The labour and loss that went into understanding genetics: Read Siddhartha Mukherjee's 'The Gene'

Genetics is accepted as a science now, but the road that led to this acceptance was an arduous one. From Aristotle to Charles Darwin, philosophers and scientists across the world developed theories on why humans reproduce the way they do and why like always does not beget like. A few like Darwin rose to fame, while others such as Gregor Mendel were ignored for decades.

In a compelling tale, Pulitzer Prize-winner Siddhartha Mukherjee weaves together the discoveries made by various scientists as they sought to understand the building blocks of human life. Read an extract from The Gene...

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As Darwin was beginning to write his opus on evolution in the spring of 1856, Gregor Mendel decided to return to Vienna to retake the teacher’s
exam that he had failed in 1850. He felt more confident this time. Mendel had spent two years studying physics, chemistry, geology, botany,
and zoology at the university in Vienna. In 1853, he had returned to the monastery and started work as a substitute teacher at the Brno Modern
School. The monks who ran the school were very particular about tests and qualifications, and it was time to try the certifying exam again. Mendel applied to take the test.

Unfortunately, this second attempt was also a disaster. Mendel was ill, most likely from anxiety. He arrived in Vienna with a sore head and a
foul temper—and quarreled with the botany examiner on the first day of the three-day test. The topic of disagreement is unknown, but likely con-cerned species formation, variation, and heredity. Mendel did not finish the exam. He returned to Brno reconciled to his destiny as a substitute
teacher. He never attempted to obtain certification again.

Late that summer, still bruising from his failed exam, Mendel planted a crop of peas. It wasn’t his first crop. He had been breeding peas inside the glass hothouse for about three years. He had collected thirty-four strains from the neighboring farms and bred them to select the strains that bred “true”—that is, every pea plant produced exactly identical offspring, with the same flower color or the same seed texture. These plants “remained constant without exception,” he wrote. Like always begat like. He had collected the founding material for his experiment.

The true-bred pea plants, he noted, possessed distinct traits that were hereditary and variant. Bred to themselves, tall-stemmed plants generated
only tall plants; short plants only dwarf ones. Some strains produced only smooth seeds, while others produced only angular, wrinkled seeds.
The unripe pods were either green or vividly yellow, the ripe pods either loose or tight. He listed the seven such true-breeding traits:

1. the texture of the seed (smooth versus wrinkled)
2. the color of seeds (yellow versus green)
3. the color of the flower (white versus violet)
4. the position of the flower (at the tip of the plant versus the branches)
5. the color of the pea pod (green versus yellow)
6. the shape of the pea pod (smooth versus crumpled)
7. the height of the plant (tall versus short)

Every trait, Mendel noted, came in at least two different variants. They were like two alternative spellings of the same word, or two colors of the same jacket (Mendel experimented with only two variants of the same trait, although, in nature, there might be multiple ones, such as white-,
purple-, mauve-, and yellow-flowering plants). Biologists would later term these variants alleles, from the Greek word allos—loosely referring
to two different subtypes of the same general kind. Purple and white were two alleles of the same trait: flower color. Long and short were two alleles of another characteristic—height.

The purebred plants were only a starting point for his experiment. To reveal the nature of heredity, Mendel knew that he needed to breed hybrids;
only a “bastard” (a word commonly used by German botanists to describe experimental hybrids) could reveal the nature of purity. Contrary to later belief, he was acutely aware of the far-reaching implication of his study: his question was crucial to “the history of the evolution of organic forms,” he wrote. In two years, astonishingly, Mendel had produced a set of reagents that would allow him to interrogate some of the most important features of heredity. Put simply, Mendel’s question was this: If he crossed a tall plant with a short one, would there be a plant of
intermediate size? Would the two alleles—shortness and tallness—blend?

The production of hybrids was tedious work. Peas typically self-fertilize. The anther and the stamen mature inside the flower’s clasplike keel, and the pollen is dusted directly from a flower’s anther to its own stamen. Cross-fertilization was another matter altogether. To make hybrids,
Mendel had to first neuter each flower by snipping off the anthers—emasculating it—and then transfer the orange blush of pollen from one flower to another. He worked alone, stooping with a paintbrush and forceps to snip and dust the flowers. He hung his outdoor hat on a harp, so that every visit to the garden was marked by the sound of a single, crystalline note. This was his only music.

It’s hard to know how much the other monks in the abbey knew about Mendel’s experiments, or how much they cared. In the early 1850s, Mendel had tried a more audacious variation of this experiment, starting with white and gray field mice. He had bred mice in his room—mostly undercover— to try to produce mice hybrids. But the abbot, although generally tolerant of Mendel’s whims, had intervened: a monk coaxing mice to mate to understand heredity was a little too risque, even for the Augustinians. Mendel had switched to plants and moved the experiments to the hothouse
outside. The abbot had acquiesced. He drew the line at mice, but didn’t mind giving peas a chance.

By the late summer of 1857, the first hybrid peas had bloomed in the abbey garden, in a riot of purple and white. Mendel noted the colors of the
flowers, and when the vines had hung their pods, he slit open the shells to examine the seeds. He set up new hybrid crosses—tall with short; yellow with green; wrinkled with smooth. In yet another flash of inspiration, he crossed some hybrids to each other, making hybrids of hybrids.

The experiments went on in this manner for eight years. The plantings had, by then, expanded from the hothouse to a plot of land by the abbey—
a twenty-foot-by-hundred-foot rectangle of loam that bordered the refectory, visible from his room. When the wind blew the shades of his window
open, it was as if the entire room turned into a giant microscope. Mendel’s notebook was filled with tables and scribblings, with data from
thousands of crosses. His thumbs were getting numb from the shelling. “How small a thought it takes to fill someone’s whole life,” the philosopher Ludwig Wittgenstein wrote. Indeed, at first glance, Mendel’s life seemed to be filled with the smallest thoughts. Sow, pollinate, bloom, pluck, shell, count, repeat. The process was excruciatingly dull—but small thoughts, Mendel knew, often bloomed into large principles. If the powerful scientific revolution that had swept through Europe in the eighteenth century had one legacy, it was this: the laws that ran through nature were uniform and pervasive. The force that drove Newton’s apple from the branch to his head was the same force that guided planets along their celestial orbits. If heredity too had a universal natural law, then it was likely influencing the genesis of peas as much as the genesis of humans. Mendel’s garden plot may have been small—but he did not confuse its size with that of his scientific ambition.

“The experiments progress slowly,” Mendel wrote. “At first a certain amount of patience was needed, but I soon found that matters went better
when I was conducting several experiments simultaneously.” With multiple crosses in parallel, the production of data accelerated. Gradually,
he began to discern patterns in the data—unanticipated constancies, conserved ratios, numerical rhythms. He had tapped, at last, into heredity’s
inner logic.

Extracted from Siddhartha Mukherjee's The Gene, with permission from Penguin India