Nobel Prize in Medicine: The blueprint of life continues to be decoded

Packaged in the double helix of DNA, organisms pass on genetic information from generation to generation. However, since James Watson, Francis Crick and Maurice Wilkins published the structure of DNA in 1953, it has become clear that it takes much more than DNA to translate genetic information into differentiated organisms. This year’s Nobel Prize for Medicine or Physiology is one of the breakthroughs in decoding the building blocks of life. The US researchers Victor Ambros and Gary Ruvkun are being honored for the discovery of microRNA.

The two researchers discovered microRNA back in 1993 when they discussed the mutations of certain genes in the nematode Caenorhabditis elegans, a model organism in molecular biology. It turned out that the smaller microRNA can regulate the slightly larger messenger RNA (mRNA). The mRNA is at work in gene expression and translation, i.e. the reading of genetic information from the DNA. This “messenger” in turn contains the information for the construction of proteins.

Victor Ambrose

AFP/Faith Ninivaggi

Victor Ambroseborn in Hanover in 1953, is a professor at the University of Massachusetts Medical School.

Since the first work of this year’s laureates, it has become increasingly clear that it is not only the mRNA that regulates which cells grow when and how, but also the microRNA, which can block certain sections of the mRNA and thus influence the transformation of the genetic information . Research laboratories worldwide have now been able to identify tens of thousands of microRNA sequences in 271 different organisms; over 1,000 microRNAs are known in humans. This form of gene expression probably developed over 500 million years as more and more complex organisms evolved.

However, in the complex control of growth and tissue properties, there are also countless ways in which errors that lead to disease can creep in. It is currently known that microRNAs are involved in the development of the DICER1 syndrome, which often leads to the onset of various cancers in childhood. Mutations of microRNA sequences are also linked to a rare eye disease and a congenital skeletal disorder. “Progress is being made in the development of micro-RNA-based diagnoses and therapies, such as metabolic disorders, cardiovascular diseases, neurodegenerative diseases and cancer,” writes Rickard Sandberg, member of the Nobel Committee, in an explanation of this year’s selection.

Gary Ruvkun

dpa/Steven Senne

Gary Ruvkunborn in Berkeley in 1952, works at Massachusetts General Hospital and Harvard University.

As the University of Massachusetts reports, the development of treatments for chronic lymphocytic leukemia is already looking for the microRNAs linked to this type of cancer. In the field of cardiac medicine, researchers are investigating whether microRNA could be used as an early diagnostic tool to detect cardiac arrhythmias, atrial fibrillation or heart attacks. “Several research studies have shown that miRNAs play a key role in the development of the heart muscle and that the amount of miRNA changes in hearts that have been damaged by a heart attack,” says the university.

A diagnostic or therapeutic application of the findings about microRNA is unlikely to be imminent. One problem here is that a microRNA is likely to influence various genes that are involved in coding proteins. When manipulating a specific microRNA, undesirable effects, so-called off-target effects, are to be feared. As the Nobel Committee explains, research has also shown that different microRNAs can have the same target sequence. The system is therefore robust and cannot easily be manipulated by viruses. This of course raises the question of the extent to which people will be able to intervene with therapeutic intentions.