It's in Your DNA

From Discovery to Structure, Function and Role in Evolution, Cancer and Aging

Eugene Rosenberg

• Publisher: Academic Press
• Year: 2017
• ISBN:
  9780128125687
• Topic: Biological Sciences
• Subtopic: Evolution
• Index: Biological Sciences

It's in Your DNA: From Discovery to Structure, Function and Role in Evolution, Cancer and Aging describes, in a clear, approachable manner, the progression of the experiments that eventually led to our current understanding of DNA. This fascinating work tells the whole story from the discovery of DNA and its structure, how it replicates, codes for proteins, and our current ability to analyze and manipulate it in genetic engineering to begin to understand the central role of DNA in evolution, cancer, and aging.

While telling the scientific story of DNA, this captivating treatise is further enhanced by brief sketches of the colorful lives and personalities of the key scientists and pioneers of DNA research. Major discoveries by Meischer, Darwin, and Mendel and their impacts are discussed, including the merging of the disciplines of genetics, evolutionary biology, and nucleic acid biochemistry, giving rise to molecular genetics.

After tracing development of the gene concept, critical experiments are described and a new biological paradigm, the hologenome concept of evolution, is introduced and described. The final two chapters of the work focus on DNA as it relates to cancer and gerontology.

This book provides readers with much-needed knowledge to help advance their understanding of the subject and stimulate further research. It will appeal to researchers, students, and others with diverse backgrounds within or beyond the life sciences, including those in biochemistry, genetics/molecular genetics, evolutionary biology, epidemiology, oncology, gerontology, cell biology, microbiology, and anyone interested in these mechanisms in life.

• Highlights the importance of DNA research to science and medicine
• Explains in a simple but scientifically correct manner the key experiments and concepts that led to the current knowledge of what DNA is, how it works, and the increasing impact it has on our lives
• Emphasizes the observations and reasoning behind each novel idea and the critical experiments that were performed to test them

Chapter 1

The Beginning

Abstract

The DNA story begins in 1871 with the isolation of DNA from pus cells by the Swiss scientist Friedrich Miescher, working in the laboratory of the eminent biochemist Felix Hoppe-Seyler in Germany. Since the material was isolated from nuclei, he called it “nuclein.” When nuclein was purified, it became clear that it was an acid, and it was then referred to as nucleic acid. Just prior to Miescher’s publication on his findings, Charles Darwin published his book Origin of Species by Natural Selection and Gregor Mendel published the laws of inheritance. The circumstances of these three discoveries and their impacts are discussed.

Keywords

Miescher

nuclein

DNA discovery

The Past—the dark unfathomed retrospect!

The teeming gulf—the sleepers and the shadows! The past!

The infinite greatness of the past!

For what is the present after all but a growth out of the past?

—Walt Whitman, Passage to India in Leaves of Grass

The past is never dead. In fact, it’s not even past.

—William Faulkner in Requiem for a Nun

Theoretical physicists hypothesize that the universe began with a colossal explosion often referred to as the Big Bang theory, approximately 13.8 billion years ago. The key idea is that the universe is expanding. Consequently, the universe must have been denser and hotter in the past. In particular, the big bang theory suggests that at some moment all matter in the universe was contained in a single point, which is considered the beginning of the universe. After the initial expansion, the universe cooled sufficiently to allow the formation of subatomic particles, including protons, neutrons, and electrons. The gases and dust from that explosion produced the earliest generation of stars, and over a period of billions of years, the stars exploded, and their debris formed other stars and planets. Our solar system was formed in this way 4–5 billion years ago. During the next billion years, the molten Earth cooled, forming a hardened outer crust.

About 3.8 billion years ago, earth’s atmosphere consisted of gases, such as hydrogen (H₂), nitrogen (N₂), hydrogen sulfide (H₂S), methane (CH₄), and water (H₂O). As the temperature decreased, water vapor condensed causing millions of years of torrential rains, during which time the oceans formed. Gases and water from the earth’s core came to the surface through volcanoes. Ultraviolet radiation bathed the earth, and the simple compounds interacted with one another to form more complex organic molecules, including the building blocks for life. Organic molecules are those containing carbon and that are typically found in living systems.

