The Secret Body

How the New Science of Human Biology Will Change the Way We Live

Daniel M. Davis

• Publisher: Princeton University Press
• Year: 2021
• ISBN:
  9780691230481
• Topic: Ciencias biológicas
• Subtopic: Biología

"A perfect blend of cutting-edge science and compelling storytelling."—Bill BrysonA revolutionary new vision of human biology and the scientific breakthroughs that will transform our lives Imagine knowing years in advance whether you are likely to get cancer or having a personalized understanding of your individual genes, organs, and cells. Imagine being able to monitor your body's well-being, or have a diet tailored to your microbiome. The Secret Body reveals how these and other stunning breakthroughs and technologies are transforming our understanding of how the human body works, what it is capable of, how to protect it from disease, and how we might manipulate it in the future.Taking readers to the cutting edge of research, Daniel Davis shows how radical new possibilities are becoming realities thanks to the visionary efforts of scientists who are revealing the invisible and secret universe within each of us. Focusing on six important frontiers, Davis describes what we are learning about cells, the development of the fetus, the body's immune system, the brain, the microbiome, and the genome—areas of human biology that are usually understood in isolation. Bringing them together here for the first time, Davis offers a new vision of the human body as a biological wonder of dizzying complexity and possibility.Written by an award-winning scientist at the forefront of this adventure, The Secret Body is a gripping drama of discovery and a landmark account of the dawning revolution in human health.

1 Super-resolution Cells

Seeing comes before words. The child looks and recognises before it can speak.

John Berger, Ways of Seeing

In 1665 the English scientist Robert Hooke, then aged thirty, published the world’s first picture book of microscopy, Micrographia.¹ The London diarist Samuel Pepys called it ‘the most ingenious’ book he had ever read.² In it, Hooke presented detailed drawings of various everyday objects dramatically enlarged for the very first time, including the unexpectedly blunt end of a needle, the mountainous edge of a razor blade and a monstrous, giant-sized flea.³ Within a thin piece of cork, the magnified image revealed boxlike structures. Hooke named them ‘cells’ because they reminded him of the spartan sleeping quarters of a monastery. Three years later, the Dutch textile merchant Antonie van Leeuwenhoek probably saw Hooke’s book while visiting London and went on to build microscopes himself which turned out to be better than Hooke’s. In 1676, Leeuwenhoek saw tiny organisms lurking in a droplet of water: the first sighting of bacteria. A year later, by closely examining his own ejaculate, he made another crucial discovery: sperm.⁴

Then as now, microscopes uncover worlds we simply had no idea about before. And so it follows that improving microscopes – to expose ever finer details – is a sure-fire route to new revelations. But in 1872, the German physicist Ernst Abbe showed that there was a limit to how powerful a microscope could be.⁵ It wouldn’t matter how well made or how perfectly aligned the optical lenses were. Even a flawlessly assembled optical microscope, Abbe’s mathematical analysis showed, could not zoom in endlessly, because of the way light spreads out and bends around small objects: a feature called diffraction. The highest resolution any microscope could achieve would be about half the wavelength of light, roughly 200 nanometres (200 x 10^-9 metres), or about 1,000 times less than the width of a human hair.⁶ It’s hard for us to imagine such a minuscule distance, but all sorts of wondrous and important things are smaller than this, from the structures within a butterfly’s wing that provide their iridescent colouring to the HIV virus that has killed 35 million people. Other scientific instruments allow us to detect these things, albeit with difficulty, but crucially none works with living specimens. An electron microscope, for example, requires its specimen to be bathed in chemicals and then placed in a vacuum chamber.⁷ Only a light-operated microscope lets us witness processes in a living cell directly, and Abbe’s law seemed an insurmountable barrier to doing so beyond a certain point. On a memorial to Abbe in Jena, Germany, where he lived and worked, his law, given in mathematical notation, is literally written in stone.

And yet now, thanks to a series of discoveries so ingenious and circumstances so unlikely that they would be dismissed as ridiculous were they not the truth, we are able to see at magnitudes at least ten times smaller than Abbe predicted possible. As a result, the discovery of new human anatomy on a minuscule scale is enjoying a global renaissance, to the extent that we have had to rethink what the fundamental unit of biology – the cell – really is.

The story of this remarkable feat begins with a Japanese scientist named Osamu Shimomura and his fascination with jellyfish.

