IN VIVO #13 ENG by IN VIVO

Think health

No. 13 – DECEMBER 2017

BACTERIA

FRIEND AND FOE SYLVAIN TESSON “By walking, I left my pain behind” TRENDS My name, my disease INNOVATION Biomimicry: borrowing a page from nature Published by the CHUV www.invivomagazine.com IN EXTENSO THE HUMAN BODY UNDER EXTREME CONDITIONS

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IN VIVO / NUMBER 13 / DECEMBER 2017

CONTENTS

FOCUS

11 / DOSSIER Bacteria: friend and foe BY MARISOL HOFMANN AND STÉPHANIE DE ROGUIN

MENS SANA

22 / INTERVIEW Sylvain Tesson: “By walking, I left my pain behind” BY BÉATRICE SCHAAD

26 / DECODING BY YANN BERNARDINELLI

30 / TRENDS My name, my disease BY PATRICIA MICHAUD

IN SITU

07 / HEALTH VALLEY How to attract start-ups

CORPORE SANO

CURSUS

34 / TRENDS

43 / COMMENTARY

Falls: a difficult challenge BY ANDRÉE-MARIE DUSSAULT

38 / INNOVATION Biomimicry: borrowing a page from nature BY ANNE-SOPHIE DUBEY

Incorporating complementary medicine

44 / TANDEM The historian Aude Fauvel and the practician Patrick Bodenmann

Hundreds of different types of bacteria and microbes use public transport every day without a valid ticket. Fortunately, most of the species that have been identified are harmless. However, the public transit system is an especially useful ecosystem for identifying these organisms and understanding how they spread. In fact, nearly half of the 562 bacterial species collected during a study done in the New York Subway two years ago had never been seen before.

KEVIN JAAKO

Understanding endocrine disruptors

CONTRIBUTORS

MARISOL HOFMAN

GARY DRECHOU

Marisol Hofmann, a journalist completing her internship with LargeNetwork, co-authored the article on bacteria (p. 11). She interviewed Professor Thierry Calandra about sepsis, a serious bacterial infection.

A “jack-of-all-trades”, Gary Drechou has over ten years of experience in press and emerging media in Switzerland and Canada. In July, he joined the CHUV Communications Service as editorial and social media manager.

A graphic artist based in Geneva, Linda Roberts Matzinger contributed to this issue’s layout design and helped research images. She especially enjoyed depicting the medical world with illustrations, such as in the article on gene networks (p. 37).

LINDA ROBERTS MATZINGER

Editorial

AN UNKNOWN KILLER

BÉATRICE SCHAAD Chief editor

PATRICK DUTOIT

*CZURA CJ. “MERINOFF SYMPOSIUM 2010: SEPSIS – SPEAKING WITH ONE VOICE”, MOL MED 2011; 17:2-3. **FLEISCHMANN, SCHERAG, ADHIKARI, ET AL.: GLOBAL SEPSIS INCIDENCE AND MORTALITY. AM J RESPIR CRIT CARE MED VOL 193, ISS 3, PP. 259–272, FEB 1, 2016.

What happens when everything starts to go wrong? When the body malfunctions so profoundly that an infection becomes systemic? Hippocrates cut straight to the point when he named the condition sepsis, a term that means “putrefaction” and more or less sums up everything you need to know. The phenomenon has since been called septicaemia and septic shock syndrome. It’s possible the many name changes are one of the reasons why it’s so poorly understood today. Despite the threat presented by this condition, sepsis is still dangerously misunderstood. Indeed, sepsis is widespread. In the United States, more people die from it than colon cancer, breast cancer and HIV combined.* Current estimates point to 31 million cases and 6 million deaths in highincome countries,** i.e. the same death toll as tobacco. Slowly but surely, this public health nightmare is starting to worry health authorities. At the end of May, the World Health Organization adopted a new resolution encouraging its members to develop national plans to combat the “deadliest killer you’ve never heard of”. It seems the thorniest problem, and the reason why international health authorities finally decided to act, is that too few clinicians know how to properly diagnose an at-risk patient. As a result, it seems the majority of deaths caused by sepsis were not correctly reported. According to a recent article published in “The Guardian”, sepsis was only mentioned on 40% of the death certificates of patients who actually died from the condition. In United Kingdom, the National Health Service has tackled the problem by developing a large-scale training plan for its physicians. As a result, and even though other factors contributed to this change, the mortality rate of patients admitted to intensive care wards in UK hospitals dropped from 35% to 27% in just a few months. In Switzerland, several specialists, following the example of Dr Thierry Calandra, head of the Infectious Disease Service at CHUV and a pioneer in the field, have long been working to create a sepsis treatment system and large-scale public awareness campaigns (read p. 13). Their goal is to help people suffering from this condition to receive a quick diagnosis. This is the only way this previously unknown killer will finally come out of the shadows. /

Thanks to its university hospitals, research centres and numerous start-ups specialising in healthcare, the Lake Geneva region is a leader in the field of medical innovation. Because of this unique know-how, it has been given the nickname “Health Valley”. In each “In Vivo” issue, this section starts with a depiction of the region. This map was created by the Polish illustrator Nikodem Pręgowski.

IN SITU

HEALTH VALLEY

NIKODEM PRĘGOWSKI

Panorama of the latest innovations.

NEUCHÂTEL P. 06

The start-up 1Drop Diagnostics is one of the winners of the Swisscom StartUp Challenge.

EPALINGES P. 06

The start-up ADC Therapeutics just completed the largest fundraising round since 2015.

LAUSANNE P. 06

An application uses facial recognition technology to identify patients’ pain levels.

LAUSANNE P. 08

IMD students are developing an anti-tremor gripper designed for patients with Parkinson’s disease.

IN SITU

HEALTH VALLEY

START-UP ANALYSE

The Neuchatel start-up 1Drop Diagnostics is one of the winners of the Swisscom StartUp Challenge. The jury was impressed by its technique for detecting biomarkers in a single drop of blood as a way to provide quick and minimally invasive diagnostics. Four other start-ups were awarded and invited to meet with mentors in Silicon Valley.

STERILISATION

The sterilisation solution developed by Sterilux just received another award at the Design Preis Schweiz ceremony. This start-up, which was founded by EPFL alumni, is developing a technology that uses 10,000 times less water than the conventional sterilisation process.

New antibodies to combat neurodegenerative diseases BIOPHARMACEUTICS Lausannebased company AC Immune has discovered new-generation antibodies that target two proteins involved in neuro degenerative diseases, namely alpha-synuclein, which causes Parkinson’s disease, and TDP-43, which causes orphan diseases like frontotemporal lobar degeneration and plays a key role in Alzheimer’s disease. The NASDAQ-listed company focuses on treating proteopathies that cause neurodegenerative diseases and develops antibodies, molecules and vaccines to that end.

APPLICATION

PAIN TRACKER The idea behind this new application from Australian developer ePat is to use artificial intelligence to analyse pain in individuals who are incapable of describing it themselves, such as children or patients with dementia. The programme uses facial recognition technology developed by the Lausanne- based start-up nViso. The application is set for release in late 2017.

SURGERY

KB Medical was purchased by the American group Globus Medical, a specialist in manufacturing surgical instruments. The start-up, which is developing a robot to help surgeons perform operations, will remain in Lausanne. The purchase amount was not made public.

The amount in millions of dollars just invested in the start-up ADC Therapeutics. This is the largest fundraising amount collected in Europe since 2015. Located at the Biopôle science park in Epalinges, the company develops new treatments for blood and bone marrow cancer. It plans on bringing its first two lymphoma medications to market by 2020.

DIAGNOSTICS

2 Linkage Biosciences, a specialist in molecular diagnostics, was purchased by the American multinational Thermo Fisher. The start-up, which is partially based in Geneva, was incorporated into the Transplant Diagnostics division, which determines donor-recipient compatibility before and after the operation.

“In the future, medical protocols will be based on algorithms, and patient care will improve as a result.” XAVIER COMTESSE THIS INNOVATION SPECIALIST WROTE IN “BILAN” IN SEPTEMBER 2017 TO MARK THE RELEASE OF HIS BOOK, “SANTÉ 4.0” (GEORG PUBLICATIONS). THE AUTHOR BELIEVES THE CURRENT TREND TOWARDS DIGITISATION IN THE MEDICAL SECTOR WILL HELP IMPROVE THE QUALITY OF HEALTHCARE WHILE ALSO REDUCING COSTS.

IN SITU

HEALTH VALLEY

How “Health Valley” is attracting start-ups The Lake Geneva region retains its best entrepreneurs thanks to a dynamic ecosystem. STRATEGY Out of the 909 million Swiss francs of venture capital invested in Switzerland in 2016, over half was invested in “Health Valley”. Unlike IT start-ups, the best of which often leave Switzerland for the United States, these health companies are happy where they are. “Medical startups are typically more firmly rooted in their area because they often require highly advanced equipment. A company focused on digital applications can relocate more easily because they are less dependent on their equipment,” says Claude Joris, managing director of BioAlps, a life sciences cluster based in Geneva. The association’s database includes nearly 700 Health Valley companies. Only 20 have been struck from the list in the past few years, including companies that went bankrupt. However, some departures, like that of Biocartis, a specialist in personalised medicine founded in 2007 in Lausanne that left for Belgium a few years later, show that the industry is not completely spared from the phenomenon. For one, foreign investment plays a critical role. Eighty-seven per cent of the venture capital that flows into Switzerland comes from outside the country. This isn’t bad in itself, but it’s important to not underestimate the influence that certain major investors can have on the structure of a young company, as Claude Joris explains. According to the expert, two major factors can convince start-ups to stay. The first is partnerships. “The more companies partner with local actors like EPFL or CHUV, the harder it is for them to leave.” He pointed out that the Lake Geneva region is well equipped to take on this challenge. “Here, there’s a real convergence between IT and the medical industry that creates a very dynamic and competitive environment.” 7

TEXT ROBERT GLOY

ABOVE: THE VIRUAL REALITY “MASK" DEVELOPED BY MINDMAZE AND CLAUDE JORIS, MANAGING DIRECTOR OF BIOALPS

An increasingly mature market Funding is even more important. “Startups in the biotech or pharmaceutical industries must complete several steps before marketing a medical application. To do so, they need funding quickly — as much as several million Swiss francs,” he says. Federal Councillor Johann Schneider-Amman is very aware of the issue. He created the Swiss Entrepreneurs Foundation in July 2017. The goal is to raise 500 million Swiss francs from the private sector to support young entrepreneurs. Currently, UBS, Credit Suisse and the insurance provider Helvetia have provided over 300 million. Two other venture capital funds that focus on supporting young Swiss start-ups have also contributed: NanoDimension 3, which will receive over 200 million Swiss francs and is supported by Patrick Aebischer (former president of EPFL) as well as Medicxi, a new Geneva-based venture capital company that wants to invest 300 million Swiss francs in the life sciences sector here. For Claude Joris, the incredible growth of companies like AC Immune, Sophia Genetics and MindMaze in the Health Valley ecosystem are very encouraging signs. MindMaze, which uses virtual and augmented reality to neurologically rehabilitate stroke patients, is one of the most prominent companies at the moment because it obtained unicorn status (i.e. it was valued at over one billion dollars) last year. “The fact that MindMaze recently bought another Vaud-based start-up, Gait Up, shows its involvement in the region and indicates that the market is mature,” he says. /

IN SITU

HEALTH VALLEY

THE DEVICE

3 QUESTIONS FOR

SANDY WETZEL

BENEFITING FROM THE WATCHMAKING TRADITION OF THE CANTON, NEUCHÂTEL’S START-UPS DISTINGUISH THEMSELVES IN THE FIELDS OF MICRO AND NANOTECHNOLOGIES.

WHAT ARE THE SPECIFICITIES OF THE LOCAL START-UP ECOSYSTEM?

First is its highly industrial orientation, a reflection of the canton’s economic structure. Many start-ups have their origins in the private economy. Secondly, their area of expertise relies heavily on the micro technology know-how of the region. It is therefore a very coherent ecosystem with respect to its environment. But it still lacks a bit of visibility.

WHAT ABOUT START-UPS ACTIVE IN THE MEDICAL FIELD?

