The future of medicine

U N I V E R S I TĂ„T B A S E L

Susan M. Gasser The future of medicine Mit einem Vorwort von Antonio Loprieno

Schwabe Verlag Basel

Susan M. Gasser T h e f u tu re o f m e d i c i n e M i t e i n e m Vo r wo rt vo n A n to n i o L o p ri e n o

Basler Universitätsreden 112. Heft Rede gehalten am Dies academicus der Universität Basel am 29. November 2013

Schwabe Verlag Basel

Reihe Basler Universitätsreden, herausgegeben von der Stelle für Öffentlichkeitsarbeit der Universität Basel im Auftrag des Rektorats © 2013 Schwabe AG, Verlag, Basel, Schweiz · www.schwabeverlag.ch Gesamtherstellung: Schwabe AG, Druckerei, Basel/Muttenz, Schweiz Gestaltung: Lukas Zürcher, Riehen ISBN 978-3-7965-3262-7

Vo n L e i t b i l d e rn u n d S t ra te g i e n

Antonio Loprieno Die akademische und administrative Organisation der Universität Basel findet in einer Reihe von Schriften ihren Niederschlag, die wir zwar nicht täglich konsultieren, auf die wir uns jedoch beziehen, wenn wir die Korrektheit unserer Handlungen überprüfen oder eine Entscheidung juristisch absichern wollen: Staatsvertrag, Statut, Reglemente, Richtlinien, Wegleitungen. Solche Texte verfolgen das Ziel, unsere Routine (im besten Sinne des Wortes!) zu regeln und unsere Verhältnisse widerspruchsfrei zu gestalten. Es handelt sich also um universitäre Gebrauchstexte. Es gibt aber seit einiger Zeit an Universitäten zwei Textgattungen, die wir nicht nur nachschlagen, sondern aktiv als Orientierungsquellen heranziehen. Ein Leitbild entwickelte die Universität Basel in Verbindung mit einem neuen Universitätsgesetz und der Entlassung in die Autonomie, eine Strategie besitzt sie seit der Erweiterung der kantonalen Trägerschaft. Die humboldtsche Universität Basel brauchte kein Leitbild, und den Begriff Strategie hätten Basler Dozierende wie Studierende vor zwanzig Jahren höchstens mit ihrem Militärdienst in Verbindung gebracht. Beide Begriffe hat die Universität von ihrem gesellschaftlichen und ökonomischen Umfeld übernommen. Leitbild und Strategie stehen in einem zwar typologisch eindeutigen, an unserer Universität jedoch historisch unscharfen Verhältnis zueinander. Ein typologisch eindeutiges Verhältnis: In der Regel wird eine Strategie von einem Leitbild abgeleitet und versucht, letzterem durch explizite Zielsetzungen Konkretisierung zu verleihen. Ein historisch unscharfes Verhältnis: Die Strategie 2014 wurde nicht direkt vom Leitbild aus dem Jahr 1993 abgeleitet, sondern von einer Gruppe von Mitgliedern des Universitätsrates und der 3

Universität sozusagen ex novo – oder höchstens auf der Basis der vorherigen Strategie von 2007 – erarbeitet. Wird also durch die Strategie das Leitbild der Universität ausser Kraft gesetzt? Keineswegs. Vielmehr handelt es sich um zwei Texte, die – anders als etwa der Staatsvertrag und das Statut, aber auch anders als Leitbild und Strategie eines Betriebes – nicht untereinander hierarchisch gegliedert sind, sondern die den Universitätsmitgliedern und der Öffentlichkeit zwei unterschiedliche Zugänge zur akademischen Realität ermöglichen. Auf eine Formel reduziert heisst das: Die Strategie bietet eine pragmatische, das Leitbild eine ethische Orientierung. Die Strategie regelt die tägliche Entscheidungsfindung in unserem Gemeinwesen. Wenn uns zwei Optionen paritätisch anmuten, beziehen wir uns auf das Leitbild. Wie ist es aber, wenn Leitbild und Strategie in unterschiedliche Richtungen zu weisen scheinen? In welchem Verhältnis steht der Leitsatz, die Universität Basel biete ein breites Bildungs- und Ausbildungsspektrum, das auf der Pflege der traditionellen Wissensgebiete beruhe und offen sei für Neues, mit der Kernaussage der Strategie 2014, wonach sich die Universität Basel zur Gestaltung der Forschung an der Maxime ‘Stärken stärken’ orientiere? Klaffen da unsere Orientierungen nicht auseinander? Ich glaube nicht. Im Gegenteil möchte ich Ihnen zeigen, dass auch in einem solchen Fall und ohne Rekurs auf exegetische Kapriolen die strategische Aufforderung, ‘Stärken [zu] stärken’, durch das Gebot der Offenheit für das Neue desambiguiert werden kann. Man kann zunächst die Arbeit von uns allen an der Universität Basel – ob Forschende, Lehrende, Lernende oder Verwaltende – als Ergebnis der Verbindung zwischen zwei Achsen verstehen:

