Have not held the book yet and have no idea how long it will take to get a copy from my library but I found this conversation pretty exciting.I’m hoping some of you working in biology will have come across such discussions before and have a more informed reaction. But I’m sure I won’t be the only layperson interested in these developments. Even the author Ball (former editor of Nature magazine) admits not to be expert in all the areas discussed and the same goes even more so for McGilchrist. But they both feel some effort must be made to communicate to the rest of us how the overview of the subject is changing. I look forward to reading it eventually but even more so appreciate these kinds of discussion which meet me where I am with my limited science background.
Philip Ball is the author of the book being discussed. I suppose Iain McGilchrist was chosen as his discussion partner because In his own most recent book The Matter With Things, Iain McGilchrist wrote a lot about the revolution in physics in which a strictly mechanistic understanding had to admit its short comings but noted that in biology that day still had not yet come. I take it that what is being questioned is the adequacy of mechanistic models to explain biological processes and the idea that there is any ‘final cause’ determining the formation of an organism. For instance DNA and genes obviously play an important roll but they do not make for a sufficient explanation. Mechanistic models have their place and utility but should not relied on too heavily when it comes to understanding what is going on.
Better yet this talk by Ball is much more informative than the chat with McGilchrist.
While looking for more from Philip Ball I first came across this seven minute video about life by Paul Nurse which probably exemplifies the old idea of what life is and how it works.
@MarkD I’m interested in how this conversation goes, but swamped these days.
I’m curious about this:
What did IM say about the shortcomings of a strictly mechanistic understanding in physics? I wonder how that statement has been evaluated by physicists.
I will never live long enough to study or grasp all the things I’m curioius about!
A strictly mechanistic theory of the fundamental stuff of the universe leads, necessarily IMO, to abiogenesis: The prevailing theory is abiogenesis, which proposes life arose from non-living matter through natural processes.
The New Biology in the 21st Century that Philip Ball has attempted to explain in his latest book(s) says–if I understand him correctly–"Hold on! I think we’ve got it wrong. Something already alive constructs/makes/creates living things ‘clothed in non-living (i.e. mechanistic) things’ ".
And it seems to me, that idea appeals to Iain McGilchrist.
My current spin on Ball’s comments: ***We humans, and in effect all living things, are not “AI-bots. We’re all Life-bots. varying in capabilities, task, and functions.”
I will try to watch the video and comment later, but in the mean time . . .
People who work in biology do understand how complex and messy biology is. Without some sort of tools, the human brain has no way of dealing with it directly. For example, this is a relatively simple gene interaction map:
I went ahead and downloaded the book to my Kindle. Sure glad I got it.
I’ll share some quotes soon. Read the Prologue which was interesting last night. Of course that is about biology though, not the physics you asked about. One interesting tidbit is that we have less quantity of information in our DNA than a banana. But Ball explains that some of ours is coded in less rigid ways so that the same sequences can play more roles than in simpler organisms. One of the main changes in perspective is in seeing organisms as less mechanistic even though, as he and McGilchrist agree, the machine is sometimes a good tool for predicting effects even if it doesn’t help to understand the big picture. Another is in recognizing that development of the organism is not always built up from lower levels, that sometimes it is the region of cells affected which collaborate on a solution rather than carrying out immutable changes. This is not my area but Ball as a former editor of Nature magazine is writing with us in mind which I appreciate.
As for McGilchrist’s claims about physics, I believe they are the majority opinion now. Doesn’t change how you chart a mission to Mars. Newton’s science is capable of that. But as with the biology, looking at the unfolding of the cosmos in a strictly mechanical manner simply ran into a number of difficulties. But that was a hundred years sooner than with biology.
If we were AI (algorithmic invention) users we could just ask the program to assemble something about where things stand with physics. But I’d rather rely on the intelligence of people (preferably those with more preparation than I have in the subject).
Title: Unraveling Life’s Secret: Exploring DNA and Genetic Information with Philip Ball
✦Exploring the mystery of life and how it works
[00:07]
Despite centuries of pondering, understanding of life’s inner workings remains limited
DNA’s discovery by Watson and Crick was once believed to hold the key to how life operates
✦Our DNA stores genetic information through a code of four chemical building blocks.
[02:33]
Genes are short segments of this genetic code, which make up the human genome of three billion letters.
Human Genome Project decoded the instructions in the genome, likened to an instruction booklet or blueprint.
✦The central dogma of molecular biology is not a dogma, but a set of instructions for making proteins.
[07:30]
Francis Crick’s central dogma of molecular biology opened up a new understanding of genes and proteins.
Genes encode instructions for making proteins, which are essential for biochemical reactions in the cell.
✦Genes are transcribed into messenger RNA, then translated into proteins.
[09:38]
Messenger RNA is produced by copying a gene and moves to the ribosome.
