Better prevention as the key to healthy living
Remaining healthy while growing old, until shortly before death, is the goal of most people. In Switzerland, the prospects for this are relatively good. On average, residents of Switzerland live to the age of 84 years, which corresponds to the highest life expectancy in Europe. However, the healthy life expectancy (“healthy lifespan”) measured from birth is much lower, at just 72 years. This means that the last 12 years of the life of an average Swiss person are shaped by health restrictions.
The aim of all public health efforts must therefore be to shorten the endoflife period of illness and impairment, or to extend the healthy lifespan. The ETH Domain is also pursuing precisely this goal, with the Strategic Focus Area “Personalised Health”, and in future as of 2025 with the new Strategic Area “Human Health”. A better understanding of the mechanisms underlying health and disease should help develop new treatment options and prevention strategies.
Rejuvenating treatment for cells
A better understanding of such processes begins on a very small scale, with the cells. At PSI, Professor G.V. Shivashankar and his team want to understand how diseases develop in individual cells. For this purpose, the researchers have developed a method that uses light microscopy and AI to analyse the threedimensional packaging of the genetic molecule DNA in the cells – the chromatin structure. It turned out that the packaging pattern of diseased cells differs significantly from that of healthy cells.
But that is not all: “Based on the pattern of the altered chromatin structure alone, we can now tell whether the diseased cells are cancer cells or brain cells from Alzheimer’s or Parkinson’s patients,” says Shivashankar, Professor of Mecano-Genomics at ETH Zurich jointly with PSI.
A second development in Shivashankar’s laboratory is even more revolutionary. The team was able to show that it is not only the genetic programme that determines the fate of a cell, as long believed, but that the geometry or architecture of the cell is also important. This refers to its embedding in the tissue and how it is pulled or compressed there by shear mechanical forces. “Depending on whether a cell is stretched or compressed, it produces different proteins,” explains Shivashankar. The technical term for this process is mechano-genomics.
Shivashankar’s team has now been able to show with ageing connective tissue cells (fibroblasts) that they revert to stemcelllike cells when they grow and divide under confirmed mechanical constraints. When the researchers then turned them back into fibroblasts, using a dense scaffold of fibres, the stemlike cells appeared rejuvenated. Wounds treated with the rejuvenated fibroblasts healed much faster than wounds in which the original fibroblasts were transplanted. According to Shivashankar, this method could open the door for novel cell-based therapies.
Probiotics against resistant bacteria
Researchers at Empa in St. Gallen are also working on improved wound healing. They have developed a portable sensor with which they can measure the acidity (pH), glucose content and the amount of the protein MMP directly in the wound fluid. “These three biomarkers can indicate when a wound becomes chronic,” says Professor René Rossi, Co-Head of the Department Materials Meet Life at Empa. If the pH value remains elevated for too long, it is a sign of chronicity. “And if the glucose level drops too much, it indicates that the wound is infected with bacteria,” adds Rossi.
An infection with bacteria is usually treated with antibiotics. Sometimes, however, the germs in the wound develop resistance to one or more of these remedies. As a result, the resistant pathogens can cause inflammation, suppuration and even blood poisoning. In Switzerland, an estimated 300 people die from infections with antibioticresistant bacteria every year.
Empa researchers are using a new strategy to combat resistant germs in wounds. They place lactobacilli into the wounds – probiotic bacteria such as those found in yoghurt – packed in a gelatinebased, porous hydrogel. The probiotics enclosed in the hydrogel then develop an antibacterial effect on site in the wound. In laboratory tests, the researchers were able to practically eliminate two of the most dangerous pathogens – Pseudomonas aeruginosa and Staphylococcus aureus – using this method. However, according to Rossi, it will probably be several years before this promising technology can be used on patients.
Protection against endometriosis
Professor Inge Herrmann works with her group at the Department of Mechanical and Process Engineering at ETH Zurich and Empa, on a hydrogel, but for a completely different application in the area of women’s health. The engineer and her team have developed a hydrogel that can be inserted into the fallopian tubes, killing two birds with one stone. On the one hand, the very soft hydrogel, which is initially compact but swells considerably when implanted in the fallopian tube, could serve as a contraceptive. On the other hand, it could be used for the prophylaxis of endometriosis.
Endometriosis is one of the most common gynaecological diseases. Affected women have benign, usually very painful growths of endometrial tissue that settle outside the uterine cavity. The exact cause of endometriosis is still largely unexplained. According to Inge Herrmann, the most likely explanation is that menstrual blood, together with the cells of the uterine lining, flows backwards into the fallopian tubes and from there into the abdominal cavity.