They have a part to play in the medical device sector. For example, Coat-X, winner of the Neode Prize* in 2015, is developing micro-encapsulated components to be used as implants, or Novostia, which is working on a new generation of artificial heart valves.

WHAT ARE NEODE’S GOALS FOR 2018?

We hope to establish a closer dialogue with R & D partners and industrial companies in the region. We also want to develop our support offer for start-ups. Finally, we have a lot of work in terms of image and communication, to better highlight the skills in high-tech innovation coming out of the canton of Neuchâtel. / After managing Y-Parc in Yverdon-les-Bains, Sandy Wetzel took over earlier this year the direction of Neode Technology & Industrial Parc in Neuchâtel. *The 2017 Neode Prize award ceremony will be held on December 7th. More information and free (but mandatory) registration on www.neode.ch.

ANTI-SHAKE GRABBER A cross between an endoscope and the gyroscope on a GoPro camera, the anti-shake grabber is designed for people with early-stage Parkinson’s disease, the elderly and any individual with shaking hands. Its goal is to allow these patients to pick up a glass and drink it without spilling — an embarrassing situation that typically causes them to renounce their social lives. The grabber at the end of the endoscope opens with a simple squeeze of the hand and can accommodate any size of glass. The gyroscope absorbs unwanted movement. The device was designed by a team of MBA students at IMD Lausanne and was one of the six finalist projects selected for the 2017 DebiopharmInartis Challenge.

In millions of CHF, the amount of funding behind the partnership between Roche, the University of Lausanne, CHUV and EPFL to develop innovative cancer treatments. The research will focus on oncology, immunotherapy, imaging and molecular therapy, and pay particular attention to the tumour’s micro-environment.

IN SITU

Viral hepatitis often goes undetected, but can flare up into a chronic condition, cause cirrhosis or cancer and even require a liver transplant. Several initiatives involving testing, public depositions, and vaccination campaigns are encouraging citizens and authorities to address the issue.

Hepatitis A outbreak

In the first half of the year, the number of cases of hepatitis A in Switzerland has tripled over the same period in 2015, rising from 13 to 41 according to a report by the Swiss Federal Office of Public Health (OFSP). Most patients are between the ages of 25 and 44, and three times more men are affected than women. The OFSP has recommended that men who have sex with men, which represent an at-risk group, get vaccinated. Hepatitis A is caused by a virus that is transmitted through the absorption of faecal matter by the body, generally through water, food, or person-to-person contact. In adults, it causes jaundice in 70% of cases and does not require treatment, but the disease can last up to six months.

HIGH ALERT FOR HEPATITIS Hepatitis B and C testing

Hepatitis E in the spotlight

In response to a question submitted by Swiss National Councillor Ignazio Cassis regarding the growing number of hepatitis E cases in Tessin, the Swiss Federal Council studied the disease’s evolution in Switzerland and the launch of a potential vaccination campaign. Even though the number of cases was likely to rise and an estimated 1,500 new cases of severe hepatitis E were occurring each year, it concluded that a vaccination recommendation was not warranted. In most cases, the infection is asymptomatic or benign. The hepatitis E virus is typically transmitted through water that has been contaminated with faecal matter. It can also be found in raw pork liver products such as mortadella sausage. A vaccine was developed in China but has not yet been certified for use in Switzerland.

For the first time in Switzerland, free hepatitis B and C testing was offered last summer under the impetus of the Hépatite Suisse network. According to the association, around 80,000 people live in the country with one of these two infections, but only half are aware of their status. The main risk factors include receiving a blood transfusion before 1990, drug use, or getting a tattoo in non-hygienic conditions. Hepatitis B can also be transmitted through unprotected sex, while hepatitis C mostly affects people born between 1950 and 1985, when the virus had not yet been identified.

Improving diagnostics with a virtual heart CMCS (PROF A.QUARTERONI) – EPFL, LAUSANNE

MATHEMATICS Personalised computer modelling of the heart could one day help doctors better diagnose or prevent cardiac disease without having to perform surgery or invasive clinical interventions. EPFL researcher Alfio Quarteroni designs mathematical tools based on a patient’s MRI results to simulate heart function with a growing level of precision. The tools can also be customised for each heart. The project is part of the European initiative iHeart, which seeks to construct virtual cardiovascular models that are specific to each patient.

IN SITU

HEALTH VALLEY

BENOÎT DUBUIS President of Inartis Foundation

Support programmes must accommodate entrepreneurial diversity

Why isn’t Switzerland more welcoming of diversity? Every time someone delivers a high-handed opinion about an innovation support programme or questions the value of such-and-such an initiative, I’m surprised by the ill-founded nature of their reasoning and their limited knowledge of these programmes. Is it out of laziness? A lack of perspective? A stubborn determination to defend their “baby”? Let’s get one thing straight: diversity is a boon for both Switzerland and the entrepreneurs who expect its support. Indeed, this lead us to the very heart of the question: what do Swiss entrepreneurs truly need right now? By definition, their needs are as varied as their projects and the wide range of circumstances they come from. When we try to fine-tune support opportunities too much, we turn a blind eye to the diverse nature of entrepreneurs’ needs and end up supporting a small fraction of initiatives that don’t represent the full reality of the entrepreneurial environment in Switzerland.

But what is truly new about looking for a simple, efficient and cheap solution to a problem? Isn’t this the basic rationale of every entrepreneur, who must overcome challenges while looking for funding and use their resources as sparingly as possible? Is this approach truly revolutionary? Not in the slightest. At most, it’s an interesting basic principle that could become a new focus in the debate surrounding innovation, as long as it’s not used to make sweeping generalisations. This viewpoint has been brilliantly defended by Carlos Ghosn through the principle of the low-cost car, a concept that closely resembles the Indian technique of Jugaad, which, intellectually, appears promising. However, is frugal innovation alone enough to justify the creation of a new economy? No. In fact, through further discussion of the topic with its originator, Navi Radjou himself acknowledges that frugal innovation is just one approach among many that make the new economy so diverse and powerful. What’s true for approaches to innovation is also true for support programmes, whether in the form of incubators, accelerators, vertical and horizontal assistance schemes, long-term and short-term funding, or programmes focused on all manner of topics. No single solution can meet the needs of all of the country’s entrepreneurs. Each programme targets a specific set of needs involving entrepreneurs who have a wide range of financial capabilities, availability, training and experience.

I can’t help but be amused by the dozens of approaches trying to dictate the future of innovation. Taken individually, these ideas are Therefore, instead of standardising these support intriguing, and yet not a single one can be applied to every instance. One of these approaches involves programmes, isn’t it much wiser to encourage a the recent trend towards “frugal innovation”. synergistic and complementary approach so everyone This concept consists of addressing a need can have access to the type of environment that will as simply and effectively as possible using a allow him or her to flourish and succeed? A mosaic isn’t minimum amount of resources. beautiful because every tile is the same, but because each part is unique. /

FURTHER READING

www.healthvalley.ch www.inartis.ch

FOCUS

BACTERIA

BACTERIA: FRIEND AND FOE /

The human body contains 2 kilograms of bacteria. While most are beneficial to health, some cause serious infections that can lead to sepsis or mutate into antibiotic-resistant “super bacteria”. The question remains—are bacteria our friends or our enemies?

/ BY

CRAIG WARD

MARISOL HOFMANN AND STÉPHANIE DE ROGUIN

The British artist Craig Ward travelled through New York’s twenty-two subway lines in the summer of 2015 to collect bacterial samples. He produced a series of images from his work, demonstrating the complex ecosystem of a city with millions of inhabitants. 11

FOCUS

BACTERIA

acteria helped shaped the world as we know For many years, antibiotics were an effective way of it today. You can find them almost every- combating pathogenic bacteria. However, their overuse where – on doorknobs, in the depths of the has led to the development of multidrug-resistant “suocean and, naturally, in our bodies. There per bacteria”. At the start of the year, the World Health are billions of bacteria in the human body. They Organization (WHO) sounded the alarm by reporting function like a fully-fledged organ and we have that super bacteria could kill up to 10 million people by 2050, placing it on a par with almost as many of them as we cancer. Scientists are considering do cells. While most are essenFIGURES several alternative solutions for tial for our health, not all bacteaddressing this emergency. One ria are our allies. Some types, of them is phage therapy. Discovcalled pathogenic bacteria, ered a century ago and then abancause infectious diseases that The number of bacteria present doned in favour of antibiotics, this can range from a simple sore on our skin. method has once again become throat to a life-threatening case / promising (see inset on p. 19). of septic shock.

1,012

86%

The probability of identifying an individual based on their intestinal microbiome according to a study from the Harvard School of Public Health.

60,000 The estimated number of existing bacteria.

BACTERIA

FRIEND OR FOE? Starting at birth, bacteria colonise our bodies and build what we call the microbiome. “The composition of the bacteria in our bodies changes quite a bit during our first three years of life. It then stabilises to form the microbiome we see in adults,” says Vladimir Lazarevic from the Genomic Research Laboratory at Geneva University Hospitals (HUG). Later, our microbiome changes again when we become elderly due to a weakened immune system and new dietary habits. Each individual has their own microbiome, which changes depending on one’s environment and diet. The bacteria in the body are mostly contained in the skin or mucous membranes, i.e. the digestive, respiratory, and uro-genital tracts. They exist in symbiosis with the body, which provides them with nutrients and an ideal place to survive and grow. According to 12

Lazarevic, our intestinal tissue and immune system do not develop normally without bacteria. “Bacteria serve a metabolic purpose. For example, through a process of fermentation, they break down indigestible food residue, such as fibre, into useful components the body can absorb. They can also produce energy substrates like fatty acids and vitamins K and B12,” says the researcher. Bacteria also stimulate the immune system and make the body more resistant. A pathogenic micro-organism, such as a fungus or bacteria, must first fight against the body’s local flora to colonise the environment. These endogenous bacteria are, so to speak, our allies. However, there are also bacteria that are pathogenic to the human body. These bacteria can cause disease. “Out of the 13,000 scientifically recognised bacterial species, around 150 are pathogenic to humans,” says Lazarevic. The best-known types include Staphylococcus, Streptococcus, Clostridium difficile, and Enterobacteria such as Salmonella and Escherichia coli.

FOCUS

BACTERIA

“PEOPLE NEED TO BE MADE MORE AWARE” Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to an infection. Thierry Calandra talks about what steps have to be taken to limit the risk posed by a condition that is as serious as it is unknown. INTERVIEW BY

N MARISOL HOFMANN

Organization, which adopted a resolution to spread the word about the disease. What steps can hospitals take to fight the spread of the disease? tc It is important to educate paramedical personnel like ambulance drivers and other healthcare staff so they can quickly recognise the signs of sepsis. At CHUV, we provide general training sessions in each unit, but we need to address this issue more specifically. In order to reduce the risk of mortality and serious side effects, we should also create specialised units or centres to quickly treat septic patients. It takes hours to receive treatment at a hospital. The Surviving Sepsis Campaign issued recommendations about the actions that should be taken in the first three hours of diagnosis to reduce mortality risk. ⁄ iv

The number of sepsis cases is increasing. However, this disease is still not well known among the public. What is the situation in Switzerland? thierry calandra We are behind other countries like Germany, which has conducted several public awareness campaigns. There is an urgent need to inform people about sepsis so they can learn to identify the symptoms more quickly. A survey about people’s knowledge of sepsis was conducted in various countries a few years ago. in vivo

Germany was ranked first. Fifty percent of people there had heard of sepsis. This figure was 40% in UK, 20% in Sweden and 7% in Brazil. Switzerland is on a par with Sweden. People need to be made more aware. What is being done to improve this situation? tc We need to create the appropriate structures such as groups and organisations and include sepsis survivors in order to carry out educational and public awareness campaigns. Sepsis has become a priority for the World Health iv

THIERRY CALANDRA IS HEAD OF THE INFECTIOUS DISEASE SERVICE AT CHUV.

LAURIANNE AEBY

early 31 million cases of sepsis are reported every year throughout the world. In Switzerland, the CHUV Emergency Ward noted nearly 400 cases of sepsis during a census it took in 2012. Head of the Infectious Disease Service at CHUV, Thierry Calandra points out the need to improve the public’s knowledge of this issue.

