Spinoza Prize

Prof. Dr. Maria Yazdanbakhsh (2021)

Prof. M. Yazdanbakhsh (2021)
Department of Parasitology

Maria Yazdanbakhsh (1959) is a scientist who transcends boundaries in more ways than one. Her research group is multidisciplinary; she conducts fundamental research at the interface of demographic studies and immunology, and she applies the outcomes of molecular and cellular research conducted in her laboratory at Leiden University Medical Center (LUMC) to clinical trials and field research in Africa and Asia. Furthermore, her research helps to improve both vaccines against parasitic infections (which benefit the residents of developing countries) and medicines against inflammatory diseases (which occur mainly in wealthy countries).

Yazdanbakhsh’s spectacular discovery that, besides their detrimental effects, parasitic infections can also modify the immune system in a way that protects us against inflammatory diseases such as allergies or Type 2 diabetes marks a significant advance for public health. The mechanisms that were discovered represent an important contribution to the so-called Hygiene Hypothesis, which states that exposure to microorganisms and parasites can protect us against inflammatory diseases.

Yazdanbakhsh is a pioneer in the worldwide search to discover how parasites manipulate the immune system. She began her research in Leiden in 1989 with a study of the cellular immunology of worm infections. In 1997, she expanded her research to cover the relationship between these infections, the altered immune response and the development of allergic diseases. In the same year, she won the MSD-AWARD 1997 for Human Parasitology. In the ensuing years she also started to pay attention to the downside of this modified immune response: how is it that a successful vaccine against malaria can have an efficacy rate of 100% in Europe, but only 30% in Africa. Yazdanbakhsh is constantly innovating in her field of research. For example, at the Leiden Controlled Human Infection Center (L-CHIC), where she is the scientific coordinator, healthy volunteers are infected with parasites. With this approach, candidate vaccines and potential medicines can be tested rapidly and the most promising ones can enter large clinical trials in Europe, Africa and Asia. Such unique studies provide excellent opportunities to fully understand how parasites modify the immune system.

Yazdanbakhsh sits on the scientific advisory councils of various large international research consortia in Europe and elsewhere, and is a member of the Academia Europaea. With her team, she has strengthened the research capacity of research groups in Indonesia and various African countries including Gabon, Ghana, Senegal and Uganda. She also plays a crucial role in maintaining long-term partnerships with scientists in these countries, where she is also a visiting professor. She organises and participates in workshops, symposia and training programmes in Africa and Asia, designed for students, PhDs and post-doctoral fellows. In parallel, she has established a special minor programme at LUMC for international students who wish to study a specific aspect of (bio)medical sciences in Leiden. She is an inspiration to talented young researchers, whom she encourages to work independently and be ambitious with their dream to eventually start their own research group.

In the Netherlands, Yazdanbakhsh is a member of the Royal Netherlands Academy of Arts and Sciences (KNAW) and various scientific advisory committees and was until recently the president of the Dutch Society for Parasitology. She has been the coordinator of nine major collaborative scientific projects (with a combined budget of over €8 million) and is chair of LUMC Global and LUMC’s internationalisation committee. Yazdanbakhsh has been awarded various prestigious international prizes for her scientific work.

The committee praises Yazdanbakhsh as an excellent scientist who plays a pioneering role in multidisciplinary fundamental research and the translation of laboratory research to medicine in general and field studies in particular. Her research has generated insights that would not have been revealed without her work and dedication.

Prof. Dr. Sjaak Neefjes (2020)

Prof. J.J.C. Neefjes
Department of Cell & Chemical Biology

Sjaak (Jacques) Neefjes (1952), Professor of Chemical Immunology at Leiden University and Leiden University Medical Center (LUMC), and head of the Department of Cellular and Chemical Biology (LUMC) is a multidisciplinary scientist. He develops ingenious techniques and combines insights from chemistry, cell biology, immunology and biochemistry to visualise and understand processes of cellular life. This has led to fundamental discoveries about the functioning of the immune system and uncovered new mechanisms of drug action, which can be used in clinical applications for cancer and infectious diseases, and autoimmune diseases such as rheumatism and multiple sclerosis.

Neefjes is responsible for various significant breakthroughs that have had a tremendous impact on a wide range of disciplines. For example, he fathomed the complexity of the processing of antigens (substances that elicit a response from the immune system) in infected cells. He discovered that many newly made proteins are immediately broken down again, which allows the immune system to respond rapidly to infections. This fundamental research resulted in the development of radioimmunotherapy for the treatment of specific tumours.

Neefjes also discovered how bacterial infections, such as salmonella, can cause cancer. As salmonella infections are treatable, these findings can be translated into a preventative approach for certain types of cancer.

