Linus Pauling Discovery

Meet the Scientist Linus Pauling (1901-1994) Do you know that different cells have certain unique proteins that have unique jobs? Muscles have proteins that contract, enabling the muscle cell to contract. Pancreas cells make the protein insulin, which regulates blood sugar levels. There are unique cells in the part of the brain called the hypothalamus that make small unique proteins that trigger the release of pituitary hormones. There are proteins in nerve cells that work to create new axon terminals and synapses that store your memories? How many other examples can you think of cells with specific proteins? A British journal included only Linus Pauling and Einstein from the 20th Century in their list of the greatest scientists in the history of the world. As you will see, Linus made major discoveries about chemical bonding and the structure of proteins―pretty heady stuff for a high-school dropout. He didn’t drop out because school was too hard. For him, it was too easy. Some scientists are born with a silver spoon in their mouth. But not Linus Pauling. From age 4 to 9, Linus lived in a small Oregon town, which was like an outpost in the Old West. The town had one street, lined by stores with false fronts on many of the buildings, as you see on cowboy movie sets today. Real cowboys lounged in front of the general store, and real Indians camped on the edge of town. His father, Herman, was a self-taught pharmacist and "medicine man." He ran a drug store in town. Maybe that is why Linus developed a lifelong interest in chemistry. The family was very poor. In fact, they had to move to town in order to get help from his mother's family. But Linus was happy. For him, life was cowboys and Indians. But Linus' happy childhood came to an end at age nine when his father died. His mother struggled alone to raise Linus and his two younger sisters. Linus found comfort in reading and collecting insects and minerals. By age nine, he had already read the entire Bible and Darwin's book, Origin of the Species. His father had made certain that Linus read important books. However, in those Figure 1. Linus as a young boy. From days good books were hard to find in a frontier town. https://paulingblog.files.wordpress.co Linus's interest in chemistry apparently came from his childhood experiences with a chemistry set that a playmate had. They spent many hours tinkering with it. They also spent many happy hours collecting rocks and minerals in a creek bed near town. Linus wondered about the internal structure of rocks and minerals. Many years later, he answered some of those questions in his research lab. By the time Linus was in high school, he had become devoted to learning. But he dropped out of high school at age 16, because he had taken all the science they offered. He felt that he could learn everything else on his own by reading. His mother let him drop out, but insisted that he stay home and help support the family. He did such jobs as delivering milk, running film projectors, and working in a shipyard. He got a good job as an apprentice machinist, but he knew he had to go to college to fulfill the potential he knew he had. Linus commented in later years that his mother did not seem to understand his interest in science and research. Similar comments have been echoed by many scientists about their parents and old school friends. Unlike many scientists who go to prestigious universities like Harvard, Oxford, and Cal Tech, Linus went to his local college, Oregon State Agricultural College (now Oregon State University), where he majored in chemical engineering. He supported himself by working at all sorts of jobs. He chopped wood, butchered cattle, and mopped floors for a quarter an hour. He even provided much of his family's financial support in addition to completely supporting himself. The college courses were not very challenging for Linus. He took the most difficult courses they had and still found time to join a fraternity, to participate in varsity track, and to work 25 hours a week. In his third year of college, he temporarily stopped classes in order to work full time. In the summer, Linus worked as a paving inspector, checking the blacktop and later analyzing it in the lab. This work yielded $125 per month and stimulated his interest in chemistry. He sent this money to his mother to place in the bank for him to use to return to school for the fall term. However, when it came time to go back to school, Linus discovered that his mother had become ill with pernicious anemia and had spent all the money. But, he was such a good student that the college gave him a job helping to teach. At age 18, he was teaching the sophomore class that he had taken the year before. In the fall of his senior year, Linus met the girl of his dreams. She was a home economics major taking the chemistry class he was teaching. He met her by calling out the simplest name on the class roster: "Miss Miller, will you please tell us what you know about ammonium hydroxide?" Miss Miller, it turned out, knew quite a bit about ammonium hydroxide, and it did not take long for her to know about Linus. In a few months, they became engaged. When he graduated as a chemical engineer, Linus' mother wanted him to come home and make money, perhaps as a secondary school teacher. However, from reading some of the textbooks in college, Linus realized that he wanted to do research. His abilities and test scores were good enough to get him admitted to a PhD program at Caltech (California Institute of Technology). He obtained his PhD at age 24. One reason he chose Cal Tech was because they had a professor, Alfred Noyes, who specialized in the study of bonding of atoms. After graduation, Linus went to Europe for three years to conduct research in laboratories that were at the cutting edge of research on atomic structure. He then went back to Cal Tech as a faculty member and rose to the rank of full professor in only three years. He was a science superstar. Linus became interested in atomic bonding, and quickly became the leading authority. In the same year in which he was promoted to professor, Pauling published the paper that made him famous: "The Nature of the Chemical Bond." At age 32, Linus was inducted into the National Academy of Science, becoming the youngest person ever to be admitted. In his research, Pauling used the latest ideas about atoms to explain how atoms share electrons and how this sharing formed a bond to make a molecule. This is common knowledge today, but we forget that we owe these ideas largely to Linus. This work was the basis for Linus receiving the Nobel Prize in chemistry in 1954. Pauling pioneered discoveries of the hydrogen bond. In water, for example, hydrogen loosely holds on to the oxygen atom by sharing its sole electron with an electron of oxygen. It can similarly bond with some other atoms. For other atoms, like carbon, for example, hydrogen bonding is very strong (such bonds are called covalent). Linus showed scientists how to study molecules and how to measure the angles, bond energies, and distances between the atoms in a molecule. One of his key ideas was to make a "footprint" of