Sixty years in the past this week, one of many biggest British scientists, Francis Crick, gave a lecture in London through which he precisely predicted how genes work, setting the course for the genetic revolution we are actually dwelling via. Right here, evolutionary biologist Professor Matthew Cobb from Manchester College unpicks the predictions that set a brand new course for the way we perceive the very stuff we’re created from.
In a single lecture, it has been stated that Francis Crick “completely altered the logic of biology”.
Solely 4 years earlier, he and the younger American Jim Watson had solved the double helix construction of DNA, utilizing information gathered by Rosalind Franklin. Aged 41, Crick was nonetheless 5 years away from successful the Nobel Prize for this work, however he had a fame as a strong and profound thinker.
He gave his lecture – “On protein synthesis” – at College School London for the Society for Experimental Biology. In it, Crick spoke about how genes do what they do. On the time, this topic was nonetheless very murky – some scientists weren’t even satisfied that genes have been made from DNA.
However Crick delivered 4 predictions about genes – and their hyperlink to the proteins that construct our our bodies. In every of those concepts, he was proper.
Cracking the code
Crick began with the principle factor that genes do: they management the manufacturing of proteins.
The issue Crick explored was that the DNA in a gene is solely a chemical code – a string of one thing referred to as bases – A, C, T, G.
Crick needed to clarify how the cell might get from this one-dimensional sequence of bases in DNA to the advanced three-dimensional buildings of proteins. Much more puzzling was the truth that proteins can fold themselves into almost any form.
Crick’s reply was easy: the order of bases within the gene – what he referred to as “genetic data” – corresponded to the order of the amino acids that make up every protein, and nothing extra.
There was no structural details about the protein that was encoded within the gene, he claimed. He referred to as this the sequence speculation.
In some way, the cell “learn” the knowledge within the gene and assembled the amino acids collectively like beads on a string. The ensuing protein folded itself – spontaneously – into its remaining Three-D construction. We nonetheless can not simply predict the construction of a protein from the order of its amino acids, however Crick’s sequence speculation holds good.
To clarify how precisely cells assemble proteins, Crick predicted there should be some small molecules – he referred to as these “adaptors” – that might recognise every of the 20 totally different amino acids within the physique, and would carry them to the place they might be become a protein in the appropriate order.
As Crick gave his discuss in London this molecule was being recognized in an American laboratory. It’s now referred to as switch RNA. It’s the organic messenger that reads and “interprets” the genetic code within the cell’s protein-building manufacturing unit.
Probably the most controversial and influential a part of the lecture although was what was referred to as the central dogma. Crick defined that as proteins are synthesised, data is taken from the DNA molecule, first into an RNA molecule, and is then used to make a protein.
Earlier than the lecture, he drew somewhat diagram to elucidate what he meant. The arrows present what Crick referred to as the move of knowledge going from DNA to RNA to protein. DNA and RNA might additionally copy themselves, so there are additionally arrows going from DNA to DNA and from RNA to RNA.
As a result of the experimental information weren’t clear, Crick accepted that it’d simply be doable that DNA might straight result in the manufacturing of proteins, so he drew an arrow there, too (this isn’t in truth the case).
An important level was that, as Crick put it, as soon as the knowledge had gone from DNA right into a protein, it couldn’t get again into your DNA. There was no biochemical route for a protein to vary your DNA sequence.
Crick thought it could be doable for data to go from RNA to DNA, and this later turned out to be the case, when it was found that some RNA viruses can get into our DNA. However the route from protein to DNA is unattainable.
This central dogma emphasises that our DNA sequence can’t be modified by our proteins, or by how they’re modified by expertise. Over the past 60 years this has proved to be appropriate. Regardless of the joy about what is known as epigenetics, which explains how genes may be turned on and off by the surroundings, this by no means results in a change in our precise DNA sequence. Crick’s dogma was completely proper.
Crick later cheerfully admitted that when he coined the phrase, he did not know what a dogma was. What he actually meant was that it was a primary assumption about how genes labored. No matter its identify, it nonetheless guides scientists immediately.
Crick’s remaining good prediction was to counsel that sooner or later biologists would use sequence information to grasp evolution, by evaluating the sequences of various species.
In 1957, when Crick was talking, protein sequences have been recognized from solely 5 species, whereas DNA sequencing was science fiction and 20 years sooner or later. However that is precisely what occurred, and we will now perceive how organisms advanced in unprecedented element, by evaluating their sequences, simply as Crick instructed.
Crick’s lecture, which was revealed the next yr, continues to be learn and cited by scientists everywhere in the world. It’s a monument of clear and penetrating considering by one of many 20th century’s biggest minds. In all his key predictions, Francis Crick was proper, and he did certainly change the logic of biology.