19 February 2024

The Secret of Life according to Philip Ball.

In this blog I discuss two remarkable statements I encountered in Philip Ball's How Life Works. The first is about Watson and Crick's proposal for the structure of Deoxyribonucleic acid (DNA) and 'the secret of life'. The second is about the ENCODE project. That's enough for today.

Plaque 'DNA The Secret of Life'  [1]
 

Here is the first quote:

"Some consider the discovery of DNA's double helix to be the most important scientific discovery of the twentieth century. It's not clear how a meaningful ranking of that sort could ever truly be made, but the work certainly launched the genetic age." (chapter 2).

In these two remarkable sentences Ball tries to downplay the importance of the discovery of the structure of DNA. Some consider...? At least the five members of the Nobel Prize committee in Sweden awarded the structure of DNA with the 1962 Nobel Prize in Physiology or Medicine. It's not clear how a meaningful ranking of that sort could ever truly be made? Do I understand him right? Is he really suggesting that the structure of Deoxyribonucleic acid (DNA) does not deserve a Nobel Prize? Ball must be the first scientist suggesting such a thing. If it is impossible to compare and rank the discovery of DNA with other discoveries, why bring it up at all? It is an odd way to suggest that rewarding it with a Nobel Prize is completely arbitrary. The work certainly launched the genetic age? This must be the understatement of the century. A quick search for Nobel prizes concerning DNA results in about 20 prizes! [5]. The most well-known are: the genetic code (1968), restriction enzymes (1978), DNA sequencing (1980), recombinant DNA (1980), mobile genetic elements (1983), PCR (1993), split genes (1993), DNA repair (2015), CRISPR/Cas9 (2020).

Ball is certainly right that there is more to life than DNA (see my previous blog). And probably he has good reasons for de-emphasizing the relative importance of DNA in the biochemistry of the cell and in the development of an organism. That is one thing. However, it is quite another thing to retroactively cast doubt on the importance of the discovery of DNA. The Nobel Prize was awarded for the scientific merit of the discovery of the structure of DNA, not for 'discovering the secret of life' [4]

Now 'the secret of life': 

"A lesser-known fabrication, however, is Watson's claim (which he only recently admitted was pure invention) that when he and Crick finally realized what the structure of DNA molecule must be, Crick regaled the occupants of The Eagle pub in Cambridge, the duo's favorite watering hole, with the claim  that they had discovered 'the secret of life'." (chapter 2).

In the eBook version I could not find any source for 'Watson's recently admission', but I found in Francis Crick (1990) What Mad Pursuit,

"I think we realized almost immediately that we had stumbled onto something important. According to Jim, I went into the Eagle, the pub across the road where we lunched every day, and told everyone that we'd discovered the secret of life. Of that I have no recollection." (chapter 6)
which is good evidence that Watson's story is wrong. But, Crick could have forgotten it. Furthermore, in his book The secret of life Howard Markel (2021) refers to this blog: Happy 100th birthday, Francis Crick (1916-2004) which was written by Matthew Cobb:

"Watson’s own description of the discovery of the structure of DNA did not contain any striking new revelations, with one exception. He finally admitted that when he wrote in The Double Helix that Crick strode into the Eagle pub and proclaimed ‘We have discovered the secret of life’, this was not true. Watson said he made it up, for dramatic effect. Crick always denied saying any such thing." June 8, 2016 [2].

In the past I have written many blogs about the extraordinary and surprising properties of DNA and I could add several more. For now, here are a few remarks about the importance of DNA for evolutionary biologists. Firstly, evolution is the modification of DNA. It is rewriting the code. If genes do not change during evolution how can new species originate? How can species adapt? Secondly, if any modification of metabolism –no  matter how useful it may be– is not encoded in DNA, it is lost forever. Metabolism is necessary for life. The laws of chemistry and physics determine 'how life works', but they don't need to be encoded in DNA. Without a carrier of hereditary information there would be nobody contemplating the secret of life [3]. There would be no human beings at all. Whether you like it or not, life on earth is based on DNA.

My second remark is about a few curious statements about ENCODE:

"Just how much of that noncoding DNA really makes a difference is another matter. It's probably not 80 percent - ENCODE member Bradly Bernstein guesses that 30 percent might be a more realistic figure.' (chapter 3).  

That's only a small difference: 80% or 30%! I leave that up to Larry Moran.


24 Feb: edits in the text and Note 5 about Nobel prizes added.

 

Notes

  1. Secret of Life Plaque at The Eagle Inn (Cambridge): it really exists! 
  2. I still can't trace the exact location of 'Watson's admission'. Ball did not give a source.
  3. So, what Watson and Crick ultimately discovered was the (nearly) universal language of life on earth, the language of DNA, which is evidence for common descent of all life. 
  4. If the discovery of the structure of DNA is not the most important scientific discovery of the twentieth century, then it's no big deal that Rosalind Franklin did not receive the Nobel Prize for her contribution. See also: What Rosalind Franklin truly contributed to the discovery of DNA’s structure. [22 Feb 2024
  5. All Nobel Prizes in Physiology or MedicineAll Nobel Prizes in Chemistry. [24 Feb 2024] Post 1953 Nobel Prizes concerning DNA (the list depends on how precisely the criteria are defined):
    • 1957 nucleotide coenzymes
    • 1959 DNA and RNA synthesis
    • 1968 genetic code
    • 1972 ribonuclease
    • 1978 restriction enzymes
    • 1980 DNA sequencing
    • 1980 recombinant DNA
    • 1983 mobile genetic elements
    • 1989 catalytic RNA
    • 1993 PCR
    • 1993 split genes
    • 1995 genetic control of development *)
    • 2006 transcription
    • 2006 RNA interference
    • 2009 telomeres
    • 2015 DNA repair
    • 2020 CRISPR/Cas9
    • 2022 paleogenomics
    *) This one is mentioned by Ball, chapter 8.
     