4

EXZELLENZ

GLOBALITÄT

LOKALITÄT

RELEVANZ

Auf der ersten Achse gliedert sich die Ausrichtung der akademischen Arbeit, die sich zwischen den zwei Polen der «Exzellenz» und der «Relevanz» bewegt. Unter Exzellenz verstehen wir das Streben nach einer hervorragenden wissenschaftlichen Leistung, wie sie etwa durch die Einwerbung kompetitiver Drittmittel oder durch Erfolge im interuniversitären Wettbewerb belegt wird. Ein Symptom der institutionellen Aufmerksamkeit für diesen Pol ist etwa unsere Begeisterung im Falle der Vergabe eines Nationalen Forschungsschwerpunktes oder eines europäischen Forschungsprogramms. Relevanz nenne ich hingegen eine besondere gesellschaftliche Anerkennung unserer Arbeit, ihre erfolgreiche Einbindung in Diskurse und Strukturen der Zivilgesellschaft, wie sie sich etwa durch die Zufriedenheit der Studierenden, die Beteiligung des Lehrkörpers an gesellschaftlichen Debatten oder eine überzeugende Nachwuchspolitik manifestiert. Sichtbare Beispiele für Be5

mühungen in diese Richtung sind die Beseitigung von Engpässen in den Betreuungsverhältnissen, die Organisation wissenschaftlicher Anlässe für breite Bevölkerungsgruppen oder die Publikation eines wissenschaftlichen Zeitungsbeitrags. Die zweite Achse der zeitgenössischen akademischen Landschaft betrifft nicht die Ausrichtung, sondern den Kontext universitären Handelns und verbindet die zwei Pole der ‘Globalität’ und der ‘Lokalität’. Globalität bedeutet eine erfolgreiche Präsenz der Universität in der internationalen Welt der Bildung und der Wissenschaft. Beispiele dafür sind etwa die Entwicklung von Massive Open Online Courses oder die Vereinbarungen mit anderen Universitäten, um joint degrees oder um internationale Forschungskooperationen. Unter Lokalität verstehe ich hingegen die Dialektik zwischen der Universität und dem gesellschaftlichen oder wirtschaftlichen Kontext ihrer Trägerschaft: Sowohl die öffentliche als auch die private ­Finanzierung der Universität hängen sehr stark von einer erfolgreichen Interaktion der Universität mit ihrem Umfeld ab. Beispiele für die Wichtigkeit dieser Verzahnung sind etwa die Gründung eines Inkubators oder eines Innovationsparks in unmittelbarer Nähe einer Hochschule oder die Zusammenarbeit mit dem Schaulager im Rahmen des Nationalen Forschungsschwerpunktes ‘Bildkritik’. Es ist wichtig hervorzuheben, dass diese zwei Achsen akademischer Tätigkeit im Prinzip gleichwertig sind. Weder ist wissenschaftliche Exzellenz (wie bei einem Forschungsinstitut) unter allen Umständen gesellschaftlicher Relevanz vorzuziehen (dies wäre das primäre Anliegen eines Think Tank), noch verspricht eine uneingeschränkte globale Positionierung (wie im Falle einer Musikakademie) automatisch mehr Erfolg als eine robuste lokale Verankerung (an der sich in der Regel eine Fachhochschule orientiert). Welcher 6

Verbindung jeweils der Vorzug gegeben wird, hängt mit der Strategie zusammen. Es können gegebenenfalls sogar Anliegen privilegiert werden, die naturgemäss schwer vereinbar wären und die erst durch die Spannung in der Interaktion zwischen diesen Polen entstehen. Denn die universitäre Community selbst spiegelt in ihrer Vielfalt die Varietät gesellschaftlicher Interessen an der Universität als Institution wider.

