NATURE
BOOK REVIEW
- 05 February 2024
It’s time to admit that genes are not the blueprint
for life
The view of biology often presented to the public
is oversimplified and out of date. Scientists must set the record straight,
argues a new book.
By
https://www.nature.com/articles/d41586-024-00327-x
How Life Works: A User’s Guide to the New
Biology Philip Ball Pan Macmillan
(2024)
[I bolded that pars of Noble's article I thought were crucial. D.G.]]
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.
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 by many genes. For example, mutations in almost 300 genes have been
identified as indicating a risk that a person will develop schizophrenia.
A tour of the evolution of minds
It’s therefore a huge oversimplification,
notes Ball, to say that genes cause this trait or that disease. The reality is
that organisms are extremely robust, and a particular function can often be
performed even when key genes are removed. For instance, although the HCN4 gene
encodes a protein that acts as the heart’s primary pacemaker, the heart retains
its rhythm even if the gene is mutated1.
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.
Classic views of evolution should also be
questioned. 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.
DNA alone cannot reveal how life works.Credit: Philippe Plailly/SPL
Later in the book, Ball grapples with the
philosophical question of what makes an organism alive. Agency — the
ability of an organism to bring about change to itself or its environment to
achieve a goal — is the author’s central focus. Such agency, he argues, is
attributable to whole organisms, not just to their genomes. Genes, proteins
and processes such as evolution don’t have goals, but a person certainly does.
So, too, do plants and bacteria, on more-simple levels — a bacterium might
avoid some stimuli and be drawn to others, for instance. Dethroning the genome
in this way contests the current standard thinking about biology, and I think
that such a challenge is sorely needed.
Neuroscience needs some new ideas
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 others2–4. All outline reasons to redefine what genes do. All highlight the
physiological processes by which organisms control their genomes. And all argue
that agency and purpose are definitive characteristics of life that have been
overlooked in conventional, gene-centric views of biology.
This burst of activity represents a frustrated
thought that “it is time to become impatient with the old view”, as Ball says.
Genetics alone cannot help us to understand and treat many of the diseases that
cause the biggest health-care burdens, such as schizophrenia, cardiovascular
diseases and cancer. These conditions are physiological at their core, the
author points out — despite having genetic components, they are nonetheless
caused by cellular processes going awry. Those holistic processes are what we must
understand, if we are to find cures.
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.
Nature 626,
254-255 (2024)
doi:
https://doi.org/10.1038/d41586-024-00327-x
References
- Noble, D. Prog. Biophys. Mol. Biol. 166,
3–11 (2021).
2.
Noble, R. & Noble. D. Understanding Living Systems (Cambridge
Univ. Press, 2023).