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Saturday, October 12, 2024

Misleading Statements in a Recent Nobel Prize Announcement

 This week they announced the winner of the 2024 Nobel Prize in Chemistry. The award went to David Baker "for computational protein design" and Dennis Hassabis and John M. Jumper "for protein structure prediction." The Nobel Prize committee released a press release on this prize which contained quite a few examples of very misleading information. 

The press release had the extremely misleading title "They cracked the code for proteins’ amazing structures." No such thing was done by the winners of this year's Nobel Prize in Chemistry. There is a real code used by protein molecules, what is called the genetic code. That is the code by which particular triple combinations of nucleotide base pairs represent particular amino acids. That code was cracked in the middle of the 20th century. No new code involving proteins was cracked by any of this year's Nobel Prize winners. The work done by Dennis Hassabis and John M. Jumper was work in developing a computer program (AlphaFold2) that achieved a higher  level of success in predicting the three-dimensional structure of proteins, using inputs of the amino acid sequences of such proteins. 

Rather than involving any great insight on how proteins achieve their three-dimensional structures (still a very great unsolved mystery called the protein folding problem), the AlphaFold2 program achieves its limited success by frequentist prediction. Frequentist prediction involves crunching data to find cases such as where someone or something with characteristic X is more likely to have characteristic Y, allowing you to predict that having characteristic X makes you more likely to have characteristic Y, even though you don't understand any causal relation between the two.  For example, you might have some computer program that crunches tons of data, and finds odd little facts such as that people who watched a particular movie are more likely to die of cancer. You might then create some program that predicts your likelihood of dying based on what movies you saw this year.  But you probably would not understand what causal relations were involved. It might be all kinds of hidden causal relations such as the fact that some movie might be preferred by older people more likely to die of cancer, and the fact that some other movie (maybe one of those car daredevil movies) might be preferred by people who drive more dangerously.

The press release misleads us in its very first paragraph by stating this: "Demis Hassabis and John Jumper have developed an AI model to solve a 50-year-old problem: predicting proteins’ complex structures." What is called the protein structure prediction problem (not to be confused with the protein folding problem) is the problem of trying to predict the three-dimensional structure of a protein from its amino acid sequence. Dennis Hassabis and John Jumper made progress on such a problem, but certainly did not solve it.  The three-dimensional structure of the more complex proteins cannot be reliably predicted from their amino acid sequence. 

We have here more of the triumphalist hogwash that institutional science is so often guilty of. Someone may make some progress on some problem, and then people in the world of science academia start shouting "Problem solved!" Often the claimed progress is no real progress at all, or only some very small progress that leaves 90% of the problem still unsolved. 

The Nobel Prize announcement press release then proceeds to  mislead about the nature of protein molecules and life. The press release claims that proteins "control and drive all the chemi­cal reactions that together are the basis of life." Chemical reactions are a very important part of life, but it is nonsense to claim that the totality of chemical reactions are "the basis of life." Life is a state of vast physical organization, and that is something vastly more than just chemical reactions. Human life requires amino acids that are organized into 20,000+ types of protein molecules, which are organized into many types of protein complexes, which are organized into many types of organelles, which are organized into hundreds of different types of cells, which are organized into many types of tissues, which are organized into many types of organs, which are organized into different types of organ systems.  None of those things is a chemical reaction.  So it is a glaring falsehood to refer to "the chemi­cal reactions that together are the basis of life," as if a human body was merely chemical reactions. 

It is also very false to claim that proteins "control and drive all the chemi­cal reactions that together are the basis of life," because there are very many chemical reactions in the body that are not controlled and driven by proteins. Some of these reactions involve other types of molecules such as nucleic acids and other molecules simpler than proteins. And since a protein molecule has no mind or will or intentions, it is misleading to claim that protein molecules "control and drive" chemical reactions.  An accurate statement would be that protein molecules participate in incredibly complex chemical reactions. 

