Francis Crick Quotes - Page 3

Trying to determine the structure of a protein by UV spectroscopy was like trying to determine the structure of a piano by listening to the sound it made while being dropped down a flight of stairs.

It is notoriously difficult to define the word living.

Anybody who believes that the earth is less than 10,000 years old needs psychiatric help.

We are sometimes asked what the result would be if we put four +'s in one gene. To answer this my colleagues have recently put together not merely four but six +'s.

How is the base sequence, divided into codons? There is nothing in the backbone of the nucleic acid, which is perfectly regular, to show us how to group the bases into codons.

The major credit I think Jim and I deserve ... is for selecting the right problem and sticking to it. It's true that by blundering about we stumbled on gold, but the fact remains that we were looking for gold. Both of us had decided, quite independently of each other, that the central problem in molecular biology was the chemical structure of the gene. ... We could not see what the answer was, but we considered it so important that we were determined to think about it long and hard, from any relevant point of view.

Our ... advantage was that we had evolved unstated but fruitful methods of collaboration ... If either of us suggested a new idea, the other, while taking it seriously, would attempt to demolish it in a candid but non-hostile manner.

Protein synthesis is a central problem for the whole of biology, and that it is in all probability closely related to gene action.

If the code does indeed have some logical foundation then it is legitimate to consider all the evidence, both good and bad, in any attempt to deduce it.

This seems highly likely, especially as it has been shown that in several systems mutations affecting the same amino acid are extremely near together on the genetic map.

It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.

Moreover the incorporation requires the same components needed for protein synthesis, and is inhibited by the same inhibitors. Thus the system is most unlikely to be a complete artefact and is very probably closely related to genuine protein synthesis.

A comparison between the triplets tentatively deduced by these methods with the changes in amino acid sequence produced by mutation shows a fair measure of agreement.

A final proof of our ideas can only be obtained by detailed studies on the alterations produced in the amino acid sequence of a protein by mutations of the type discussed here.

It has yet to be shown by direct biochemical methods, as opposed to the indirect genetic evidence mentioned earlier, that the code is indeed a triplet code.

Unfortunately it makes the unambiguous determination of triplets by these methods much more difficult than would be the case if there were only one triplet for each amino acid.

Jim and I hit it off immediately, partly because our interests were astonishingly similar and partly, I suspect, because a certain youthful arrogance, a ruthlessness, an impatience with sloppy thinking can naturally to both of us.

Attempts have been made from a study of the changes produced by mutation to obtain the relative order of the bases within various triplets, but my own view is that these are premature until there is more extensive and more reliable data on the composition of the triplets.

If poly A is added to poly U, to form a double or triple helix, the combination is inactive.

It would appear that the number of nonsense triplets is rather low, since we only occasionally come across them. However this conclusion is less secure than our other deductions about the general nature of the genetic code.

If, for example, all the codons are triplets, then in addition to the correct reading of the message, there are two incorrect readings which we shall obtain if we do not start the grouping into sets of three at the right place.

Finally one should add that in spite of the great complexity of protein synthesis and in spite of the considerable technical difficulties in synthesizing polynucleotides with defined sequences it is not unreasonable to hope that all these points will be clarified in the near future, and that the genetic code will be completely established on a sound experimental basis within a few years.

Do codons overlap? In other words, as we read along the genetic message do we find a base which is a member of two or more codons? It now seems fairly certain that codons do not overlap.

For simplicity one can think of the + class as having one extra base at some point or other in the genetic message and the - class as having one too few.

The meaning of this observation is unclear, but it raises the unfortunate possibility of ambiguous triplets; that is, triplets which may code more than one amino acid. However one would certainly expect such triplets to be in a minority.