2024 Wolf Prize: Blindness Treatment, Encryption and Plant Cloning

The Wolf Prize, a prestigious international award presented by the Wolf Foundation in Israel, is an annual prize that recognizes outstanding achievements in various fields of Science and the Arts. This year, the prize will be awarded to seven male scientists and one female scientist in the disciplines of medicine, physics, mathematics, and agriculture. Additionally, one artist will receive the arts prize. Each recipient will receive a diploma and a monetary award of $100,000 in their respective field.

A New Perspective on Blindness

The Wolf Prize in Medicine will be awarded to two researchers who have led the development of groundbreaking genetic methods aimed at halting degenerative eye diseases. José-Alain Sahel from France and Botond Roska from Hungary will share the prize for developing an optogenetic method to restore and preserve vision.

Millions of people worldwide suffer from degenerative retinal diseases such as retinitis pigmentosa, age-related macular degeneration, or Leber's hereditary optic neuropathy (LHON), which cause the gradual loss of eyesight. These conditions result from genetic mutations, some of which are hereditary, leading to the progressive death of photoreceptor cells in the retina. These cells contain molecules that respond to specific wavelengths of light, triggering a cascade that ultimately transmits electrical signals to the optic nerve. The brain's visual center translates these neural signals into the visual images we perceive. The death of photoreceptor cells impairs vision, potentially leading to complete blindness. Continued damage may also cause the degeneration of nerve cells responsible for transmitting information to the brain, rendering the visual impairment irreversible.

One approach to addressing such diseases is gene therapy, which aims to replace faulty DNA responsible for cell death with a correct DNA sequence, thereby restoring normal cellular function. However, implementing this concept is challenging as it requires repairing DNA in numerous cells or at least introducing correct DNA to them. Sahel and Roska took a slightly different approach. Instead of inserting DNA into damaged cells, they bypassed them and directly targeted the nerve cells, which typically receive signals from photoreceptor cells in the retina. The researchers introduced DNA into these cells, enabling them to produce a light-sensitive protein derived from algae. Known as optogenetics, this technique enables controlling the functions of biological systems using light flashes, even at the level of activation or deactivation of specific cells or genes. In this case, patients wore special smart glasses that translated visual input into appropriate light signals, activating the proteins in the nerve cells of the eye.

In 2021, in a collaborative study published in Nature Medicine, Sahel and Roska demonstrated their method on a 58-year-old 58-year-old patient with retinitis pigmentosa who had lost his sight gradually until he was completely blind. They introduced the appropriate genes into his eye's nerve cells using a genetically engineered virus designed for this purpose. Six months after the treatment, when the patient wore specialized glasses, he could discern certain objects and even navigate outside his home, including recognizing pedestrian crossing stripes. The prize committee defined their achievement as "a major milestone in the fight against blindness”. 

The glasses convert the captured image to the color and intensity best suited to activate the algal protein. Illustration of using the glasses | Veronique Juvin, SciArtWork

José-Alain Sahel, born in 1955 in Algeria, pursued his medical studies in Paris and Strasbourg, France, specializing in ophthalmology in Strasbourg. He later joined Louis Pasteur Hospital in the city, where he crossed paths with Roska in 2001. At that time, Roska was a Ph.D. student at the University of California, Berkeley, who came to train under Sahel. Botond Roska, born in 1969 in Hungary, studied medicine at Semmelweis University in Budapest and completed his Ph.D. in neurobiology at Berkeley. Subsequently, Sahel took up research positions at institutions such as the Sorbonne in Paris and the University of Pittsburgh in the United States, while Roska pursued his career in Basel, Switzerland. Despite their separate career paths, their collaboration continued, leading in one of the most significant breakthroughs in ophthalmology.

Successfully restored partial vision in a person blinded by a degenerative retinal disease. Sahel (right) and Roska | Photo courtesy of the Wolf Foundation

Stargazer

The Wolf Prize in Physics will be awarded to British cosmologist Martin Rees for his research that has helped shape our understanding of the universe. Born in York, England, in 1942, Rees was admitted to study mathematics at the University of Cambridge, later switching to physics. He earned his PhD in astrophysics from Cambridge in 1967. Rees's research spans diverse areas of cosmology; among other things,as a theoretical physicist, he was among the first to propose groundbreaking measurements of cosmic background radiation—radiation leftover from the Big Bang, discovered in 1964. He provided explanations for the processes of formation of the earliest stars and galaxies, proposed mechanisms for the formation of supermassive black holes at the centers of galaxies, suggested ideas on supernova star explosions, and provided an explanation for gamma-ray bursts in neutron star collisions, among other achievements. Many of his theories and hypotheses have been later corroborated through observations and measurements.

