In the early 1900s, Thomas Hunt Morgan (1866–1945), a biologist who studied fruit flies, was about to make his contribution to the science of genetics. The scientific name for the common fruit fly is Drosophila melanogaster (D. melanogaster). Morgan found that when he crossed a red-eyed female fly with a white-eyed male fly, all of their offspring had red eyes. But when he took some of these red-eyed offspring and crossed them with their siblings, the white-eyed trait reappeared in the offspring. Morgan noticed that all of these white-eyed F2 generation flies had something in common—they were all male. From the results of his experiments, Morgan determined that eye color in the fruit fly is linked specifically to the X chromosome.



Morgan also proposed the idea that genes are lined up, one after another, on a chromosome. His work firmly established the idea that traits are inherited via chromosomes. In 1933, Morgan was awarded the Nobel Prize in Physiology or Medicine for his discovery of how chromosomes are involved in heredity. In 1913, a student of Morgan’s named Alfred Sturtevant (1891–1970) created a genetic map of the D. melanogaster genome. This was the world’s first genetic map. Sturtevant published the map for his Ph.D. thesis.

Thomas Hunt Morgan studied fruit flies—which are easy
to breed in large numbers and have therefore been used for years
in genetic studies—and learned that eye color is linked to the X
chromosome in fruit flies.

Alfred Sturtevant was not the only student of Morgan’s who was studying D. melanogaster. Hermann Joseph Muller (1890–1967) also studied in Morgan’s laboratory. But Muller got tired of waiting for the fruit fl ies to mutate on their own. In 1927, Muller tried to use heat to increase the rate of mutation. However, he was unsatisfi ed with the number of mutations that resulted. So he exposed the flies to X-ray radiation. In that experiment, Muller not only got the mutations he was looking for, but he also proved that exposure to radiation could change genetic material.

After these experiments, Muller became a vocal advocate for limiting unnecessary exposure to radiation. He warned about radiation’s link to increased genetic mutations and cancer. In 1946, Muller was awarded the Nobel Prize in Physiology or Medicine for his discovery that X-rays produce genetic mutations.

The first American woman to win an unshared Nobel Prize was Barbara McClintock (1902–1992), an American geneticist who was recognized for her discovery of “jumping genes.” McClintock did her experiments on maize, or corn, in the mid-1940s. She was studying the color variations on a single cob of corn and found that two genes, called “controlling genes,” determined the color of each kernel. However, these controlling genes did not always show up in the same place on the corn’s chromosomes, and kernel color also depended on where these controlling genes ended up on the chromosome. Transposable genes, or transposons, are sequences of DNA that can move from one region of a chromosome to another. They can even move to a different chromosome entirely. Because of their mobility, transposable genes have also become known as “jumping genes”.

Although McClintock discovered jumping genes in the 1940s, her research was largely ignored for several decades because her ideas about moving genes did not agree with anything known about genes at the time. Finally, in the 1970s and early 1980s, better scientific techniques were discovered that allowed other scientists to confirm McClintock’s findings. In 1983, McClintock was awarded the Nobel Prize for Physiology or Medicine for her discovery of transposons.

Because transposons can disrupt normal gene function if they land in the wrong place on a chromosome, scientists today suspect that transposons may be responsible for some genetic diseases such as hemophilia, leukemia, and breast cancer.

Scientists in the 1830s and early 1840s knew that chromosomes were passed from one generation to the next, but they did not know what chromosomes were made of. This mystery started to unravel in 1869, when Johann Friedrich Miescher (1844–1895), a Swiss biochemist, was doing experiments on white blood cells that he obtained from the pus-filled bandages of wounded soldiers in a local hospital. During these experiments, Miescher added some chemicals to the white blood cells, which resulted in the formation of a white precipitate (a solid that is separated from a solution or suspension by a chemical or physical change). This precipitate was a new substance, and Miescher believed, correctly, that this new chemical came from the nuclei of the white blood cells. He named the new chemical nuclein.

