R Introduction

More than two centuries ago, a group of American colonists boldly declared their independence from a distant king at the same time that a young chemist in Paris started a much quieter revolution. In his laboratory next door to the king's Office of Gunpowder, Antoine-Laurent Lavoisier (1743-94) was performing a series of experiments that would eventually overturn the leading theory of life. His colleagues still believed that plants and animals were made of four basic elements—earth, air, water, and fire—which required a mysterious vital force to animate. In the 1770s that was the extent of people's knowledge of the chemical basis of life, and it was a scientific dead end.

Lavoisier discovered that air was composed of two substances: oxygen and nitrogen. Then he showed that oxygen could be re-combined with another substance—hydrogen—to produce water. Suddenly he understood that most liquids, gases, and solids—including living tissues—were mixtures that could be separated into more basic components and analyzed. Lavoisier eventually lost his head to the guillotine when the French toppled their monarchy. But by that time he had helped usher in the modern age of chemistry, which would lay the groundwork for a new approach to the study of life. Within 200 years of Lavoisier's work, scientists had identified the main building blocks of life—DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and proteins, lipids, and carbo-hydrates—and begun to understand the basic principles by which they work. Most of today's biology and biomedicine centers on studies of these molecules, and comprehending the nearly daily headlines about exciting developments in these fields requires a basic understanding of what they are and how they function. This book introduces the main molecules of life and how modern science investigates them. While the book touches on some general principles of chemistry and physics, it starts from the assumption that the reader has no background in these fields and is written for high school students and the general public.

The roles of DNA, RNA, and proteins finally began to become clear in the 1950s, and since then the pace of new discoveries has been very rapid. Today the entire genetic codes of humans and many other organisms have been read, and scientists are able to manipulate them by designing new genes or transferring them from one organism to another. These discoveries have ushered in a revolution that is beginning to have a tremendous impact on medicine and many other fields. Biology, chemistry, and physics are being drawn together into a new synthetic vision of life. Thanks to new technology, scientists are able to observe the dance of organic molecules as they work together in the cell, as parts of "molecular machines," and build tissues, organs, and whole organisms. Understanding how these levels of structure work together is not only answering fundamental questions about life; it also promises to help cure some of the major diseases that plague our species. Sometimes a person's entire existence is intimately linked to a single molecule. There are 3 billion letters in the genetic code in each of a person's cells, and thousands of diseases have now been traced to changes in single, key letters. Finding cures to genetic diseases will require a deep understanding of the mechanics of single molecules.

The Molecules of Life introduces how the chemistry and physics of organic molecules drive processes within cells and permit the construction of amazingly complex plants and animals. The first chapter describes some of the basic concepts needed to understand the field and discusses the methods used to explore the structures and behavior of DNA, RNA, and proteins. The rest of the book is devoted to stories about how these molecules carry out the business of life. Each chapter describes one of the major functions they perform: how the cell uses hereditary information stored in DNA; how signals are passed between cells and transmitted within them, and how molecules are delivered to specific locations, giving cells their shapes and forms. The final chapter is devoted to two of the most interesting areas of modern biomedical science: understanding how defects in molecules lead to disease and new molecular approaches to finding cures.

The Physics and Chemistry of Life: Basic Principles and Methods

An ancient, mystical Jewish tradition called Kabbalah teaches that the Bible holds all of the secrets of the universe, including power over life and death: If the words of the prophets could be read correctly, they could be used to perform miracles. According to a legend from the 16th century, the rabbi Judah Loew of Prague summoned this power to animate the golem, a man made of clay. Bringing the dead to life was also the theme of Mary Shelley's book Frankenstein, published in 1818, in which Victor Frankenstein assembles a monster out of the parts of dead bodies. Shelley did not describe how the body was brought to life, but in the introduction she claimed to have been inspired by the experiments of Luigi Galvani (173798), inventor of the battery. He had discovered that stimulating the nerves of dead frogs with electricity caused their legs to kick.

Today scientists know that the difference between inanimate and animate objects is not the result of incantations or electricity. Instead, life is made possible by interactions between organic molecules, chiefly DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and proteins. These molecules behave in certain ways because of their structures, which means how their atoms fit together to make three-dimensional building blocks that combine into larger

and larger structures, ultimately making a body. Very little was known about the structures or functions of these molecules until the 1950s. Then a series of major discoveries in chemistry and physics exposed their roles in cells, changing biology so dramatically that it needed a new name. In a speech given in 1938, Warren Weaver (1894-1978), director of natural sciences at the Rockefeller Foundation in New York, had already coined a term for it. Seeing that the focus of the life sciences was moving toward the fundamental chemical units within cells, he suggested the field should be called "molecular biology."

This chapter introduces the basic concepts and methods needed to understand how DNA, RNA, proteins, and other molecules work together to create living beings. The main discoveries that have been made about these molecules have come from a combination of methods from chemistry, physics, biology, and computer science. As such technologies continue to be created and improved, they are changing the way scientists see the structure and functions of molecules and their relationships to larger processes in organisms.

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