The life of a designer cell

By Oliver Morton

The clear plastic bags contain a liquid somewhere between orange and pink; quite fetching, but more importantly an indication that the alkalinity is just right. They sit on metal shelves in a small, steel-lined room which, at a steady 37˚C, is more than warm. The setting, fragrance-free and almost silent, looks and feels purely industrial. But it is dedicated to life—as a molecular process of bewildering complexity, and as something worth saving.

This room is on a campus in South San Francisco where the biotech company Genentech—the first of its kind, now part of the Swiss pharma giant Roche—produces designer proteins. The liquid in the bags is an exacting cocktail of 50 nutrients and trace elements, mixed to a precision of a few parts per million. The purpose of the mixology, and of the temperature, and of all the other technologies and procedures here, is to create the best environment you could imagine—if your sense of what is good had been built up by the millions of years of evolution that were required to create the ovaries of the Chinese hamster, and then modified with a few decades of intensive genetic tinkering. Because it is on keeping such ovary-derived cells as happy as possible that Genentech’s fortunes are based; they are the cells res­ponsible for mass-producing antibodies that recognise and help the body regulate various sorts of target, notably cancers.

Quite how fast these fine-tuned cells make antibodies is not something Genentech likes to discuss, but the scientific literature has similar cells producing hundreds or even thousands per second. When you consider that each antibody requires the carefully co-ordinated production of four interwoven proteins and some precise adding of sugars to make a final product hundreds of times bigger and spectacularly more complex than an everyday pharmaceutical such as aspirin or morphine or warfarin, that rate sounds remarkable. But when you think of how many antibodies it takes to intervene in even a single human life, you realise that you need a remarkable amount of that remarkable quantity. You need remarkable squared—a system to mass-produce mass production.

The cells that get inoculated into the growth medium in that steel-lined room pass through a series of bespoke receptacles and careful checks until they end up in 12,000-litre steel canisters. By that time there are tens of trillions of them—more cells than in a human body. But where a body is made of hundreds of types of cells arranged in complex tissues and systems, every cell in the big steel flask is on its own, doing exactly the same thing. And whereas the body has more bacteria than human cells, not to mention an unknowable number of viruses, in the tanks there are just the genetically identical designer cells, their nutrients, their waste and their products. If there were one virus particle in just one out of every million doses of antibody, the whole batch would be sacrificed to the stringent rules of the Food and Drug Administration.

Today’s culture encourages an affection for variation and a disdain for conformity. When we look at a meadow of hundreds of types of sedge and grass and flower, we feel a greater sense of nature’s abundance than a wheat field provokes, even if the wheat feeds more people. The altar at which nature is worshipped is that of biodiversity, not gross primary productivity.

In the industrialisation of life that sits at the heart of biotechnology, the reverse is true. No meadows, only monocultures, more harshly policed than anything agribusiness could dream of. Trillions of identical cells, producing exactly the same molecules. Steel containers, plastic bags, identity, conformity: a world whose badge is a pinky-orange that never changes in the slightest. It may be efficient, and it may be profitable, but it is hardly what life is meant to be like. It is a thing of blueprints instead of beauty.

No. It is the other side of the coin. Life’s variety hides a deep uniformity. Living things depend on mechanisms machined molecule by molecule, every atom in its place; when the machinery goes wrong, things fall apart. In the meadow as in the wheat field, in the mouse as in the elephant, in the orchid and the lichen and the algal bloom, polymerases try to make perfect copies of genes, ribosomes try to build proteins with unerring exact­itude. What happens in South San Francisco is that that side of nature—the uncom­promising machine—is given an expression fuller than anything seen in the wild.

If cells could choose their environment, these pampered tanks would be top of their list. Tens of thousands of hours of meticulous engineering design, years of research by acute minds, billions of dollars in capital expenditure, all devoted to letting one biological process unfold with less hindrance than has ever been possible before. The ability to design environments that so suit their inhabitants may be second only to the ability to design those inhabitants themselves when it comes to the human revolutionising of biology.

And the relation of this fierce focus to diversity is not an either/or. These antibodies are designed for a purpose. I have friends whose cancers have responded to treatments of which these antibodies are a part. Those friends have lives as unique as all human lives, as unique as any sport of creation and far more precious. And mass-produced molecules, copied in numbers that dwarf those of the stars in the sky, have intervened in the machinery that supports that life and helped to prolong it.

Illustration Pete Gamlen