medium to medium to large large small INSTANT small GENIUS WHAT IT’S MADE OF THE HUNT FOR NESSIE HOW IT CAN SOLVE CRIMES DNA HOW DO WE KNOW? How do we know? THE STRUCTURE OF DNA BY KATHERINE NIGHTINGALE Before the discovery of the gene-carrying molecule DNA, we had no idea of the fundamental mechanics of life. How we described its iconic double helix form is one of the greatest scientific achievements HE YEAR IS 1869 and a enormous diversity of life. As late as that characteristics are inherited in young researcher is toiling the 1940s, most scientists thought that discrete units. When his research away in a laboratory in an proteins – large biological molecules was rediscovered in the early 1900s, old castle in Germany, on which come in all shapes and sizes a flurry of work determined that course to make a remarkable – were the only substances complex these units, or genes, must be in discovery. The lab studies enough to be the agents of heredity. chromosomes. But what were they the composition of cells, Chromosomes, the coils of DNA made of – DNA or protein – and what and Friedrich Miescher is and protein that contain genes, had did they look like? analysing relatively simple first been spotted in cells in the early A German doctor named Albrecht T white blood cells, which 1840s. Later that century, researchers Kossel made some of the first steps he extracts from the pus in a local saw them double in number and then towards finding out. Working under clinic’s discarded bandages. Having halve again into separate ‘daughter’ Hoppe-Seyler in the late 1800s, he exhausted his efforts in classifying cells during cell division. In 1865, discovered DNA’s ‘bases’ (the chemical the cell’s proteins, Miescher turns his the Austrian monk Gregor Mendel opposite of acids) and named them attention to another substance that used pea plants to explore theories thymine (T), adenine (A), cytosine keeps appearing in his samples. He on genetic inheritance, proposing (C) and guanine (G). This work was finds it odd – an acid that contains continued by Phoebus Levene, a phosphorus – and declares he has Lithuanian researcher driven to New discovered a completely new type of York in the early 1890s because of substance. Nuclein, or DNA as we now anti-Semitism in his adopted home call it, has been found. of St Petersburg. For three decades Like any good sceptical scientist, from the mid-1890s, Levene studied Miescher’s boss Felix Hoppe-Seyler the structure of DNA, identifying > IN A NUTSHELL is wary, and waits to repeat the its other components: a sugar called experiments before, two years later, deoxyribose and phosphate groups. allowing publication. But this delay He also discovered that DNA is It’s the key to all life on Earth: a would turn out to be negligible; it was made up of units that he called simple molecule known as DNA that many more decades before scientists nucleotides. Each of these is made sits in every cell of your body. It saw the importance of DNA. Misecher up of a sugar, phosphate group and took several breakthroughs to realise its true form and understand went on to find DNA in a variety of base, and they are linked by bonds The double helix of DNA: the extent of its role in biology, cells, but even he couldn’t believe Gregor Mendel cross-bred different coloured peas in what between the phosphate groups Nature’s elegant solution that just one substance generated the were some of the earliest experiments into heredity of one nucleotide and the sugar to file the blueprint of life triggering a scientific revolution. PHOTO: SCIENCE PHOTO LIBRARY, THINKSTOCK LIBRARY, SCIENCE PHOTO PHOTO: How do we know? How do we know? of the next, forming a so-called to determining DNA’s structure. His more practically minded father was headed by William Astbury, who backbone. But this was as far as William Henry Bragg, a physicist at built the first X-ray spectrometer – a began working at the University of his correct findings went. He thought the University of Leeds, and his son device for shooting a narrow beam of Leeds in 1928, having studied under CAST OF It took the efforts of these science greats that each DNA molecule contained William Lawrence Bragg, a researcher X-rays at substances – and together William Henry Bragg at the Royal CHARACTERS to finally realise the structure of DNA only four nucleotides, one with each at the Cavendish Laboratory in they tested the theory on salt crystals. Institution. In 1937, Astbury was type of base, linked together in a ring Cambridge, laid the foundations for In these experiments, they placed a sent samples of calf DNA by Swedish he called a ‘tetranucleotide’. the field of X-ray crystallography photographic plate behind the