Designation: Professor of Immunology at University of Mainz, Germany
Date of birth: 1965
Work: Development and Clinical Testing of mRNA-based Cancer Vaccines that are tailored to the Mutation Profile of a Cancer Patient
Field of the Prize: Life & Medical Science and Technology
A Warrior in the ‘Valley of Death’
To fight a tricky disease such as cancer, you need a weapon at least as tricky
Some time ago there was a debate in media about if physician-scientist is an endangered species or a new species evolving through hybridization. A physician-scientist, an effective bridge between these two worlds, is a physician who is doing some forms of basic science research to solve clinical problems.
The importance of this kind of research in medicine is not just academic. In a sense, physician-scientists ‘translate’ practicing physicians’ language into research scientists’ one, and vice versa. Thus they play a critical role in so-called translational medicine, or as sometimes called, bench (laboratory) to bedside (clinic).
If a doctor is supposed to be committed to do everything possible to save his patient, it may not suffice just to order from the menu, prescribing whatever drugs are available and using whatever tools already developed; It may sometimes means going back to laboratory and doing some basic biomedical research to find a new medicine or invent a clinically effective tool.
The Valley of Death
Can an eminent scientist be an eminent physician too? Well, yes, but it’s not something you see every day. Currently, there is a chronic severe, even growing, shortage of physician-scientist at the global level – only about 2 percent of the total number of doctors in the US. “Translation as such is not taught in any university program, it is something that you learn by being involved with interdisciplinary research teams,” says Ugur Sahin, Professor for Translational Oncology and Immunology and Managing Director of Science and Research at Translational Oncology (TRON) biopharmaceutical research organization.
TRON, founded in 2010 with the initial financial support of €30 million, situated in a newly built research building on the campus of the Medical Center of the Johannes Gutenberg University in Mainz, Germany. As it has been stated on the webpage of the organization, TRON “pursues new diagnostics and drugs for the treatment of cancer and other severe diseases.” It defines its mission as putting inspiration into practice to find viable solutions for challenges and translating scientific insight into clinical practice.
Translational medicine is an interdisciplinary approach and needs overlapping expertise. Physician-scientists have formally trained both as a medical practitioner and as a scientific researcher; hence they have an M.D. and a Ph.D., usually in biological sciences. The main difference between a physician-scientist and a typical biomedical researcher is in the firsthand intimate experience the former has with the patient that could be used to guide research in the lab.
However, teamwork doesn’t take place automatically. As they say, ‘getting good players is easy, but getting them to play together is the hard part.’ This is not an easy challenge “to form a team of interdisciplinary scientists, as it takes time for such a diverse group to function smoothly,” says Sahin.
TRON tries to explain why this new approach is dramatically different from the traditional one: “Historically, the pharmaceutical industry carried discoveries from basic research into clinical trials; recent developments have effected a dramatic change in this process. The basic and clinical research sectors have as a result diverged and the emerging gap is considered ‘the valley of death’ in translational research.”
One of the ugliest demons in this ‘valley of death’ is cancer, undoubtedly. “The treatment of choice for some forms of cancer has hardly changed for decades, so new clinical solutions are needed as soon as possible,” Shain says. There are two research departments at TRON, both of them pursuing promising methods to treat cancer, though by different approaches: The Biomarker Development Centre searches for clinical biomarkers or state indicators of each particular kind of cancer, and the Immunotherapy Development Centre is after beating cancer using the human immune system.
A Crazy Idea
Using the immune system to tackle cancer - or cancer immunotherapy - considered a ‘crazy idea’ from the beginning. Sahin and his wife, Özlem Türeci, both born to Turkish immigrant families in Germany, were thinking about cancer vaccines when they were medical students at Johannes Gutenberg University in Mainz in the early 1990s.
“There is huge medical need. Each year about 10 million patients die due to cancer. My research focusses on immunotherapy. We are developing cancer therapies such as vaccines and antibodies to inform and enable the patient’s immune system to attack cancer cells,” Sahin explains.
The logic is simple: No two patients have exactly the same genetic mutations in their cancerous cells and thus each patient’s treatment should be individualized. The only system capable of adapting is the immune system. Therefore, it is the immune system that should be used as a defense. Bingo!
Unfortunately, translating this idea into reality and recruiting the immune system to fight cancer in practice is not as simple as it may seem. Three decades ago, most pharmaceutical companies considered the idea of cancer vaccines crazy and refused even considering immunotherapy concepts.
Sahin, the recipient of the 2019 Mustafa Prize for ‘development and clinical testing of cancer therapeutic vaccines based on the mRNA for the individual patients regarding their mutation profile,’ says “my research is about empowering the patient´s immune system to fight cancer and other diseases.”
