After the Genetic Paradigm: Why We Need a New Biology

Philip Ball on The New Biology Project at Marginalia

The New Biology project is seeking to establish new narratives for biology that recognize the advances in understanding that have happened over the past several decades. I have attempted to describe some of the most important of these advances in my book How Life Works and to weave them into an integrated picture of how lifeless molecular components collaborate to generate agential organisms. I argue that recent research in molecular, cell, and developmental biology has made it no longer tenable to suggest—as has typically been the case during the ascendancy of the gene-centred view of biology—that organisms are simply “readouts” of the information or the blueprint encoded in the DNA of the genome. I argue too that, while some of this new understanding has depended, and must continue to depend, on what is commonly called a reductionistic view that looks at processes at the molecular level, this does not mean that cells or organisms should be understood through a machine metaphor. Considering organisms as machines made by genes—and indeed for genes—does not do justice to the marvelous way nature works, and risks devaluing life itself.

This new perspective fits in many ways with what cell, developmental and organismal biologists, and even some evolutionary biologists, are increasingly saying. The “genetic blueprint” picture implicit in the Modern Synthesis of Darwinian theory and genetics has long been at odds with the developmental view: the idea that there is some kind of plan in the genome that is simply enacted during development does not sit easily with the evident fact that the developmental process accommodates contingency and accident, and is often able to respond to perturbations in an “intelligent” manner that looks purposive. As our understanding of developmental processes has increased, these tensions have become ever more apparent. As evolutionary biologist Andreas Wagner has put it,

The architects of the modern synthesis focused on the genotype at the expense of the organism and its phenotype. They neglected the marvelous complexity of organisms with their trillions of cells, each inhabited by billions of molecules whose functions are themselves incredibly complex. And they neglected how all this complexity unfolds from a single fertilised cell, and how genes contribute to this unfolding. By neglecting this complexity, the architects of the modern synthesis effectively ignored its product: the organism itself.

In an article in the journal Development, biologist Duygu Özpolat and colleagues say that

Although many types of explanations are possible for understanding how a biological phenomenon works (e.g. on a molecular, genetic, cellular, organismal, biophysical or systems level), molecular/genetic mechanisms are widely perceived to be the gold standard for a mechanistic explanation of development.

They caution against “seeking simple genetic explanations” and say we need to “reduce our reliance on reductionism and allow for conceptual advances at any level to be recognized based on their contribution to the field.” According to developmental biologist Alfonso Arias Martinez, “Cells, and not DNA, are the master builders of life.”

And in an article in Cells and Development, biologists Alan Rodrigues and Amy Shyer say that “viewing life as if it emanated from a set of molecular machines is the main bottleneck in addressing key questions in biology.” Citing How Life Works, they add that “the need for deep conceptual thinking has never been more pressing, despite the fact that many key figures in biology have taken a technocratic focus that has downplayed the role of conceptual thinking.”

These are just a few examples of what seems now to be a sea change in the way many biologists regard their subject. I argue that one sign of this shift is that biology is becoming more ready to accept and to speak of concepts long considered taboo: in particular, agency, purpose, and meaning. To some, these notions are suspiciously mystical or teleological, seeming to suggest some hidden design or motive force behind the way organisms work. That, however, is to misunderstand what the words connote in this context. There should be no question that living organisms do exhibit goals and behave purposefully: a suggestion unproblematic to most organismal biologists, at least. The traditional view that such behavior is merely “as if”—a kind of automated, mindless activity impelled by genes—was always questionable, for it shifts all agency to mere inert pieces of DNA and then demands that this “merely metaphorical” way of speaking performs real action in the world. That picture is all the more untenable now that we better understand the processes once vaguely designated as “gene action” and recognize that they involve multidirectional information flow to and from all levels of the organizational hierarchy of living things. It is this openness of organisms as living systems that enables them to exhibit genuine agency at the level of the whole: to develop goals and to select actions and make decisions that help them to be achieved.