Another discovery concerned anthracyclines, a category of cancer drugs that many patients only use for a short time because, otherwise, they cause heart damage. Neefjes demonstrated that certain anthracyclines not only kill cancer cells by causing breaks in the DNA, as had been thought until then. They also damage the chromatin (the “packaging material” of DNA) by dismantling the nucleosomes (protein spheres the DNA is wrapped around) and leaving certain regions of the DNA exposed.

He demonstrated that substances which are only capable of this second activity are, in principle, just as effective in treating cancer but without detrimental side effects. Thanks to this discovery, cancer patients can soon be treated for longer, the treatment of patients with reduced heart function should be possible, and cancer survivors could enjoy a better quality of life. This discovery resulted in Neefjes deciding to restart the production of a “forgotten” drug, the non-cardiotoxic cytostatic aclarubicin, and also a non-toxic variant of doxorubicin, the drug with which cancer patients are currently treated.

The Spinoza Committee calls Neefjes ‘an outstanding scientist with an intelligent audacity’. The professor played a key role in two patented technologies and is a member of various scientific societies, such as the Royal Netherlands Academy of Arts and Sciences, the Royal Holland Society of Sciences and Humanities, the Norwegian Academy of Sciences and the Academia Europaea. Furthermore, he’s a member of dozens of juries and scientific advisory committees at European institutes and universities. He leads the NWO Gravitation programme Institute for Chemical Immunology (ICI), is affiliated with the Oncode Institute and has been awarded various grants, including an ERC Advanced Grant on two occasions. Many of his former PhDs and postdocs have since become professors, group leaders, or assistant or associate professors. Neefjes is a member of the scientific advisory councils of the Dutch Cancer Society and Kika (Children Cancer-free Foundation) and is also active in the Princess Máxima Center for paediatric oncology. He regularly appears in the media to talk about his research.

In the future, Neefjes wants to investigate when salmonella bacteria initiate the last step in the development of intestinal cancer. And he also hopes to work together with social scientists to prevent cancer by setting up smoking prevention programmes for high school pupils. Thanks to the Spinoza Prize, he now has the funding for what is possibly his most important project: introducing two less toxic anthracyclines – aclarubicin and modified doxorubicin.

Prof. Dr. Michel Ferrari (2009)

Prof. Michel D. Ferrari, MD, PhD, FANA, FRCP
Department of Neurology

Michel Ferrari (1954) is a professor of Neurology at Leiden University and Leiden University Medical Center. Professor Ferrari received the NWO-Spinoza Prize in 2009 for his groundbreaking migraine research. He was the first to identify migraine genes, has developed new drugs to treat migraine attacks, and acts as an ambassador for headache patients. Michel Ferrari (15 July 1954, Tandjong Pandan, Indonesia, Swiss nationality) gained his degree in medicine at Leiden University in 1980 and obtained his doctorate there with distinction in 1992. In 2002, Leiden University appointed him as a professor of neurology. Ferrari has received many influential prizes and grants, including a Vici grant from now in 2004. In addition to this, he has fulfilled many prestigious positions in national and international scientific organisations.

For example, he is ex-president of the International Headache Society and currently chair of the Dutch Headache Society and the Leiden Centre for Translational Neuroscience. Ferrari is not only a scientist but also a practising clinical neurologist. Michel Ferrari is the migraine expert of the Netherlands and one of the six so-called 'Headache Masters' in the world. He has made various major contributions to our understanding of migraine and how to treat it. This is of immense societal value, as 12% of the general population suffers from migraines. His research maxim has always been: translational multidisciplinary collaboration. During his doctoral research into the role of serotonin in migraine, Ferrari made crucial contributions to the development of triptans. These were the first specific drugs that effectively suppressed migraine attacks. The headache specialist is also searching for treatments to prevent attacks. Within this context, his research group was the first to identify a gene for a rare, severe form of migraine, associated with prolonged half-sided paralysis. This discovery in 1996 was referred to by one of the referees as 'comparable to placing a flag on the moon'.

His research team has since discovered four other migraine genes. According to Ferrari, migraine is all too easily dismissed as 'a fuss about nothing'. Therefore, he champions the interests of headache patients. The book ‘Alles over hoofdpijn en aangezichtspijn’ [Everything about headache and facial pain] that he wrote with a colleague is a bestseller among headache sufferers.

Michel Ferrari is a highly productive and passionate scientist. He currently has about 350 publications to his name and has been cited almost 10,000 times. Moreover, he’s the author or co-author of around a hundred book chapters. He’s an internationally renowned opinion leader in the field of neurology and a much sought-after speaker at scientific congresses and patient events. Ferrari attracts many talented young researchers from the Netherlands and further afield, and also finds time to arouse the interest of talented school pupils by actively involving them in scientific research. Considering this impressive record, the Spinoza committee is convinced that the Spinoza Prize of 2.5 million euros shall be well spent. The committee hopes that this boost will enable Ferrari to realise his dream: finding a good migraine drug that people can take daily to completely prevent migraine attacks.

