This article is part of a Global Geneva reporting initiative to highlight in the public interest innovative developments in science, medicine and education by the International Switzerland community.
Douglas Hanahan was happily ensconced at the University of California in San Francisco when he received a call from ISREC, the Swiss Institute for Experimental Cancer Research, part of the EPFL. Hanahan is an expert in translational oncology, basically, translating the known knowledge about cancer mechanisms into parameters that can be applied in real-life clinical situations. ISREC was created in 1964 with the goal of fostering cancer research in the Lake Geneva area. Although Switzerland had a number of modern hospitals capable of treating cancer, and two Swiss pharmaceutical companies, Roche and Novartis, accounted for a nearly a third of the worldwide sale of drugs for cancer, there was no single centre dealing simultaneously with all aspects of cancer research.
Doug Hanahan was interested in integrating different disciplines into what amounted to a distributed centre for cancer research. The centre would operate as a virtual network of hospitals and academic institutions, all working closely together toward the same objective: improving the outcome of cancer patients.
It would also operate as a virtual network of hospitals and academic institutions, all working closely together toward the same objective of improving the outcome of cancer patients.
Bridging the gap between knowledge and application
As it happened, Hanahan had been looking for an opportunity in the United States to do exactly what ISREC now proposed to do in Switzerland. “What I wanted,” Hanahan says, “was to bridge the gap between knowledge-based research and its application in the clinic.”
“I found that it was challenging to interact with clinicians, who were usually extremely busy,” Hanahan adds. “My lab worked on pre-clinical models of cancer that made new therapeutic strategies possible. The clinicians were interested in principle, but in practice it was difficult to pin them down. I was on one campus. They were on a different one. Even when a meeting was on their campus, they wouldn’t show up, or if they did, a beeper would go off. Time was the major problem. I became convinced that even in this world of instant communications, proximity was still important.”
In discussions leading up to his hiring, Hanahan kept emphasizing the need to create an environment in which research scientists and clinicians could work together. To his surprise, EPFL’s leadership agreed. Not only that, they showed a readiness to push the idea even further.
The obvious partner for such a new hub for clinical work was the CHUV, the University Hospital of the Canton of Vaud. Located in the hilly northern part of Lausanne, the hospital was still a half-hour drive from the ultra-modern EPFL campus, overlooking the shores of Lake Geneva. (See Global Geneva sidebar on EPFL) Hanahan suggested devoting a floor of a nearby building to lab space for clinicians and basic scientists.
The idea fell through, but by then, Hanahan had developed a close relationship with Yves Paternot, president of the ISREC Foundation. The foundation had previously concentrated on supporting the ISREC Institute, but after its merger into the EPFL, the foundation expanded its focus to cancer research and its applications in Switzerland. Paternot was enthusiastic about the idea of encouraging clinicians and research scientists to work together. Instead of a floor, he suggested constructing an entire new building. Project AGORA and a startlingly innovative approach to cancer research was born.
Additional brainstorming led to the conclusion that the project called for more than traditional research. “It’s not enough to put a clinician randomly next to a scientist,“ Hanahan explains. ”They need to have something to talk about.” Encouraging interactivity was written into the architectural requirements, and ISREC launched a design competition. Eventually, the German firm, Behnisch Architekten, headed by Stefan Behnisch, was chosen.
Instantaneous feedback: opportunities for innovation leveraged to the maximum.
The City of Lausanne and the Canton of Vaud made a tract of land available adjacent to the CHUV. This gesture fit nicely into the ongoing political and financial support that local authorities had already committed to the development of a world class cancer research pole in the region. Three floors would be devoted to the different aspects of cancer research.
Their layout would be designed to place the lab space of fundamental cancer researchers side-by-side with the work space of clinician-scientists involved in the day-to-day treatment of the particular forms of cancer being investigated by their neighbouring fundamental scientists. The feedback and identification of problems would be almost instantaneous. The opportunities for kindling innovation would be leveraged to the maximum. The ISREC Foundation soon found CHF 80 million in financing for the project.
Even before plans for the AGORA building were crystalized,Hanahan set out to attract further top talent in the world of cancer research to the region. A key success of this collaborative effort was the recruitment of Dr. George Coukos of the University of Pennsylvania in Philadelphia, who was chosen by the CHUV and the University of Lausanne to launch a new Department of Oncology and by the Ludwig Institute for Cancer Research to direct its Lausanne Branch . Today, Coukos, along with Hanahan and Professor Pierre-Yves Dietrich of the Geneva University Hospitals (HUG), also co-directs the new Swiss Cancer Centre Léman, of which the AGORA is the latest state-of-the-art platform to be inaugurated.