crystal, researcher Torbjörn Caspersson. A William Astbury Levene’s tetranucleotides were too between 1912 and 1914. onto which the scattered X-rays few years previously, Caspersson had (1898-1961) was a simple to carry a genetic code, and so They were inspired by the work would produce a characteristic pattern. shown that DNA is a polymer – a long British molecular reinforced the idea that proteins must of Max von Laue, who discovered in William Lawrence Bragg came up chain of nucleotides – rather than the biologist and physicist be the hereditary agent. Revealing 1912 that X-rays bend when they pass with an equation, known as Bragg’s short lengths Levene had suggested. who spent much DNA’s hidden complexity was going through crystals, substances with highly Law, which allowed them to work Astbury’s PhD student, Florence of his working life to require a closer look. While Levene ordered structures. The younger backwards from the patterns to deduce Bell, took the first of hundreds of in Leeds. His work was unravelling the complexities of Bragg reasoned that because they have the crystal’s structure. The pair won a X-ray diffraction pictures of DNA that focused originally DNA in New York, across the Atlantic ordered patterns of atoms, the way the Nobel Prize in 1915. year. The fact that it produced a on the structure of a father-and-son team was establishing X-rays bend through crystals would One of the first groups to apply this pattern at all suggested that DNA had Francis Crick proteins in textiles but, a technique that would prove key reveal something about their structure. technique to biological molecules a ‘solvable’ structure. Astbury and Bell’s (1916-2004) was born along with his PhD pictures look like smears compared to near Northampton to student Florence Bell, the clear images that Rosalind Franklin the owner of a shoe he took the first X-ray produced in the early 1950s, but they factory and became a photographs of DNA did reveal one crucial fact: the distance British biophysicist and in 1937. THE KEY It was a photo taken by biophysicist and crystallographer Rosalind Franklin that held the between the bases in the DNA molecule. molecular biologist. EXPERIMENT key to determining the make-up and structure of the DNA molecule In 1938, Astbury used the images to After co-discovering propose a structure for DNA in which the structure of the bases are stacked on top of each DNA, he went on to other, but the pictures weren’t detailed determine how DNA enough for him to get much further. codes for proteins, before venturing Maurice Wilkins ROSALIND FRANKLIN’S KEY experiment – the into neuroscience. (1916-2004) was a results of which Watson glimpsed – was a CLUES IN BACTERIA British physicist and series of painstaking X-ray crystallography Meanwhile, back in the US, a medical molecular biologist experiments with DNA samples containing researcher named Oswald Avery was who was born in New different amounts of water. The most busy refining a 1928 experiment by Zealand. As well as famous outcome of this is May 1952’s a British microbiologist called Fred his DNA research, he ‘photo 51’, which revealed key details Griffith. He had shown that it was worked in fields such as about the structure of DNA. possible to make harmless bacteria and radar and microscopy. The more a feature is repeated their progeny dangerous by mixing He remained at King’s within a structure, the more the them with virulent bacteria, suggesting College until his film will be bombarded with that something was being transferred retirement in 1981. X-rays diffracted in the same from the virulent to harmless bacteria. way, and the darker the Avery and his colleagues deliberately corresponding patch in the created conditions in which only DNA Rosalind Franklin image. The large dark patches – not protein – could be transferred. (1920-1958) was born at the top and bottom of the In this way, they determined that only in London to a rich picture represent DNA’s bases, DNA could pass on traits. Though Jewish family. The and the X-shaped blobs indicate many would refuse to believe it, DNA X-ray crystallographer a helix. The arms of the cross had been strongly implicated as the and biophysicist represent the planes of carrier of inheritance, and science had provided much of the James Watson symmetry in a helix viewed from the tools to find out what it looked experimental evidence (1928- ) is an American the side; the ‘zig’ and the ‘zag’ of like. The stage was set for the race to for the structure of geneticist and molecular its turns. There are 10 spots on find the structure of DNA in the 1950s DNA before switching biologist born in each arm of the cross before you – only not everyone knew it was a race.