Prof. Dr. Els Goulmy (2002)

Prof. E.A.J.M. Goulmy
Department of Immunohematology and Blood Transfusion

Els Goulmy (b. 1946) was awarded her NWO Spinoza Prize in 2002. She’s a professor of Transplantation Biology, in particular Minor Histocompatibility Antigens, at Leiden University and Leiden University Medical Centre. Professor Goulmy received the Spinoza Prize in 2002 for her groundbreaking work in unravelling the significance of transplantation antigens (non-HLA minor antigens). Els Goulmy is a top international expert in human tissue typing and a leader in the field of non-HLA minor antigens. These antigens were previously not considered important in reactions between transplant and recipient.

Thanks to Goulmy's work, we now know that they do indeed play an important role in humans. We are all familiar with the human immune system in the form of white blood cells, Medics call this the Human Leukocyte Antigen (HLA) system. However, transplants can fail even if the HLA of the donor and recipient are a perfect match. This happens because the 'less important' (i.e. minor) antigens of the donor and recipient do not match. Such cases often result in death. The 'minor antigens' were discovered in mice in the 1970s. Goulmy showed that they play a crucial role in humans. She also proved that typing tissues for these antigens is necessary for successful bone marrow transplantation.

All the referees consulted describe Els Goulmy as the best in the Netherlands in her field, and she’s one of the top experts worldwide. Professor Goulmy often works with six or seven other groups in the world that are active in this field and is frequently the driving force in these partnerships. Els Goulmy has a very clear sense of what she needs to do. She has an unerring knack for finding the experts who can help put her plans into practice. Her work is published by top journals such as Nature and Science. She has received various awards, including the Van Loghem Prize from the Dutch Society for Immunology (NVVI) in 2001. Goulmy has had a very unusual, exceptional career, showing evidence of great dedication, intellect, perseverance and insight. She started as a lab technician following a degree in Nijmegen. Next, she worked for a while in Leiden and then in Madison, USA. She finally obtained her PhD in Paris, as technicians could not take PhDs in the Netherlands at the time. Following a sabbatical at Stanford in 1990, Els Goulmy was appointed professor in Leiden in 1999. Some of her young students are now starting to break through on their own accounts.

Prof. Els Goulmy retired in 2011.

Prof. Dr. Frits Rosendaal (2002)

Prof. F.R. Rosendaal
Department of Clinical Epidemiology

Frits Rosendaal (b. 1959) was awarded his NWO Spinoza Prize in 2002. He’s a Professor of Clinical Epidemiology at Leiden University and Leiden University Medical Center. Professor Frits Rosendaal received the Spinoza Prize in 2002 in recognition of his achievements in understanding hereditary forms of thrombosis and their consequences. He’s among the world’s leading experts in the field of hereditary clotting factors and associated risks of conditions such as venous thrombosis and cardiac infarction. The Leiden University Medical Center has a global reputation in the field of hereditary blood clotting disorders.

Without Frits Rosendaal's contribution, this research would never have gained such status. Or, as one of the referees expressed it: 'The foundations were there, but Frits built a unique house on them.' Rosendaal's great merit is that he can identify key aspects quickly and accurately and is hugely enthusiastic about setting up the right studies. Rosendaal's original focus was on the risk factors that cause thrombosis – the development of blood clots – in the veins.

He now also studies arteries, cardiac conditions, cerebral infarctions and cerebral haemorrhages. The strength of his research is that he links genetic mutations with environmental factors, which was how he discovered new risk factors for thrombosis. One of those risk factors is an abnormal gene responsible for the production of clotting factor V. This disorder is known as 'Factor V Leiden'. Rosendaal discovered that women with the mutation are seven times more likely to develop thrombosis than 'normal' women. In women with the mutation who were using the contraceptive pill, the risk was found to be ten times higher than in other pill users.

Rosendaal is among the world leaders in his field and is the undisputed top scientist in the Netherlands. He is a prolific author, with a string of high-quality publications. Many of his studies have been published in top periodicals such as Blood, the New England Journal of Medicine and The Lancet. In the latest Science, he ranks second in terms of the number of citations. Eight of his articles are top publications, which feature among the best one per cent in the world. One referee aptly summed up the epidemiologist and internist: 'He is a bright, new star; very few people make a name for themselves so quickly in this research field.'

An encouraging factor in his research is that Frits Rosendaal collaborates well with both clinicians and fundamental research scientists, and he’s able to rely on an extensive international network. He gives keynote addresses at nearly all the major conferences and he has the ability to convey his message effectively, even to a lay audience. And what about the future? Everything that Frits Rosendaal has taken on has been a success, and he’s considered capable of leading a large research group. He’s brimming with ideas and will work passionately for many years to come. In particular, his new research into risk factors in arterial diseases is expected to generate interesting results.