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Scrapie, a disease of sheep, which refuted the dogma of Francis Crick

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The central dogma of molecular biology is a concept that illustrates the mechanisms of replication and transcription of genetic inheritance. It proposes that information is stored in the form of DNA, uses RNA as an intermediary and proteins either as enzymatic machinery or as cellular structures.

When Francis Crick, the co-discoverer of the structure of the double helix of DNA, proposed it (1958) defended unidirectionality. Thus, in your flowchart the ADN is transcribed in Messenger RNA and this, in turn, translated into proteins on ribosomes, the factories of life.

The British scientist postulated that only DNA could replicate and, therefore, reproduce and be transmitted to the offspring and that, in addition, it did so faithfully, that is, that the information was not modified during transmission.

However, science is dynamic, it is not based on dogmas and some viruses and certain proteins “refused to agree” with English and dismantled its molecular scheme.

Enzymes and transgressive molecules

The first blow to dogma came from virology. Some viruses, such as the human immunodeficiency virus, were shown to store their genetic information in the form of RNA and that, with the help of an enzyme (reverse transcriptase), they are able to duplicate it in DNA. When these viruses are introduced into a host cell, they convert their single-stranded RNA into double-stranded DNA, which is eventually introduced into the cell genome.

Reverse transcriptase is an enzyme with certain singularities that make it very interesting, one of them, perhaps the main one, is that it makes many mistakes when copying genetic material, this generates variants that are less biologically effective but that, at the same time, increase variability.

In 1982, a further step was taken to challenge the central dogma of biology by discovering the existence of ribozymes, RNA molecules with catalytic capacity, which ruined that all enzymes were proteins.

Ribozymes are RNA molecules capable of accelerating specific chemical reactions that carry out RNA maturation and protein synthesis.

Scrapie

In addition, there are certain proteins –priones– lacking nucleic acid but with the ability to self-perpetuate, being capable not only of forming protein clusters but also of infecting other proteins and making them defective.

In the 18th century, several Spanish Merino herdsmen described the strange behavior of some of their sheep. They reportedly suffered from movement disorders (shivering), intense itching that forced them to scratch against fences, excessive licking and lip smacking.

This disease scrapie, scrapie or scrapie is a neurodegenerative disease and the first to become part of an entity that has been called transmissible spongiform encephalopathy (TSE) and where, for example, Creutzfeld-Jakob disease and mad cow disease.

We now know that scrapie is due to an abnormal prion protein that translates part of the alpha helical structure (secondary structure) of the normal protein into a beta sheet fold. This protein, of just over two hundred amino acids, dared to contradict the dogma of a Nobel Prize winner more than a hundred years before it was formulated.

In honor of the truth, some time later the English scientist recognized his error and that he should not have used the word ‘dogma’ in his statement but rather ‘central hypothesis’.

M. Jara

Pedro Gargantilla is an internist at the Hospital de El Escorial (Madrid) and the author of several popular books.

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