How bacteria solved the mystery of inheritance - Works in Progress Magazine

In the 1940s, scientists made a discovery now fundamental to biology: genes are encoded in DNA. The story involves bacteria, dead mice, and a kitchen cream separator.

In the TV miniseries Lessons in Chemistry, chemist Elizabeth Zott presents her research on de novo nucleotide synthesis to a panel of suited and bespectacled colleagues. ‘Unlike the amino study group’, says Zott, ‘we are starting with the basic assumption that DNA, not protein, is the basic foundation of life’. The panel scoffs at this apparently ridiculous claim. The head of her department dismisses DNA as a ‘dead end’ and Zott’s method for making it from scratch as ‘nothing more than a party trick’. Zott’s proposal is rejected.<br>Zott was a fictional character, but the scientific debate was real. The fact that DNA encodes genetic information is now taught in biology classrooms worldwide, but until the late 1940s it was a fringe idea. Most scientists instead believed genes were made of protein. James Watson and Francis Crick are now household names for discovering DNA’s double helix structure, but the importance of that discovery rested on earlier work establishing that DNA, not protein, carries genetic information. The scientists who made this more fundamental discovery have often been overlooked.

Get the print magazine

Subscribe for $100 to receive six beautiful issues per year.

Subscribe

The organisms that enabled this discovery were similarly unexpected: bacteria. At the time, few scientists, even microbiologists, thought that bacteria could offer anything of value to genetics. Many doubted they even had genes! Those primitive blobs swimming under microscope lenses were thought to be nothing more than tiny bags of enzymes – a totally different kind of life. So it came as a surprise when the pivotal discovery of modern genetics emerged not from a geneticist but a microbiologist.<br>What parents pass on<br>Evolution by natural selection requires that organisms inherit characteristics from their parents. Heredity wasn’t a new idea when Darwin published On the Origin of Species in 1859. Farmers had exploited it for centuries, selectively breeding livestock and crops for desirable traits. But neither Darwin nor anybody else at the time could explain how traits were passed down from parents to offspring.<br>Inheritance was full of mysterious patterns: skin color tended to be a blend of the parents’, eye color could differ from either, and sex only matched one. How could such variation be explained? There were plenty of theories – including Darwin’s own provisional hypothesis of ‘pangenesis’, in which every cell in the body shed tiny particles called ‘gemmules’ that traveled to the reproductive organs and were passed to offspring – but nobody had persuasive evidence to support one over another.<br>Nobody, that is, except a little-known Austrian monk named Gregor Mendel. Mendel’s experiments with pea plants showed that inheritance depended on discrete factors transmitted from parents to offspring. Some traits, such as peas being wrinkled rather than smooth, could disappear and then pop up again in later generations – an impossibility if traits were a simple blend of both parents. Mendel’s work went unnoticed in his lifetime, but in 1900 three botanists independently rediscovered and confirmed his findings. By 1909 these factors had been given a name: genes. But the original meaning differed significantly from today’s. Wilhelm Johansen, who coined the term, explicitly rejected the idea that genes were physical particles, instead conceptualizing them as a chemical or physiological process.<br>The geneticist Thomas Hunt Morgan hypothesized that genes might either be a ‘chemical molecule’ or a ‘fluctuating amount of something’, but concluded: ‘I see at present no way of deciding’. By 1933, the confusion hadn’t resolved. Morgan wrote in his Nobel Prize lecture: ‘There is no consensus of opinion amongst geneticists as to what the genes are – whether they are real or purely fictitious’.<br>A common thread was the assumption that genetic information must be encoded in protein, not DNA. Proteins are made from long chains of simpler molecules called amino acids, joined in sequence like beads on a string. With 20 different amino acids for each position, like letters in an alphabet, even short protein sequences can produce an astronomical number of combinations. Meanwhile, the alphabet of DNA has only four ‘letters’, made from the four simpler molecules called nucleotides that join in sequence to make strands of DNA. Today, a four-letter alphabet may seem luxurious compared to the binary language of computers (1 and 0), but while information theory would eventually come to influence biologists’ thinking, this would not take hold for a few decades more.<br>Further, the best evidence suggested that the four letters of DNA were present in equal proportion in every organism, and arranged in repeated...