Evolution May Be Purposeful And It’s Freaking Scientists Out

“Where are all the genetic cures?” asks Denis Noble, a frustrated biophysicist, Royal Society fellow and pioneer of the field of systems biology. “They don’t exist. Where will they be? They won’t exist.” Since mapping the human genome in 2003, research priorities and funding shifted significantly towards genetics. The investment improved disease detection and management but failed to deliver on its promise of cures for our most common deadly diseases like heart disease, type 2 diabetes, Alzheimer’s and most cancers. Compounding the issue, a large-scale, 2023 study concluded that genetic risk scores perform poorly at predicting who’s going to develop common diseases. For Noble, the billions invested annually in genetic research represents less of a strategy and more of a scientific confusion—that we are our genes.

The scientific story of who we are is a reductionist, gene-centric model that forfeits natural phenomena like purpose due to its association with intelligent design and a transcendent, intelligent designer. Noble is neutral on religious matters. Yet he sees compelling evidence that purpose may be fundamental to life. He’s determined to debunk the current scientific paradigm and replace the elevated importance of genes with something much more controversial. His efforts have enraged many of his peers but gained support from the next generation of origins-of-life researchers working to topple the reign of gene-centrism. If successful, the shift could not only transform how we classify, study and treat disease, but what it means to be alive.

Emergent Heart Beats

One of the earliest biomedical computer programmers, Noble created the first model for a working human heart in 1960 on a vacuum tube computer. The project led to his discovery that heartbeats are emergent properties—new phenomena—arising from feedback loops, transforming our understanding of heart function and underpin treatments for heart conditions that we use today. His research on the heart’s pacemaker demonstrates a prioritization of the organism as a whole over its genes alone. “Several genes could individually be knocked out but the process continues,” says Noble. These genes are responsible for heart rhythm, yet other mechanisms can take over to get the job done.

In the 1960s, Noble served as the dissertation examiner for the then-unknown Richard Dawkins. Dawkins—a prominent figure in the New Atheism movement—would go on to author the 1976 classic The Selfish Gene that popularized the gene-centric theory of evolution. Gene-centrism says evolution acts on genes, not individual organisms. We are merely vessels for our genes that are driving evolution by Darwinian natural selection. Noble's analysis suggests that evolution acts on the organism as a whole, with the organism harnessing randomness and variation to create and heal itself—on purpose. In this re-evaluation, Noble believes that purpose, creativity, and innovation are fundamental to evolution. He argues that we experience these processes as drives, but they are not purely subjective. They also progress non-consciously in other parts of our body. These natural processes harness randomness and unpredictability—stochasticity—to survive, make decisions, and thrive. “Stochasticity is the center of creativity in organisms,” says Noble.

Evolution on Purpose

Noble’s formal training is in cellular electrophysiology, the study of the differences in electrical charges inside and outside of a cell membrane. He suspects that crevices of ancient rocks served as cradles for emergent self-sustaining systems. Eventually, membranes evolved from lipid-coated bubbles, replacing the fissures in rocks as containers for these emergent systems. This gave rise to the first living entity—a single-celled organism. According to Noble, the constraints of a cell’s membrane and the restriction of freedom of molecules inside a cell, made purpose both possible and necessary. This development required a sort of intention or cognition within emergent networks of molecules to create and sustain biological functions.

Reinterpreting Existing Evidence

Noble sees evidence of purposive and intentional evolution in our immune response to viruses. Detection of the invader triggers a flurry of rapid mutations in the genes of B cells, creating a legion of gene variants. These variants are antibodies, the most effective of which are deployed to combat the virus. In a defensive assault, the immune system self-modifies its own DNA. “It changes the genome. Not supposed to be possible,” says Noble. “Happens all the time.”