EXZELLENZ

AKADEMIE Peers in der scientific community

WIRTSCHAFT Stakeholders in der Industrie

LOKALITÄT

GLOBALITÄT KULTUR ‘Mittendrin am Rande’ Theater, Architektur

POLITIK Akteure auf kantonaler und Bundesebene

RELEVANZ

Aus der Kombination der zwei Achsen der Ausrichtung (Exzellenz vs. Relevanz) und des Kontextes (global vs. lokal) resultieren vier Quadranten, die interessante Berührungspunkte mit Donald E. Stokes’ Taxonomie der möglichen Formen von Forschungstätigkeit aufweisen. Dieser in der Wissen7

schaftsforschung bekannten Klassifikation liegen die zwei Achsen des ‘Erkenntnisgewinns’ und der ‘Anwendung’ der Forschung zugrunde; daraus resultieren die phänomenologische Grundlagenforschung (paradigmatischer Vertreter: Carl von Linné mit der Taxonomie von Pflanzen und Tieren), die erkenntnisorientierte Grundlagenforschung (Niels Bohr mit der Erforschung der Struktur der Atome), die angewandte Forschung (Thomas Edison mit den Erfindungen im elektrischen Bereich) und die anwendungsorientierte Grundlagenforschung (Louis Pasteur mit der Entwicklung von Impfstoffen). Auch die zwei Achsen akademischen Handelns erzeugen vier idealtypische Optionen für eine strategische Entscheidungsfindung, wobei sie selten in prototypischer Form, viel häufiger in Kombination auftreten: (1) Man kann die Verbindung von wissenschaftlicher Exzellenz und internationalem Renommee als Richtschnur für strategische Entscheidungen zugrunde legen. Zur Privilegierung dieses Quadranten tendiert die wissenschaftliche Community; Wissenschaft auf Weltniveau ist und bleibt deshalb der erste Bezug für die universitäre Arbeit. (2) Man kann aber auch genauso gut der Verbindung von wissenschaftlicher Exzellenz und lokalem Standortvorteil den Vorzug geben. Das ist die bevorzugte Perspektive unserer stakeholders in der regionalen Industrie. Ein gutes Beispiel für die Berücksichtigung solcher Anliegen ist etwa der Status der Nanowissenschaften als Schwerpunkt an unserer Universität. (3) Der dritte Quadrant, der gesellschaftliche Relevanz und Orientierung an lokalen Bedürfnissen verbindet, ist insbesondere für unsere politische Realität kennzeichnend. Eine solche Priorisierung rechtfertigt etwa die erhöhte Aufmerksamkeit für die Medizin in der gegenwärtigen Schweizer Hochschullandschaft. (4) Im vierten Quadranten treten schliesslich gesellschaftliche Relevanz und Orientierung an globalen Aspekten des zeitgenössischen Lebens und der zeitgenössischen Kultur kombi8

niert auf. Auf unsere Verhältnisse übertragen bedeutet dies die Privi legierung Basels als eines gesellschaftlichen Gebildes ‘mittendrin am Rande’, um den glücklichen Ausdruck von Peter Habicht aufzugreifen. Diese Lektüre der Universität als Motor auch kultureller Dialektik liegt etwa den ­Bemühungen um eine höhere akademische Präsenz von Kunst oder Architektur zugrunde. Diese Verflechtung zwischen verschiedenen Aspekten der Leistung und des geistigen Lebens einer Universität wie unserer ist auch der Grund für die scheinbaren Widersprüche, die wir manchmal in unseren Orientierungsschriften – ob Leitbild oder Strategie – zu entdecken glauben. Scheinbar sind diese Widersprüche deshalb, weil sie nicht einer undisziplinierten Redaktion, sondern einer bewussten Wahrnehmung der Vielfalt akademischer Arbeit ihre Entstehung verdanken. Denn die Universität ist bewusst vielfältig. Und es wäre schwierig, einen Menschen zu finden, der diese bewusste Vielfalt der universitären Realität besser widerspiegelt, in ihrer Person verkörpert und durch ihre Arbeit mitgestaltet als unsere diesjährige Dies-Rednerin. In ihrer Forschungstätigkeit gleichzeitig wissenschaftlich exzellent und gesellschaftlich relevant, in ihrem individuellen Wesen global und lokal zugleich, steht Professor Susan Gasser ‘mittendrin am Rande’ der Universität Basel. Ihre Stimme ist heuer die Stimme unser aller, die wir heute den 553. Geburtstag der Alma Mater ­Basiliensis mit Ihnen feiern dürfen.

