What is Life?
“Biology expands our vision of life, letting us see beyond our experiences of being alive, look back over billions of years of living history, and peer down into the microscopic confines of a cell”. This is Carl Zimmer’s manifesto for his trade, generalist biological science writing, in his new book: Life’s Edge: The Search for What it Means to Be Alive (Picador).
What Zimmer and other generalists such as Philip Ball do is valuable beyond educating the rest of us. Zimmer follows this manifesto with the observation that the scientists he interviews don’t have his luxury: they need to pursue a narrower slice of life’s riches. Biology today is such a teeming empire, the panoptic view of a Zimmer helps to make sense of a discipline so awash with data that much of the work has to be entrusted to computer algorithms. Yale University recognised the importance of Zimmer’s work by appointing him Professor Adjunct of Biophysics and Biochemistry; the only science writer to hold such a post.
Zimmer is prolific and what he does is to find a canny theme that allows him to hang many of biology’s pearls on a plausible narrative thread. In Life’s Edge, he explores the puzzle that biologists have never been able to come up with a consensus definition of “life”. So he embarks on a tour of the usual hallmarks — generating and using energy; the ability to find food (demonstrated by the apparently primitive but actually very smart slime moulds which, despite being single-celled organisms are so smart that their food-seeking strategies have been used to solve computational problems in AI); reproduction; homeostasis (the ability to keep constant the conditions for life, such as internal temperature, salt concentrations etc); evolution — and proceeds to demonstrate, biology notoriously being the science of exceptions, that they are not as clear-cut as we had imagined.
Take the hallmark “Reproduction”. As sexual creatures, we take sexual reproduction to be the only way to create a whole new individual, but as long ago as 1740 the humble but nevertheless multicellular hydra shocked naturalists and the lay public when Abraham Trembley revealed that this small see-through aquatic animal (up to 30 mm long), with its eponymous tentacles, could reconstitute itself after being carved into pieces. This startling fact challenged the received wisdom of the day, which was nothing more informative than the idea that God had formed every creature immutably according to his whim or that every creature had a tiny future one inside it and another inside that, Russian-doll fashion.
But the hydra suggests that whatever forces shape an organism in the normal process of growth and maturation after sexual reproduction, there is another force that is actually capable of putting Humpty Dumpty back together again. Although it did cause a sensation at the time, such a notion had no real purchase on scientific minds for almost 250 years. We now know that the hydra’s ability resides in the complex chemistry of cellular components that are not themselves alive.
The conundrum of the essence of life has sparked probably more speculation than experiment, some of it outlandish and — across the history of biology — most of it wrong. Zimmer runs, as a leitmotif, the case of John Butler Burke — a now forgotten physicist who briefly caused a sensation in 1906 by proposing that radium, discovered by Marie and Pierre curie in 1902, could somehow inculcate the vital spark of life into inanimate matter. Before biology came of age in the mid 20th century, there was always supposed to be one magic ingredient: the élan vital, protoplasm, radium. It is shocking how much has been staked on theories that were no more than an expression of ignorance and a wishful desire for a simple answer. Before the dangers of radioactivity were known, radium enjoyed a cult as a cure-all.
For the book, Carl Zimmer talked to a range of biologists who are probing the boundary between the living and non-living and wonders whether they will go down in history as another John Butler Burke or will they be the Einstein or Schrödinger of biology? The book ends with Leroy Cronin, a prolific Glasgow chemist who wants to create artificial life-forms, built entirely from chemicals not derived from anything living. “I’m either mad”, Cronin declared, “or completely right”.
Despite not being able to agree on a definition of life, Scientists working at life’s cutting edge do tend to agree that there are three broad necessities. All living cells have a boundary that separates them from what is beyond their confines and contains all the machinery of life. There must also be within the cells a means of generating and using energy to power the reactions that allow the cell survive until it reproduces. Then there is reproduction or self replication. Biologists who work on one of these three tend to argue about which came first in evolution. But in all the life-forms we see now all three are needed — so how did we get to the point of the first cell? It seems to be a three-handed version of the old chicken-and-egg conundrum.
We are a long way from solving that, but meanwhile we can enjoy the curiosities that emerge from studying life’s edge. And perhaps the three-way chicken-and-egg problem does suggest a clue to that elusive definition of life? Elsewhere, Carl Zimmer has written a great deal about viruses and they are the classic locus of the problem — they don’t have cells, they don’t have metabolism. Nothing moves within a virus; it’s just an aggregation of proteins and DNA or RNA crystals. But, in a curious echo of Trembley’s hydra, some viruses — phages, for example, which prey on bacteria — can perfectly reconstitute themselves after being minced in a blender. Does this mean that, sharing this trait with an animal, viruses must be alive? No — the opposite is the case. The chemical machines of life — and I mean machines because the engines of life are giant assemblies of molecules, pieces of nano-engineering: veritable giants of the infinitesimal — are not in themselves alive but possess moving parts and use energy just like our large-scale human machines. The kinship between phages and hydra, evidenced by their ability to recompose their smashed selves, demonstrates the chemical roots of life — not some “vital principle” conferring the spark of life. The nanomachines inside cells can still function when extracted from the cell and put to work in a test-tube.
Despite all they lack, viruses do have two key properties of living things: they reproduce and they evolve. To do that, when they land on an appropriate living cell, they invade it, hijacking their genetic machinery to make copies of themselves. We’re all now familiar with this in the form of the Covid virus: proteins on the Covid spike can lock onto cells in our lungs because in evolution they have parasitically hacked the open sesame code.
So the best conclusion is that none of the contents of the cell are alive — only the full assembled kit of the cell has this property. The best working definition of life is that it is what cells do. Some living things are autonomous single cells such as bacteria and they had the earth to themselves for almost 3 billion years; others are creatures like us with trillions of cells all acting in concert as a single organism. But there are no living things without cells. Viruses are the spanner not the works.
Through delving into these conundrums, Life’s Edge enlarges and refreshes the vision of we who inhabit life’s middle zone, extending it down into the nanoworld, where, as the great physicist Richard Feynman pointed out, more than 60 years ago in his classic lecture ‘Plenty of Room at the Bottom’, nature does her best work.