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Denis Noble in Nature: “Time to Admit Genes Are Not the Blueprint For Life”

Denis Noble
Photo: Denis Noble, via Wikimedia Commons.

Last November I reviewed an article in BioEssays which declared a Kuhnian “paradigm shift” away from the concept of junk DNA. That article compellingly argued that we need to abandon the notion that genes only make proteins because our genome is full of “RNA genes” that produce RNAs which perform vital functions. Now another groundbreaking article in Nature by Oxford emeritus biologist Denis Noble is calling for a major “rethink” of biology by charging that “It’s time to admit that genes are not the blueprint for life” because this “view of biology often presented to the public is oversimplified and out of date.” Noble is reviewing a new book, How Life Works, by Philip Ball. 

This is not to say that genes aren’t important for life — of course they are. It’s that they aren’t the fundamental blueprint that controls an organism. In fact, in a surprising twist, Noble argues that it’s the organism that controls the genome! Before we get there, we must review some of Noble’s striking discussions of the complexity of life. 

Life is Complicated

Those who travel in the intelligent design (ID) community know that we have often compared biological systems to machines. Now we have never intended to say that living organisms literally are machines — but rather that machine-like structures exist within living organisms, alongside many other features which may or may not be comparable to machines. The idea that life contains machine-like structure was explained eloquently by former U.S. National Academy of Sciences president Bruce Alberts, who famously wrote in the journal Cell:

[T]he entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines.… Why do we call the large protein assemblies that underlie cell function protein machines? Precisely because, like machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts.

Noble’s current Nature paper seemingly disagrees with Alberts’s use of machine-metaphors for biology. I think the metaphor still works in many cases, but before we explore Noble’s view, it must be understood that the reason for Noble’s disagreement with machine-metaphors isn’t because life is less complex than machines, but rather because it is MORE complex and the machine comparison fails to capture the true nature of life’s incredible complexity. Here’s what Noble writes:

For too long, scientists have been content in espousing the lazy metaphor of living systems operating simply like machines, says science writer Philip Ball in How Life Works. Yet, it’s important to be open about the complexity of biology — including what we don’t know — because public understanding affects policy, health care and trust in science. “So long as we insist that cells are computers and genes are their code,” writes Ball, life might as well be “sprinkled with invisible magic”. But, reality “is far more interesting and wonderful”, as he explains in this must-read user’s guide for biologists and non-biologists alike.

I don’t think that Noble is saying that the comparison between life and computers or machines is entirely inappropriate or completely irrelevant to anything we find in biology. Rather, I take him to be saying that life is “far more interesting and wonderful” than the idea that life is merely a computer or machine. If that’s what he’s saying, then I agree completely. 

Proteins More Complex than Initially Thought

Another area where Noble argues that biological systems are more complex than often appreciated is “intrinsically disordered proteins” (IDPs) — proteins that don’t have a stable three-dimensional shape. Brian Miller and I wrote about IDPs in a response to critics of Douglas Axe posted last year:

Venema (2018) cites intrinsically disordered proteins (IDPs), noting they “do not need to be stably folded in order to function” and therefore represent a type of protein with sequences that are less tightly constrained and are presumably therefore easier to evolve. Yet IDPs fulfill fundamentally different types of roles (e.g., binding to multiple protein surfaces) compared to the proteins with well-defined structures that Axe (2004) studied (e.g., crucial enzymes involved in catalyzing specific reactions). Axe (2018) also responds by noting that Venema (2018) understates the complexity of IDPs. Axe (2018) points out that IDPs are not entirely unfolded, and “a better term” would be to call them “conditionally folded proteins”. Axe (2018) further notes that a major review paper on IDPs cited by Venema (2018) shows that IDPs are capable of folding — they can undergo “coupled folding and binding”; there is a “mechanism by which disordered interaction motifs associate with and fold upon binding to their targets” (Wright and Dyson 2015). That paper further notes that IDPs often do not perform their functions properly after experiencing mutations, suggesting they have sequences that are specifically tailored to their functions: “mutations in [IDPs] or changes in their cellular abundance are associated with disease” (Wright and Dyson 2015). In light of the complexity of IDPs, Axe (2018) concludes:

