sample I, as well as the other samples, were kept at room temperature for 11 days. The other samples behaved as expected. After a delay of 11 days, sample I was heated above 60°C. Interestingly, no g - photon was detected at 411.8 keV and after a second NAA (on the same, i. e. 11th day) no trace of Au was present anymore. A tentative theoretical explanation of this phenomenon is given by assuming that water can be considered as a semiconductor. Thus, also a photonic band gap can be expected. In other words, and in this context, the 411.8 keV g - rays were localized, if the temperature of the solution is kept below 60°C. This hypothesis is validated by the experimental results, since after heating up sample I above 60°C a mirrorless lasing happened. The fact that no trace of gold was visible is the proof of concept, that the remaining 197Au nuclei show a photonuclear reaction 197Au (g, n) 196Au decaying rapidly into 196Hg. However, in a first step the 198Au (g, n) 197Au reaction occurred leading to a reversal of the 197Au (n, g) 198Au reaction. In other words, the photonuclear reaction excited the collective movements of the neutrons and protons of the 197Au nucleus leading to giant g resonances, and to the ejection of a neutron. In a second experiment the gold electrode was activated by exposure to thermal neutrons. Very similar results were obtained with the exception that between 15% to 20% of the unheated sample showed the 411.8 keV transition.