BACTERIA LAURIANNE AEBY

FOCUS

“EVERY MINUTE COUNTS”

Dominique Loosli is a sepsis survivor. She became ill seven years ago and now helps patients recover from the disease. “In July 2010, I was visiting Grisons for the weekend with my husband. That Saturday night, we went out for dinner at a very nice restaurant. I woke up at 5 a.m. with fever and severe vomiting. The local doctor gave me medicine to relieve my symptoms so I could travel home. By Monday, the fever had still not gone down. My husband insisted on going to A&E, even though he had never been in his life! They took a blood sample and told me my diagnosis: sepsis. They put me into an artificial coma for five weeks. I had a 20% chance of survival. I woke up in intensive care and was completely paralysed. I didn’t recognise my children because the anaesthesia had affected my memory. It was a really difficult time. I had to use an electric wheelchair for a month. I had

a bad reaction to the antibiotics they were giving me and developed neutropenia (editor’s note: a blood disorder). I still could have died. My body finally started to recover then. I was able to move my toe and eat a bit. I had to relearn how to do every movement. Still today, I haven’t quite recovered fine motor function in my right hand. The hardest thing is tying my shoes! In all, it took three months to recover major function, five months to get out of the hospital and two years to feel well. I started working again in January 2011. The company where I worked had been completely reorganised. I didn’t know hardly anyone and they didn’t treat me very well. Plus, that kind of experience changes your values. The complaints of other people seem trivial. The administrative red tape was really tough. I had to constantly justify myself to my health insurance, employer and disability insurance. Sepsis is still not well known. For the past five years, I’ve been working at the

Paraplegia Centre as a hospital pharmacist. I also help patients who are recovering from sepsis. In addition to this, I work with a centre in Germany dedicated to helping sepsis survivors. This same organisation supported me when I was sick. No one knows why some people survive and others don’t. Septic shock, the final stage of the disease, drastically increases your heart rate. My heart rate was at 260 beats per minute. I was also lucky that I was diagnosed so quickly. With this disease, every minute counts.”

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BACTERIA

“If these bacteria successfully invade and reproduce, they cause disturbances in the body,” explains Thierry Calandra, head of the Infectious Disease Service at CHUV. “An infectious disease is caused when a pathogenic agent encounters the host organism.” However, the presence of pathogenic bacteria in the body doesn’t always result in a reaction. “For example, some people carry Staphylococci in their nasal passages without getting sick,” says Vladimir Lazarevic.

SEPSIS

A LIFE-THREATENING CONDITION ON THE RISE Infectious diseases can range from small, benign, localised infections, such as a sore throat or a bladder infection, to more serious conditions that can even be life threatening. Sepsis is the most serious level of infection. It consists of a generalised inflammatory response in the patient’s body as a result of a severe infection. According to the WHO, sepsis is a major cause of maternal and neonatal morbidity and mortality in low-income countries. However, it also affects millions of hospitalised patients in higher-income countries; these areas are seeing a rapid increase in the number of cases as the population ages and the number of immunodeficient patients increases. The bacteria that are most likely to cause sepsis include Streptococcus, Staphylococcus, Enterobacteria, and Pseudomonas. Sepsis can develop due to any kind of severe systemic infection via a number of ways. It can be the result of a delayed response in the host’s body to an infection that the immune system did not immediately recognise. The infection can then spread to such an extent that the body is no longer able to stop it. In other cases, “the host can react so violently to the infection that it can harm the body,” says Calandra. These excessive inflammatory reactions can cause organ failure and other serious consequences, including the loss of a limb, kidney or pulmonary damage, loss of motor function and neurological disorders. Septic shock is the most severe form of sepsis. It causes blood pressure to drop precipitously and stops blood flow to the body’s organs. According to Calandra, 10% of septic patients die from the 15

A LARGE NUMBER OF HOSPITALISED CHILDREN CONTRACT SEPSIS Several million children throughout the world die every year from sepsis. In Switzerland, an average of one child per day contracts a potentially deadly infection according to a national, four-year study conducted by the ten largest paediatric hospitals in Switzerland, including CHUV. The results were published on 20 July 2017 in “The Lancet Child & Adolescent Health”, a specialised medical journal. The majority of these infections are contracted at the hospital. “Following a study conducted by the Swiss Pediatric Sepsis Group, we noted that out of the 1,181 recorded cases of blood infection, 32% involved previously healthy children, 34% affected newborns and 34% involved children with underlying co-morbidities,” says Sandra Asner, manager of the Paediatric Vaccination and Infectious Disease Unit at CHUV. Asner took part in the study involving pneumococcal disease. “A third of the hospital-acquired infections mostly affect children undergoing chemotherapy, meaning they have a compromised immune system, as well as children in intensive care and premature babies. These three groups are especially at risk of sepsis due to their frequent hospital stays and the use of catheters, which are risk factors for infection.”

GLOSSARY MICROBIOME This term refers to all micro-organisms (yeast, bacteria and viruses) that are invisible to the naked eye and located within a specific environment (skin, intestine, mouth, etc.). MICROBE A microbe is a living organism that can’t be seen with the naked eye. The term includes various life forms, including bacteria, fungi and single-cell algae. Some people also include viruses in this category. However, not everyone in the scientific community considers viruses to be alive. BACTERIA Bacteria are living, single-cell microscopic organisms that do not have a nucleus. Bacteria were the first life forms to appear on Earth around 3.5 billion years ago. VIRUS A virus is a small, infectious, microscopic particle that requires a host, in theory a cell, to reproduce and survive. In this respect, it can be considered a parasite. The debate is still open as to whether or not viruses can be considered living organisms.

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BACTERIA

DIAGNOSING SEPSIS USING A BIOCHIP A team from the University of Illinois in the United States developed a biochip that can diagnose sepsis using a single drop of blood. Because it often takes some time to diagnose the disease, researchers created a device that can count the number of leucocytes and detect the expression of CD64 on the surface of neutrophils, which are a kind of white blood cell. These two indicators are strong evidence for sepsis. The small device has been tested to verify its reliability and the results were published in “Nature Communications” this summer.

Different types of bacteria

CELL WALL THICKNESS

Bacteria are typically classified based on two characteristics, namely their shape and the thickness of their cell walls.

To measure the thickness of a bacteria’s cell wall, scientists use dyes. Bacteria with thick walls turn blue or purple. These are called Gram-positive bacteria. On the other hand, bacteria with thin walls turn pink or red when dyed. These are called Gram-negative.

The main shapes include:

Cocci

A Streptococcus is made up of a chain of cocci

A Staphylococcus is made up of a cluster of cocci

Bacilli

Spirilla

Borrelia, which causes Lyme disease, is transmitted through tick bites

Vibrio

condition; this figure increases to 40% in the case of septic shock. Even though immunodeficient patients are the most vulnerable to sepsis, he points out that “being young and healthy doesn’t prevent the immune system from failing. If you’re unlucky enough to come across a bacterium that breaks through your defences, you could become septic.” The specialist goes on to explain that it’s not always easy to spot the preliminary symptoms of sepsis because they can resemble the flu. “You should immediately contact your doctor or go to the emergency room if you start shivering, develop a high fever, and experience general discomfort and an altered mental state. These symptoms indicate sepsis.”

SUPER BACTERIA

A GLOBAL CONCERN

Nowadays, antibiotics are still our most common weapon against bacterial infections. This class of medication became widespread following WWII and represents one of the most significant medical breakthroughs in the twentieth century. “Antibiotics have a spectrum of activity. Some have ‘holes’ in their spectrum, meaning they aren’t effective against all types of bacteria. Broad-spectrum antibiotics, however, can stop the growth of a large number of bacteria belonging to a variety of classes,” explains the head of the Infectious Disease Service at CHUV. Antibiotics don’t discriminate between beneficial bacteria and harmful varieties. As a result, antibiotic use can cause side effects. “For example, they can disrupt a person’s intestinal flora and lead to diarrhoea,” says Calandra. Antibiotics have significantly reduced mortality throughout the world. Without them, certain surgeries such as heart transplants would be impossible. However, their success has also led to an increase in antibiotic resistance over the past few years. According to the WHO, this trend is currently one of the most serious threats to global health. An estimated 700,000 people die every year due to antibioticresistant pathogenic agents. At the start of the year, a woman died in the United States due to multidrug-resistant bacteria despite taking over twenty different antibiotics.

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ANTIBIOTICS: VALUABLE ALLIES AGAINST BACTERIA Manufacturing Microscopic fungi are put through a fermentation process.

Method of action Antibiotics block or inhibit bacterial growth by attacking four parts of their anatomy.

Damaging of the cell wall.

Disruption of DNA processes.

Selection A specific strain is placed in a container with the nutrients it needs to grow.

Fermentation This resulting culture is then placed in a larger container, which is mixed and fertilised in a sterile environment to encourage further growth.

Filtering After three to five days, the culture mixture is subjected to various filtering methods to isolate the antibiotic, which is then transformed into a powder.

Halt of proteins synthesis.

4 IV

Refining Antibiotics can be marketed in a wide variety of formats, including pills, gel capsules, and serums. 17

Permeable membrane, dispersion of cellular components.

INFOGRAPHIC: BENJAMIN SCHULTE

III

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“Phage therapy can be a solution when there are no other treatment options”

Christophe Novou was saved from amputation through a phage therapy treatment. He tells his story.

In 2011, the pain came back. I was once again diagnosed with a Staphylococcus infection. I then fell from a ladder while I was helping a friend install some shelves. I had another fracture that became infected. In two

and a half years, I underwent seven operations. In June 2013, I was told the only solution was to amputate my leg at my hip. I refused to give up. My sister-in-law told me about a report she had seen on TV about how a patient with a similar prognosis, Serge Fortuna, had been healed with a treatment based on phage therapy. Fortuna, who co-founded the organisation Les Phages du Futur (Phages of the Future), organised a trip to Georgia to treat other patients. The departure date was set for a month later. I held a fundraiser and collected 5,000 euros out of the 8,000 I needed to travel to Tbilisi. At the hospital, the doctors found five strains of multidrug-resistant bacteria compared to the two they had found in France. I started phage

treatment. After 15 days, the doctor told me I could return to France. I thought, ‘It’s no use, I might as well go home’. But actually, I was completely cured! Phage therapy is no miracle solution. It doesn’t work every time. However, it can be a solution when there are no other options, and it doesn’t come with any side effects. With my organisation (editor’s note: www.phages-sans-frontieres.com), we’ve already helped and saved nearly 10 people. I’m fighting for phage therapy to be introduced in France. No one knows what it is, even though it was invented a century ago. We shouldn’t have to go abroad to get treatment.”

LAURIANNE AEBY

“I was hit by a car when I was 10 years old. The accident left me with a fractured femur and a brain injury. I was living in Côte d’Ivoire at the time and was operated on in rather rudimentary conditions. When I came back to France, I was diagnosed with a Staphylococcus aureus infection and brittle bone disease, meaning my bones had lost calcium and become fragile. I underwent several curettage treatments and was constantly taking antibiotics. At times, it seemed to be working. In 1998, after a final curettage, my leg seemed strong enough. I started to go about my normal life, riding a motorcycle and practising martial arts.

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Bacteria can develop resistance to an antibiotic through a mutation in its genome or by acquiring resistant genes from another type of bacteria. “Some mutations increase the expression of efflux pumps, i.e. the mechanism that allows cells to evacuate toxic compounds like antibiotics,” says Lazarevic. “Other mutations prevent the antibiotic from entering the cell or change the structure of the medication’s target.” The selective pressure created by the antibiotic leads to the survival and growth of the resistant strain.