Miescher went on to show that nuclein could be isolated not just from white blood cells, but also from many other types of cells. He discovered that nuclein was slightly different from the organic molecules that scientists had found so far. Up until this moment, organic molecules were known to contain the elements carbon, hydrogen, oxygen, and nitrogen. But nuclein also contained the element phosphorous. Miescher was not exactly sure what role nuclein played in the body, but by the end of his scientific career, he suspected that it had something to do with fertilization.

Miescher’s discovery was the first crude extract of the DNA molecule. His extract also contained proteins. Over time, other scientists discovered ways to separate out the proteins and leave behind just the DNA molecule. About 10 years after Miescher’s discovery of nuclein, Albrecht Kossel (1853–1927), a German biochemist, discovered that nuclein contained four organic bases—adenine (A), thymine (T), guanine (G), and cytosine (C)—a discovery that earned him the Nobel Prize in Physiology or Medicine in 1910.

A Russian-American chemist named Phoebus Levene (1869–1940) was working with Kossel, and he identified the sugar in nuclein as deoxyribose. Eventually, nuclein was renamed for its structure (a ribose-based, sugar-phosphate backbone) and its properties (its acidic nature). Its new name was deoxyribonucleic acid, or DNA. Then in 1943, Oswald Avery (1877–1955), an American researcher, discovered that the DNA molecule actually carried genetic information. Before Avery’s discovery, scientists thought hereditary information would be carried by a protein, not a nucleic acid. But, by the late 1940s, most scientists were convinced that the DNA molecule did indeed carry genetic information on to the next generation.

Part of the mystery unraveled again in 1950, when Erwin Chargaff (1905–2002) discovered that while the arrangement of the nitrogen bases in DNA (adenine, thymine, guanine, and cytosine) varied, the ratio between certain bases was always 1 to 1. The amount of adenine always equaled the amount of thymine, and the amount of guanine always equaled the amount of cytosine. This led to the idea that adenine always pairs with thymine and guanine always pairs with cytosine in the DNA molecule. This idea later became known as “Chargaff’s Rules.”

Meanwhile, in the early 1950s, Maurice Wilkins (1916–2004) and Rosalind Franklin (1920–1958) were also studying the DNA molecule. They were trying to figure out the shape of the DNA molecule by taking pictures of it using a technique called X-ray diffraction. This technique shows the structure of a substance when X-rays hit the atoms in the substance and bounce off of them in specific patterns. Franklin thought that her X-ray diffraction patterns showed that the DNA molecule was a helix, but she was not entirely sure. She wanted to do more testing. But in 1953, Wilkins decided (many scientists believe without Franklin’s knowledge or consent) to show James Watson (b. 1928), an American geneticist, Franklin’s images of the DNA molecule.

That same year, Watson and Francis Crick (1916–2004), a British biophysicist, put all the pieces together and determined that the DNA molecule was indeed a helix. In fact, they proposed that the DNA molecule was actually made up of two helixes—one going up and the other going down. This formed the backbone of a double helix. But the X-ray images of the DNA molecule also showed that the helixes were always at the same distance from one another. So what kept them from collapsing into one another and tangling?

In 1952, Crick had learned of Chargaff ’s base pair research that showed adenine and thymine paired in a 1 to 1 ratio and so did cytosine and guanine. And Watson, while playing with a molecular model of the nitrogen bases, realized that an adenine-thymine pair and a cytosine-guanine pair would have identical shapes. So in 1953, Watson and Crick proposed that the bases paired up in the middle of the double helix, keeping the chains at a constant distance from each other (Figure 4.3).

Watson and Crick went on to suggest that the way the DNA molecule makes a copy of itself during cell division is to “unzip” the double helix. Another strand of DNA forms that is complementary to the bases on the “unzipped” part of the molecule, and an exact copy of the DNA molecule is made (except for the occasional mistake in copying). In 1957, experiments done by Matthew Meselson (b. 1930) and Frank Stahl (b. 1929) proved Watson and Crick correct—this was, indeed, the way DNA replicated itself. In 1962, the Nobel Prize was given to Watson, Crick, and Wilkins, even though Franklin had provided a key piece of experimental evidence. Unfortunately, Rosalind Franklin had died of cancer in 1958 at the age of 37. The Nobel Prize is only awarded to the living, so she could not receive part of the prize.