Rees has also held senior positions, including British Astronomer Royal and President of the Royal Society of Science. In addition to hundreds of scientific articles, he has authored several popular science books that communicate complex cosmological concepts to the general public, while also advocating for sustainability and environmental issues.

Theoretical explanations for a multitude of phenomena, from the beginning of the universe to star explosions. Martin Rees | Photo courtesy of the Wolf Foundation.

Encryption and Combinatorics

The Wolf Prize in Mathematics will be awarded to two Israeli researchers for their work in computer science. Adi Shamir from the Weizmann Institute of Science will receive the prize for his groundbreaking research in cryptography—methods for securing and encrypting information—and Noga Alon, currently at Princeton University, will receive the prize for groundbreaking research in combinatorics.

Adi Shamir was born in Tel Aviv in 1952. After earning a bachelor's degree in mathematics from Tel Aviv University, he pursued a PhD in computer science at the Weizmann Institute of Science.During a fellowship at the Massachusetts Institute of Technology (MIT), he collaborated with colleagues Ron Rivest and Leonard Adleman to develop the RSA encryption method, named after their initials. This method allows for the encryption of information, which can only be decrypted by those possessing a specific "key."  It relies on mathematical principles involving prime numbers and other functions, becoming a fundamental tool in online commerce and secure communications. Their work earned them the Turing Award, the most prestigious accolade in computer science, in 2002.

Shamir has made numerous other contributions to the field of information security. He pioneered the "secret sharing" method, which is used as a basis for secure computations, and developed identification and signature methods based on zero-knowledge proofs. He introduced the "ring signature" for encrypting and decrypting information within a defined group of participants. Additionally, Shamir is involved in exposing vulnerabilities in encryption systems and developing general mathematical methods for both direct and indirect attacks on such systems. In recognition of his achievements, he was awarded the Israel Prize in computer science in 2008.

Noga Alon was born in Haifa in 1956 and earned his bachelor's degree at the Technion, his master's at Tel Aviv University, and his PhD at the Hebrew University of Jerusalem. Following a fellowship at MIT, he became a researcher at Tel Aviv University, where he conducted the majority of his research. His work primarily centers on combinatorics - the branch of mathematics dealing with finite structures, crucial in various areas of mathematics and computer science. Most algorithms used in computer programming, computer communications, and even biological information processing are based on combinatorial methods.

His extensive contributions in the field have transformed modern combinatorics, introducing important concepts, structures, and methods to the discipline. Alon is renowned for proving the Combinatorial Nullstellensatz theorem, a powerful algebraic technique that has yielded highly significant applications in graph theory and combinatorics. Among his notable achievements is the development of the polynomial method—another powerful algebraic tool with numerous applications in combinatorics, graph theory, additive number theory, and information theory. Alon used this tool to solve a problem posed by Claude Shannon, the father of information theory, that had puzzled scientists for over fifty years. He demonstrated that certain combinations of communication channels can achieve transmission capacities far exceeding the sum of individual channel capacities.

Professor Alon is also the leading scientist in the application of the probabilistic method in discrete mathematics—a technique that allows for proving mathematical results utilizing tools from probability theory. His research in this area and the book co-authored on the subject with Joel Spencer have had a significant impact on the field. In recognition of his contributions, he was awarded the Israel Prize in mathematics research in 2008.

Groundbreaking research in encryption and combinatorics that earned them the Israel Prize 16 years ago. Adi Shamir (right) and Noga Alon | Photos courtesy of the Wolf Foundation.

Hormones, Light, and Plant Reproduction

The Wolf Prize in Agriculture this year will be shared among three researchers from the United States, who have separately contributed to the field of plant yield improvement.

Elliot M. Meyerowitz from the California Institute of Technology (Caltech) is a pioneer in using the plant Arabidopsis thaliana as a model for research in genetics, molecular biology, and plant development. He and his colleagues have elucidated the molecular and developmental foundations of flower structure using advanced molecular methods. Their research, along with many other research studies, has demonstrated the applicability of this model to all flowering plants. Their pioneering studies paved the way for targeted modifications of flower traits through genetic engineering, enabling researchers to introduce various changes in plants and study their impacts more easily.

Meyerowitz and his colleagues also identified and characterized the ethylene receptor, the first receptor for a plant hormone, enabling precise control over plant aging and fruit ripening. This discovery has significantly enhanced the shelf life of agricultural produce. He was also the first to develop a mechanical model of intercellular connections at plant growth tips, shedding light on the proteins involved and their functions. These discoveries have collectively contributed to improving crop yields in many agricultural plants.