PHAGES

CLINICAL TESTING OF ANTIBIOTIC ALTERNATIVES When antibiotics are no longer effective, doctors turn to other treatment options. “When the infection is localised, surgery is a possibility,” says Calandra. “For example, if a tuberculosis infection is resistant to all antibiotics, you can remove the part of the lung that’s affected.” Another alternative is phage therapy, which uses phages, natural viruses that only attack bacteria, to treat infections. “The virus attaches itself to the surface of the bacteria and injects its genetic material inside the cell to reproduce,” says Grégory Resch, project director at the Department of Fundamental Microbiology at the University of Lausanne (UNIL). “The new phages then explode out of the bacteria.” This treatment was discovered exactly 100 years ago by the French scientist Félix d’Hérelle and was widely used throughout the world prior to the discovery of antibiotics. It is still common in post-Soviet states such as Georgia, Russia and Poland. A specific cocktail of viral phages must be prepared for each species of bacteria. Bacteriophages are now administered on a much more localised basis to infected injuries such as wounds and burns. They can also be administered through inhalation to treat pulmonary infections or through instillation to treat eye infections. This type of treatment is available over the counter in the aforementioned countries. In Western countries, where this technique was abandoned in favour of antibiotics, clinical trials are currently being conducted to study its validity. ⁄

Unusual uses for bacteria Self-tanners Some self-tanning lotions contain an organic compound made with an industrial bacterial fermentation process. Biogas Some countries, including China, use animal or human excrement to produce domestic biogas through bacterial fermentation. Art The work of British artist Anna Dumitriu is entirely sewn using microbial strains, which are sterilised before being integrated into the fabric. For example, one of the artist’s projects involved weaving a strain of Staphylococcus into a blanket.

The promises of phage therapy Grégory Resch, project director of the Fundamental Microbiology Department at UNIL, participated in the PhagoBurn project, the first clinical trial on phage therapy. With funding from the European Union, the trial sought to evaluate the effectiveness and tolerance of bacteriophages in the treatment of infected wounds in severely burned patients. “It was the first such study in the world. The clinical trials were conducted in France, Belgium and Switzerland in accordance with Western best practices,” he says. PhagoBurn ended in late June 2017, and the results will be published by the end of the year. Resch hopes the experiment will pave the way to the widespread use of this promising technique in the next few years. “Phage therapy can also be used in conjunction with antibiotics,” says the researcher. “We observed a synergistic effect with the two treatments.” Phage therapy also stands out due to its lack of side effects. “We are in constant contact with bacteriophages. They are 10 to 100 times more numerous than bacteria. For example, there are billions in Lake Geneva alone,” says Resch. The fundamental microbiology researcher is getting ready to take part in another clinical trial on phage therapy. It is being funded by CHUV and UNIL and will take place over a period of five years. This time, phages will be used to treat people with cystic fibrosis.

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BASED ON AN INTERVIEW BY

STÉPHANIE DE ROGUIN

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INTERVIEW “YOU CAN IDENTIFY INDIVIDUALS BASED ON THE UNIQUE FEATURES OF THEIR MICROBIOMES”

French science philosopher Thomas Pradeu explains how bacteria make up a part of who we are. Science tells us that intestinal bacteria are unique to each individual and represent one of the most conclusive ways of identifying someone. Is this method even better than DNA analysis?

in vivo

Over the past 15 years, the scientific community has come to understand that we can be identified by factors other than our genes. Our intestinal microbiome is one example, as are the microbiomes of our lungs and skin. In the early 2010s, the scientific community started to discuss a number of applications based on the unique characteristics of each person’s microbiome. The microbiome’s relevance to forensics in particular was a subject of much debate. This method consists of identifying individuals based on the unique features of their microbiomes. While twins share the same DNA (except for a few mutations), their microbiomes can contain a number of differences depending on where they live and their personal history. However, this doesn’t mean that genes are no longer useful in understanding what makes us unique individuals. Recent discoveries only add to our knowledge base about the incredibly diverse range of elements that influence what happens inside us.

thomas pradeu

Biography Thomas Pradeu is the director of research at CNRS in Bordeaux, where he conducts research into the philosophy of science at the ImmunoConcept Laboratory (UMR5164). In 2010, he published “L’identité: la part de l’autre” in collaboration with the immunologist Edgardo D. Carosella. 20

What is revolutionary is how much our knowledge has improved when it comes to the many factors that determine our identity and individuality.

What other factors define us and make us unique?

In addition to our microbiome and DNA, other factors include epigenetics, the nervous system, and the immune system. The microbiome is considered separate from the body, while the other four are thought to be a part of it. How can we objectively make the distinction (which is often intuitive) between what is intrinsic to the body and what is separate from it? Research into the topic is currently under way. In some cases, can the body transform these external features into internal ones by incorporating elements that originally appeared foreign? These questions lead us to a philosophical understanding of the individual by defining it in both temporal and spatial terms.

Do we still need to distinguish between nature and nurture?

In the 1970s, some people were already speaking out about how this distinction wasn’t useful any more. However, this concept keeps coming up in current research. Generally speaking, biological phenomena are thought to include some innate and some acquired elements. The line between nature and nurture is actually quite thin, even if we have a hard time letting go of the distinction because of our education. In her exceptional book, the American psychologist Susan Oyama described the “ontogeny of information”, emphasising that even DNA is shaped by a person’s context and environment. For example, nowadays, developmental biology is studying how the microbiome can activate certain genes that play an important role in the body’s development. The microbiome can be transmitted

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vertically between a mother and her child – this is especially the case in insects. In humans, babies have microbiomes that are distinct from those of their mothers after 18 months. However, the fact remains that the mother’s microbiome influences the foetus during a pivotal stage in his or her development.

Thomas Pradeu has long been interested in the construction of individual identity.

Is each person’s identity a combination of what makes them unique, what they share with others, and who they are intrinsically?

Our identity is fashioned by the contact that we have with the outside world. When someone gets a vaccine or interacts with a micro-organism, his or her immune system adapts and changes as a result of this new stimulus. Our identity is also based on our social influences, like our friends and teachers. This is where psychology and sociology intersect with biology, which is rare. The other can become a part of you. In some cases, for example, the immune system can recognise a part of the microbiome, such as a bacteria or virus, then come to tolerate it. It can even play an essential role in the body.

Why is it so important for us to know “who we are”?

This question is a fundamental part of philosophy. It means knowing what defines humanity and discovering what sets us apart from other humans, what makes us unique. Throughout time and depending on the philosopher in question, we have defined humanity through our ability to laugh, reason or use language. The concept of each person being a unique individual has existed since ancient times but became especially popular in sixteenth- and seventeenth-century philosophy. People have always felt a need to understand themselves, find meaning in their lives and realise

that they are a part of nature. All the environmental issues that are so popular today come from this same need to understand. Will humanity soon have to pay for all the damage it is doing to the world? The idea of giving purpose to our lives, which we know are temporary, while also standing out from our peers can be seen in the traditions and signs we adopt to show we belong to a specific group. However, these same signals also include a distinct feature. For example, we might get a tattoo to show we belong, but set ourselves apart by using a design that shows our individuality. It is in this narrow space between belonging to a collective and separating oneself from others that the identity of every human being is fashioned. ⁄

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“Suffering is a wake-up call. Life is short, and you shouldn’t waste it.” SYLVAIN TESSON

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INTERVIEW

SYLVAIN TESSON The Parisian author had built his life around

travelling until one day a fall confined him to a hospital bed. He then promised himself that he would walk across France if he recovered. Sylvain Tesson offers an in-depth look at life in a hospital, learning about weakness and the road to recovery. INTERVIEW: BÉATRICE SCHAAD PHOTO: DANIEL BERES

“By walking, I left my pain behind” less. As I was travelling through Jérôme In 2014, you suffered 20 fractures after a fall and Bosch’s famous tunnel, I realised that everywere confined to a bed at Pitié Salpêtrière Hospital in one is chasing after happiness. Yet, after facing Paris for two months. You said it was almost “lights out” down this kind of challenge, it becomes clear for you. Three years later, what do you remember from that physical pain is the absolute worst kind of the hospital? SYLVAIN TESSON I don’t remember everything. pain there is. I can no longer close my eye beI was there for two months, but I experienced partial amcause of my skull fracture. It’s extremely painful nesia for almost four weeks of that time. That being said, because the nerve is directly connected to the my memories of the hospital are quite positive. I was in brain. I received a transplant made out of gold that much more pain once I got out. Compared to some, lets me lower my eyelid. I have 18-carat gold on the what happened to me wasn’t that serious. I had some inside of my eyelid because that’s the only metal the broken bones, a few rib fragments in my heart and human body can tolerate. Now that I think about it, I screws put into my skull. It was annoying, but it could actually smuggled gold into Switzerland yesterday have been worse. Plus, I was never in pain because of on the sly! the medicines I was on. I think medicine’s ability to control pain and deliver anaesthesia is much more impressive than the invention of the steam engine, IV You said you started to be in pain once you left the tumble dryer or any of this other modern stuff. hospital? ST After I left, I had a tough year. Especially Whenever we try to come up with a philosophisince I decided to cross France on foot exactly one year cal definition of modernity, we tend to talk after my fall, even though it was way too early. I hurt everyabout the growing role of digital technologies. where and had constant inflammation when I was walking. But modernity, true modernity, is the ability to If I had fallen into a stream during my walk, I would have allow a certain number of patients to suffer polluted it with chemicals. I was a walking pharmacy. IN VIVO

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INTERVIEW

Did you need the challenge of walking across France? ST I wanted to put an end to all of my aches and pains with the walk. It was something I really wanted, and needed, to do.

IV You write that you shouldn’t be rebellious or resigned in response to the accident. Instead, you have to “invent a new approach to life, a new way to continue your journey in the company of another IV Is walking a good way to heal? ST Physically speaking, it’s person, weakness.” Is this what you’ve a good treatment method because you toughen up and regain done? ST I haven’t become wise, as much as I’d muscle tone. There’s also a physiological and emotional benefit. What is walking? It’s a small, low-intensity victory of a like to. But my life has changed. The accident few kilometres. Plus, it’s completely harmless. You’re not changed me on a biological level: I move more winning by hitting someone over the head with a club. slowly, I lose my breath, my lungs aren’t in as You’re not stealing – you’re not taking anything, actually. good a shape, I can’t drink a drop of alcohol, and You’re not passively going through life because you are free. I’m epileptic, so I have to be careful about getYou have no constraints on your time or your direction. For ting regular sleep. All of this means I can no me, it was wonderful. It was how I recovered. longer have the same lifestyle I enjoyed before: the life of a bad boy roaming the streets of Paris by night. I’ve become wiser not because I’ve actuIV You also say you had to have an accident to realise ally gained wisdom but because my body has what you had. Isn’t this a very moral perspective: no forced me to do so for health reasons. awareness without suffering? ST Why aren’t we outside by the lake right now, eyes closed and simply enjoying the feel of the sun and the wind? Because we think we’ll live IV Isn’t accepting your own weakness a kind of forever. Otherwise, we’d be elsewhere, taking in the sun, wisdom? ST No; you’re confusing a limitation with wind and water. We’re crazy, actually. When you can’t get a choice. Wisdom means suddenly changing yourself. out of your bed, you think: “How in the world could I It results in a metamorphosis because you’ve come to have wasted this much time? I should have been enjoya certain conclusion. I just have to come to terms with ing these things every day.” Suffering is a wake-up call. a new pace of life. I didn’t rebel because I’m the only Life is short, and you shouldn’t waste it. You shouldn’t person responsible for what happened to me. I fell waste what you have, especially when it comes to your off a roof when I was drunk. But I didn’t give up either. friends and loved ones. We humans tends to denigrate I changed my lifestyle. I accept help sometimes, and I what we have and want what we don’t have. Not to accept being last in line, being second string, and bringbeat a dead horse, but the fact is that all of a sudden ing up the rear, something I always hated in the past. you have a big warning sign waved in front of you, Before my accident, I was a bit wild. That’s what I call telling you, “Don’t forget you have all these people acceptance. I have a lot of pain that I’ve learned to live around you. Don’t forget you have the sun and the with. Alphonse Daudet named his pain. He called it wind. Don’t forget to live.” “Doulou”. The way Daudet contracted his disease, syphilis, was pleasant, and he kept it at arm’s length by naming it like you would an object. Personally, I beIV Now that you’ve recovered, have you lieve in the power of forgetting. For example, been able to retain this same awareness? BIOGRAPHY this is the first time in three years that I’ve ST That’s the rub. Life outside of the hospital Sylvain Tesson is talked about it. I hate the idea of constantly is all about following through with the ser- a French travel thinking about yourself. It’s terrible to obsess mons you gave yourself on your sickbed. I writer born in Paris in 1972. He over, publicise and explain your disease. It have to be worthy of the person I was on my was awarded the prolongs the pain. Hence why I wanted to sickbed, otherwise it’s a betrayal of myself Prix Goncourt for walk. It wasn’t the best idea to leave just one after my fall. In any case, I’m trying to keep Une vie à coucher year after my accident and sleep on a mat on all the promises I made to myself back then. dehors and the Prix Médicis for the ground outside. It was idiotic, but it also I enjoy my life more. My joy for things has Consolations of saved me. By walking, I left my pain behind. become more intense. the Forests. He IV

is the author of enchanting works such as Berezina and Sur les chemins noirs, the story of his tour of rural France one year after a serious accident.