According to Sahin, the greatest challenge for the treatment of cancer is that every patient has a different type of cancer. Even within one patient, there are billions of cancer cells that are all different. The current way of how cancer is treated ignores this challenge. That is the reason why usually only 20-30% of patients with cancer respond to therapy.
“The key question of my research is how we can develop cancer therapies that acknowledge and address the challenge. My research has led to the development of individually tailored cancer immunotherapies. That means we analyze the individual cancer of the patient, we identify the unique features of the patient´s cancer and make a vaccine which is individually tailored. That means every patient gets a unique therapy,” he says.
To create cancer immunity, you should direct T cells - a type of lymphocyte which plays a critical role in the body’s immune response – to attack new proteins expressed by mutated genes on the surface of cancerous cells. However, spontaneous immune recognition of such mutations is too late and too insufficient.
The ingenious solution of Sahin and his team is the personalized vaccines that train the body’s T-cells to attack tumors. They use synthetic mRNA and code it to include all the necessary information to tell T-cells what proteins to make. This engineered mRNA enables them to identify uniquely mutated proteins on the surface of an individual’s tumor cells and mobilizes immunity against a spectrum of cancer mutations.
However, this would work only if you can find any unique mutation not found elsewhere in the body. The process of finding the mutations and putting them in mRNA has facilitated and accelerated through faster computing and gene sequencing technology.
The Spirit of a Warrior
In 2017, Nature published a pair of curious papers showing the efficacy of the treatment. Both studies have applied the concept for the first time on human. One of them has been conducted by BioNTech, a biotechnology company pioneering individualized immunotherapies founded in 2008, of which Ugur Sahin is Chief Executive Officer. Sahin and his co-authors showed the vaccine has stopped the spread of melanoma or skin cancer and shrink tumors in five patients.
“Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer,” they write. It seems that mRNA-based cancer immunotherapies and vaccines are entering clinical utilization: A true case of the bench to bedside studies.
In the past couple of years, many drug companies were eager to invest in this novel genetic information delivery method and the potential new drug class that may result from it. Cancer vaccines, however, are still unproven and many such efforts in the past boiled down to nothing but another spark of hope died and added to the long list of failed attempts. Nevertheless, to fight a tricky complicated disease such as cancer, you need a weapon at least as tricky and complicated, and of course, the spirit of a warrior.
Professor Sahin's photos in the 2019 Mustafa Prize award ceremony and the 6th Science and Technology Exchange Program (STEP) held by the Mustafa Science and Technology Foundation (MSTF) are available here:
In November 2020, amid the world’s desperate struggle against the novel Coronavirus, it was announced that the COVID-19 vaccine developed by Ugur Sahin was found to be 90% effective.
The New York Times:
Lauding Ugur Sahin’s remarkable achievement in fighting the deadly COVID-19 pandemic, The New York Times wrote: In 2019, Dr. Sahin was awarded the Mustafa Prize, a biennial prize for Muslims in science and technology.
“BioNTech: Moving at the speed of light toward the first Corona vaccine”
DW published a report on Ugur Sahin’s success in developing a COVID-19 vaccine with 90% efficacy, highlighting a part of his Mustafa Prize acceptance speech: “‘I realized very early that I was interested in science,’ said Sahin on the occasion of the 2019 Mustafa Prize.”
With the announcement of this COVID-19 vaccine’s high efficacy, DW’s Arabic-language television channel commenting on Ugur Sahin’s being selected as a 2019 Mustafa Prize laureate, said: “It is safe to say that Mustafa Prize commended Ugur Sahin’s achievements prior to any other scientific institution.”
“‘Muslim Nobel Prize’ and COVID-19 vaccine”
Sahin’s success in developing a 90% efficacious COVID-19 vaccine received widespread media coverage in Indonesia.
Elaborating at length on how this mRNA vaccine works, Kompas noted that Sahin’s outstanding achievement in the area of mRNA technology that brought him the 2019 Mustafa Prize, is now regarded as the glimmer of hope for putting an end to COVID-19 pandemic.
The Mustafa Prize, “an award that the Science Journal called ‘the Nobel Prize for Muslims,’” announced five winners in 2019 among which was Ugur Sahin—a 55-year-old Turkish scientist who has completed his academic career in Germany, wrote Kompas and Republika.
Referring to the 2019 Mustafa Prize award ceremony, Republika wrote: In November 2019, an event was held which was attended by representatives from at least 30 countries of the Organisation of Islamic Cooperation (OIC). “This time it was not politicians, but scientists” from hundreds of research institutes gathered under one roof.