9

T h e f u tu re o f m e d i c i n e

Susan M. Gasser Medicine sits at a cross-roads, imposed by a changing world. Medicine was one of the four original faculties of the University of Basel when it was founded in 1460. Over the centuries, the university has boasted a number of revolutionary thinkers in medicine – starting with Paracelsus, who burned the ancient books of Galen and urged doctors to adopt evidence-based, rather than doctrine-based, practices; Daniel Bernoulli, who applied his mathematical brilliance to physiology, and contributed – among other things – a means to monitor blood pressure; Friedrich Miescher, who applied chemistry to biology, to define the major constituent of the nucleus as “nucleic acid”; and his uncle Wilhelm His, who as professor of anatomy, invented the microtome, which opened organs and embryos to the probing eye of the microscope. Not only then, but now, medicine and the healthcare it ensures form a pillar of our university. Moreover, world-wide, over the last 150 years, medical care has assumed gargantuan proportions: 3 thousand million dollars or 18 % of the American Gross Domestic Product is spent on healthcare annually; in Switzerland, it is 12 %. Moreover, as vividly demonstrated for us this autumn, divergent opinions about healthcare can stymie, if not close, governments. And indeed, the past 150 years have been a golden age for doctors. In some ways, their job is unchanged – physicians examine patients, diagnose their ailments and try to make them better. Over the last century, however, medicine has gained new eminence. Medical associations, licensing and prescribing laws help separate doctors from quacks. The scientific definition of the basis 10

of disease and integration of technology into medical treatment have enabled doctors to diagnose consistently, treat effectively and advise on public health interventions, such as hygiene and vaccination. These measures have reduced childhood mortality rates dramatically. In Singapore, for example, mortality dropped from 60 per 1000 to 3 since 1950, in Switzerland from 30 to around 4. We have eradicated many of the infectious diseases that were epidemic killers in the past, and few doubt that the synergy of science-driven medicine and public health policy are largely responsible for this change. They are responsible as well for the dramatic increase in life expectancy, which means that a man or woman born in Switzerland today can expect to live, on average, twice as long as his or her ancestor born in 1850. So here at the crest of the wave, why worry about the future of medicine? Indeed, in the 21st century, soon with 20 % of the population being over 65, the demand for healthcare will increase. The frequency of chronic, lifestyle-induced diseases, like diabetes or hypertension, will continue to skyrocket, along with neurological degeneration. Heart disease and cancer will remain the most common killers in our advanced society, yet living to 80 is no longer considered a privilege, but an expectation. Surely a future for medicine is secure … but which future? On the academic side, medicine is probably the most immediate interface of the university with the society that supports it. Exactly that privileged position makes it, as well, the most vulnerable to public opinions, social trends and – as costs increase – social distrust. While it is easy to convince academic doctors that scientific knowledge benefits mankind, the flow from science to human benefit is not always easy to deliver, especially in an ever less trusting world. 11