The conventional view is that this is still random natural selection—cranked up to warp speed inside the body during the lifetime of an individual organism. Noble agrees, but adds the observation that the organism’s immune system initiates and orchestrates the ramped up process, harnessing natural selection to fight off the invader. For Noble, this routine procedure offers clear evidence of the organism actively participating in its own evolution—it’s doing natural selection. This is an alternative theory of evolution where cognition is fundamental. In this theory, the smallest unit of life—cells—have some version of intelligence and intent that allows them to detect and respond to their environment. Noble clocks the immune response as a goal-directed pattern of behavior at the cellular level that scales to every level of organization within a living system. He believes we’re working ourselves into a sweat to exclude something so essential to evolution and to life as purpose and intention.

The Future of Evolution

Noble is part of The Third Way, a movement in evolutionary biology that views natural selection as part of a holistic, organism-centered process. He co-authored Evolution “on Purpose," published by MIT Press in 2023, which argues that organisms evolve with intention.

Recent research calls into question whether genetic mutations are even entirely random. A 2022 study in Nature shows a mutation bias supporting the organism as a whole. Noble doesn’t understand why studies like these aren’t making bigger waves. “Do you, you people working in gene-centric biology, do you realize what has already been published?” asks an incredulous Noble.

This is one of his central criticisms of Richard Dawkins, whom Noble dubs the primary exponent of gene-centrism. Dawkins is one of the world’s foremost science communicators. Noble considers Dawkins an exceptional writer who simply hasn’t kept up with the science. When asked for comment, Dawkins responded, “I have a whole chapter dealing with Denis Noble in my next book, The Genetic Book of the Dead. It will be available in September.”

Where Evolution Went Wrong

Noble attributes our legacy of missteps to rigid assumptions put in place over a century ago to stand in for a lack of evidence. Darwin’s namesake theory of evolution by natural selection was first published in 1859. This slow process alters instructions to build an organism only through genetic mechanisms like random mutations and recombination that get passed down to offspring.

Near the end of his life, Darwin was corresponding with physiologist George Romanes, exploring additional mechanisms of inheritance and the role of physiology. Despite Darwin’s broadening views, his theory was scaled back posthumously. Following Darwin’s death in 1882, biologist and ‘Neo-Darwinist’ August Weismann promulgated the idea of a one-way barrier cordoning off reproductive cells from the rest of the body. This barrier required that reproductive cells were the sole vehicles for inheritance. Neo-Darwinists would go on to revive a theory of genes and genetic recombination. Mendelian genetics with Darwin’s natural selection were synthesized. The reproductive cells became the housing for genes which ascended to the centerpiece for evolution.

In 1894 at age 46, Romanes died of a cerebral hemorrhage. And so died the lone voice advocating for Darwin’s ultimate views—views of evolution which emphasized more complexity and physiology. Noble suspects if Romanes had survived, we may have avoided a gene-centric paradigm paralysis. Instead, Noble feels “our genetic hope is more about faith than facts.”

Mortality And A New Biology

Noble is urgently reviving and expanding on Darwin and Romanes. Last month, a special edition of The Journal of Physiology, co-edited by Noble and Michael Joyner of the Mayo Clinic, featured 21 articles challenging current evolutionary theory and advocating for the inclusion of phenomena like agency and cognition.

These articles corroborate the general theme that Genes Are Not The Blueprint For Life, the title of Noble’s review in the journal Nature, heralding science writer Philip Ball’s primer How Life Works: A User’s Guide to The New Biology. Ball, a former editor of Nature, admonishes the life sciences for ignoring obvious natural properties of living systems like agency and purpose because of “quasi-mystical” associations with intelligent design. In the book, Ball illustrates the resistance to letting go of the “tidy tale” of gene-centrism and the idea that genes control health more than “‘a bit’ and ‘somewhat’.” Like Noble, Ball is advocating for a new biology.

Noble’s urgency is more than academic. “This is critical to the future of health care,” says Noble, who feels the public is paying the ultimate price for gene-centrism. “I face the same problem as many other people face,” says Noble. “Families having to deal with serious illness, with social care that costs more than you can ever afford. I've been through all of that. I know what it does to families.” He considers it a foregone conclusion that aging populations will strain health systems to the point of rupture if we continue with gene-centrism.