Osamu Shimomura was ‘a quiet and brilliant researcher’⁸ working at Princeton University with his wife Akemi in the 1960s. Nearly every summer they travelled to Friday Harbor on the San Juan Islands, around ninety miles north of Seattle, to collect jellyfish.

We collected jellyfish from 6 a.m. to 8 a.m., then after a quick breakfast we would cut rings from the jellyfish until noon. We devoted all afternoon to the extraction. After dinner, we again collected jellyfish from 7 p.m. to 9 p.m., and the catch was kept in an aquarium for the next day.⁹

His children Tsutomu and Sachi helped, but they weren’t usually up as early as their parents.¹⁰ Locals sometimes wondered what the family were up to with their nets and buckets, scooping up so many jellyfish; they often asked, ‘How do you cook them?’

In 1955, these jellyfish had been observed to emit a green glow at the rim of their umbrella-shaped bodies.¹¹ Shimomura wanted to understand the biological process that made them glow. At least initially, he didn’t have any practical application in mind for his work. He was simply fascinated by the way some animals glow. All kinds of life – including fireflies, worms and deep-sea fish – use light to attract mates, warn off predators and communicate in ways we hardly appreciate. Life continues to surprise us with its colour: flying squirrels have recently been found to shine pink under UV light, and nobody knows how or why.¹² Shimomura wanted to understand the basic principles of how this happens.¹³

Shimomura’s success was partly owing to his characteristic approach to solving problems. Rather than foraging through books and scientific papers to find a suitable method, he would devise his own procedure from scratch with unusual resourcefulness. Instead of using one of the filters that happened to be available from the lab supply store, for example, he would think about the kind of the fabric that would work best and seek that out, wherever it was to be found. His daughter Sachi recalls how her father would often wander around a hardware store looking for things he could repurpose in the lab. He used dental floss to sew netting onto metal wire frames to make the shallow dip-nets his family used to collect the jellyfish. His jellyfish-cutting machine was essentially made from a juice blender.¹⁴ Shimomura would often emphasise this as an important ethos: that young scientists need to learn how to learn, and inventing one’s own procedures is an important way of doing so.

This approach to science came from his upbringing. His family moved homes several times, and his father, an army captain, was away a lot. Shimomura’s school education was frequently disrupted by military exercises and later abandoned entirely. At sixteen, he was at work in a factory just 15km away from Nagasaki when the atomic bomb was dropped. He witnessed two B-29 planes drop parachutes without any people hanging from them and, as he recalls in his autobiography, ‘a powerful flash of light hit us through the small window. Then, maybe forty seconds after the flash, we heard a loud sound and felt a sudden change of air pressure.’¹⁵ On his way home that day, a black rain fell. His grandmother gave him a bath as soon as he got in, which probably saved him from radiation poisoning.¹⁶ Growing up in Japan during the Second World War taught Shimomura to be strong, independent and resourceful.¹⁷

Ultimately, by comparing extracts from the jellyfish cells, seeking any that showed optical activity, Shimomura identified two types of protein molecule that make jellyfish cells glow. One emits blue light in the presence of calcium and a second takes up the blue light and emits green light.¹⁸ It was this second protein, later named green fluorescent protein or GFP, that was to play such a crucial role in microscopy.¹⁹

It was not until years later, though – at just after noon on Tuesday, 25 April 1989, to be precise – that Chicago-born Martin Chalfie, working at Columbia University, New York, happened to sit in on a talk which mentioned Shimomura’s work, and a new chapter in the story of GFP began.²⁰ Immediately, Chalfie began to fantasise about how this green-glowing protein might be used inside cells of other animals – specifically a small worm that he was studying – to highlight the location of specific types of cell or even certain molecules within cells.²¹ In an era before Google and Wikipedia, he spent the next day phoning people in order to find out all he could about it.²²

One person he was led to call was Douglas Prasher, then at the Woods Hole Oceanographic Institution, who was working to identify the gene which carried the instructions for the production of GFP. Prasher agreed to send Chalfie the gene once he had isolated it, but soon afterwards they lost touch. In time, Chalfie went on a sabbatical. Unable to reach him, Prasher assumed he had left science altogether. And when Chalfie never heard from Prasher, he assumed Prasher had never isolated the gene. It was not until 1992 that Chalfie stumbled upon a scientific paper by Prasher saying that he had.²³ Chalfie got back in touch, and Prasher sent him the gene.

