An Object Lesson in How Not to Do Science
British science writer Philip Ball, looks back on the mapping of the human genome and what has followed from it. Writing at Aeon, he senses a need for change in the way we look at Earth’s life forms. But he doesn’t seem to want too much change.
As the author of How Life Works (University of Chicago Press 2023) and Beautiful Experiments (University of Chicago Press 2023), Ball admits,
Talk of a genetic blueprint, of selfish genes, of instruction books and digital codes gave us a narrative we could grasp. Even though we now know this to be at best a partial and at worst a misleading picture, it’s likely to remain in place until there is something better on offer.
PHILIP BALL, “WE ARE NOT MACHINES,” AEON, JULY 12, 2024
What Most of Us Learned in School Was Faulty
He is aware of the limitations of that point of view but sees it as part of the inherent conservatism of science. Still, he looks for another, more accurate story. Thus, he reveals — surprising many of us perhaps — that most of what we learn in school gives rise to misconceptions. For example,
Only around 1-2 percent of the entire human genome actually consists of protein-coding genes. The remainder was long thought to be mostly junk: meaningless sequences accumulated over the course of evolution. But at least some of that non-coding genome is now known to be involved in regulating genes: altering, activating or suppressing their transcription into RNA and translation into proteins. Many disease-linked regions are in these regulatory sequences, where mutations don’t change the proteins themselves but, rather, the rate or chance of them being made at all. So, to understand how life really works at the genomic level, we need to understand gene regulation. And that, as we’ll see, is not just eye-wateringly complicated but not at all what we have learnt to expect from the conventional molecular biology of the past 50 years.
BALL, “WE ARE NOT MACHINES”
And not all genes even encode proteins. Also RNA seems to have some functions other than serving as a messenger for making proteins.
Ball grasps the strangeness of the fact that the public still hears the same Central Dogma story about the human genome as it did in the 1960s and thus has little idea how complex it all really is — and how poorly understood:
Thetemptation is to throw up one’s hands and conclude that, for humans at least, how life works surpasses all understanding. Some biologists have implied as much, suggesting that we might never truly understand life mechanistically, but will just have to rely on data mining with black-box AI to make predictions about what will lead to what.
BALL, “WE ARE NOT MACHINES”
Leaving it all to the computer does not, of course, seem like an obviously sound idea. And Ball goes on to say something quite profound:
… it’s not hard to see why, the more complex the organism, the fuzzier its molecular mechanisms have to be. A huge machine that works only if all its countless components interlock in precisely coordinated ways is far too fragile —especially if those parts are, like molecules, constantly moving about randomly in a warm, wet environment. By the same token, if life relied on the accurate readout of innumerable genomic instructions in exactly the right order, it would be far too vulnerable to errors. It’s for these reasons that we are not machines — not, that is, like any machine humans have ever built. It’s a far better and more robust solution to find principles that work over many hierarchical levels, with the operation at one level being not too sensitive to the fine details of the levels below. Gene regulation by rather loosely defined condensates rather than by specific molecular switches, say, means that it can still work without every molecule having to be present and correct.
BALL, “WE ARE NOT MACHINES”
Yes But how is this astonishing feat accomplished?
Evolution has, to speak anthropomorphically, evidently ‘designed’ our molecules to work in this fuzzy way. In contrast to the lock-and-key principle by which protein enzymes were long thought to recognise and transform their target molecules, some of the most important proteins in our cells, including many transcription factors, have shapes that are only loosely defined, enabling them to stick to others without being too choosy about it. And those little regulatory RNAs are generally too small to carry enough information for their unions to be very selective; they too work collectively, arriving at a decision, as it were, by committee.
BALL, “WE ARE NOT MACHINES”
The Unthinkable Thought
In short, the life we know can only be envisioned by appealing to intelligent design, while pretending not to.
Ball goes on to address the question of why the problems with the current picture are not better known: “Having long interacted with scientists of all persuasions, I’ve noticed a contrast between how physicists and biologists receive and communicate new ideas.”
Oh for heaven’s sakes, why can’t he just come right out and admit the reality? There is no reasonable hope that Darwinian evolution could have done all that is required in the time allowed — or in any amount of time. And, given how much has been invested in Darwinism over the years, no one wants to be first to stick a trowel in that beehive. That’s why.
Ball goes on to discuss the ENCODE project, which found that supposedly “junk DNA” often does have a biological function:
Some biologists responded by saying, in effect: ‘No no no, nothing to see here – our existing understanding is just fine.’ (This was mild stuff compared with the furious reaction the ENCODE paper itself elicited from some biologists, who accused the team of evolutionary heresy on a par with intelligent design.) Others said that, even if biology was indeed more complicated that we’d thought, what was to be gained by telling the public that? In other words: don’t upset the status quo.
BALL, “WE ARE NOT MACHINES”
Investment in a Belief System
That’s not about science; it’s about investment in a belief system. When Ball, admirably, checked the story out in the Systems Biology department at Harvard one summer, he learned that the whole thing was “much worse than that!” He now thinks that biologists are too invested in the Human Genome Project approach and that we need “new narratives” in biology. But then he also argues,
It has also become much harder in recent years for scientists to admit to gaps in knowledge and understanding, which will be exploited by everyone ranging from creationists to climate-change deniers to anti-vaxxers as evidence that we shouldn’t believe a word they say.
BALL, “WE ARE NOT MACHINES”
In short, the story the public is told is contrary to evidence — and to reason, actually — but scientists have to keep telling it because otherwise the wrong people might benefit. That is practically an object lesson in how not to do science. But Ball has thought and said as much as he can while remaining safe.
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