From bacteria, the keys to therapies of the future

The Thoeris system, on the other hand, when it detects a virus, triggers a response that leads to the death of the infected cell. The Wadjet system is still different. Normally, bacteria have proteins that help organise their DNA; Wadjet takes these organiser proteins and uses them to recognise and block small pieces of invading DNA called plasmids. Four years later, in 2022, Sorek applied his method on an even larger scale and discovered 21 more defence systems. In all, over 50 systems were discovered, a huge number considering that only a handful were known prior to his work. Even more varied and sophisticated systems: some use parts similar to those found in animals and plants to fight viruses. Others directly manipulate the DNA and RNA of viruses to render them harmless. Still others use 'poison and antidote' systems: they produce toxic substances that would normally kill even the bacterium itself, but they also use the antidote. When a virus arrives, the system stops producing the antidote, killing the infected cell before the virus can reproduce.

But Sorek's most sensational discovery is not just about bacteria, but about the human immune system. Many of the defence weapons that our immune system uses to fight viruses and infections already existed in bacteria billions of years ago. Such as the cGas-Sting system, first discovered in animals as an important mechanism for detecting viruses. It works like this: when a human cell detects viral DNA, it produces an alarm molecule that activates a protein, which sets the whole immune response in motion. Sorek found that bacteria use the same type of alarm molecules and the same mechanisms to activate their defences.

Another fascinating defence mechanism unites humans and bacteria: when our cells are severely infected, they sometimes 'sacrifice' themselves to protect the rest of the body by creating holes in their membrane; the proteins that create these holes are called gasdermines. Sorek found that bacteria also have gasdermines that function in the same way: when infected with viruses, they commit suicide to protect the other bacteria in the colony. Bacteria also have identical parts of proteins, such as the Toll-like receptors that recognise when there is an infection and activate defences, or the viperin protein that creates special molecules to block the reproduction of viruses.

This discovery has completely overturned what we thought about the evolution of human immunity and also provides new ideas for developing medicines and therapies.

According to the theory of endosymbiosis, millions of years ago a bacterium and an archaeon (another type of microorganism) fused together to form the first eukaryotic (i.e. nucleated) cell. This primitive cell became the ancestor of all complex organisms: plants, animals, fungi. Sorek proposes that when this ancestral fusion occurred, the new hybrid cell not only inherited the DNA of the two microorganisms, but also their defence systems against viruses. Once these bacterial defence systems were inherited, the primitive eukaryotic cell modified and refined them in the course of evolution. What were initially simple systems to protect a single bacterial cell from viruses, evolved into the complex immune mechanisms that today protect organisms like us, made up of trillions of cells.

Many of these bacterial molecules are now being studied as potential antiviral therapies for humans. What makes them interesting is their inherent ability to distinguish between 'self' and 'non-self', i.e. to recognise what belongs to the cell and what is foreign, and to target specific molecules with great precision: they are therefore promising candidates for future biotechnological applications, for instance to modulate the human immune response more precisely.

Sorek founded a whole new field of research that did not exist before, because prior to his systematic studies, research into bacterial immune systems was fragmentary and occasional. It is a field that involves groups all over the world: the defence systems he discovered are now being studied by structural biologists (who study the shape of proteins), biochemists (who analyse their chemical reactions), bioinformaticians (who analyse their genetic sequences) and immunologists (who study their defensive functions).

At the award ceremony for the Gruber Prize 2025, Sorek will receive half a million US dollars. This is one of the most prestigious international prizes in the field of genetics, awarded annually by the Gruber Foundation in collaboration with Yale University, and considered one of the 'alternative Nobel Prizes' due to its importance and impact in the global scientific community.