In the process of translation, proteins are formed from amino acids, leading to various traits and behaviors.
✦Genome is full of non-coding genes with diverse functions
[14:32]
The genome contains many non-coding genes that outnumber protein-coding genes
The discovery of smaller RNA molecules in the genome of metazoans adds complexity to gene encoding
✦Messenger RNA is chopped up and edited before translation.
[16:47]
The splicing machinery, spliceosome, chops messenger RNA into fragments, removes introns, and stitches together exons.
The editing and splicing of messenger RNA is influenced by information from a higher level, leading to the production of different proteins in different tissues.
Gene regulation controls cell-specific functions despite same genome
✦The Lac operon acts as a switch for turning on and off the production of the Lac enzymes.
[23:08]
The Lac operon consists of a protein that recognizes a patch on the DNA and blocks the production of RNA, thus stopping the transcription of the Lac genes.
Gene regulation in metazoans like us is much more complicated, involving transcription factors that are intrinsically disordered proteins and have less selectivity in binding to DNA or other molecules.
✦Complex organisms cannot rely on a strict blueprint for functioning.
[27:27]
Molecular world is full of randomness and noise, making perfect execution of instructions unlikely.
Complex networks rely on multiple routes for the same outcome, but it doesn’t solve the problem of fragility.
✦Compensation for mistakes at lower levels in the hierarchy of complex organisms
[29:35]
The development of a perfectly viable organism despite cells not ending up where they should be in the embryo
Example of higher-level principles like Sonic Hedgehog protein triggering villous growth in intestines
✦Genes provide resources for body plan, but plan not in genome.
[33:46]
Key genes & proteins are general purpose for development.
Behavior of complex systems show causal emergence at higher levels.
✦Causal spreading explains traits at higher levels beyond genes.
[35:51]
Traits like cystic fibrosis can be traced to a single gene, but most traits are influenced by higher levels above genes.
The ultimate expression is the brain, where decisions face diverse challenges beyond genetic programming.
✦Living organisms display agency and have their own goals
[40:15]
Cells exhibit individual behaviors due to internal settings determining their responses
Understanding agency is crucial in explaining how life works and the concept of free will
✦Understanding how life works is crucial for medicine
[42:26]
Causal spreading is important in medicine to intervene at the right place for effective change
Most common diseases are associated with non-coding regions of the genome, making interventions challenging
Brain organoids are structures that resemble developing embryonic brains in anatomy and structure.
Understanding the potential of stem cells to assemble into different forms may lead to the creation of new structures and appreciation of the astonishing nature of life.
✦Life as more than machinery or program
[49:02]
Life requires an explanation that truly captures its amazing complexity
The aliveness of living matter remains a profound mystery in modern biology
??? Say what? Reasonable and rational “Chaos Theory” affirms the Deterministic nature of physical matter, so where does “free will” come into the picture? Perplexed the heck out of me, when my tutor first described his mechanistic cosmos.
Lo and behold, now Ball says it appears that “living organisms” display agency and have their own goals", LOL! LEGGO blocks and machines don’t have goals. Unless they’re alive?
Does Ball actually say individual cells have free will? Perhaps they just have inborn goals, the same goals which led them to take up residence in the environment provided by all the cells that have been drawn into their ongoing relationship. The goals don’t have to be consciously held, indeed they probably are not capable of recognizing how their contribution fits into the metazoan. From their perspective -if they were capable of our mode of thinking- the metazoan they call home would probably be regarded as God, never seen or known directly.
But individually the goals they hold as part of their creaturely inheritence would be the precisely the goals that fit the need. Nothing like what agency means to us but far more like us than like lego blocks.
“… one important truth about the way life works and that is, that the best metaphors for talking about it aren’t ones that come from technologies, clockwork, or computers, but are metaphors that are drawn from life itself. What really distinguishes living things from any machines that we’ve yet made is that they’re not automata, but they have real agency. And what I mean by that is that they’re able to manipulate and alter themselves and their environment in order to try to attain some self-determined goals.
Now, when we recognize that organisms have goals, we usually sort of say, “Well, the goals for all organisms are to survive and reproduce.” Right, but while an awful lot of behavior can of course be explained that way, I don’t think it’s enough. I’ll hazard the guess that the goal you set yourself in coming here tonight wasn’t about eating and reproducing. And if it was, I’m afraid you’re probably gonna be disappointed, (audience laughs) although who am I to say? But I think that we’re not the only animals in having agendas and purposes of our own that we decide that are not obviously linked to evolutionary imperatives and aren’t wholly predictable. Even single celled organisms and single cells of our body set their agendas to some degree so that for example, what can seem like identical cells might behave in different ways to an identical stimulus because there is some internal setting that they have that determines that.
