Investing in Nobel Prize Achievements – Autophagy

Nobel Prize History

The Nobel Prize is the most prestigious award in the scientific world. It was created according to Mr. Alfred Nobel’s will to give a prize “to those who, during the preceding year, have conferred the greatest benefit to humankind” in physics, chemistry, physiology or medicine, literature, and peace.

A sixth prize would be later on created for economic sciences by the Swedish central bank, officially called the Prize in Economic Sciences, often better known as the Nobel Prize in Economics.

The decision of who to attribute the prize to belongs to multiple Swedish academic institutions.

Legacy Concerns

The decision to create the Nobel Prize came to Alfred Nobel after he read his own obituary, following a mistake by a French newspaper that misunderstood the news of his brother’s death. Titled “The Merchant of Death Is Dead”, the French article hammered Nobel for his invention of smokeless explosives, of which dynamite was the most famous one.

His inventions were very influential in shaping modern warfare, and Nobel purchased a massive iron and steel mill to turn it into a major armaments manufacturer. As he was first a chemist, engineer, and inventor, Nobel realized that he did not want his legacy to be one of a man remembered to have made a fortune over war and the death of others.

Nobel Prize

These days, Nobel’s Fortune is stored in a fund invested to generate income to finance the Nobel Foundation and the gold-plated green gold medal, diploma, and monetary award of 11 million SEK (around $1M) attributed to the winners.

Source: Britannica

Often, the Nobel Prize money is divided between several winners, especially in scientific fields where it is common for 2 or 3 leading figures to contribute together or in parallel to a groundbreaking discovery.

Over the years, the Nobel Prize became THE scientific prize, trying to strike a balance between theoretical and very practical discoveries. It has rewarded achievements that built the foundations of the modern world, like radioactivity, antibiotics, X-rays, or PCR, as well as fundamental science like the power source of the sun, the electron charge, atomic structure, or superfluidity.

“Self Eating” Recycling

When progress in microscopy allowed us to learn about the inner workings of complex cells, scientists discovered that they contained many sub-units, each performing a special function.

This discovery was rewarded by the Nobel Prize in Physiology or Medicine in 1974, in part to the Belgian scientist Christian de Duve for the discovery of the lysosome.

Lysosomes are specific structures dedicated to digest/recycle components of the cells. This way, a no-longer-wanted or damaged part of the cell can be destroyed safely and its components reused.

It can also be a reaction to a lack of resources, with the cell consuming some of its components to keep working.

Source: Frontiers

Progressively, they discovered that lysosomes can absorb and recycle not only smaller components but entire parts of the cell like whole organelles (ribosome, mitochondria, etc.).

De Duve investigated this process and discovered a dedicated type of vesicle existed to transport what was to be recycled into the lysosome.

De Duve calls this process autophagy, which comes from the Greek words auto-, meaning “self,” and phagein, meaning “to eat.” And the vesicles involved would be called autophagosomes.

Source: Nobel Prize

Autophagy was clearly a very important cellular mechanism, preserved among a wide range of organisms throughout evolution, from amoebas to insects, frogs, and mammals.

However, how this process actually worked stayed a mystery. At least until clever analytical methods were invented by Yoshinori Ohsumi, the winner of the 2016 Nobel Prize in Medicine, for his discovery of autophagy mechanisms.

Source: Nobel Prize

Spotting Autophagosome

Yoshinori Ohsumi, when starting to direct his own lab in 1988, went on to focus on vacuole, the cellular organ equivalent to the human lysosome in microorganisms and plant cells.

His primary model was yeast, mostly because it was easier to grow and study yeast than more complex cells. The yeast genome would also be elucidated much sooner than the human genome and was easier to modify genetically.

However, yeasts’ internal structures are difficult to distinguish on a microscope, and it was not clear at the time if autophagy was a mechanism present in yeast.

To elucidate it, Ohsumi created mutant yeast that lacked the genes for the degradation enzyme in the vacuole. The idea was that if the vacuole could not degrade absorbed components, the still theoretical yeast’s autophagosomes would pile up in the cell.

To make the results more clear, Ohsumi also starved the yeasts, forcing them into an intense autophagy activity. The results were almost instantaneous, with a massive accumulation of autophagosomes in the yeast cells easy to spot using simple microscopy.

Source: Nobel Prize

Autophagosome Genes Hunting

Now armed with an easy-to-analyze model to create abundant autophagosomes, Ohsumi would go hunting for the genes responsible for these structures.

To do so, he exposed his yeast to a chemical that created mutations and then induced autophagy. So when one gene responsible for autophagosome was damaged, the process would break, and he could find the mutation and the gene in question.

While somewhat simple in theory, this was a complex affair in practice, and took a lot of work to identify 15 different genes responsible for autophagosome in yeasts.

These genes would be first named APGI-1 to APGI-15, and later on, renamed ATG genes for all autophagy-related genes.

Autophagosome Genes Functions

Ohsumi would also look at these genes and the corresponding proteins and elucidate their biochemical functions.