The press release then makes this misleading statement: "Proteins generally consist of 20 different amino acids, which can be described as life’s building blocks." A  large fraction of the people reading the claim that "proteins generally consist of 20 different amino acids" will get the idea that a protein consists of only 20 amino acids.  No, instead the reality is that human protein molecules consist of hundreds or thousands of amino acids, and that there are 20 different types of amino acids. The press release should have said "proteins are built from 20 different types of amino acids," but instead it used a phrase prone to make us think that protein molecules are gigantically simpler than they are. And by using the misleading language in which amino acids are referred to as "building blocks," the press release furthered the misimpression that amino acids can be put together in no special sequence, because building blocks do not have to be arranged in any special order. Instead, amino acids must be arranged in sequences as special and hard-to-achieve as the characters in functional well-written prose. 

building blocks of life deceit

I can imagine some readers of the press release:

Bob: Wow, it says in this Nobel Prize announcement that "proteins generally consist of 20 different amino acids." I never knew that a protein molecule is so simple, with only 20 parts. 

Bill: That's strange, I could have sworn I read somewhere that protein molecules each consist of very many well-arranged parts, usually hundreds, and sometimes thousands. 

Bob: But the Nobel Prize guys say that proteins are made of only 20 amino acids, and surely they must have got things right. So a protein molecule must have only 20 parts. 

We can only wonder how many people were equally misinformed by the misleading press release of the Nobel Prize committee. Then there's a visual released with the press release. The visual makes it look like an amino acid has only one part. Instead amino acids have between 7 to 33 atoms each, which have to be arranged in special structures. The average human protein molecule has about 470 amino acids (according to the paper here), meaning that human protein molecules typically require thousands of atoms that have to be arranged just right.  Similarly, a page of well-written grammatical prose in fine print requires thousands of characters that have to be ordered just the right way to achieve a particular end, in contrast to "building blocks" that can be assembled just fine when no particular order is used. 

Failing to ever refer to cells, the Nobel Prize press release also describes proteins as "the building blocks of different tissues." The hierarchical structure of life is actually that proteins are components of protein complexes, which are components of organelles, which are components of cells, which are components of tissues. Saying that proteins are the building blocks of different tissues is like saying that body cells are the building blocks of football leagues, a statement ridiculous because there are four or five layers of organization (tissues, organs, organ systems, human beings and football teams) between a body cell and a football league. And it is misleading to use the term "building blocks" to describe proteins that require a very special arrangement of hundreds of thousands of parts (unlike building blocks, which require only a single part). 

Why do such mistakes of grotesque oversimplification and misrepresenting complexity keep happening over and over again in the literature of chemistry and biology? What's going on is that our scientists are misteaching us in the way they need to misteach us, in order to foist their triumphal boasts upon us. The groundless boast that human origins are well-understood cannot be widely sold if the vast complexity and enormous physical organization of organisms are realistically depicted, nor can such a boast be widely sold if human minds are depicted in their true complexity and diversity of experiences and capabilities.   So the people selling that false boast must constantly depict bodies and minds as being enormously simpler than they are. And so our biology educators keep miseducating us in so many ways, by doing things such as publishing phony cell diagrams that make cells look as if they have a thousand times fewer organelles than they have, and making statements prone to give people the false idea that a protein molecule has only 20 parts, and making absurdly false claims that life is just some chemical reactions. 

You might call it the Simplicity Scam. Here is how the scam works:

1. You keep claiming that life or mind is “just chemistry.”

2. You keep speaking as if life can be built from simple, unordered parts called “building blocks.”

3. You keep publishing diagrams that make cells look a million times simpler then they are.

4. You keep saying that humans are just “carbon stuff” or “star stuff.”

5. You keep saying that humans are just animals or little more than apes.

6. You keep trying to make the mind look a million times simpler than it is, by saying it is “just consciousness.”

7. You keep speaking as if biological innovations can appear by mere accumulations of genetic accidents, without mentioning the gigantic levels of fine-tuned arrangement, hierarchical organization and component interdependence required everywhere in the body. 

8. You tell the lie that DNA (which has no anatomy information) is a body blueprint, a deceit that makes bodies seem a million times simpler than they are, something simple enough to be built from a blueprint. 

9. You don't tell people about undisputed medical case histories that defy your simple little story that brains make minds and that brains store memories. 

10. You don't tell people about the many neuroscience facts that defy your simple little story that brains make minds and that brains store memories, facts such as the fact that each chemical synapse transmits a nerve signal with a reliability of 50 percent or less (meaning accurate recall should be impossible if it occurs from reading of information stored in brains).

11. You tell people hand-waving simplistic nonsense such as the claim that human memories (of such enormous diversity and information richness) can be stored by some mere bulking up of synapses. 