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INTERVIEW

Would you describe yourself as being resilient? ST What is resilience? That word is everywhere. I never use it. I find it a bit irritating, actually, because to me it sounds like digital, international or management jargon. Big, flashy words that try to sum up entire concepts. Nowadays, you sprain your ankle, trap your finger or have a leg amputated, and people talk to you about resilience. It’s used in reference to problems big and small, which dilutes its meaning.

“IT IS MEDICALLY CRAZY THAT HOSPITAL ROOMS HAVE TVS.”

to once again appreciate the beauty of language, music, travel, adventure...it’s great. But at the same time – sorry, Do you prefer the word “recovery”? What this is going to sound harsh – I think it’s absolutely terare the signs of this term? When do you rible that hospital rooms have TVs. Medically, it’s crazy. know that you’re getting better? ST I think one I was in a two-person room with another guy. He wantsign is pretty obvious. It’s when the world no ed to watch TV and I didn’t. In France, though, the perlonger means your hospital bed. For patients, the son who wants to watch TV gets to watch it. So, I had world starts at their pillow and ends at their feet. to put up with the television, but he never had to deal And then, suddenly, you become aware of sufferwith silence. Are you familiar with Nabilla? I had to ing that isn’t your own. That can be a sign of reput up with her for two days because she caused covery. In my case, I remember it was at the height some mischief somewhere. I thought to myself, of the terrible cruelty of the radical Muslims from “This is terrible. I’ve seen the darkness. And now, the Islamic State. The courage of the people who here I am, starting to see the light of day once were standing up to them was incredible. So many again, but I have to keep earplugs shoved in as far of them were dying because the West had abanas they will go...all because of Nabilla.” doned them and they were caught up in the underhanded dealings of the Turkish government. It was terrible. Once you realise there are different degrees IV You wrote about a particular maxim: you of pain, and that yours is not the worst, that’s a sign should always ask a situation’s permission bethat you’re on the way to recovery. fore turning it in your favour. ST I like playing with words. You’ve hit a roadblock. Now, plough through it with a bulldozer. It’s true, I took conIV Is healing an accumulation of many signs? ST I was trol. But I didn’t ask permission. ⁄ lucky to have another sign of my recovery that was less internal, less striking and less solemn than the realisation that other people experience pain. That sign was reading. I love books. I’m an avid reader, and books really helped me when I was in hospital. I never stopped reading. I took pleasure in reading, but my brain could still only enjoy it in the moment. It was an organic, simple kind of pleasure. It was like an anemone had suddenly learned how to read. I was happy just floating along, filtering plankton. Nothing stuck, however. Then, suddenly, my brain started to remember. IV

You write that books, just like walking, helped you “stay standing”? ST Of course, it’s amazing when you start

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DECODING

UNDERSTANDING ENDOCRINE DISRUPTORS Endocrine disruptors are being blamed for a wide range of problems nowadays, even if an exact causal link is difficult to prove. Explanation. TEXT: YANN BERNARDINELLI

FRAGILE SIGNALLING PATHWAYS

Products containing the most endocrine disruptors

PLASTICS

Plastics contain several additives that are classified as endocrine disruptors. Phthalates are added to polyvinyl chloride (PVC) to make objects more flexible. Alkylphenols like bisphenol A make them transparent. They also contain flame retardants such as PCB, PPDE and organophosphates. Most of these compounds are carcinogenic and harmful to human reproduction. They can also cause behavioural disorders. They don’t bond to plastic polymers and rub off upon contact. PET baby bottles, toys, pipes, packaging and bottles all contain these substances.

An endocrine disruptor is “an exogenous substance or mixture that alters functions of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or entire sub-populations,” according to the definition of the World Health Organization published in 2002. In order to understand how these disruptors work, it’s important to first know how the endocrine system functions. Our organs have to communicate with each other to work properly. They do so via two major transmission pathways – the nervous system and the endocrine system. The second is made up of organs, called endocrine glands, which secrete

BERTRAND GUAY / AFP

ndocrine disruptors can be found throughout our environment in the form of micropollution. These substances can interfere with the hormonal systems of a number of species and ultimately end up in our own food chain. They are even in the products and containers that fill our closets and bathroom drawers. Because these compounds are so diverse, they can be hard to evaluate using toxicological tests and protocols – so much so that scientists struggle to even identify them. Read on for an in-depth look at substances that are making us question the way we use products created with industrially-synthesised chemicals.

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PESTICIDES

The updated European definition of endocrine disruptors now includes insecticides. Glyphosate, which is found in the Monsanto herbicide Roundup, appears to be carcinogenic. Pyrethroids, which represent 30% of insecticides in the world, might lead to an accelerated onset of puberty. In addition, the French government recently published an impressive list containing the names of around 1,500 biocides and phytosanitary products that could contain endocrine disruptors.

DECODING

hormones into the bloodstream that are then carried to distant organs. These glands include the hypothalamus, adrenal glands, thyroid, ovaries and testicles. However, that’s not all that the endocrine system entails. Cells distributed throughout our organs have endocrine properties as well. The pancreas, stomach and placenta are just a few examples. To top it off, these two signalling pathways are interconnected. As a result, there are many opportunities for disruption. Because all our vital functions depend on our hormones, which regulate our development, sexual differentiation, behaviour, and digestive and cardiovascular systems, endocrine disruptors can cause a large variety of adverse effects.

UNATTAINABLE PROOF

Scientists struggle to identify these disruptive substances, which makes it difficult to ban the products that might contain them. Thierry Buclin, Head Physician of the Clinical Pharmacology Division at Lausanne University Hospital (CHUV), reports that around 900 substances have been classified as endocrine disruptors to date. The first such chemicals were identified in the wake of environmental disasters. “They were discovered after amphibians, alligators and fish were observed to have changed sex in the United States,” explains Nathalie Chèvre, an environmental toxicologist at Lausanne University (UNIL). In the late 1990s, studies showed these anomalies were due to substances that had an oestrogen-like effect. Oestrogen is the female sexual hormone. Exposure resulted in the

Protest in front of a Parisian supermarket in March 2014 against the use of pesticides containing toxic substances.

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DECODING

feminisation of males and ultimately led to sterility. However, for most of these substances, no causal link has been identified in humans. The relevant authorities recognised the potentially dangerous nature of this phenomenon and decided to ban them based on the precautionary principle. Today, epidemiological data is more telling. Among men, average sperm counts, which measure fertility, are declining. “It has dropped by a third in the past fifty years,” says Thierry Buclin. These data don’t just pertain to fertility. Cancer, autism, early-onset puberty, diabetes and obesity are all on the rise. Some hypotheses regarding the cause of these pathologies point to endocrine disruptors, and the corresponding mechanisms have mostly been confirmed in laboratories. Because they haven’t been tested in humans, however, bans against these substances have been slow in coming.

means the compound has to reach a certain concentration in the body before a measurable effect can occur. Nathalie Chèvre points out that endocrine disruptors are present in minuscule amounts and involve millions of substances, including known compounds and their degradation products. Taken separately, the compounds are never abundant enough to reach toxic levels. “However, out of millions of substances, it’s likely there are several that affect the same target.” The expert goes on to say that by simply adding their concentrations, it’s possible to achieve a biologically active dose through what’s known as the cocktail effect.

Blends of endocrine disruptors present a difficult challenge. New analytical techniques, such as the one developed by the French company WatchFrog, appear promising. Rather than try to pinpoint the toxicity of any given substance, the company created a system that uses the larva of amphibians to determine if a solution Why are there so many barriers to regulais able to alter the test subject’s hormonal tion, while “in any other situation, when system. “Our procedure uses the endofaced with such a broad range of indirect crine system of the larva as a sensor. The proof, the precautionary principle would larvae carry a genetic marker that becomes be applied and the product controlled”? It’s fluorescent once disruption has occurred,” difficult to obtain incontrovertible proof, explains Gregory Lemkine, director of explains the specialist, because the effect WatchFrog. The technique is of endocrine disruptors must currently being tested by the be demonstrated in the clinic, COSMETICS Lausanne Water Authority. which means human testing. Our bathrooms are However, this would involve home to 400 to 500 administering a potentially different chemical subs- NO TO SUBSTITUTION – toxic molecule for several years, tances. Cosmetics are no YES TO PRAGMATISM exception and contain which is ethically unacceptable. Once a substance is declared an impressive cocktail toxic, industrial manufacturing of known endocrine TOXICOLOGY PUT TO THE TEST disruptors. For example, processes simply substitute it “In conventional toxicology, the parabens have antibac- for something else. This was the case for polychlorinated biphedose determines the poisonous terial and antimycotic properties and are used nyl (PCB), which was once used effect,” says Thierry Buclin. as preservatives in sham- as an electric insulator. When An active compound like an poos, creams, foaming its harmful effects on reproendocrine disruptor binds with products and toothpaste. its target receptor in a doseThey have been shown to duction were discovered, it was response relationship, which cause decreased fertility replaced by polybrominated in men and promote the growth of certain types of tumours. The UV filters used in creams and lotions are also detrimental to human reproduction. Phthalates (see Plastics) are in most perfumes.

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DECODING

diphenyl ethers (PBDE), which turned out to be just as toxic and were later substituted by organophosphates. These compounds were then shown to negatively impact neuronal development. As Nathalie Chèvre explains, “Substitution is not a useful way to fight endocrine disruptors”. From a public health perspective, it’s nearly impossible to say whether the observations that have been made so far are just the tip of a deadly iceberg or if the scope of the effect will remain limited. Without a consensus or formal proof regarding these substances, Thierry Buclin suggests the most practical way to move forward is to first target the largest sources of pollutants. Before our internal communication networks become completely disrupted, our external communication organs can be used to shed light on the topic. Immediate risks stem from the substances we ingest, breathe in, or apply to our skin. Because endocrine disruptors act over the long term, the most at-risk populations include pregnant women, children and unborn babies. Care must be taken to avoid the main sources of these toxins, namely plastics, insecticides, wood varnish and lacquer, elective drugs, and especially cosmetics. ⁄

“Frightening people is not useful” For Nathalie Chèvre, an environmental toxicologist at the University of Lausanne, it’s important to explain the effect of repeated exposure to problematic substances. What is the current state of legislation on endocrine disruptors?

nc Right now, it’s crucial – for both the industry and the protection of citizens – that we define these substances. On 4 July, Europe accepted a definition that only applies to chemicals that have been identified as endocrine disruptors. The text indicates that a clear causal relationship in humans must exist in order for a substance to be labelled an endocrine disruptor. NGOs are challenging this definition because such a link is impossible to determine for most substances. The law should also cover potential disruptors to be more effective. iv

MEDICINES

What are the biggest polluters?

Humans and their day-to-day lifestyles are the largest source of pollution – not agriculture. For example, with respect to the medicines that can be found in Lake Geneva, the most abundant is metformin, an anti-diabetic used in humans. After the Lausanne marathon, a rise in anti-inflammatory medication is clearly measurable at water treatment plants. nc

The active ingredients in some medications were created to deliberately disrupt the hormonal system for therapeutic reasons. This is especially the case for the contraceptive pill and its main ingredient, ethinylestradiol. It is ten times more powerful than female oestrogen and breaks down more slowly. It accumulates in the environment and eventually ends up in our diet. Most medications also use parabens as preservatives (see Cosmetics).

What’s the best way to raise peoples’ awareness?

nc It’s a tough problem. It’s important to make people critical, but frightening them isn’t useful. Fear makes people paranoid or fatalistic. Both attitudes stop people from taking concrete action. The general public doesn’t understand the concept of doses – that’s where we should start the work of awareness-raising. Repeated exposure and the cumulative effect of the substances play a critical role. It’s best to avoid repeated behaviours. It’s better to stay out of the sun rather than slather yourself with sunscreen all summer long.