The arrival of Coukos marked the beginning of the AGORA project, and Coukos and Hanahan worked together to propose an innovative structure for the building. The building will eventually house around 300 scientists from the three Lausanne institutions (CHUV, EPFL, UNIL) and the two Geneva institutions (UNIGE and HUG) as well as the from the Ludwig Institute. A year round atrium, envisaged as a gathering place for collegial discussions, links the AGORA building to an adjacent building housing the CHUV’s Pathology department.
The opportunity to foster interaction is factored in at every level and extends to an open-plan lobby and café which serves both the hospital’s staff and the scientists, along with interaction areas on all three research floors. Construction of the AGORA building finished in 2018, and its laboratories are expected to start functioning during the summer 2019.
What also makes the project unique is its readiness to engage the best science, regardless of nationality. This is an approach steadfastly pursued by the institutions occupying AGORA. Douglas Hanahan, who has championed it at EPFL for almost a decade, himself still does not speak French. Francis-Luc Perret, currently director of the ISREC Foundation, and a member of the committee that oversaw AGORA’s construction, points out that the New York Times ranked EPFL as one of the most international campuses in the world, with faculty and students representing more than 124 nationalities.
A unique melting pot for scientific ideas
At a time in history when there is growing pressure in Switzerland and Europe to control immigration, Perret, who served as vice-president of EPFL for more than a decade, says that convincing Swiss sponsors to support a budget for a student body that was often more international than Swiss, frequently required forceful arguments. In contrast, a striking feature of both the Swiss Cancer Centre Léman (SCCL – see below) and the AGORA building is the smooth level of cooperation among local and cantonal government officials, the private sector and academic institutions. “That kind of collaboration is rare,” says Perret.
Coukos, a Greek national, who did his early medical training in Italy and then spent two decades at the University of Pennsylvania in the US, where he created and directed its Ovarian Cancer Research Center, describes the AGORA as a unique “melting pot for scientific ideas.” Coukos says that he thought he would never leave Penn, but Lausanne was an incredibly attractive opportunity thanks to the presence of its important research institutions. The establishment of an important branch of the Ludwig Institute, which has operated for more than 40 years, and the important new investments that the Canton of Vaud was willing to put into the oncology programmes at the CHUV and the University of Lausanne, were equally compelling incentives.
Coukos notes that the AGORA project and the Swiss Cancer Centre Léman fill a fundamental gap in medical science. “In many medical centres doctors and scientists are physically separated, and daily collaboration between the two communities suffers.” Coukos expects AGORA to change that. “We will have the facility to develop new procedures and new technologies in proximity to the hospital,” he says, “and thanks to the close collaboration between the research and the medical communities, take these directly to the patient within the same programme.”
Freddy Radtke, a senior scientist working on the molecular aberrations in tumors at the ISREC Institute at EPFL, agrees. AGORA, he says, will help enable his lab to carry out phase 1 trials locally, rather than rely on lab facilities in Barcelona, Madrid and the Netherlands, where their studies are currently performed.
Numerous innovative approaches to cancer treatment are earmarked for development within AGORA: Professor Jean Bourhis, who heads radio-oncology at the CHUV, is experimenting with a new concept that includes bursts of radiation at 3,000 to 4,000 times the normal rate, lasting only for a fraction of a second. Until now, conventional treatment might require an exposure to radiation for ten minutes or more. Remarkably, these short bursts of high radiation can destroy a tumour without damaging the healthy tissue that surrounds it.
Another compelling area for investigation is the development of immune therapy, Coukos’ specialty. Coukos explains that it has already been possible to take lymphocytes called killer or cytotoxic T-cells from a patient with advanced metastatic cancer and use them to attack the patient’s tumours. In the past, tumours were often invisible to the body’s immune system, but it is now possible to reprogramme these cells to recognize and fight the tumour effectively. “It is the first time in human history when we’ve been able to reprogramme the entire immune system of the patient with a single transfusion,” notes Coukos.