Plaque at The Eagle (Google streetview)

The Eagle, Cambridge (Google streetview)

King's College London
(1) Franklin-Wilkins Building

 

(2) Franklin and Photo 51



(3) Wilkins. Clearly a helix

(4) The Double Helix

 

The Francis Crick Institute, London

 

(pictures Google streetview)

12 February 2024

What's wrong with a DNA-centric view? Philip Ball (2024) How Life works

Philip Ball: How Life Works

In his new book How life works science writer Philip Ball makes fun of the gene-centric and DNA-centric view of biology. The figure below illustrates this view. First, there is DNA, then complex stuff happens, and then ... there is life. What's wrong with that view?

The popular view of how genes create living things
according to Philip Ball

According to Ball understanding genes will not enable us to understand life. Genes are not alive, cells and organisms are alive. Genes were never alive. If there is anything like a language of life, it will not be found in the genome. The genome as a "blueprint" for the creation of an organism is a favourite but misleading metaphor. There is no 'book of life'. DNA is no 'instruction book'. In biology every explanation starts with DNA. But according to Ball, it is trying to understand literature with a dictionary. (In my opinion, you can't learn a language without learning the words first! And that is what biologists are doing!). The complete sequence of the human genome did not produce insight in what life is. It is more complicated than that. DNA doesn't solve all the problems of biology. DNA doesn't tell us how cells work. The cell is not a machine. The cell is not a computer. No computer today works as cells do. The problem is we put genes at the start and bodies at the end. Genes are not a sufficient explanation of the organism. DNA is not the Master. DNA is the servant. That is Ball's new view of biology. In short.

My reaction is: There are good reasons to start with DNA. Crick's so-called Central Dogma of molecular biology (the illustration is in Balls' book) starts with DNA for a good reason. The information flows from DNA to RNA to proteins. The defining property of the central dogma is: directionality. The information flows from DNA to proteins, not from proteins to DNA. Crick's central dogma starts with DNA because that is how information flows. There isn't a process in the cell that creates DNA. DNA isn't the endpoint. So, necessarily DNA must be the starting point.

Secondly, Darwin had a very speculative and wrong theory about heredity. We now know that DNA is the carrier of heredity. Not proteins. DNA is by far the most important substance that is transmitted from parents to children. It explains why children are similar to their parents. Delete DNA from the egg cell and forget about the baby. The complete DNA sequence of a species defines the species. It is the difference between us and chimpanzees. Humans produce humans, chimps produce chimps because of different genomes. All this is not denied by Ball, but he isn't impressed by this kind of biological knowledge.

I think, we should not underestimate the enormous progress in scientific understanding of life, heredity and evolution. If we have a look at the history of biology since Aristotle, we can certainly claim that we finally know what Mendelian genes are, finally we know what chromosomes are made of, finally we can link genes and chromosomes and explain Mendelian laws in molecular and chromosomal terms, finally we know that species are characterized by the number of chromosomes, equally that males and females differ in their chromosomes, finally we understand sex in chromosomal terms, finally we know that genes, not proteins, are the material basis of heredity, finally we know the chemical structure of DNA (Watson & Crick), finally we know precisely how genes code for proteins (the genetic code), finally we know the complete sequence of the genetic material in an individual (the genome), finally we know in biochemical detail what mutations are, finally we know that mutations are necessary for natural selection and evolution. We can now explain many genetic diseases. We can even correct some of them. These are powerful scientific explanations previous generations of scientists only dreamed of. This is a tremendous scientific progress fully comparable to what Newton and Einstein did for the physical sciences. Ball seems to forget all this.

In chapter 2 Ball points out that despite all our new knowledge of genes and genomes, biologists still don't understand life. But hold on, which of the natural sciences could claim complete understanding of the field they study? Furthermore, is it really true that progress in molecular biology is slowing down? Or has come to a standstill? Is there really a crisis?

12 Feb 1809
What about evolution?

"I must stress there is nothing in this new view that conflicts with the neo-Darwinian idea that evolution shapes us and all other organisms and that it depends on the genetic transmission of information between parent and offspring. However, in this new view genes are not selfish and authoritarian dictators. They don't possess any real agency at all, for they can accomplish nothing alone." (Prologue) .

No real agency? Accomplish nothing alone? Viruses like SARS-CoV-2 know that very well. They absolutely need the help of the human host. They can accomplish nothing alone.  Without the help of humans SARS-CoV-2 could not have caused a pandemic.


Note. In a next blog I will continue writing about How Life Works

See Wikipedia about Philip Ball: Ball holds a degree in chemistry from Oxford and a doctorate in physics from Bristol University.