TEXT PATRICIA MICHAUD ILLUSTRATION MARCO MELGRATI

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MY NAME, MY DISEASE

For some patients suffering from a chronic disease, giving their condition a name, be it “Rosy”, “the Green Lady”, or “my best friend”, helps them live with it more easily.

“S

Common names

ometimes I feel like I know Pamela better than my own mother!” It’s hard to know if Eric (name has been changed) is joking when he shares this titbit. The 23-yearold is living with cystic fibrosis, and the disease has set the pace of his life since childhood. He refers to it as Pamela, a woman’s name that calls to mind bleachblond hair and California beaches. “Five years ago, I found myself watching a show on TV that was featuring series from the 1990s. When that blond lady in the red swimsuit started running on the sand (editor’s note: Pamela Anderson, leading actress from the series Baywatch), it was like an epiphany. Don’t ask why...” Ever since, the young man almost always uses the name to refer to his disease – at least, with his family. “In the beginning, my parents and friends looked at me a bit strangely when I’d say things like ‘Pam is still sleeping this morning’ or ‘Pamela is really not in a good mood today’. But they got used to it. Now, they’re the first ones to ask me about how my ‘girlfriend’ is doing!”

Names usually associated with certain behavioural disorders

ANOREXIA Ana/Rex BULIMIA Mia/Bill DEPRESSION Deb/Dan SELFMUTILATION Cat/Sam PARANOIA Perry/Pat INSOMNIA Izzy/Isaiah SCHIZOPHRENIA Sophie/Skip ANXIETY Annie/Max SUICIDE Sue/Dallas OCD Olive/Owen

By giving his cystic fibrosis a name, Eric successfully navigated a challenge that many patients living with a serious disease struggle to manage – namely, the issue of describing a condition that lasts for months, years, or even an entire lifetime and adapting to such a life-altering reality. Eric is not an isolated case. Online health forums are full of people living with cancer, multiple sclerosis, or severe diabetes who talk about “Mark”, “the Green Lady”, or “my Faithful Companion” on a daily basis. “This down-to-earth approach to disease, in which a patient personifies their condition and establishes a relationship with it, is mostly seen in chronic patients” says Francesco Panese, a professor of medical social studies at Lausanne University (UNIL). He goes on to explain that this isn’t a new phenomenon. “It seems cultures have always considered diseases as separate entities, with their own wills and personalities. This idea was undermined by modern western medicine, which started to take shape in the nineteenth century.” TREATMENTS, TOO

“However, anthropologists have observed that people continue to think of disease in the same informal terms. You can think of it as a subjective way of trying to cope”

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explains the sociologist. Patients often say their disease must be both treated and respected for this coexistence to function properly. Naming it helps forge a truce while also enabling the patient to give meaning to the challenge that lies before him or her. Indirectly, the patient’s quality of life can improve as a result because “we typically feel better when we give meaning to our disease”. In some patients, this same need can manifest itself in other ways, such as by “trying to know everything about the disease to take control of their anxiety”. Francesco Panese notes that modern society is more accepting of the complementary nature of an approach that blends medicine and the mundane: “In the 1960s, a doctor might have laughed if a patient referred to their disease by name.” Patients aren’t just naming their conditions. Other components related to the disease, especially treatments and medical equipment, can be christened as well. On her blog, “My Life with EDS”, a young Belgian woman with Ehlens-Danlos (EDS) syndrome explains that she calls Lévocarnil “my little Levovo” and baclofen “Bacloclo”. To talk about her physical therapy sessions, she says she’s “going to see Harry”, and when it’s time for hydrotherapy, she “heads to the pool”. As for her bottle opener, she calls it “Canari”. The blogger explains that her use of nicknames “came pretty naturally” without any conscious effort on her part, and that the trick makes her day-to-day life “so much better”. During her research into the impact of HIV treatments on patients’ lives, Noëllie Genre, a PhD candidate at UNIL’s Social Science Institute, also noticed that people tended to personify their treatments. “At the start of their treatment, some patients refer to the medicine as a bomb.

The adventures of “Rosy” In 2015, Marine Barnérias was diagnosed with multiple sclerosis at the age of 21. Rather than feel sorry for herself, the university student decided to live out her dream of going on a long trip to far-flung corners of the world. For eight months, she travelled solo with her backpack through New Zealand, Myanmar, and Mongolia. During the first part of her trip, the young French woman called her MS “Rosy”. For her, she thought of it as a way to give a pretty name to something that was very ugly. In doing so, she freed herself from a part of the burden of her disease. Barnérias decided to tame Rosy and travel with her to their next adventure. One of these trips became a book, Seper Hero, that was published this year by Flammarion. The title refers to the French acronym for MS: SEP.

Over time, however, they establish a relationship with it by creating a more familiar frame of reference.” Genre gives a few examples of terms she’s heard during her interviews, including “the friend I see every day”, “my buddy”, or even “my best friend”. MIA, ANA, SKIP AND OTHER CODE NAMES

In addition to the names some patients give to their disease or treatment, there is another category of names that is much more standardised. These terms are used to refer to behavioural disorders, and eating disorders in particular. The vast majority of young anorexic women from Generation Y and Z use the name “Ana” when speaking about their condition, while women from the same group talk about “Mia” when referring to bulimia. Male names include “Skip”, meaning schizophrenia, and “Owen”, or obsessive compulsive disorder (see box). These names became standardised in the late 1990s and early 2000s, when massive communities focused on eating disorders started forming online. Major internet providers were worried about the trend and started to censure the use of the terms “anorexia” and “bulimia”. “Ana” and “Mia” were invented to get around the restrictions. Today, an online search for these names will yield hundreds of blogs and forums dedicated to eating disorders. “Sometimes, it’s easier to say ‘Ana is such a pain in the ass. I want to throw her out the window’ than ‘I want to get better’, because it’s easier to take action against someone else than against yourself,” says the author of the blog Mia-solitude. ⁄

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COMMENTARY

MAËL LEMOINE Lecturer at the University of Tours

A philosophical view of medicine.

Within their own field, philosophers have developed a separate discipline, “medical philosophy”, which focuses on the nature of pathology, disease classification, population health, the nature of medical explanations, the power and limits of prediction, the role of proof in medicine, the difficulties of medical decisions, the concept of causality in medicine, and, of course, all of the specific issues surrounding psychiatry.

Like their peers, philosophers are concerned about suffering, ageing, dying, and watching others suffer, age and die. Since the early 2000s, a growing number of philosophers have started to study medicine. In fact, they now teach their field to doctors, investigate sciences and medical practices, and contribute to medical knowledge.

Some philosophers also study research With respect to teaching, ethics (traditionteams in an effort to contribute to medical ally a philosophical theme) is a key topic of knowledge. Indeed, advances in technology discussion. In response to pressure from the inevitably open the door to conceptual chalpublic and the suffering of carers themselves, lenges. As specialists in convoluted problems we have turned to philosophy to “restore meaning” to healthcare and shed light on ques- where careful reasoning can resolve ambiguitions that the law does not always adequately ties and provide helpful insight, philosophers address. Philosophers are neither censors nor have recently taken an interest in “personalised mentors. Instead, they help health profession- medicine”, sometimes referred to as “precision als clarify issues related to the end of life, the medicine”, as well as cancer and immune system support of vulnerable patients and impossible modelling. For example, the possibilities created dilemmas involving ambition and charity or by high-throughput DNA sequencing and big free will and justice. data far outstrip our traditional ways of reasoning, forcing us to imagine new methods for using this information. It’s perfectly acceptable to call on the skills of a philosopher, as well as those of a mathematician and biologist, when taking on such a task.

PROFILE

What is a disease? How can we define it scientifically? These are just a few of the questions Maël Lemoine studies. This lecturer at the University of Tours’ Faculty of Medicine and an author and co-author of several books and articles, just published Introduction to the Philosophy of Medical Sciences this past spring.

It’s clear that medical philosophy is here to stay. The final step for medical philosophers could be to communicate their approach to the public at large. ⁄

READ ON

“Introduction à la philosophie des sciences médicales” (Introduction to the Philosophy of Medical Sciences), Hermann, 2017

TEXT ANDRÉE-MARIE DUSSAULT ILLUSTRATION LINDA ROBERTS MATZINGER

FALLS: A DIFFICULT CHALLENGE As the Swiss population has become older, falls and the problems they cause have become a real public health issue. While the key to preventing the worst is often catching yourself, new technologies can also make it easier to anticipate falls.

t age 88, Berthe was healthy, fully independent and living on her own with her cat. That is, until the day she tripped at home, bumped into a piece of furniture and fractured her hip. The former librarian is one of the 30% of people aged 65 and older who fall every year in Switzerland according to data from the Federal Statistical Office. Currently, falls are second only to car accidents as a cause of fatalities from accidents or involuntary trauma. In addition to suffering, time away from work, surgeries, and hospitalisations, falls cost millions of Swiss francs in health expenses every year. UNAVOIDABLE FALLS AND SELF-PROTECTION

While children heal from broken bones caused by falls in a matter of weeks, the same fracture can mean the beginning of the end for the elderly according to Olivier Borens, physician in chief at the Trauma and Septic Surgery Unit at Lausanne University Hospital: “A fall can cause elderly patients to start to lose their independence and lead to a significant decrease in quality of life.” IN CORPORE SANO

Strategies for reducing risk It’s important to eat well and get exercise to increase your strength and balance. Another strategy is to carefully examine your home and behaviour for any potential risks. For example, you could cover any cables lying on the ground, secure corners of rugs to prevent them from curling up and improve your lighting. You can also wear non-slip socks and shoes, add a mat and handles in the bathtub, and hold on to the railing when climbing or going down stairs. Finally, another strategy is to avoid the abuse of alcohol, drugs and medicines.

Children’s bones are more elastic and less frail – plus, they’re used to protecting themselves, explains the doctor. “When children fall, they tend to fracture a bone in their arms, whereas people over the age of 65 tend to break a bone in their legs, like their ankle, knee, or femur, rather than a bone in their arms, like the wrist, radius, or humerus.” There are two groups of people who are especially vulnerable to injuries caused by falls. Men between the ages of 20 and 30 are the most at risk; the falls that occur in this age bracket are most often associated with high-intensity activities such as car or work accidents. Women aged 70 to 80 are just as much at risk, however, because they are more likely to suffer from osteoporosis, which reduces bone mass and density, explains Olivier Borens. “In this age group, in absolute terms, women are three times more likely than men to break a bone in a fall”. After a certain age, falls become practically unavoidable. “We become less stable, we lose our balance more easily and we react more slowly,” says the specialist. “Naturally, if a patient has been an athlete all her life, she will have stronger bones and muscles and will be more active. On the other end of the spectrum, if she has led a sedentary

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FALLS AND FIGURES

life, eats a poor diet, and doesn’t get enough calcium and vitamin D, her bones will be more fragile.” After completing two sessions of physical therapy, some older people can become more alert, have a better posture, learn to protect themselves better, and – most importantly – get better at catching themselves when they start to fall. Indeed, the seriousness of falls often depends on how people catch themselves. A TOOL TO BRING FALLS TO HEEL

Given that the population is ageing and more prone to falls, geriatric trauma must evolve, says Olivier Borens. “In the near future, we’ll have to invest in fall prevention, methods for strengthening porous bones, surgical techniques, and centres for accommodating and rehabilitating elderly patients after a fall.” Technological solutions could also help prevent and anticipate falls. One example is the smart exoskeleton developed by researchers at EPFL and Italy’s Scuola Sant’Anna; this robotic suit prevents the wearer from loosing his or her balance. A walk analysis system designed by Vaud start-up Gait Up has created quite a stir. “It’s a type of mobility ‘thermometer’ specifically developed for use by health professionals, clinicians, physical therapists and researchers,” says Sales Manager Cléo Moulin.

280,000: the average number of victims of falls in Switzerland between 2010 and 2014. Out of this group, 1,400 people died from their injuries. Ninety-six per cent of these deaths involved the elderly. Onethird of people aged 65 and over fall each year. The vast majority of falls (94%) occur at home. Nine out of 10 hip fractures are caused by falls. In a report published this year, the World Health Organization estimates that nearly 37.3 million falls are serious enough to require medical attention each year, and that 424,000 of these falls are deadly.