The procedure has proved effective in melanoma so far. The advantage is that, once treated successfully, if the patient experiences a complete response, the cancer rarely returns. The next step is to expand the number of patients who react to the treatment. “It’s only a matter of time before we make these cells smarter and smarter,” suggests Coukos. At the Ludwig Institute a large programme is devoted to building the next generation T-cell therapies that will then move to the clinic at the CHUV.
Coukos, supported by Hanahan, successfully recruited to UNIL and the Ludwig Institute Prof. Johanna Joyce, a leading expert on the cellular environment that drives the growth of tumours, who had held a top position at the prestigious Memorial Sloan-Kettering Cancer Center in New York. Joyce, an Irish national, had been a postgrad researcher with Hanahan back in California. “I never thought we would get her to leave Sloan-Kettering,” he says. For Joyce’s part, she was attracted by the idea of having scientists and clinicians work in close proximity to each other. “A lot of institutions say they are doing this kind of thing,” she says, “but to have clinicians physically side-by-side with the researchers is unusual. It is still not typical for cancer centers.”
Joyce’s research focuses not only on brain tumors, but also on the entire universe in which the tumour exists. The advantage of AGORA is that it will provide an ongoing view, in real time, of the cancer’s progress as opposed to a mere snapshot of a brief moment. It effectively introduces a 4th dimension– time–into the research process. The new AGORA building will have a specialized state-of-the-art imaging facility to enable researchers to accurately follow responses to innovative new therapies used to treat cancer.
“We need to see how cancer cells behave in real time and how they dynamically interact with immune cells and other cells in their milieu,” Joyce says. “Typically, what we have had to do until now is to stop the experiment at a certain moment in time, which means that we were looking at a snapshot and not visualising these complex dynamics.” AGORA is designed to change that. “This will fundamentally change our understanding and we will be able to leverage that understanding to develop new patient treatments” says Joyce.
An added value: talking to people on a regular basis can trigger new research
Dr. Michele De Palma, another research scientist from ISREC@EPFL who will move into the AGORA notes that the environment surrounding the tumour may be as important as the tumour itself. “When you think you have eliminated the cancer, a few cells may just grow back,“ he says, “and you are back to where you started from. If you can kill or re-programme the cells that the cancer depends on to grow, that can be more effective than targeting the cancer cells alone.” De Palma also sees AGORA as making a fundamental difference. “Proximity is not as important as it once may have been,” he points out. “But there is an added value in talking to people on a regular basis. If you have colleagues who share your interests, it will very likely trigger new research.”
The Swiss Cancer Centre Léman (SCCL), which the AGORA serves, is a multi-institutional cancer community that is already achieving impressive results. The collaboration between clinician oncologists at HUG, CHUV and the larger community of oncologists has enabled the establishment of a regional oncology network. Tumour specimens from cancer patients anywhere in the region can be sent either to Lausanne or Geneva for analysis. CHUV in Lausanne and HUG in Geneva co-chair a ‘molecular tumour board’ that involves a weekly videoconference, where the latest cases and their results are presented and discussed. Doctors can log into the meetings by smartphone from anywhere in French-speaking Western Switzerland. Key clinicians from the CHUV such as Professors Solange Peters and Olivier Michielin, and Professor Pierre-Yves Dietrich from HUG, are building clinical innovation around the AGORA and the regional network.
What AGORA will bring to this impressive regional galaxy, besides a dynamic new way of approaching cancer research, is a new wave of talent concentrated in the Lake Geneva region. In that respect, it promises to do for Lausanne and Geneva, what the installation of CERN has accomplished in the domain of high energy physics, and the ‘Human Brain Project’ is chartered to do for neuroscience. The eventual outcome will be to turn Lausanne, Geneva and the surrounding region into an even more impressive world-class focal point for scientific innovation in cancer research and therapy. Although it will certainly take some time for the larger ‘Swiss Cancer Centre Léman’ to evolve, the AGORA Project is already promising significant inroads. For the moment, George Coukos suggests that he would be satisfied to see AGORA assuredly evolve into the innovative hub of this ascendant new cancer centre in Europe.
William Dowell, a former TIME magazine foreign correspondent and writer, is the Americas’ editor of Global Geneva based in Philadelphia. He reported the piece out of Geneva and Lausanne.
Further reporting by Amanda Norchi, a student of Colby College in Maine, as part of a Global Geneva Young Journalists’ and Writers’ Programme funded by the Swiss-based ALCEA Foundation.