In Chalfie’s lab, they found that the jellyfish gene could indeed be re-deployed to make bacteria or worms glow green.²⁴ It was a PhD student, twenty-six-year-old Ghia Euskirchen, who was the first person ever to see this. The bacteria’s green glow was so faint that Chalfie’s lab microscope couldn’t detect it. Luckily, she double-checked on a microscope in another lab and discovered that her experiment had worked.

It was already well established that genes could be transferred between species – because the basic chemistry of genes is the same in all life on Earth – but the fact that it took only a single gene to make an organism glow green was a vital revelation: it could have easily been the case that GFP would only work in concert with a suite of other proteins that were only found in those particular jellyfish. Chalfie’s lab first described these results in the October 1993 issue of Worm Breeder’s Gazette – not a widely read publication, and certainly not a usual source for paradigm-shifting new technology.²⁵ ‘We have lots of ideas of how GFP might be used and imagine that other people will have many more,’ they wrote. ‘If you are interested in obtaining [the GFP gene], please write … we’d like to know what you are interested in doing, but that’s not essential.’ Soon after, in February 1994, they published their work in the pre-eminent journal Science.²⁶

Eventually, the green jellyfish protein would be used in a vast array of experiments to study all kinds of life, from yeast to humans, but when Chalfie first talked to others in his university department about it, few grasped its potential. He thinks this is probably because it’s hard to realise the full importance of anything new the first time you hear about it.²⁷ But one person who did appreciate the work very early on – and she undoubtedly heard about it far more than once – was his wife, Tulle Hazelrigg, also a professor at Columbia. It was in Hazelrigg’s lab that the major step was taken that turned GFP into such a useful device: her team attached GFP to another protein by fusing together the two genes that encoded for them, allowing scientists to ‘tag’ that protein with GFP and thereby detect its location inside a cell. With this, Chalfie’s fantasy had come true: the green-glowing jellyfish protein had become a tool for watching life on a minuscule scale – because any particular type of protein could be tagged with GFP and watched.²⁸ A biological laser pointer, as Discover magazine called it.²⁹

In 2008, Shimomura and Chalfie, along with Roger Tsien at the University of California, San Diego, who improved the brightness of GFP and developed other proteins to glow in different colours, won the Nobel Prize for Chemistry. But the Nobel committee left out Prasher – the rules of the prize allow a maximum of three winners. When he heard the news, he was working for a Toyota car dealership in Huntsville, Alabama. He had struggled to get funding for his research at the Woods Hole Oceanographic Institution, worked for a while at the US Department of Agriculture, then took a job with a NASA contractor in Huntsville. Politics then changed NASA’s priorities and his project had been shut down. After a year of unemployment and bouts of depression, he had taken the job at the dealership so that he wouldn’t have to move city and his daughter could stay at the same high school.³⁰ So while the Nobel winners were set to receive several hundred thousand dollars each in prize money, Prasher was on $10 an hour.

Chalfie and Tsien got in touch and paid for him and his wife to attend the prize ceremony in Stockholm.³¹ Both mentioned his contribution in their Nobel lectures. Over a three-year period, Prasher, like Shimomura before him, had caught many tens of thousands of jellyfish.³² He had eventually isolated the gene for GFP, which was undoubtedly a crucial step towards its use as a tool, but he didn’t begrudge others winning the Nobel: ‘Do I feel cheated or left out? No, not at all. I had run out of funds, and these guys showed how the protein could be used, and that was the key thing.’³³

Nobody could possibly have known how research into jellyfish would lead to something so valuable to so many branches of biology. Scientific breakthroughs happen in all sorts of mysterious ways. Late in his life, Shimomura noted that after about 1990 the jellyfish became scarce in the waters where he used to collect them, probably because of pollution and perhaps specifically as a result of the Exxon Valdez oil spill off Alaska in 1989.³⁴ If the jellyfish had disappeared from there thirty or so years earlier, he would never have discovered GFP.

And if Shimomura had never discovered GFP, then a middle-aged, retired scientist from Michigan might never have built a groundbreaking new kind of microscope in his friend’s living room.

Born in Ann Arbor, Michigan, Eric Betzig had always been driven to do something transformative: ‘I grew up with Apollo and Star Trek and wanted to make a warp drive.’³⁵ After completing a doctorate at Cornell, he went on to work at Bell Labs, where the transistor and laser were invented and developed, and famous for its go-getting atmosphere.³⁶ Here Betzig worked on the improvement of microscopes, but after six years at Bell, he was fed up. The type of microscope he was working on seemed to him a technological dead end, and he thought others in his field were jump...