“If Venema (2018) pictures these conditional folders as being easy evolutionary onramps for mutation and selection to make unconditionally folded proteins, he’s badly mistaken. Both kinds of proteins are at work in cells in a highly orchestrated way, both requiring just the right amino-acid sequences to perform their component functions, each of which serves the high-level function of the whole organism. (Axe 2018)”

Noble’s essay provides a direct vindication of our view of IDPs as dynamic, multi-functional systems. Yes, IDPs can adopt different three-dimensional structures, but that isn’t because their shape doesn’t matter but rather because they can switch from one shape to another — like miniature transformers — to perform different functions. And the shape is undoubtedly vital to their proper function in each case. Noble’s description of IDPs is striking:

Another metaphor that Ball criticizes is that of a protein with a fixed shape binding to its target being similar to how a key fits into a lock. Many proteins, he points out, have disordered domains — sections whose shape is not fixed, but changes constantly.

This “fuzziness and imprecision” is not sloppy design, but an essential feature of protein interactions. Being disordered makes proteins “versatile communicators”, able to respond rapidly to changes in the cell, binding to different partners and transmitting different signals depending on the circumstance. For example, the protein aconitase can switch from metabolizing sugar to promoting iron intake to red blood cells when iron is scarce. Almost 70% of protein domains might be disordered.

In other words, IDPs can switch from one shape to another in response to environmental cues or signals they encounter, and this allows them to perform multiple vital functions. Once again, the complexity of life appears to be greater than we expected. 

But what are the implications of all this for evolution? 

Questioning Classic Views of Evolution

In his review, Noble comes right out and says that “Classic views of evolution should also be questioned.” Now Noble is an evolutionist and not an ID proponent to be sure. But he seems open to more rapid forms of evolution that, from our vantage in the ID community, seem preprogrammed to yield favorable results that benefit the organism. Here’s what he writes:

Evolution is often regarded as “a slow affair of letting random mutations change one amino acid for another and seeing what effect it produces”. But in fact, proteins are typically made up of several sections called modules — reshuffling, duplicating and tinkering with these modules is a common way to produce a useful new protein.

Noble also thinks there’s a place for “agency and purpose” in biology. He’s not talking about the intelligent design of life by an external agent, but he is acknowledging that much in biology is purposeful, noting that multiple experts now argue that “argue that agency and purpose are definitive characteristics of life that have been overlooked in conventional, gene-centric views of biology.” Again, this isn’t the modern theory of intelligent design, but once we begin to allow agency and purpose into our understanding of how life works, we’re taking important steps towards being able to recognize design in biology. 

So, Where’s the Blueprint?

Noble offers various lines of evidence that the “blueprint” of life cannot be found in the DNA. He notes examples where hundreds of genes are involved in the development of certain diseases, suggesting that “It’s therefore a huge oversimplification … to say that genes cause this trait or that disease.” Moreover, rather than genomes controlling the organism, Noble notes that organisms themselves can “control their genomes” — suggesting genomes aren’t the foundation of life:

Ball is not alone in calling for a drastic rethink of how scientists discuss biology. There has been a flurry of publications in this vein in the past year, written by me and others. All outline reasons to redefine what genes do. All highlight the physiological processes by which organisms control their genomes. 

If “organisms control their genomes” rather than the classical reductionist view that genomes determine organisms, then perhaps it is time for a radical “rethink” of how biology works. Here’s Noble’s vision of the future:

Ultimately, Ball concludes that “we are at the beginning of a profound rethinking of how life works”. In my view, beginning is the key word here. Scientists must take care not to substitute an old set of dogmas with a new one. It’s time to stop pretending that, give or take a few bits and pieces, we know how life works. Instead, we must let our ideas evolve as more discoveries are made in the coming decades. Sitting in uncertainty, while working to make those discoveries, will be biology’s great task for the twenty-first century.

Noble’s vision of biology is one where dogma is discarded, new ideas are considered, agency and purpose are acknowledged, cells are more complex than computers and machines, proteins are like miniature transformers, and organisms control their genomes, is highly compatible with intelligent design — certainly far more compatible than the biological thinking of the past hundred years. This means biology is moving in the right direction.