If this theory is correct, the hydrogel used in the fallopian tubes could possibly prevent the formation of new endometriosis by blocking the reflux of menstrual blood. So far, Herrmann’s team has tested the hydrogel in a model and for three weeks in a pig. “These trials have proven to be very promising,” says Herrmann. Nevertheless, according to Herrmann, many tests are still needed before women can use the hydrogel. It must be absolutely certain that the implant is not toxic, that it does not damage the fallopian tubes, that it remains stable for a long time and that it can be removed without leaving any residue. “It will still take a few years before approval is granted,” says Herrmann.
Noise also causes stress in green spaces
Such technological developments are immensely important for the goal of improved public health, but new prevention strategies are also needed on other levels. It has long been known that a green environment can reduce stress and that people can concentrate better after spending time in nature. Whether and how noise plays a role in this, however, is still largely unclear.
A team led by Nicole Bauer from WSL investigated this question. They took over 500 test subjects for a walk through noisy and quiet forests as well as noisy and quiet urban areas. It was found that the test subjects felt they recovered best after a walk in a quiet forest, better than in a noisy forest, a quiet urban environment or a noisy urban environment.
The researchers also measured the levels of the stress hormone cortisol in the test subjects. These went down after walks in all four situations and did not differ significantly. “That’s the interesting thing!” says Nicole Bauer. “We believe that this has to do with movement itself.” Exercise has a substantial effect on cortisol levels. At least where the perceived reduction in stress is concerned, however, she adds: “Noise is an important factor in relaxation.”
AI for medical knowledge
A project at EPFL is focusing on human health in general. The artificial intelligence (AI) “Meditron” developed there is intended to simplify access to medical knowledge and assist doctors worldwide with diagnoses and treatment strategies. In a first step, the Meditron team led by physician and bioinformatics specialist Professor Mary-Anne Hartley and doctoral student Zeming Chen fed the existing general language model Llama2 from the Meta group with a large amount of highquality medical data.
To test the performance of the language model, the team then evaluated Meditron using three standard medical tests and compared its performance with existing language models. “Meditron performed better in these tests than all opensource models,” says Chen. In order to further improve Meditron, the researchers had the AI evaluated by medical doctors in a next step. The result: Meditron is currently 80% accurate. “That’s better than any previous models,” says Chen. “But of course, we want to get close to 100%.”
Meditron is what is known as an opensource language model. It is intended to be available free of charge to researchers for further development and to all physicians for use in medical practice. “Our goal is to democratise technology,” explains Chen. Currently, however, Meditron is not yet ready for use in medical practice. At least one clinical trial is needed for the AI to be validated. Such a project is currently under way in several hospitals in West Africa as part of the Moove project. “It’s about finding out whether Meditron is ready for use and whether doctors can integrate the AI into their work,” says Chen.
Clean drinking water
Researchers at Eawag are looking into a global health problem. More than two billion people on this planet do not have access to safe drinking water. They are constantly exposed to the risk of ingesting the enteric pathogens that can cause severe diarrhoea. According to the WHO, 829,000 people die every year from diarrhoea, 60% of them due to contaminated drinking water, lack of sanitation or poor hygiene. What is particularly tragic is that this especially affects the most vulnerable, with around 800 children under the age of five dying each day due to diarrhoeal diseases.
That is why a team headed by Eawag environmental engineer Sara Marks is testing simple and affordable technologies in rural areas in Guatemala, Nepal and Uganda, in collaboration with local organisations, to improve the local population’s access to safe drinking water. The researchers primarily rely on passive
inline chlorination, a promising technology for treating drinking water supplies in remote settings. In Guatemala, for example, the partner organisation Helvetas Guatemala has developed a PVC device that provides consistent chlorine dosing in water tanks, thus ridding the water of germs and eliminating the need for people to treat their water at home.
While the project in Guatemala has ended, the research has informed improvements that Helvetas is carrying forward. Marks and her team are currently focusing on collaborations in Nepal and Uganda through action-research partnerships that have been running for over a decade. Marks believes that there is a large and growing global market for simple and affordable passive chlorination technologies. “In Nepal great progress is already being made in the commercial development and use of such systems.”
Regardless of whether globally, as in Nepal, or at the cellular level, as at PSI, efforts to improve human health are important at all levels and can make a difference everywhere. The challenge is to combine all the promising approaches and then put them into practice. In future, this could actually make it possible to extend the healthy lifespan of many people.