The device, which is just three centimetres long and one centimetre wide and attaches to the patient’s shoe, takes a range of measurements, including walking speed, symmetry, and foot height. Walking is a good indicator of a person’s general health, according to Moulin. “Mobility is the result of a patient’s cardiac, pulmonary, muscular and bone condition. By analysing CORPORE SANO

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mobility, we can precisely predict an individual’s fall and morbidity risk. For example, it has been shown that a walking speed of 1.2 metres per second is needed to cross a road safely and that walking 0.6 metres per second predicts a risk of falling and hospitalisation,” she says. Tracking how these statistics change over time makes it possible to anticipate risk even before the patient starts exhibiting the early signs of decreased mobility. As with a patient’s temperature and blood pressure, many gerontologists are now incorporating the device into their daily routine and medical exams. The mobility system’s main advantages are its speed, precision, and user-friendly design. The test, which consists of asking the patient to walk 10 metres and then walk back, can be completed in two minutes. The results are then analysed and can be viewed on a tablet or computer. “The system replaces a laboratory of sophisticated equipment requiring trained personnel.” Costing between 3,000 and 7,000 Swiss francs, the device can also show how a patient is recovering after a joint replacement surgery, if a treatment is effective, and even diagnose neurological disorders like Parkinson’s disease. “In a society where you always have to justify your decision to prescribe or not prescribe a treatment, it’s useful to have such precise and concrete data. It also helps you find the right treatment plan for the patient.” At Lausanne University Hospital, the Geriatric Service has been using Gait Up’s device for about 15 years. “It’s improved significantly over the years. Nowadays, it’s as small as a matchbox and provides much more data than before,” says Christophe Büla, chief of the geriatric and geriatric rehabilitation service, who is happy to see that use of the device is growing. /

37 RESEARCH

In each issue, “In Vivo” shares the work of a team of researchers from the Faculty of Biology and Medicine of the University of Lausanne.

DANIEL MARBACH

Researcher at the Computational Biology Department at UNIL’S Faculty of Biology and Medicine.

Understanding complex diseases through gene networks TEXT: WILLIAM TÜRLER

enetic variants, or the “letters” that make up our DNA and vary from person to person, influence our likelihood of developing a complex disease like diabetes, cancer and depression.

In Lausanne, research out of the Computational Biology Department (DBC) at the University of Lausanne’s (UNIL) Faculty of Biology and Medicine, shows how these variants can disrupt gene networks in our bodies’ various tissues. “The challenge is that over 90% of genetic variants are located outside of genes in regions of the genome we don’t yet understand,” says Daniel Marbach, a researcher at regulatory interactions between over 19,000 genes, the DBC. In response, scientists providing our first-ever overview of the “control in Lausanne have created system” that manages these cells and tissues. specific “maps” of the regulation networks that control the activity “For example, we were able to show that of genes within a cell or type patients with schizophrenia have genetic variants of tissue. that disrupt the genes in cerebral better understanding of how They were able to map out around tissue, while variants associated complex diseases are triggered 400 different types of human cells with obesity interfere with genes and progress, which in turn will that interact within intestinal and tissues, which is the largest lead to more effective and tissues.” Headed up by Professor collection of this kind to date. targeted treatments with fewer Sven Bergmann, director of the Each of these networks includes side effects. ⁄ DBC, this research will provide a hundreds of thousands of

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LAB

BIOMIMICRY: BORROWING A PAGE FROM NATURE Many researchers are turning to the natural world for inspiration in the medical industry. Focus on some promising “bio-inspired” projects. TEXT: ANNE-SOPHIE DUBEY

hark skin is made up of sawtoothed nanostructures that prevent molluscs, algae, and even bacteria from attaching to its surface. The American company Sharklet took inspiration from this fact to develop surface coatings that reduce the proliferation of bacteria in a hospital environment, all without using antibiotics or disinfectants. This protective film, which is already available on the market, has become one of the best real-life examples of biomimicry in the medical field today. Biomimicry or biomimetics, consists of copying nature’s solutions and adapting them to resolve human problems. Some medical innovations in French-speaking Switzerland CORPORE SANO

have also been inspired by the natural world. For example, at EPFL, an interdisciplinary platform has been studying this phenomenon for the past two years. It includes 33 laboratories and around 60 different bio-inspired projects covering a wide range of fields, including robotics, mechanics and bioengineering. “Even though our programme brings together researchers from many different areas, everyone shares the same sense of wonder towards the natural world,” says Platform Coordinator Darja Dubravcic. “Especially when it comes to long-term solutions, there can be no better model than the living world. After all, the processes that work in the environment are the product of a long evolutionary process.” INNOVATION

THE CHALLENGE OF CARTILAGE

“Imitating nature is especially useful when we can’t come up with any other solution,” says Dominique Pioletti, director of EPFL’s Orthopaedic Biomechanics Laboratory. In collaboration with Pierre-Etienne Bourban, from the High-Performance Composite Laboratory (LPAC), Pioletti creates bio-compatible implants based on the structure of natural cartilage. “Unlike bone, cartilage isn’t vasculated, which makes the healing process even more difficult,” says Dominique Pioletti. Currently, there are only two treatments for damaged joint cartilage located at the ends of long bones: injecting in vitro cells taken from healthy cartilage tissue and creating micro-fractures in the underlying bone

IAN GOWLAND/SCIENCE PHOTO LIBRARY

to expose the damaged cartilage to blood and stem cells. “We chose biomimicry because the two existing therapies did not provide satisfactory results.” Along with his team, the researcher set out to synthesize a porous matrix that could reproduce the mechanical properties of three areas of human cartilage, namely a soft tissue surface that could allow bones to glide against each other, a harder median area that would help cartilage to support a heavy load, and an even more rigid base network of fibres to anchor the cartilage to the bone. “The higher the fibre density, the stronger the tissue,” says the CORPORE SANO

THE ENTICING PROMISE OF SLUG SLIME

Slug mucus is both sticky and elastic. Researchers from Harvard University have taken inspiration from this substance to invent an incredibly strong surgical glue to repair tissues. After trials on pig and rat hearts and arteries, the scientists are now getting ready for the first clinical trials on humans.

specialist. “Initially, we used a process similar to 3D printing to superimpose the fibres while also altering their density. The idea and the challenge consisted of reproducing the mechanical variations seen in natural cartilage. Next, we added specialised cells called chondrocytes so the matrix more closely resembled the structure of natural cartilage. This also helped it be resorbed once INNOVATION

the healing process is underway.” While the two researchers have already achieved promising results with experimental models, their biomimetic cartilage must still pass a long list of tests before it can one day be implanted in a human subject. WHEN ROBOTICS AND BIOLOGY COME TOGETHER

Biomimetics doesn’t just involve

A TIMELESS PHILOSOPHY

the reproduction of biological structures. Researcher Jamie Paik, director of EPFL’s Reconfigurable Robotics Laboratory, uses this same philosophy to imitate, rather than reproduce, natural phenomena. “A part of my research focuses on creating soft, rubber robots that imitate the function of human muscles without necessarily resembling their appearance,” she explains. “The robot must follow the natural movements of the body, not be unpleasant to wear, and be rigid enough to generate a minimum amount of force. It’s important to have a keen understanding of muscular biomechanics to find the perfect balance between softness and rigidity.” Just like human muscles, which work like balloons (except they’re filled with blood), these soft robots are made up of long tubes filled with air that expand and change direction based on pressure. Once it’s perfected, this technology could be used to support the oblique muscles and the muscles of the lower back in people suffering from stiffness. “Engineers can also draw inspiration from nature to first understand

The term “biomimetics”, from the Greek words bios, meaning life, and mimesis, meaning imitation, first appeared in 1969 in an article written by the biophysicist Otto H. Schmitt. However, this practice has been developing on three levels in the medical field since ancient times: FORMAL BIOMIMETICS

Ancient Egyptians based their medical innovations on shapes they observed in nature. The first functional prostheses were created nearly 3,000 years ago. These devices were made out of wood and were used to replace a patient’s big toe.

and then improve something,” points out Selman Sakar, director of the Micro-Bio-Robotics Systems Laboratory (MICROBS) at EPFL. Sakar develops microscopic robots that mimic the movements and properties of micro-organisms and eukaryote cells in order to make them interact with their cellular environment and better understand how cells communicate

“ENGINEERS CAN ALSO DRAW INSPIRATION FROM NATURE TO FIRST UNDERSTAND AND THEN IMPROVE SOMETHING.” CORPORE SANO

INNOVATION

FUNCTIONAL BIOMIMETICS

Using micro and nano technologies, scientists can now shift their focus from form to function. In 2015, a Swedish team designed the first prototype for a biomimetic neuron consisting of an artificial ionic pump and a biosensor connected by an electric wire. The technology could help patients with neurodegenerative diseases.

SYSTEMIC BIOMIMETICS

Despite these technological breakthroughs, the study of systems remains an important part of biomimetics. Ever since the 1960s, engineers and biologists have been trying to develop exoskeletons that imitate the human nervous system in an effort to help paraplegics to walk.

through mechanical signals. “What mechanical stimuli trigger tissue formation? In the case of disease, what goes wrong? How can we stimulate cellular regeneration? These are the kind of questions our biomimetic machines could answer,” explains the specialist. Biomimicry seeks to reproduce nature’s example as closely as possible to either imitate one of its mechanisms or simply better understand it in order to optimise some of its processes. Even though it’s applied in a wide variety of ways, this discipline conveys a strong ideological message. “Biomimetics helps us resolve our problems by working with nature, not separating ourselves from it,” summarises the biologist Darja Dubravcic. ⁄

VALÉRIE GARDAZ Department Treatment Director, CHUV

The fight against hospital infections requires daily vigilance.

Everyone is now aware of the emergence of bacteria that are resistant to conventional antibiotics as well as the consequences this phenomenon could have on public health and the safety of care. Hospitals are especially at risk because they are populated by patients with infections as well as patients in poor health, which makes them more vulnerable. Up until now, contagious patients were kept isolated in their own rooms. However, this simple measure is no longer enough to prevent the cross-transmission of pathogenic agents. This situation results in what’s called hospital-acquired infections.

Another method is to closely monitor individuals exposed to or infected with these problematic micro-organisms, which can now be identified as soon as patients check in to the hospital thanks to a new generation of quick diagnostic tests. More conventional methods, such as continuing education for health professionals, are also being pursued. Despite the wide range of strategies being put in place, these efforts will prove unsuccessful if we fail to consider a key factor: human behaviour. In a hospital, good hand hygiene is the most iconic and well-known measure, but it’s also the most problematic. Making sure each and every person disinfects their hands several dozen times a day is a major challenge. This level of vigilance requires seamless collaboration between the various professionals who interact with patients, the cooperation of the friends and family who come to visit, solid scientific knowledge to implement proven strategies and the day-to-day commitment of managers and clinicians when it comes to preventing disease.

In response, hospitals have been taking a As is the case in many other fields, technical new approach to disease. Structural methods and scientific progress have led to major breakinclude keeping patients with the same strain throughs. Nevertheless, we must focus on the of resistant bacteria together in a single human component to achieve success. ⁄ part of the hospital during epidemics and gradually getting rid of multiple-occupancy rooms as the hospital building is renovated or new constructions are added.

