Science in culture

Books & arts

PETER MENZEL/SPL

DNA sequencing has become routine, but the roles of individual genes can be hard to be pin.

Genes are not the

F
or too long, scientists have been content
in espousing the lazy metaphor of
living systems operating simply like

blueprint for life

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 pub-
lic understanding affects policy, health care
The view of biology often presented to the public is and trust in science. “So long as we insist that
cells are computers and genes are their code,”
oversimplified and out of date. By Denis Noble writes Ball, life might as well be “sprinkled

254 | Nature | Vol 626 | 8 February 2024

 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.
When the human genome was sequenced
in 2001, many thought that it would prove
to be an ‘instruction manual’ for life. But
the genome turned out to be no blueprint.
In fact, most genes don’t have a pre-set
function that can be determined from their
DNA sequence.
Instead, genes’ activity — whether they are
expressed or not, for instance, or the length
of protein that they encode — depends on
myriad external factors, from the diet to
the environment in which the organism
develops. And each trait can be influenced
PHILIPPE PLAILLY/SPL

by many genes. For example, mutations in

almost 300 genes have been identified as
indicating a risk that a person will develop
schizophrenia.
It’s therefore a huge oversimplification, DNA alone cannot reveal how life works.
notes Ball, to say that genes cause this trait
or that disease. The reality is that organisms philosophical question of what makes an This burst of activity represents a frustrated
are extremely robust, and a particular func- organism alive. Agency — the ability of an thought that “it is time to become impatient
tion can often be performed even when key organism to bring about change to itself or its with the old view”, as Ball says. Genetics
genes are removed. For instance, although the environment to achieve a goal — is the author’s alone cannot help us to understand and treat
HCN4 gene encodes a protein that acts as the central focus. Such agency, he argues, is attrib- many of the diseases that cause the biggest
heart’s primary pacemaker, the heart retains utable to whole organisms, not just to their health-care burdens, such as schizophrenia,
its rhythm even if the gene is mutated1. genomes. Genes, proteins and processes such cardiovascular diseases and cancer. These
Another metaphor that Ball criticizes is that as evolution don’t have goals, but a person cer- conditions are physiological at their core,
of a protein with a fixed shape binding to its tainly does. So, too, do plants and bacteria, the author points out — despite having genetic
target being similar to how a key fits into a lock. on more-simple levels — a bacterium might components, they are nonetheless caused by
Many proteins, he points out, have disordered avoid some stimuli and be drawn to others, cellular processes going awry. Those holistic
domains — sections whose shape is not fixed, for instance. Dethroning the genome in this processes are what we must understand, if we
but changes constantly. way contests the current standard thinking are to find cures.
This “fuzziness and imprecision” is not about biology, and I think that such a challenge Ultimately, Ball concludes that “we are at
sloppy design, but an essential feature of is sorely needed. the beginning of a profound rethinking of
protein interactions. Being disordered makes Ball is not alone in calling for a drastic how life works”. In my view, beginning is the
proteins “versatile communicators”, able to rethink of how scientists discuss biology. key word here. Scientists must take care not to
respond rapidly to changes in the cell, binding There has been a flurry of publications in substitute an old set of dogmas with a new one.
to different partners and transmitting differ- this vein in the past year, written by me and It’s time to stop pretending that, give or take
ent signals depending on the circumstance. others2–4. All outline reasons to redefine a few bits and pieces, we know how life works.
For example, the protein aconitase can switch what genes do. All highlight the physiolog- Instead, we must let our ideas evolve as more
from metabolizing sugar to promoting iron ical processes by which organisms control discoveries are made in the coming decades.
intake to red blood cells when iron is scarce. their genomes. And all argue that agency and Sitting in uncertainty, while working to make
Almost 70% of protein domains might be purpose are definitive characteristics of life those discoveries, will be biology’s great task
disordered. that have been overlooked in conventional, for the twenty-first century.
Classic views of evolution should also be gene-centric views of biology.
questioned. Evolution is often regarded as Denis Noble is emeritus professor of
“a slow affair of letting random mutations How Life Works: A physiology and biology at the University of
change one amino acid for another and User’s Guide to the New Oxford, UK.
seeing what effect it produces”. But in fact, Biology
Philip Ball
proteins are typically made up of several 1. Noble, D. Prog. Biophys. Mol. Biol. 166, 3–11 (2021).
Pan Macmillan (2024)
sections called modules — reshuffling, 2. Noble, R. & Noble. D. Understanding Living Systems
(Cambridge Univ. Press, 2023).
duplicating and tinkering with these
3. Vane-Wright, R. I. & Corning, P. A. Biol. J. Linn. Soc. 139,
modules is a common way to produce a 341–356 (2023).
useful new protein. 4. Corning, P. A. et al. (eds) Evolution “On Purpose”:
Teleonomy in Living Systems (MIT Press, 2023).
Later in the book, Ball grapples with the

Nature | Vol 626 | 8 February 2024 | 255