Today, I want to explore not only the benefits, but the risks and challenges that the medical faculty and physicians face as they embrace both the deluge of scientific data that confronts them – as diagnostics are based increasingly on high-throughput molecular data – and the risk of a public backlash and distrust of science-based medicine. I propose that distrust stems – at least in part – from an indiscriminate flood of information and testimonials about fraudulent treatments, available on the world wide web. A wave of mysticism, vitalism and prescientific thought pervades the Internet, and at the same time an equally large flood of serious scientific studies is avail­ able as well. The sheer amount of this latter makes it hard for a scientist to master his field, much less a discipline. In view of this, it becomes obvious that medicine must reflect on and design its future carefully, in order to stay at the forefront and not be destroyed by technological and societal change. I will describe three challenges that must be met for the medicine of tomorrow, the first being the data deluge, which is coupled with a severe lack of empirical studies that would allow us to appropriately interpret the information generated by high-throughput technologies. Large patient data sets and globally accessible databases play an increasingly important role in biomedical research and in medical practice. We are soon able to decipher a human genome – 3 thousand million base pairs – for under 500 CHF, and vast amounts of digital information about a given patient, perhaps gathered over the course of a treatment, will provide the basis of what is euphemistically called “personalized medicine”. In fact, it is probably only going to be “personal” to the extent that genetic make-up will differentiate one patient from another – yet genetic information is rarely identical in all cells of one’s body, and many gene-expression-controlling features of the genome 12

are invisible to deep sequencing techniques. For example, posttranscriptional control of gene expression by small RNAs often regulates cell-type determination in model organisms, and probably also in man. Moreover, for most genetic changes that might be found in a human genome, we know of no relevance. It will often be the case that toxic mutations are counteracted by other mutations or alterations that compensate, allowing a carrier of a disease-causing mutation to remain disease-free. This is not to say that genetic information is irrelevant. Indeed, for targeted cancer therapies, the mutation of an oncogene or loss of a tumor suppressor can be crucial for the success of a chosen therapeutic. But it is also clear that at present, this aspect of cancer therapy and the diagnostics for a handful of mapped genetic syndromes constitute most of the immediate medical impact of the sequencing of patients’ genomes. Nonetheless – and despite our ignorance about what it means – patients will soon be routinely subjected to an array of “objective analyses” – proteomics, metabolomics, genomics, perhaps epigenetic analyses, too, before a doctor gets a chance to diagnose a disease. A new mode of producing knowledge, based on collecting, comparing, and classifying data, has crept upon us since the last years of the twentieth century. We cannot shy away from this – large data sets will indeed facilitate evidence-based medicine, if we understand what they mean in the context of disease. Indeed, this knowledge can be useful once predictive interpretations can be made, and experiments carried out to understand their medical impact. We will have to determine where in the vast array of numbers lies “normality”. In the Gaussian distribution of mankind, will we be able to declare what is normal for a given individual, a patient based on measurements of a limited repertoire of components? 13

It will take time, but I believe there is no plausible alternative to science- or evidence-based medicine. In order to use quantitative data productively, of course, practising medics will need a rigorous basic education in biochemistry, physics and mathematics, particularly in statistics and bioinformatics. This is not music of future, it is now. Both data analysis and medical training must rise to the challenge posed by massive digital data sets, which are bound to increase, as new technologies make the information more readily obtained. Meeting this challenge is the task of academic medicine. A second concern is the relationship between physician and patient, doctor and disease. Will this relationship change, when patients monitor their vital statistics with their own iPhones, know their genomic sequence, and bring their latest lipidomic and phosphoproteomic data to the doctor’s office? I think it inevitably will. A physician will most likely be unable to interpret the mountain of digital information about his patient, without help, and will likely require a panel of experts from different specialities. One imagines a diagnostic round table, as experts from a range of disciplines discuss a patient’s data. And the resulting consensus, something like a jury’s decision, may be handed down as a hypothesis, that will require administration of a treatment, reanalysis of multiple parameters, and retesting: the result is basic scientific methodology at work in the clinic. If so, then indeed, the relationship of trusting patient to single caring doctor will change, and the medical world must be prepared for a backlash against it. We will also see a revision in how we define disease, which will cut to the very heart of what it means to be a practicing doctor. Classic disease symptoms become less and less relevant, as we understand the molecular causes behind the dysfunction, and as we accumulate an increasingly large repertoire of medicines that treat specific enzyme deficiencies. Targeted pharma14

