The death of mRNA co-discoverer François Gross disrupted biomedicine 60 years later

Fran ois Gros, one of France's preeminent founders of molecular biology and co-discoverer of the messenger ribonucleic acid (mRNA), died on February 18 at the age of 95, according to the French Academy of Sciences on Sunday.

Gross made an important contribution to the birth of molecular biology, a discipline that revolutionized the life sciences. Gross witnessed and experienced the entire course of modern biology, and his most important work was to discover the existence of mRNA molecules with another French molecular geneticist, Fran ois Jacob, which had a profound impact on gene decryption.

The discovery was used 60 years later in the development of a COVID-19 vaccine and became one of the most important disruptive biotechnologies in the entire field of gene therapy today, which was unforeseeable at the time.

The mRNA hypothesis is proposed

Despite passing by the 1965 Nobel Prize in Physiology or Medicine (discovering the regular activity of somatic cells), Gross is still regarded as one of the greatest scientists in the history of molecular biology.

He entered the Institut Pasteur in France after World War II, was appointed director of the Institut Pasteur from 1976 to 1981, and joined the French Academy of Sciences in 1979. From 1991 to 2001, Gross served as permanent secretary of the French Academy of Sciences. Until 1996, he was President of the Collège de France Cellular Biochemistry.

Gross wrote in his scientific memoir, Half a Century of Biology: "When I was a student, I was always condemned and often changed my name. As a less attentive student, he stumbled into the Faculty of Science at the University of Toulouse and thought he was on the list of medical students.

During his college years, Gross also had a passion for botany. In 1946, he conducted his first research on antibiotics at the Institut Pasteur. He said in his memoirs that almost everything had to be done on its own. To study antibiotics, he took a bus to a slaughterhouse in Paris with a large jar filled with acids to retrieve beef, liver and a cow pancreas.

Gross initially experimented with molecular biologist Jacques Monod in his laboratory in France, and he, along with scientists such as Jacob and Mono, studied the mechanisms involved in biological genetic information (DNA), which carries the code that determines the structure of proteins and is able to replicate the same identity in each cell.

At that time, a problem that attracted the attention of several French scientists was the regulation of gene expression. When they studied a bacterium, they noticed that all the genes carried by chromosomes were not expressed at the same time, such as enzyme proteins needed to metabolize sugars, which were only synthesized when sugar was present in the medium.

They concluded that the expression of genes encoding proteins is controlled by regulatory proteins whose activity depends on the presence of sugars. They are particularly interested in how the information carried by genes, DNA, is delivered to protein synthesis sites through a particle called ribosomes.

Based on this theoretical hypothesis, scientists believe that this transmission must be made through a type of ribonucleic acid (RNA) and name it "messenger RNA," or mRNA, which is a copy of the DNA sequence.

Proof of the presence of mRNA

Gross conducted an experiment at the time that was decisive in proving the existence of mRNA. When he added an inhibitor of RNA synthesis to the culture, protein synthesis stopped immediately. This suggests that an RNA acts as an intermediate for protein synthesis, and that this intermediate must be unstable and degraded by the enzyme, otherwise protein synthesis will last for a while rather than stop immediately.

Identifying this unstable substance is a particularly difficult task. At Mono's suggestion, Gross went to the United States in 1960 for further studies. He once described his days as a living and working in The Jim Watson lab at Harvard: "Jim's lab was in a very simple Harvard building flanked by two bronze rhinos, and there were some epic experiences! The heat in the laboratory is unbearable, the equipment is almost non-existent, the radiation counter is big and old, creaking... Our experiments often lasted late into the night. ”

In 1961, Gross demonstrated the existence of mRNA molecules for the first time. But almost at the same time, on the other side of the ocean in France, three researchers, including Jacob, made the same discovery. In May 1961, two articles were published simultaneously in the same issue of the journal Nature about the official discovery of mRNA, with Gross being the first author of one and Jacob the second author of the other.

Ultimately, the 1965 Nobel Prize in Physiology or Medicine was awarded to Jacob, Mono, and another French biologist, André Lwoff, for their pioneering work in discovering the gene regulation of enzyme and viral synthesis.

Gross, who missed the Nobel Prize, is still fully committed to scientific research. In the 1990s, the global genome sequencing began a frantic race, with the French being the pioneers in mapping human genetics and Gross being an important leader.

In the outbreak of the new crown epidemic in 2020, mRNA-based technology has attracted the attention of the biomedical community due to its historic success in the new crown vaccine, and has become a key technology in a large number of gene therapies in the past two years.

Although France has yet to develop a COVID-19 mRNA vaccine, French President Emmanuel Macron highlighted the Frenchman's contribution to this cutting-edge biotechnology in social media last year. Macron said: "mRNA is a discovery in France, it was not just discovered yesterday, but as early as 1961. He specifically mentioned the research done by Gross, Mono, and Jacob.

Based on the discovery of mRNA by scientists such as Gross, Hungarian female scientist Katalin Kariko, along with American scientist Drew Weissman, used mRNA technology for therapeutic purposes and became the first to achieve control of immune responses related to mRNA transcription. The two men's research work on mRNA shared the 2021 Lasker Prize for Clinical Medical Research because it was critical to the development of a COVID-19 vaccine.