If you like, they’ve sort of made up their own minds. They have their own goals. I think that displaying agency is actually a more fruitful and more general way to think about what living organisms are than to try to come up with some kind of checklist of, you know, what life is. Like say, reproduction, metabolism, homeostasis, and so on. That’s why to have an overarching view of how life works, I think that biology needs an understanding and ideally, really, a theory of agency.
What are the basic ingredients that would require? We don’t really know, although this new book by the neuroscientist Kevin Mitchell makes a superb stab at starting that conversation and along the way shows how it is that what we call our own free will is really just an aspect of the kind of agency that we, as complex, cognitive, and conscious beings, possess. But I do think that we might be able to see some of the things that agents are probably going to require. For example, they need to make predictions about their environment so that they’re not constantly wasting energy coping with things that they might have anticipated and avoided. And in order to do that, an agent needs some kind of memory in which it can build up and store information about its environment, which amounts in the end to a kind of representation of a crude model of its environment. And we all have that. You know, if you leave here tonight and you were going back to Green Park tube and you start heading north along Albemarle Street, then, you haven’t really stored a good internal representation of your environment because it’s the other way, it’s south. So you’ve wasted energy, which in that case is not a matter of life and death, but sometimes making the right prediction could be. Okay, this new view of how life works is I think it particularly matters when life isn’t working so well and when we want to put it right. It matters for medicine.”
I ordered the book at the library though it is checked out and another person waiting for it. But for me this looks like the rabbit hole biologists are led down when they try to treat life as a machine, which is hardly a surprise to me. This is very much in line with my own idea that life is a self-organizing process which seeks its own ways to do things. It reminds me of our efforts to understand why the AI plays go the way it does. We must constantly remind ourselves that it doesn’t think the way we do. It is all about getting the results which work rather than rational reasons for why it should make a particular move.
I am also reminded of the sci-fi book “Mote in God’s Eye” where we encounter aliens whose technology seems to work in such an organic fashion – the product of the evolution of a specialized class (a class which is not even considered particularly intelligent) rather than a science which people have to study.
I’ve never thought free will was anything but real just in case you thought I leaned that way as do many atheists.
Of course our will is often shaped by circumstances not unlike those individual cells. Or even down right coerced but that just shows that our normal state is relative freedom.
Certainly that has been the source of some confusion but what he is responding to is the realization that a paradigm change is immanent by getting the word out and clarifying what has been compromised and what is reliable to build on going forward. Some aspects of physiology can be gainfully understood mechanically like how muscles work. The mistake is to assume that every question in biology will have an equally simple answer.
I’ve heard that physics went through a similar shift about a hundred years ago. Does that ring true to you?
I don’t. But @marta can attest to my long-standing “belief” in determinism and rejection of free will on theological and rational grounds. I’ve changed my mind quite a bit, but my mind is still “a work in progress”.
Then your mind is still working. There is no end of the road at which point we know everything. The challenge of age is to retain enough springiness to keep adapting even as our knowledge base increases.
IM says we need both determinism and free will to account for our experience and what we observe in the world. Without determinism there would be no causal traction for effecting anything at our disposal. Without freedom we’re reduced to passive observers in the theatre of a life which is an epiphenomenal farce. The ridiculous extremes should be avoided if at all possible and as with most dilemas it turns out both horns are required to work.
One page 1277 of The Matter With Things, McGilchrist writes:
Physicist David Oliver suggests that the laws of motion and emergent quantum randomness are like the warp and weft of a single fabric, order and randomness forming the creative whole:
“The quantum spontaneity of the universe is expressed in a law of nature, the Heisenberg Uncertainty Principle. This outstanding law declares ‘there is no law’. This is no paradox. We can precisely state ‘there is no law that completely fixes the outcomes of every physical interaction, every dynamic event.’ It’s the law. But much of the outcome is lawfully ordered and predictable. Nature is neither inevitably random nor completely lawful and predictable. Quantum spontaneity is only half the story. The other half is the regularity and predictability of the universe … The Law of Motion captures the continuity and stability of motion while the quantum nips at its heels injecting wisps of novelty and new possibilities into every change of state.
@mitchellmckain are you familiar with David Oliver and do you agree with his sentiment which IM quotes there?
Still having not watched the video, here are my reactions to what you describe. It’s a bit lengthy, so don’t feel bad if you scroll past it. I thought people might want to hear reactions from someone who works in biology.
We are leaps and bounds past where we were in the 60’s and 70’s with respect to understanding life’s inner workings. I wouldn’t describe our understanding as limited. Rather, we now know so much it is hard to integrate all of it together.
Biologists still believe that DNA is a major aspect of understanding how life works.
Some genes are quite large, but that is just a nitpick. The Human Genome Project was an initial draft, as it says in the very title of their 2001 paper. The main goal of the project was to find the order of bases in the genome for as much of the genome as was practical at the time. When they published in 2001 there were still some gaps to fill, but they got over 90% of the genome sequenced (if memory serves). They were also able to propose some sort of function or history for a lot of the genome (e.g. genes, transposons), and that has only been added to in the last 20+ years.