ceuticals and large analytic data sets now start to define “normal” and “disease” states differently than in the past. A generalized concept of healthy ground state, and perturbed disease state, based on a panel of molecular markers, will become the common currency, leaving behind traditional definitions of disease. As mentioned above, diagnostics will not be the domain of a single MD, but of teams of experts contributing from discrete points of view. They will meet in a dialectic conversation, which starts by each admitting ignorance of the final answer. Will Socratic method invade the medical ward? I predict it will. As it does, the practice of medicine will become increasingly interdisciplinary, requiring clinicians to work with biologists and physicists, chemists, engineers, and computational experts to deal with diagnostics and to invent novel ways to intervene. This entails a complex clash of cultures, and not surprisingly, it will not work to simply mix these different cultures and expect results. Medical and scientific training will have to change, and we will have to find ways to make it work. This is not trivial, since the caricatures are partly true: basic scientists tend to be anarchic introverts, who sit on the fence about making decisions, and have little respect for hierarchy. Clinicians tend to be structured, social communicators, making life-saving decisions rapidly, confident, respectful of hierarchy. As we overcome this clash of cultures in our new medical world, both sides will emerge the richer. The third challenge that faces the medicine, is to maintain the trust of the general public in science-driven medical practice. As the concept of disease gets more complex, people may seek simpler and more “human” explanations. Or they may decide that what they read on the Internet from self-proclaimed experts convinces them, and healthcare decisions may be taken 15

increasingly outside of the medical establishment. While government and policy makers agree to prioritize research and innovation in matters of public health, the trust of the public itself in science actually seems to drop. At present 66 % of Europeans feel that science is making our lives healthier, easier and more comfortable, yet since 2005, the share of Europeans who express a general trust in science has declined from 78 to 66 %. Is this lost trust in academia inevitable, even as science-based medicine chalks up success? We must not underestimate the power of media and the Internet, on which one finds an argument for every possible interpretation, and its opposite, as desired. Medical websites number in the tens of 1000’s and there is no screening of the information they contain. Open access publications print unreviewed, scientific-looking articles, sometimes without examination, as recently documented in scam set up by Science. In it, an obviously flawed and fake scientific paper was sent to 255 open access journals, and was accepted for publication on-line by 60 %, without review! The same paper was accepted with review but inadequate revision by another 75 journals – yielding a 90 % on-line acceptance and publication rate. These journals sport respectable sounding names like “The International Journal of Cancer and Tumor”, yet they are pseudojournals in which anything and its opposite can be read, and “data” are most often irreproducible, if ever they were produced. This potpourri of information is available to all, and the large amounts of both true and false information, parading as science, will surely influence the public concept of medicine. It is not surprising to find an erosion of trust in scientific knowledge. Why not, after all, take a mystical or vitalist cure? In parallel we see that famous actresses or sportsmen can influence the decisions of millions with little or no scientific discussion. Let’s take the 16

case of Angelina Jolie. This attractive American actress carries a BRCA1 mutation, which indeed statistically inclines women to develop breast cancer; in her family a BRCA1-deficient aunt recently succumbed to the disease, and thus I do not contest that the double mastectomy, in her case, might be defensible. However, as a result of its internet publicity, there has been a 67 % increase in women asking for BRCA1 tests and a four-fold increase in double mastectomies in London alone. Yet, there are many reasons and instances in which a BRCA1 mutation will not lead to breast cancer. While proper medical counsel may well calm the frenzy of mastectomies, there are surely others who will seek to profit from Angelina’s near-heroine status, and poorly informed women will be victims at great expense. Serious medical science must indeed take stock of social media. As medical practice changes, becoming predictive and preventative, we must be aware that the public trust in academic medicine is at risk. There is also a general reluctance to accept change in medical practice, and even a backlash against the best-documented of preventions, vaccinations. Evidence- or science-based medicine must make an effort to gain public trust, as distrust accumulates if we leave it to chance. To counter this, we must above all communicate about the necessity of the shift to evidence-based medicine. If we want the public to accept risks associated with any change, the motivation for change must be transparent, and the benefit of change for the individual must be clear. If change is declared for “the common good”, the common good must be articulated as concrete advantages for an individual patient or for those he or she cares for. And finally, the individual must feel ensured of his autonomy. People will reject innovation, if reduces the range of personal options. Only with careful attention, to ensure that the public identifies emotionally with a changing 17