The Critics

Noble’s critics worry that entertaining religion-adjacent views subverts established science and the entire scientific project. But Noble’s research doesn’t challenge the scientific method. It challenges a scientific epoch marked by a purely mechanistic view of nature that coincided with the Industrial Revolution and age of mechanization. Noble appreciates concerns raised by skeptics, yet refuses to exclude natural phenomena from scientific inquiry.

Noble’s critics also accuse him of exaggerating the importance of physiology, while Noble insists physiology has been unjustly sidelined since Darwin. “Physiology now has to come to the rescue of evolutionary biology,” says Noble.

Another objection is that Noble is contesting a theory of evolution that has since been revised to address new evidence. For Noble, this is exactly his point. New evidence doesn’t merely refine the theory, it undermines it.

Biology’s existential crisis reached a flashpoint in 2016, when Noble and a group of scientists and philosophers organized a conference on New Trends in Evolutionary Biology with the Royal Society of London. Royal Society members petitioned—unsuccessfully—to kill it. The protest letter (Royal Society member Richard Dawkins’ signature was noticeably absent) read “...we wish to express our concern that this meeting will severely damage the reputation of the Society among the worldwide community of evolutionary biologists (it has already attracted adverse comments among colleagues in the USA).”

They never name their U.S. colleagues, although American biologist and prominent anti-creationist, Jerry Coyne uses words like "stupid," "rotten" and “blundering tyro” in his public condemnation of Noble. Canadian biologist Laurence A. Moran echoes Coyne’s outrage adding, “It's difficult not to be very angry at people like Denis Noble.” Moran writes that if science was working properly, Noble would “fade into the woodwork of the Senior Common Room at some college in Oxford.” It’s true Noble didn’t raise serious objections to evolutionary theory until after he retired as Chair of Cardiovascular Physiology at the University of Oxford in 2004. He says “coming out” would have invariably damaged the reputation and careers of the research team in his lab.

The Next GeneRation

“We need to shame them. I'm sorry, but we do,” says bioengineer and origins-of-life scientist Joana Xavier about Noble’s caustic critics. Xavier, a next-generation evolutionary theorist, resents “bullying” from prominent scientists that shuts down young biologists and stymies scientific progress. She and her peers have new tools and fresh perspectives, yet Xavier says their academic careers are jeopardized by demeaning attacks.

Xavier’s research made headlines for her discovery of emergent, cooperative networks of molecules that mutually catalyze each other's formation in ancient bacteria. These systems were first theorized by complexity scientist, Stuart Kauffman, as a candidate for the origins-of-life story that challenges gene-centrism. Xavier studied under Noble and Kauffman before launching the Origin of Life Early-Career Network (OoLEN) with over 200 young, interdisciplinary researchers from around the world. This group co-authored an inaugural scientific paper The Future of Origin of Life Research: Bridging Decades-Old Divisions.

Xavier has identified another form of intention at the cellular level of emergent systems: cooperation. She doesn’t understand why it’s acceptable to think of evolution as competitive but evidence of cooperation is considered taboo. “I think to solve life's origins, we'll need to look much more at cooperation. And emergence really brings cooperation into the scene, whether you want it or not,” says Xavier, who also sees creativity as fundamental to life. “It's so obvious, you either accept that it is true that life is creative or you don't.”

Xavier says her field is at an inflection point with gene-centrism holding back progress in health and medicine. “I think we’re completely stuck,” says Xavier. She’s actively pushing in a new direction even if she has to leave academia for the private sector to do it. “The gene-centric paradigm,” says Xavier, “That has to go. It's urgent.”

These days, Noble is surrounded by young researchers eager to reopen the case of evolution. “I have young people helping me with all of this because, believe me, I can't do all of this on my own,” says Noble. Creativity, purpose and organism-centered evolution are still only postulates that need rigorous testing. Noble is eager to explore both his theory and others. With theories of who we are, how we heal, and how we came to exist, Noble stresses “we should have more than one horse in the race.”