I was encouraged that this new picture is being increasingly accepted in biology by a recent conversation with the Nobel laureate Paul Nurse, who has agreed to be involved in this project. Nurse, whose celebrated work on the cell cycle could seem the paradigm of reductionistic molecular biology, readily acknowledged that agency and purpose are central to the living world. He added that some biologists resist that idea through an understandable but mistaken view that such things can only arise through human-level cognition involving conscious deliberation. “The word purpose is really to, in a short form, describe that something is acting as a whole to deliver something for the whole organism”, Nurse said.     

Meaning might seem an even more contentious term in biology, seeming as it might to refer to something existential and perhaps even spiritual. But in biology there is no need to take that view. Meaning refers simply to the sifting of information that an agential entity—a cell or an organism—potentially receives from its environment (and indeed that arises within its internal state), so that some of this information (that which might be useful in achieving a goal) can be integrated into a decision, while some (that which does not improve the effectiveness of such a decision) is ignored. Such attribution of meaning means that organisms are sensitive to context and to their own history—and also, crucially, that they benefit from the evolutionary learning process that really is conveyed in the genes.

Philip Ball, How Life Works: A User's Guide to the New Biology. University of Chicago Press, 2023. 522 pages. $22 (softcover)

All of this has long been up for discussion within the philosophy of biology. What we are particularly concerned about in The New Biology project is to connect what might seem like somewhat abstract discussions about the nature of life to real laboratory research. In fact it is that research, often into the minutiae of molecular and cell biology, that convinces us that this is the right time to be looking for new narratives. We can now begin to identify the molecular processes that underlie and facilitate the agency, adaptiveness and sensitivity of living organisms and their ability to innovate and improvise in the face of circumstances for which evolution could never have anticipated the “right response.” We see this, for example, in the way that many of the key interactions between molecules in cells do not have a precise on/off digital logic, but rather, operate according to fuzzy principles in which the molecules can cooperate with many different partners in a context-dependent manner. We see it in the way biomolecules tend to act collectively, often in combinatorial ways such that any given molecule can play a role in various different (and sometimes diametrically opposed) decisional outcomes, depending on the company it keeps. All of this makes it clear why, not only are the lines of connection between a gene and a trait (a phenotype) typically complex and convoluted but they are also highly contextual, to the extent that we cannot regard a gene as prescribing (being “for”) the trait but only as a source of resources that partake in such outcomes. As a result, the “causes” of organismal behaviour—including disease outcomes—often cannot be traced back to the genome in any meaningful manner.    

So the question then becomes: what stories should we tell about all this complexity? That is the project’s goal, to which end it will begin with a series of interviews (of which that with Nurse was the first) with leading thinkers and researchers in a range of disciplines, including cell and developmental biology, the origin of life, genetics, and the philosophy of biology. Nick Lane, a biochemist at University College London who has emerged as one of the most inventive thinkers in modern biology, will be a co-leader, and the project will build towards a symposium in which the participants will debate ways to understand and to present the changing picture of how life works.

The conviction behind the New Biology project is not only that such stories can be found—and that they can not only better inform the public about health and biomedical technologies but also improve professional discourse—but that they will prove to be far richer, more productive, and more satisfying than any reductive picture based on genetic blueprints. Most of all, we hope that these new narratives can help restore a sense of awe and reverence at the fact that life has arisen, at least on this planet, from lifeless matter, and has thereby introduced purpose and meaning to the universe.

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Philip Ball is a scientist, writer, and a former editor at the journal Nature. He has won numerous awards and has published more than twenty-five books, most recently How Life Works: A User’s Guide to the New Biology; The Book of Minds: How to Understand Ourselves and Other Beings, From Animals to Aliens; and The Modern Myths: Adventures in the Machinery of the Popular Imagination. He writes on science for many magazines and journals internationally and is the Marginalia Review of Books' Editor for Science. Follow @philipcball.bsky.social