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COMMENTARY

hen it comes to these rodents, it’s best to put the rat poison away. A pair of transgenic mice can cost up to 25,000 Swiss francs just to be born, while a pair from original line will set you back 1,000. “Our mice and rats are incredibly valuable animals,” says Luc Pellerin, associate professor and director of the Physiology Department at the Faculty of Biology and Medicine at the University of Lausanne. Despite a push to reduce the number of laboratory animals as much as possible, mice remain irreplaceable. “The key word is ‘mammal’,” says the specialist. “The mouse represents the ideal balance between a rapidly reproducing animal suited to experimentation and one that shares similarities with humans.” CORPORE SANO

NAME MUS MUSCULUS (HOUSE MOUSE) AND RATTUS NORVEGICUS (BROWN RAT OR SEWER RAT) SIZE 7 CM WITHOUT THE TAIL AND 12-15 CM WITH THE TAIL CHARACTERISTICS MAMMALS

The mouse and the rat These two rodents continue to play a crucial role in medical research. TEXT: MARTINE BROCARD

FAUNA & FLORA

Indeed, the gills on a fish can’t be used for respiratory studies, and the nervous system of the worm is not complex enough to serve as a model for humans. Mice are especially well suited for transgenesis, particularly with respect to disease studies. “Cancer, diabetes, sleep studies...everyone uses their own transgenic mice,” says the professor. “You can model the pathology in rodents, then use them to test treatments.” For example, Pellerin developed a mouse that is obesity-resistant. Generally, due to their size and cost, scientists prefer working with mice than rats. However, in some branches of neuroscience such as behavioural studies, rats steal the show. “They have a more extensive repertoire than their cousin,” explains Pellerin. “They are predators just like humans, whereas the mouse is more of a prey animal.” ⁄

CONEYL JAY/SCIENCE PHOTO LIBRARY

CURSUS

COMMENTARY

CURSUS

into hospital care would have been unthinkable not too long ago and is the first of its kind in FrenchPierre-Yves Rodondi speaking Switzerland. It is Director of the Integrative a small step for this field of and Complementary medicine and a giant leap Medicine Centre at CHUV for a university hospital. The two-year project will focus on better addressing and treating over these treatsymptoms like nausea, fatigue, anxiety ments which I cannot behold.” The and pain, and making difficult treatment more tolerable. The effects can then be line from Molière’s documented in order to describe the Tartuffe seems to project’s impact on patient safety and sum up what has quality of life. long been doctors’ official position on A federal referendum in 2009 cleared complementary medicine. At the same time, many patients have been using these the way for this development. At the time, 78% of the Vaud population voted in favour treatments without daring to mention it to their doctors. For example, it is estimat- of a constitutional article regarding the use of complementary medicine. In 2010, ed that over a third of cancer patients progress was made on the academic front have used complementary medicine and when complementary medicine classes consequently been exposed to all the risks were first offered to medical students. this practice can entail – not the least of Five years later, the Integrative and which is drug interactions. The past tense is used here deliberately Complementary Medicine Centre was created at CHUV with three clear missions, because the situation could dramatically namely to pursue the research and teaching change in the near future. Since October 2017, as part of a pilot project supported by efforts already begun and to consider incorporating certain types of comple CHUV’s senior management, hospitalised oncology patients have been offered complementary medicine in accordance with the regulations of a university hospital. mentary medicine consultations, acupuncTime will tell whether complementary ture, therapeutic massage, hypnosis and art medicine will remain on the sidelines or therapy to relieve some of the symptoms if, at least in oncology, it will soon be caused by cancer and cancer treatments. considered “a foregone conclusion,” to This pilot project to incorporate certain complementary medical practices paraphrase Arthur Schopenhauer. ⁄

“C

SAM

CAREER AT THE CHUV

Incorporating complementary medicine

AUDE FAUVEL

TANDEM

PATRICK BODENMANN

CURSUS CURSUS

CAREER AT THE CHUV

t first glance, The historian Aude Fauvel and and in the general from a public, and that is the Patrick Bodenmann, chair of professional need we are humbly standpoint, it’s hard to Medicine for Vulnerable Populations trying to address.” see the similarities at UNIL, head up the Health and between Doctor Their collaboration Societal Dialogue Commission. Patrick Bodenmann is a concrete example TEXT: WILLIAM TÜRLER, PHOTOS: ERIC DÉROZE and Aude Fauvel, a of how much healthhistorian – other than related topics can their shared sense of benefit from this intellectual rigour. However, since the end of type of insight and a multi-disciplinary approach 2016, the two have presided over the Health that includes input from physicians, other healthand Societal Dialogue Commission through the care providers, social scientists, patients and University Department of Community Health and specific populations. “Patrick makes me consider Medicine at Lausanne University Hospital (CHUV). what aspects of the past can be used to shed light The purpose of the commission is to organise on the future,” says Aude Fauvel. “When we’re events that allow representatives of society as studying to become historians, we’re taught to a whole to carry out in-depth discussions with steer clear of anachronisms. Working with Patrick, health professionals. Participants are encouraged I’m learning that anachronisms aren’t necessarily to engage in an exhaustive discussion and not taboo. Quite the opposite, actually – if medical take any shortcuts. history can be of use in the present, that’s a good thing.” “In the public arena, quotes from specialists are often exaggerated or even exploited,” says As a specialist in healthcare aimed at vulnerable Patrick Bodenmann, senior physician at the populations, Patrick Bodenmann pays special Policlinic Medical University (PMU) in Lausanne attention to the social and cultural dynamics that and chair of Medicine for Vulnerable Populations influence health. “Working with Aude helps me in Switzerland at UNIL. “There aren’t many appreciate the weight of history. Our patients are opportunities where you can discuss nuances often trapped within cycles that began long ago. and a wide range of viewpoints regarding We have to be aware of these patterns to provide the body or healthcare,” says Aude Fauvel, effective treatment.” Both insist on the need to look specialist in medical humanities and senior beyond the opinions of “experts” and one-sided lecturer at the Faculty of Biology and Medicine viewpoints. The challenges posed by changes in at UNIL. “However, there is a significant demand medicine must be understood as the complex for this kind of dialogue among professionals issues they are. ⁄

CURSUS

The Neonatal Service celebrates its 50th anniversary Following on from the Maternity Service’s 100th anniversary last year, it’s now time for the Neonatal Service to celebrate its fiftieth year. On 2 March 1967, the hospital opened up the “Premature Baby Wing” thanks to the work of Dr Louis-Samuel Prod’Hom. To mark the event, a photo exhibition will be on display in the Maternity Ward until 5 January 2018.

ANNIVERSARY

Healthcare Department: new website The new website for the Healthcare Department (DSO) is now available at chuv.ch/soins. It is mainly aimed at partner institutions, academic circles and professional communities both locally and internationally. The website includes discussions of topics such as clinical practice, training, research and the DSO’s strategic vision. ORGANISATION

NEWS

The Lausanne A plethora of prizes experiment Several CHUV is a success employees have AWARDS

Outpatient parenteral anti biotic therapy (OPAT) involves administering intravenous medicines outside of a hospital. This service first became available in Switzerland in 2013 in the form of a pilot project at the University Medical Polyclinic in collaboration with the Infectious Disease Service at CHUV. The project was extended when it exceeded all initial expectations. The number of patients has more than doubled since its launch, rising from 120 to 300 patients per year. The OPAT service uses innovative technologies, including the elastomeric pump. This device delivers medicine on a continuous basis. “The advantage of this system is that it allows the patient to be mobile and is less costly than home-based care,” explains Dr Serge de Vallière.

ANTIBIOTICS

been presented with awards, including Dr Rachida Marir, who received a 2017 ISFM Award. With this award, the Swiss Institute for Postgraduate and Continuing Education recognised her commitment to promoting training programmes for physicians. Sébastien Urben was presented with the Frutiger Award for his work in neuropsychiatry and neuropsychology. Dr Friedrich Stiefel received an award from the Swiss Breast Cancer League for his decisive role in designing and organising a communications training programme. The Swiss Society of General Internal Medicine also presented its Teaching Awards for the first time this year. One was given to a pair of teachers, Matteo Monti and David Gachoud.

CURSUS

New gene editing technique In collaboration NEUROLOGY with Dr Renaud du Pasquier and two French teams, Dr Nicole Déglon has developed a new gene editing method. This technique can deactivate mutated genes that are involved with familial forms of brain disease. The results of their work were just published in Cell Reports magazine.

Four health centres have joined the “Urgences Lausanne” application The paediatric A&E department of the Lausanne Children’s Hospital, the Jules-Gonin Ophthalmic Hospital, and CHUV’s Hand Centre and Maternity Service now display their availability on the “Urgences Lausanne” application. Designed for non-life-threatening emergency care, the application helps the citizens of Lausanne find the closest or most available care centre using their smartphones. INNOVATION

NEWS

A place for teens Anne-Emmanuelle Ambresin, head physician at the Interdisciplinary Division of Adolescent Health, has set out to improve the experience of teenagers when they come to CHUV.

CARE

Why create a space specifically for teens? Areas for teenagers exist already, for example at the Royal Children’s Hospital in Melbourne, Australia, and at Rigshospitalet University Hospital in Copenhagen, Denmark, in the form of “cafes for teens”. The results are compelling. Hospitalised teens feel comfortable there and their morale improves. It was important we do the same at CHUV. The educational area on the eleventh floor is open to all hospitalised children, but the decor and activities provided there are more suited to kids under the age of 12. Teens don’t want to go there, so they remain alone in their rooms. How did this project come about? Barbara Tarditi, manager of the Educational Areas at CHUV and the Lausanne Children’s Hospital

(HEL), was committed to making this idea a reality. Since July 2016, the educational areas at CHUV and HEL have been open to only children over the age of 12 for two afternoons a week. The activities, including cooking and cocktail classes, readings and karaoke, are tailored to their age group. Evening events for teens started this summer. Not all the teens in the hospital have made it a habit to go yet, but for some, these times have become important social events. They appreciate the attention, meet other teens and enjoy talking with each other. Do you plan on expanding the project? Absolutely. A 34-m2 room for teens – based on the teen cafe idea in Copenhagen – will be built in the new separate hospital that’s going up next to CHUV. The teen cafe is a way to add some normality to the lives of hospitalised teens by giving them the opportunity to talk with their peers and discuss, play and create together.

IN VIVO

Magazine published by the Lausanne University Hospital (CHUV) and the news agency LargeNetwork www.invivomagazine.com

PUBLISHER

CHUV, rue du Bugnon 46 1011 Lausanne, Switzerland EDITORIAL AND GRAPHIC PRODUCTION T. + 41 21 314 11 11, www.chuv.ch LargeNetwork, rue Abraham-Gevray 6 redaction@invivomagazine.com 1201 Geneva, Switzerland T. + 41 22 919 19 19, www.LargeNetwork.com CHIEF EDITORS

Béatrice Schaad and Pierre-François Leyvraz Gary Drechou THANKS TO

PUBLICATIONS MANAGERS

Gabriel Sigrist and Pierre Grosjean

PROJECT MANAGER AND ONLINE EDITION

PROJECT MANAGER

Melinda Marchese Erik Freudenreich (ad interim)

Francine Billote, Valérie Blanc, Gilles Bovay, Virginie Bovet, Darcy Christen, Muriel Cuendet Teurbane, Jelena Cvetanovic, GRAPHIC DESIGN MANAGERS Stéphanie Dartevelle, Diane De Saab, Diana Bogsch and Sandro Bacco Frédérique Décaillet, Muriel Faienza, Marisa Figueiredo, Pierre Fournier, EDITORIAL STAFF Katarzyna Gornik-Verselle, Aline Hiroz, Joëlle Isler, LargeNetwork (Yann Bernadinelli, Martine Brocard, Anne-Sophie Dubey, Nicolas Jayet, Émilie Jendly, Éric Joye, Léandre Duggan, Andrée-Marie Dussault, Erik Freudenreich, Sophie Gaitzsch, Cannelle Keller, Simone Kühner, Robert Gloy, Blandine Guignier, Marisol Hofmann, Charlotte Mermier, Patricia Michaud, Anne-Renée Leyvraz, Élise Méan, Laurent Meier, Stéphanie de Roguin, William Türler), Gary Drechou, Béatrice Schaad Éric Monnard, Brigitte Morel, Manuela Palma de Figueiredo, Odile Pelletier, Isabel Prata, Sonia Ratel, Myriam Rege, ICONOGRAPHIC RESEARCH Marite Sauser, Dominique Savoia Diss, Bogsch & Bacco, Sabrine Elias Ducret Jeanne-Pascale Simon, Elena Teneriello, Aziza Touel, Vladimir Zohil and the CHUV’s COVER Communications Service. Tal Danino “Microuniverse serie”, photograph: Soonhee Moon DISTRIBUTION PARTNER

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SAM (Laurianne Aeby, Éric Déroze, Patrick Dutoit), Linda Roberts Matzinger, Marco Melgrati, Nikodem Pręgowski, Benjamin Schulte

LAYOUT

Bogsch & Bacco for LargeNetwork TRANSLATION

Technicis PRINTING

PCL Presses Centrales SA 18,000 copies in French 2,000 copies in English The views expressed in “In Vivo” and “In Extenso” are solely those of the contributors and do not in any way represent those of the publisher.

IN EXTENSO

The human body under extreme conditions