29 February 2024

A review of Philip Ball (2024) How Life Works. With Postscript.

"The aim of this book is to show why these metaphors are inadequate, why they need replacing, and why we will not understand how life works until we do. It also attempts to sketch out what might be put in their place." (Prologue, How Life Works, Philip Ball, 2024).

To explain 'How life works' is an extremely ambitious venture with a 2000 year history. But first: what are these metaphors? For example this one: DNA is 'the secret of life'. The Human Genome is said to be 'our own instruction book' and 'The Book of Life'. But according to Ball this is like looking into a dictionary to understand literature. My impression is that Ball is throwing 'the dictionary' (DNA, the genome) out the window. But we haven't even finished completing the dictionary, we don't know how many words there are and how the words are used.

My problem with Ball is that he overreacts in such an extreme degree that he tries to doubt the importance of the discovery of the structure of DNA by Watson and Crick in 1953 (see my previous blog). Tellingly, Ball relegates the 1962 Nobel Prize for DNA to a footnote. I can't say it better than Bergstrom and Dugatkin in their most recent Evolution textbook:

Bergstrom,Dugatkin (2023)
"For the better part of the past 4 billion years, desoxyribonucleic acid -DNA- has been the chemical underpinning of life on Earth. At a very basic level, it is changes in DNA sequences and DNA expression that underlie the process of biological evolution by driving changes in phenotype and causing differences in fitness." 

After a description of the Watson-Crick structure of DNA they continue:

"Pause for a moment and consider what is encapsulated into those last six sentences: It is a triumph of modern biology that we are capable of describing the stuff of life in such succinct terms." [2]

Furthermore, we have good reasons to claim that DNA is the only molecule capable of sustaining life and giving rise to millions of species. There are no known rivals. There is no alternative. It would be a huge error to dismiss DNA to explain life on earth.

Ball is not the first scientist to claim that DNA is not 'the secret of life'. Nearly 30 years ago Stuart Kauffman wrote:

"Life does not depend on the magic of Watson-Crick base pairing or any other specific template-replicating machinery." [3]

Nick Lane (2022) wrote: "genes did not 'invent' metabolism, but the reverse." [4], others have similar views [6].

One can't discuss biology and evolutionary biology if one doesn't get DNA right. Philip Ball downgrades DNA to an extreme degree. But both emphasizing and de-emphasizing DNA too much is a bad thing. Emphasizing DNA too much only occurs with claims like "DNA is the blueprint of life" [5] and "DNA copies itself", "DNA self-replication", "Gene self-replication". Let's have a closer look. 

Biologists know that these statements are only true in the cellular environment. Just as viruses can't self-replicate, 'our' DNA can't 'self-replicate'. DNA needs enzymes (polymerases) to replicate. Viruses need enzymes to replicate. This view creates a unity between viruses and 'our own' DNA. There is only a gradual difference in usefulness for the host (some claim that there are useful viruses).

No biologist ever said DNA is alive. It is a big but dead polymer. It's an archive, a library. Biologists know that DNA on its own is not sufficient to explain life. The reason is that life consists of three interconnected subsystems: a hereditary system (DNA,RNA), an energy producing subsystem (metabolism) and a boundary system (membrane):

The 3 parts of life according to Tibor Gánti [1]
1. chemical motor system = metabolism
2. chemical boundary system = cell membrane
3. chemical information system = heredity, DNA

It is immediately clear from this diagram that by definition only the total system can be called alive. DNA is a subsystem. So, it follows from the logic of this definition of life that DNA isn't alive. Furthermore, I didn't realize until now that our own DNA depends just as much as viruses on the cellular environment to do anything at all. I didn't see it in that way before. Viruses aren't alive. DNA isn't alive. Interestingly, it follows also that 'our'  DNA is a kind of 'parasite' of the cell. The cell, our cells are its hosts. So, not just DNA sequences such as transposons are parasitic. Paradoxically, the whole genome is a 'parasite'. A parasite requires a host. We are the host. Did I just rediscover Dawkins' selfish gene concept? By the way, the 'parasitic' nature of DNA is also the reason it can't be involved in the origin of life. In that sense DNA can't be the start of life.

vicious circle

In the cellular environment DNA is not 'the start of everything', despite the fact that according to Crick's famous 'Central Dogma' information flows from DNA to protein. That may be confusing for some. DNA is not the start of everything in the cell. A circle has no starting point. Proteins are always required In the processes of DNA-replication, DNA transcription, mRNA splicing and translation. Those proteins must be present and have been synthesized earlier on. Indeed they have been synthesized on the basis of information in DNA. And in order to read that information enzymes have to be present...etc. That's the circle. 

Strictly speaking genes do not 'control' development, because that suggests an active involvement of genes. Genes do not express themselves, they are being expressed. I agree with Ball's criticism that genes are not actively doing anything [6]. That's a gain.