Source: https://www.forbes.com/sites/andreamorris/2024/06/14/evolution-may-be-purposeful-and-its-freaking-scientists-out/

Wrap-up

There has been much debate about whether the neo-Darwinist  modern  synthesis  needs  extending  or  replacing.  Both views are correct. It depends on the context in which they are assessed. Theories in biology, as in any branch of science, can be judged by several criteria.

1. Falsifiability

The original neo-Darwinist assumptions of the modern synthesis have been clearly falsified. I will consider the three basic assumptions outlined in the Introduction.

2. The Weismann barrier

The Weismann barrier should be seen as a relative not an absolute barrier. Strict isolation of the genome was required in order to exclude the inheritance of acquired characteristics. As we now know that acquired characteristics can be inherited, I believe it is more honest to admit that this reason for departing from Darwinism is no longer valid. In any case, the barrier could only apply in those organisms that have a separate germ line. For the great majority of the duration of life  on  the  Earth,  there  was  no  separate  germ  line.  And plants can reproduce separately from their germ line. Quite simply, then, two of the original basic assumptions, isolation of  the  germ  line  and  the  impossibility  of  inheritance  of acquired characteristics, can be seen to be incorrect.

Some criticisms of this conclusion refer to the rarity of experiments showing intergenerational transmission of epigenetic  mutations.  Originally,  this  was  based  on  the  idea that the genome was always wiped clean of epigenetic marking, so that it was thought that the idea was misconceived and impossible. As I have shown, this is simply not correct.

Another criticism was that it would not be robust. It has been demonstrated to persist for as many as 100 generations, and that it can, in some cases, be as robust as DNA transmission.  Moreover,  it  does  not  need  to  be  robust  in  all cases. As the review by Burggren [55] shows, the softness and therefore reversibility of epigenetic inheritance is one of its  evolutionary  virtues.  Sultan  and  co-workers  [56]  have also identified the factors that may determine the transience or persistence of epigenetic variation.

The third criticism is that it is observed in only rare cases. My reply is that so is speciation. Speciation is such a rare event  that  in  thousands  of  years  of  selective  breeding  of cats, dogs, fish, etc., we have not succeeded in producing new species, as defined by reproductive isolation. 

Note also that these criticisms obviously do not apply to functionally significant reorganization or hypermutation  of genomes.

3. Blind stochasticity

The other basic assumption is blind stochasticity, meaning that what are seen as random genetic variations are not functionally directed. The concept of randomness is a major topic of research in philosophy, mathematics and physics. One way to bypass these highly technical issues is to ask the question ‘random with respect to what’? The key in relation to evolutionary  biology  is  whether  variations  are  random  with respect to function and whether they can be seen to be so. Even  if  the  molecular-level  variations  do  in  fact  represent functional order at a higher level, we will almost certainly require  insight  from  the  functional  level  to  appreciate  the functional nature of the molecular variations. The randomness I am referring to is therefore epistemological: without knowing the constraints by higher levels, the variations will appear  to  be  random  and  unpredictable.  Once  we  know those constraints the possibility of prediction at the molecular level begins to exist. Whether it is computable is a very different question. Given the huge differences of scale, e.g. between molecular and cellular, it is implausible to expect molecular-level computation alone to reveal the functionality.

Even before we consider whether a theory based on blind stochasticity has been falsified, we have to examine its conceptual  status.  A  very  basic  lesson  from  physics  is  that stochasticity at lower, such as molecular, levels is not only inevitable as a consequence of molecular kinetic energy, it is also perfectly compatible with regular law-like behaviour at  higher  levels,  a  fact  that  was  appreciated  long  ago  by one  of  the  founders  of  population  genetics,  Fisher  [57].

Even if behaviour at a high level is directed, stochasticity is what  we  can  expect  at  lower  levels.  The  example in this paper concerning the evolution in different species of haemoglobins at high altitude illustrates that point perfectly. As the authors of that paper say ‘predictable changes in biochemical phenotype do not have a predictable molecular basis’ [45]. It is the physics of oxygen transport in organisms living at low partial  pressures  of  oxygen  that  dictates  the  changes  that occur to adapt to such environments, not specific changes in the genome.