the structure of molecules from the pattern formed by a stream of x-rays as it passes between atoms in the molecules of a sample. The technique is called x-ray diffraction. Atoms in a molecule affect the path of the x-rays in such a way that the pattern reveals the inner structure of the molecule Before he was 40 years old, Linus had made Figure 2. Linus Pauling x-ray apparatus at Cal Tech. many major discoveries in chemistry. He showed how molecules participate in chemical reactions, how magnetic fields affect molecules, how atoms attract extra electrons, and how atoms become polarized with negative and positive regions. Early on, Linus' main interest was in the structure of proteins. He knew that the structure of any given protein depended on its environment. For example, consider the egg-white protein of eggs. When you break a fresh egg, do you see any whiteness? No. But when it starts to fry, all but the yolk turns white. What is happening here? The answer is that heat breaks certain bonds to change the structure so that it reflects a white color to your eyes. This process is called "denaturation," that is, the natural structure of the protein is changed. Linus was interested in natural structure of proteins, because it is that natural structure that governs protein functions. Once he had mastered understanding of the hydrogen bond, Linus was poised to pursue his other interest: the structure of proteins. Proteins interested Pauling also because they controlled most everything happening inside the cell. For example, biochemical reactions are promoted by proteins that we call enzymes. In mitochondria of eukaryotic cells, for example, a variety of enzymes control the various reactions, known as the Krebs cycle, that harvest much of chemical bond energy from a break-down product of glucose. These enzymes also exist in prokaryotes, but the reactions occur in the cytoplasm. Figure 2. Linus Pauling worked with ball-andstick models of atoms to illustrate the threedimensional structure of molecules. Linus was especially interested in the chemical bonding of atoms within proteins. Originally, this interest was because he knew that enzymes attached in very specific ways to influence chemical reactions either to join molecules together or break them apart. He wondered what created the specificity of binding. There were other reasons why Linus knew proteins were really important. For example, certain proteins interact with hormones and neurotransmitters to mediate their actions on cells. They do this by selectively binding to certain proteins in the cell membrane. You might think of these "receptors" as corks floating in the sea of the membranes lipid bilayer. Proteins are even involved in the function of genes. One class of proteins, histones, forms a coating around DNA to influence which genes are turned on or off. Finally, other kinds of proteins are anchored in eukaryotic cell membranes and influence cell-to-cell interactions. (Note: the Real Research Review on concussion deals with the proteins that keep nerve cells stuck together so they can communicate with each other). In 1951, Pauling reported that some 15 years of experiments in his lab on the structure of proteins indicated that proteins had complex three-dimensional structure. In the simplest, primary form, other investigators had shown that proteins contained chains of amino acids bonded together. Think of it like a string of beads, with some strings attached to other strings by sulphur bonds (S in Fig.3.) Figure 4. Components of a protein. All proteins are made of many amino acids (shown here with abbreviated names: Ala, Lys, Pro, etc.) linked together in a chain. Some of the amino acids in one chain get tied with amino acids in another chain by sharing bonds with sulfur atoms (S). All that was known at the time was that proteins had a chain-like structure shown above. Linus and a colleague, Robert Corey, showed how the amino acids were constructed and how hydrogen bonds forced the chain into coils, appearing much like the way a telephone cord coils (Fig. 5). What they showed was that the hydrogen atom in one amino acid would form a weak bond with another amino acid four down the chain. This bonding twists the chain into a coil, like a coiled telephone wire. The twist is right to left, creating a secondary structure that is called an alpha helix. A further change in three-dimensional structure is imposed when sections of a coil line up against each other to form sheet-like structure. Finally, a tertiary structure is imposed when certain amino acids that are electrically charged and others that lack a charge caused stacking and folding to create a glob-like structure (Fig.6). The three-dimensional tertiary structure has pockets and protrusions of various surface electrical charges that govern how the protein interacts with other molecules. Still further, quaternary structure, is imposed if the protein consists of more than one amino acid chain. This complex structure dictates how that hormones, neurosecretions, and drugs act on cells, by binding at specific locations in the protein. Figure 5. Telephone-cord analogy of protein structure. Left: helix coiling to form secondary structure. Figure6. Folding and stacking to create tertiary structure. These monumental discoveries were not enough for Pauling. By now, everybody knew that hydrogen bonds had to play a role in DNA structure and function. Linus took on the challenge from a British team consisting of James Watson and Francis Crick. All of them used Pauling’s bond-length data and ideas of coiling induced by hydrogen bonding and the approach of x-ray diffraction to decode the structure of DNA. The problem for Linus was that his resounding success with protein structure made him too optimistic about his prowess for solving the DNA problem. In a few months he dashed off his conclusion that DNA was a triple helix—a serious mistake. He apparently forgot that it took him some 15 years to unravel protein structure. He would not have made this mistake if he had seen the DNA x-rays that the British group had. He had asked to see them, but they would not share their pictures with him. In their famous book, The Double Helix, Watson and Crick describe the race to be the first to understand DNA structure and, in the process, genes. They freely admit that the race was with Linus, and they used his explanation of chemical bonding as the basis for arriving at the correct structure of DNA. Linus came very close to winning a second Nobel Prize in chemistry. One of the students that Linus trained, William Lipscomb, also won a Nobel Prize. One reason for Linus Pauling's lifetime of success is explained by an exchange he had with a high school student: "How do you get so many great ideas?" the student asked. Linus replied, "To get good ideas, the important thing is to have lots of ideas." He believed that if you were wrong, some smart scientist would soon show the idea to be wrong. This, of course, happened to him, because he was wrong about the structure of DNA. But if you are right, you may have an idea that nobody else would have thought of. Pauling got that right for protein structure.