However, Ball's main point is that in order to understand 'how life works' one must understand the biochemical and physical forces involved in the cell and the organism. In the chapters Networks, Cells, Tissue, Bodies, Rethinking medicine, dozens of genes pop up again and again:

Src, Int1, TNF, bicoid, caudal, even-skipped, Hunchback, Giant, Kruppel, Dkk2, Dkk4, FGF, Sonic hedgehog, HoxD13, FGFR3, EDAR, Hsp90, Notch, Otx, Hex, Wnt, Nodal, E-cadherin, SHH, Shroom, myosin II, NF1, NF2, chordin, BMP, TGF-β, Gata1, Gata2, GPU.1, Sinr, SinI, Oct4, Sox2, c-Myc, Klf4, FBn1, CFTR, TSLP, CTLA4, IL6R, HBB, SRY, Sox9, SF1, APP, BRCA1, BRCA2, p53, ZIC4, ...


  • If you can't tell a DNA-free, gene-free story, then don't pretend you can. 
  • If you do tell a DNA-free, gene-free story, then what is its relevance to biology?
  • If you need genes to tell your story, give them a proper place in your story.

For example Ball writes in chapter 8: 

"The discovery of 'patterning genes' for the early body plan transformed our understanding of how genes affect development, and won Nüsslein-Volhard and Wieschaus the 1995 Nobel Prize for physiology or medicine". 

Christiane Nüsslein-Volhard (2006)
Coming to Life
How Genes Drive Development

Indeed! There you have it. According to the Nobel Prize website they "succeeded in identifying and classifying the 15 genes that direct the cells to form a new fly." So, 1) it's all about genes, 2) if genes are the words of the dictionary, then they discovered the meaning of those words. Those 'blueprint-geneticists' discovered which genes  are used in the early embryonic development, and when and where they are used. They discovered not only isolated words, but the context in which they are used. They are making significant progress in understanding important sentences of the 'language of life' (Francis Collins: 'the language of God'). It is part of 'how life works'. This research is opening the black box of development (see Fig. 2.1 in Ball's book).

Anyway, there are no gradients without gene products. Alan Turing invoked hypothetical morphogens and gradients. Those 'blueprint-geneticists' proved that morphogens do exist. Just as those 'blueprint-geneticists' have proven that Mendels hypothetical factors do exist. That is science. That is progress.

There is a lot more to say. But this is enough for today. I invited a physicist to comment on the physical aspects of How Life Works.


Postscript: a contradiction

2 March

I discovered a few sentences in chapter 9 which seem to nullify everything Ball wrote in chapter 2 against the importance of DNA: 

"we each have within us a deep evolutionary memory embodied in our genomes. If these are not blueprints, they nevertheless do encode information shaped and inherited over eons that is indispensable to our formation."  chapter 9. 17/123

Well, in essence this is identical to my quote from Bergstrom-Dugatkin. ('eons' is in fact 3.5 billion years). Here, Ball describes the indispensability of DNA! Does it matter whether DNA is called a 'blueprint' or 'indispensable information'? What's the difference? He continues:

"To what extent life is dictated by this Darwinian memory and to what extent it can draw on spontaneous ordering mechanisms is one of the central questions for understanding how it works."  
Indeed, that seems to be the central question of the book How Life Works. It's all about the relative importance of DNA and spontaneous order. Both are indispensable. Then, why write a whole book to downplay DNA? Maybe, the consensus view in biology is that DNA is the most important cause of the creation of an organism?



  1. Tibor Gánti (2003) The Principles of Life. See: my review. Ball points out that a living entity must have a boundary of some kind (Ch 9. 83/123)
  2. Bergstrom, Dugatkin (2023) Evolution, p 189. (textbook) see my website.
  3. Stuart Kauffman (1995) 'At Home in the Universe. The Search for Laws of Self-Organization and Complexity' (my review). Ball doesn't mention Kauffman's book.
  4. Nick Lane (2022) Transformer: The Deep Chemistry of Life and Death.
  5. No biologist uses 'Blueprint of life' literally. That's impossible: DNA is a linear sequence. A cell is 3-dimensional object. In a review of How Life Works Denis Noble wrote "It’s time to admit that genes are not the blueprint for life" (Nature). Fine, what are genes really?
  6. Ball quotes Richard Lewontin (1992): "Not only is DNA incapable of making copies of itself, but it is incapable of 'making' anything else." (end of Chapter 2) [1 March 2024]


Blogs about How Life Works


Reviews by others


    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? [6]. 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.

    28 Feb: Note 6 about 1962 Nobel prize added.



    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]  Nobel Prizes concerning DNA (the list depends on how precisely the criteria are defined):
      • 1933 Thomas Hunt Morgan chromosomes carry hereditary information
      • 1957 nucleotide co-enzymes
      • 1959 DNA and RNA synthesis, DNA polymerase
      • 1962 Watson-Crick structure of DNA (1953 discovery)
      • 1966 DNA is genetic material (Hershey–Chase, 1952) **)
      • 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- gene silencing by double-stranded RNA
      • 2009 telomeres
      • 2015 DNA repair
      • 2020 CRISPR/Cas9 **)
      • 2022 paleogenomics
      • 2023 mRNA covid-19 vaccins

      *) is mentioned by Ball, chapter 8.  **) is mentioned in chapter 11.
    6. Ball relegates the 1962 Nobel Prize for DNA to a footnote... [28 Feb 2024]
    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 black box. The popular view of how genes create living things

    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.