12. You suppress or ignore accounts of paranormal human abilities and unexplained paranormal phenomena.

13. You use “shame, blame and defame” tactics against the witnesses of such phenomena, to try to preserve the idea that minds are very simple. 

14. You make misleading claims trying to suggest that life can appear once there are "the right ingredients," thereby suggesting that the simplest life is some mere potion or mixture, rather than a state of enormous organization requiring hundreds of different types of complex protein inventions. 

15. You make equally misleading claims trying to suggest that life can arise from nonlife by a mere injection of energy, a "jumpstarting," which is like saying you can jolt your way to book authorship. 

16. You try to make very complex biological innovations look a trillion times easier to arise than they would be, by calling them mere "variants" or examples of "diversification." 

The scam artists who act this way are like the guy in the visual below:

oversimplification

The Nobel Prize press release has an "Advanced Information" link which takes us to the document here. That document starts misinforming us right at its beginning, by repeating the groundless claim known as Anfinsen's Dogma. We read, "In 1972, Christian Anfinsen was awarded the Nobel Prize in Chemistry for the remarkable finding that protein 3D structures were basically encoded by the sequence of amino acids in the polypeptide chain." No, the three-dimensional structures of proteins are not " encoded by the sequence of amino acids in the polypeptide chain."  Anfinsen should not have been given the 1972 Nobel Prize in Chemistry, because he provided no robust evidence to support Anfinsen's Dogma, doing only some poorly replicated experiments with proteins of way-below-average complexity, with only about 127 amino acids (less than a third of the average number of amino acids in a human protein). See my post here for why Anfinsen's Dogma is not credible. An encyclopedia page says that "20 to 30 percent of polypeptide chains require the assistance of a chaperone for correct folding under normal growth conditions."  Such a figure helps discredit Anfinsen's Dogma, showing that a polypeptide sequence (a sequence of amino acids) is not sufficient to explain the 3D shapes of protein molecules. 

Alarm bells should go off in your head whenever you hear a scientist using the word "basically." It's very often a clue that what you are being told is not really true. 

It's amazing that the Nobel Prize organization was this week hailing the work that got Anfinsen the Nobel Prize in Chemistry in 1972, as if it were ignorant of the 2022 paper "The Anfinsen Dogma: Intriguing Details Sixty-Five Years Later," which tried to reproduce Anfinsen's experiments that got him that prize, but was unable to reproduce them. This epitomizes how today's Big Science machinery so often fails to pay attention to replication. That paper tells us about some of the false claims made about Anfinsen's work. We read, "The statement reported in many textbooks that Anfinsen removed denaturing and reducing agents by means of dialysis has no confirmation in the literature."  The authors state flatly that the main research result claimed by Anfinsen (a claim that got him the Nobel Prize) -- the result that "RNase refolds spontaneously into correct secondary and tertiary structures" is a result that "must be completely refused" (in other words, a result that is dead wrong). 

Never forget the important reality that false claims can arise in scientific literature, and may continue to be stated in scientific literature for decades or centuries after they have been discredited or disproven.

The Anfinsen story is a classic example of folly in modern science. A scientist (Anfinsen) did an experiment with a very small molecule (less than one third the average size of a human protein), and claimed that this showed that the 3D structure of most proteins is determined solely by their amino acid sequence (Anfinsen's Dogma, also called the thermodynamic hypothesis). This was rather like a man claiming that he built a house, and claiming that this shows that a single man can build an entire cathedral. Because scientists were eager to embrace the mechanistic dogma that protein shapes are determined solely by amino acid sequences, a Nobel Prize was soon awarded to Anfinsen, and innumerable science books and articles started claiming that his work proved his dogma (even though it made no sense to make such a claim based on Anfinsen's meager experimental results involving so small a molecule). There was little work done to try to do further experiments that might verify Anfinsen's claims, such as trying tests like his with average-sized proteins. Scientists had their triumphal story, and did not want to do further tests that might spoil that story. After fifty years of the science literature making the groundless claim that Anfinsen's experiments had proven his dogma, some diligent scientists finally tried in their 2022 paper to replicate his experiments, and found they could not even replicate them. So it was fifty years of science literature misinforming us on this important topic of whether the 3D structure of protein molecules is determined by their amino acid sequence, stretching right up to the present Nobel Prize announcement. The failure to replicate Anfinsen's results has been largely ignored, and the misleading claim about Anfinsen keeps being repeated. 

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