For me, the story of technology and how it interacted with the HGP is as fascinating as anything else. It was very much like the emergence of transistors and computers earlier in history. The ability to sequence DNA improved massively during the project due to huge technological breakthroughs, as did the ability to understand the sequence itself.
The Central Dogma is often misunderstood. When Crick invented the Central Dogma he didn’t know how proteins were made from DNA/RNA. In fact, the point of the Central Dogma was to point to the best avenues for figuring that out. The Central Dogma states that sequence information can be passed between the nucleotides and from nucleotides to proteins, but sequence information can not be passed from proteins to nucleotides. IOW, once sequence information is moved into proteins it can’t get back out.
The other big piece of knowledge was that the sequence of amino acids in a protein were somehow copied from the order of bases in DNA.
I’m not sure what the current estimate is on non-coding functional transcripts compared to coding transcripts. What I will say is that about 10% of the human genome is functional, and 2% of that is coding DNA. Therefore, there is about 4 times as much functional non-coding DNA as there is coding DNA.
Descriptions like “a higher level” usually aren’t that helpful in science, a minor nitpick. One of the discussions going on right now in biology is what percentage of differently spliced transcripts are functional or just errors in splicing. I think there is a big question as to how many of the differently spliced transcripts are even translated into proteins.
It’s that cross talk that makes biology so complex and difficult to predict.
One thing that still intrigues me is identical twins. They have the same genome, and sure enough they develop exactly the same (within reason). They are the same in so many different physical attributes, so much so that strangers can not tell them apart in many cases. So why is this? Obviously, DNA has a very strong role to play here. How much is up for debate, but there is no denying the influence.
One way I think of this is that embryonic development is not nearly as rigid and brittle as computer programs. If I leave out a quote mark or parentheses somewhere in my Python script is stops working, but development seems to absorb the bumps along the way.
Again, I go back to identical twins. Why do they look so much alike? Also, it’s not as if dogs are giving birth to turtles, bats, and fish. Obviously, the plan is in the genome.
If by “higher level” he means interaction between genes and between genes and the environment, then yes.
No one chooses to be a hemophiliac. At the same time, there is an interplay between genetic destiny and freedom of choice.
It is worth noting that the humble Caenorhabditis elegans is a fascinating model used in the lab. The adult is made up of ~1000 cells, and it has a similar gene count to that of humans. Scientists were able to track gene expression in all cells from a single celled zygote to a full adult. This includes the development of neuronal cells.
Science has a tough time dealing with subjective terms like “aliveness”. Science is looking for something to measure. However, scientists are human like anyone else, so they absolutely do ponder these subjective, emotive, and philosophical ideas.
Absolutely, and it was my feeling that these fundamental changes in physics were not adequately reflected in philosophy and other sciences – that most of these seem to be operating according to the assumptions of an eighteenth century understanding.
Nope and not really. Not the first part anyway.
Nonsense! The correct conclusion is that the laws of nature are largely a matter of probability distributions. In science, impossible simply means an exceedingly low probability. But these still tell you what you can largely rely on because you certainly don’t want to build your future upon something which has an exceedingly low probability of working.
To be sure the nineteenth century understanding is wrong. Nature is not a clockwork. One way you can put it is that the laws of nature are an order imposed from above on a fundamentally chaotic reality. I suppose you can say it bears some similarity to the laws which keep order in human society. The laws don’t make individuals obey its dictates, but the laws work because most people do. Point being that there is no justification for saying “there is no law.”
Yes. But… It isn’t just quantum nipping at the heels. Because of chaotic dynamics (which applies even in gravitational situations where you have more than just 2 bodies), nothing is really predictable in the long run. All our calculations have to be constantly adjusted to fit the reality which our mathematical equations cannot completely capture.
Great! So what you’re saying is that about 90% of a human genome is non-functional and each of us carries a lot of useless baggage around?
"Science is only good for repeatable phenomena. And most of life, the most interesting parts, don’t repeat. So, science doesn’t recognize it.” [Source: Television series, “Evil, Season 1, Pilot.]”
I don’t expect anyone to be impressed, sympathetic, or even care, really; but of my favorite nephews and nieces–all of whom live in Louisville, Kentucky–all are atheists–which I think is kind of interesting since their Grandfather (my father) was a Missouri Synod Lutheran. And all of them believe in abiogenesis, and they know, or suspect, that I don’t. So I’m kind of used to people who don’t believe the same things I do, and aren’t interested in talking about those things, being able to ponder subjective, emotive, and philosophical ideas.
Fair enough. This review of his book indicates his writing style is off putting for many and made me wonder if his judgement wasn’t as skewed as his expression (or the title of his book, for that matter). But I have no basis to make that judgement.