Joanne Chory, a plant geneticist from the Salk Institute in California, focuses on how plants respond to changes in environmental conditions, particularly variations in light composition and intensity. Chory and her colleagues discovered molecular pathways that elucidate how plants adapt and grow optimally in diverse environments - an increasingly critical area given the impacts of climate change on many agricultural crops. Among other findings, they discovered a mechanism that inhibits gene expression, leaf growth, and chloroplast development in the absence of light. She also identified specific proteins, the activity of which is influenced by the plant’s light receptors. Follow-up research in other laboratories found that the genes of these proteins also play significant roles in human cells. This discovery has broad implications for one of the most agronomically important traits: shade avoidance, which is crucial for maize yield. Additionally, Chory and her colleagues have made significant contributions to understanding the activity and production pathways of various plant hormones and other fundamental mechanisms, such as the plant biological clock. Recently, her research has focused on enhancing plants' ability to sequester carbon dioxide from the air, aiming to mitigate the increase in atmospheric carbon levels that contributes to global warming through plant activity.
Venkatesan Sundaresan, a plant geneticist from the University of California, Davis, developed a method for rapidly cloning rice plants without traditional sexual reproduction. Sundaresan discovered that a gene active in plant sperm cells acts as a master regulator of embryo formation. He demonstrated that artificial activation of this gene in rice egg cells could lead to the production of asexually reproduced plants, bypassing the need for fertilization. The discovery that a single gene can bypass the need for fertilization opened the door to numerous agricultural applications. Sundaresan combined artificial activation of the BBM1 (Baby Boom) gene in rice egg cells, obtaining cloned seeds that are genetically identical to the parent plant. The method was tested in commercial hybrid rice and produced multiple generations of cloned hybrid offspring with an efficiency suitable for agricultural use. Recently, Sundaresan and his colleagues extended this approach to demonstrate asexual reproduction in maize, highlighting the feasibility of application of this approach in other major crops. This pioneering discovery paves the way to meeting increased food demands without the necessity of expanding agricultural land use.

Pioneering advancements in understanding plant adaptation and enhancing their agricultural productivity to feed humanity. From right: Elliot M. Meyerowitz, Joanne Chory, Venkatesan Sundaresan | Photos courtesy of the Wolf Foundation.

Despair and Desire for Harmony

As every year, the Wolf Prize honors outstanding achievements in four scientific fields and one cultural field. This year, the prize in music celebrates Hungarian composer György Kurtág for his avant-garde contributions to contemporary classical music. "His music, which deals with the existential questions of the human soul, focuses on fundamental emotions such as love and sorrow, fear, anxiety, despair, and a desire for harmony and reconciliation," wrote the prize committee members. "His art ranges from small forms, such as his short piano works, to a large-scale cantata or opera, and it reflects the past and present of the entire history of Western music. Kurtág’s immense influence on numerous musicians is simply magical. His scholarly environment has always been lucky to absorb from him a unique spirit of devotion to music, structural thinking and harmony and hence experiencing his tutorial work as a torch of humanity.”

Music that explores existential questions of the human soul. György Kurtág | Photo courtesy of the Wolf Foundation.

Wolf Prize - The Prize Forecasting Nobel Laureates

Ricardo Wolf was born in 1887 in Hanover, Germany, and settled in Cuba before World War I. He, along with his brother Siegfried, developed an efficient method for recycling iron from foundry waste. This invention was adopted by many factories worldwide, bringing Wolf considerable wealth. Despite his wealth from capitalism, Wolf was an ardent socialist and a staunch supporter of Fidel Castro's regime in Cuba. In 1960, Castro appointed him as Cuba's envoy to Israel (a lower-level diplomatic representative than an ambassador). Ricardo Wolf served as Cuba's envoy to Israel until Cuba severed its diplomatic ties with Israel following the Yom Kippur War in 1973, but he remained in Israel until his death in 1981.

In 1975, Wolf established the prize foundation bearing his name, dedicated to recognizing achievements in science and the arts worldwide. The foundation also awards prizes to young scientists and provides scholarships and research grants, but it is best known for the prestigious "Wolf Prize" in the sciences and arts. The prize is awarded in the fields of physics, chemistry, medicine, mathematics, and agriculture, and in various art fields on a rotating basis. The Wolf Prize has gained renown as a reliable indicator of future Nobel Prize recipients, with approximately a quarter of its laureates in physics, chemistry, and medicine subsequently receiving the Nobel Prize. Two of last year's Nobel Prize winners in physics, Franz Krausz and Anne L'Huillier, had received the Wolf Prize just a year earlier. In 2022, this trend continued with five out of seven Nobel laureates in the sciences having previously been awarded the Wolf Prize, including Carolyn Bertozzi, who was awarded both accolades in the same year.