medical world, will science and technology-driven medicine find acceptance. The risk is that the golden age of university of academic medicine will fade, giving rise to mystic practices and panaceas. Given the fact that our university is locally funded, identification of society with its academic community is crucial, and needs constant attention from our side. Whereas good communication is certainly a necessary condition for improving trust in academia, it is not sufficient. Transparency of decision-making and an effective interplay of checks and balances are crucial. Involving patients/citizens in the decision-making processes will make individuals more inclined to accept the risks inherent in medical practice. Finally, let me address how I believe that the University of Basel medical school can lead in evidence-based medicine. Modern science-driven medicine is the fruit of the Enlightenment – the 18th century movement which emphasized the roles of rationality and reason for improvement of the ­human condition. However, as Karl Marx said, “The philosophers have only interpreted the world in various ways, the point is (now) to change it.” Medicine and healthcare must embrace evidence-based definitions of disease, and continue ever more intensely its efforts to understand how living cells work. As stated above, the flow from science to human benefit is not that easy to deliver, and much of its success will lie in the integrity of the medical practitioner. If we look at the trials and tribulations of pharmaceutical development, we understand why we need to understand much better how life works, what goes wrong in disease, and how we can successfully and specifically intervene to improve disease management. Biology is fiendishly complex – and when problems or mechanisms of diseases are not understood, it is difficult to intervene effectively. Medical schools must be centers of research, focused 18

on the mechanisms of biomedical disease. Closer collaborations between physics, mathematics and chemistry – like the marriage that took place 40 years ago in the Biozentrum – is needed, but with a medical bias: Remember, man was not intelligently designed but he evolved, from equally complex pre-existing organisms, with different needs. As a consequence, every biological process has its appendix: the redundant organ of our digestive system – that is no longer strictly necessary but there all the same to distract us. What we must now do is dissect interlocking networks and pathways that intertwine to regulate human health. We need a broad base of research, extending from fundamental studies of core processes to the fine-tuning of clinical interventions. We cannot ignore the basic and focus on “translation”, for we do not yet understand even the most common diseases. One cannot translate what one does not understand. We know as well that every individual may respond to an intervention differently: every human has his own homeostasis called health, and in pop­ ulations, each parameter that we measure falls under a Gaussian curve, with “normal” spanning its entire breadth. A disease state arises when something, somewhere, imbalances the individual’s normal balance. Thus, snap-shots of quantitative data will not help us, but rather we must monitor changes during treatments, to get a true handle on effective medical care. We must also think about time scales. The university must pursue fundamental discovery research for long-term benefits, translational research for the medium-term application, and patient-based application for shortterm, if not immediate results. All three must find their place in a dialogue within the faculty. Declaring ignorance about causes of disease is the first 19

step towards finding a treatment. Thus we must be wary of short-term focus, and continue to explore the very basis of health and disease. New technologies are present and being put into practice as I speak. Induced pluripotent stem cells and tissue regeneration: organ culture, the reconstructed of tissues or organs in 3D, limb and joint and bone replacement are approaches in full bloom. With these developments we also create more realistic human models for research in vitro, and these will allow more ­realistic investigations into tissue and organ function. For any of our modern technological advances to succeed, we must understand better how normal human tissues work. And even if a patient’s genomic sequence will be but a small part of his dataset, we will nonetheless exploit human variation and genomics to understand the character of disease. We will search for correlations between human variants and disease susceptibility in large populations, we will examine correlations between environment and the human microbiome, and use somatic genetic variants to predict predisposition for cancer and neurological disease. Finally, as we are able to generate new tissues and organs, we will be able to examine the effects of genetic changes, and by the use of genetic engineering modify genes in tissues that we reconstitute in 3D. From here we must move to modeling tissue function, building upon our knowledge of biochemical interactions and enzymatic rates, we will be able to solve the relevant differential equations that predict or explain organ function. And this will require the input of theorists from the physical/ mathematical world, as an increasingly sophisticated thinking about complex biological networks requires that kind of help. The motivation of scientists is key to delivering the high-quality research that will advance and maintain the medical faculty. We must not get bogged 20