From a gene-centric viewpoint, it could be objected that the genome changes are nevertheless those that enable the beneficial changes in oxygen transport to happen. That is certainly true. But it is precisely the higher level perspective that enables us to show that fact. What we can see here is that a conceptual issue, which is the question of the level at which functionality occurs, interacts   with   an   empirical   issue, which is whether the changes at the molecular level are predictable,  from  that  level  alone.  Another  way  to  put  the conceptual  issue  is  to  say  that,  in  any  information  transmission system, whether languages or genomes, sequences by themselves do not have meaning. They acquire meaning through their context, which can only be understood at a much  higher  level.  As  a  linguistic  example,  the  three letter  alphabetic  sequence  ‘but’  has  two  totally  different meanings   and   pronunciations   in   English   and   French.

Similarly,   genome   sequences   acquire   meaning   in   their context.  Sequences  enabling  arms,  legs  and  eyes  derive from organisms that had none of these.

4. Unravelling the problem

My  paper  unravels this  problem  by showing  where  some aspects of biological thought went wrong in the twentieth century. Schrödinger's book, What is life?, was a landmark in predicting correctly that the genetic material would be found to be an aperiodic crystal. But it contained the seeds of a major  misunderstanding, leading Schrödinger, and then Crick and Watson, to maintain that, like a crystal, the genetic material could be read in a determinate way. That could be true only if the ‘crystal’, that is the linear polymer DNA, could be read and copied faithfully, with few or no copy errors. As we can now see, that is not an inherent property of DNA alone. On the contrary, it is a property of the complex system by which the copy error rate can be reduced from an unacceptable frequency of millions per genome to less than 1. That is a higher level systems property of cells, including  an  army  of  proteins  and  lipids,  not  of  DNA alone.  In  life  as  we  know  it  on  the  Earth,  this  process occurs only in the context of living cells. 

A possible objection to this conclusion is that all proteins have DNA templates that determine their amino acid sequences. That includes the proteins that contribute to the error-correcting  systems  for  DNA.  That  is  true,  but  it  is usually  taken  a  step  further  to  mean  that  therefore  the genome determines everything. That is not true. The error-correcting  systems  operate  within  cellular  structures  that contain molecular elements, such as lipid membranes, that do not require DNA templates in order to exist. Elsewhere, I have shown that the structural information in cells can be represented  as  comparable  to  that  in  the  genome  [58]. Organisms always inherit both. In one of the rare examples of a successful clone from the nucleus of one species inserted into  the  enucleated  but  fertilized  egg  cell  from  another species, both the cell and the nucleus contribute to the final structure of the adult. Reproductive hybridization between species has also been shown to produce intermediate forms which can generate speciation [59].

Experimentally, we need to re-examine the way in which functional change in organisms can harness stochasticity at lower  levels  to  create  new  functionality.  Huang  and  his co-workers have shown the way forward here by demonstrating  that  stochasticity  in  gene  expression  is  an  attractor produced by a cell population. The many studies of targeted hypermutation, e.g. by Moxon’s group, also show the way forward.  Organisms  in  their  evolution  had  to  harness stochasticity because at a low enough level, this is an inevitable property of the physics of molecular-level systems that have kinetic energy.

We can now return to the question whether the assumption  of  blind  stochasticity  has  been  falsified.  If  the  case presented in this paper is correct, then one answer would be  that  it  is  very  difficult  for  it  to  be  falsified  because stochasticity necessarily reigns at a low enough level, even if functionality reigns at higher levels. The constraints may have too subtle an effect at the molecular level. The falsifiability then depends on a prior conceptual question, which is whether  one  accepts  multi-level  functionality.  A  purely gene-centric theory does not accept multi-level functionality and  can  therefore  maintain  its  view  of  everything  being ‘blind chance followed by natural selection’.

To a physiologist or a medical scientist, this is not a useful viewpoint. Functionality arises in organisms at many different levels. This is one of the bases of my formulation of the principle of biological relativity, first proposed in a previous article in this journal, and developed more completely in a book, Dance to the tune of life. Biological relativity [60].