How organic molecules formed the first living cells, that is, the origin of life, remains one of the most challenging unsolved problems in biology. The best fossil evidence indicates that microorganisms first appeared on Earth about 3.8 billion years ago and the first multicellular creatures about 1 billion years ago. Thus, microbes were the only living organisms on this planet for more than 2 billion years. During this time, the microbes evolved most of the processes we associate with life, stored this information in the form of DNA, and passed it on to plants and animals. The vast majority of DNA information in humans (Homo sapiens), which first evolved about 200,000 years ago, is remarkably similar to the DNA of microbes.

It is truly amazing that from the big bang to atoms and molecules, to stars and planets, to microbes and the evolution of more complex animals and plants, and finally to humans, we can now begin to understand these processes. This is the DNA story.

Like a river, every story, even a scientific story, has a source, a beginning. If you ask the question: who discovered DNA? Most educated individuals, including many scientists, will answer “Watson and Crick, of course!” However, the story of DNA actually begins with the Swiss scientist Johann Friedrich (Fritz) Miescher in 1871.

Miescher was born in Basel, Switzerland, in 1844, the eldest of five sons of Friedrich Miescher-His, professor of pathologic anatomy at Basel University, and a successful practicing gynecologist. The Miescher family was well-respected and part of the intellectual elite in Basel. Friedrich’s uncle, Wilhelm His, who lived in the same house as the Mieschers, was professor of anatomy and physiology, distinguished for his work in embryology and histology. He had a life-long influence on his nephew. The young Friedrich was an excellent student despite his shyness and a hearing handicap. Initially he wanted to be a priest, but his father opposed the idea and Miescher entered medical school. At the time of his graduation in 1868, he wrote a long letter to his father, discussing his career plans. He wanted to be a practicing physician, but because of his hearing difficulties, he chose ophthalmology, where listening through a stethoscope would not be needed. On the other hand, he had a great desire to work in basic research. He wrote: “It was only in the lectures on physiology that the entire splendor of research on organic matters became apparent to me.” He therefore proposed a compromise: he would practice ophthalmology and in his spare time do research. Miescher’s father showed the letter to Fredrich’s uncle, Wilhelm His, who instantly saw that the compromise solution would not work. He proposed that “in view of the considerable mental talents which Fritz has,” he should enter the career he found most appealing, that of research in physiology. Someone as eminently theoretical in nature as Miescher would find satisfaction only in scientific research. Miescher, who idolized his uncle, followed his advice and his father agreed.

Miescher chose to be trained as a scientist in the laboratory of the eminent biochemist Felix Hoppe-Seyler at Eberhard-Karls-University in Tübingen, Germany. Hoppe-Seyler was one of the pioneers of what was then referred to as physiological chemistry, a new field aiming to unravel the chemistry of life. Hoppe-Seyler performed seminal work on the properties of proteins, most notably hemoglobin (which he named), and introduced the term proteid which later became protein. Hoppe-Seyler’s expertise and research interests were closely aligned with Miescher’s aims and his laboratory, housed in Tübingen’s Castle, proved to be a stimulating place for Miescher to work.

At 372 m, Tübingen’s Castle offers a magnificent view of the Neckar and Ammer Valleys. The castle dates back to 1078 and is of renaissance construction with four wings and a round tower. The rulers of Tübingen, who were promoted to Counts Palatine in the 12th century, lived in the castle until 1342 when they sold it to the Counts of Württemberg. Beginning in the mid-18th century, the university acquired its first rooms in the castle and in 1816 the King of Würrtemberg, Wilhelm I, transferred ownership of the castle to the university. The university library of nearly 60,000 bands was housed in the hall of knights, and an astronomical observatory was housed in the northeast tower. Hoppe-Seyler’s laboratory occupied the royal laundry room in the basement; he found Miescher space next door, in the old kitchen.

At their first meeting, Hoppe-Seyler proposed to Miescher, then aged 23, that he perform research on the composition of lymphoid cells—white blood cells. Hoppe-Seyler was aware from microscopic examinations that white blood cells have a large nucleus, so that examining these cells might reveal information on the chemistry of the nucleus. However, Miescher’s initial attempts to isolate white blood cells from lymph glands proved difficult. He was unable to obtain enough cells for analyses. Miescher then turned to surgical bandages discarded in a nearby surgical clinic where soldiers were stationed. The bandages were an excellent source because lymphoid cells are abundant in pus from infections. The problem he now faced was washing the cells off the bandages without damaging them. By trial-and-error, Miescher found that a particular salt solution containing sodium sulfate was effective. After filtering the solution to remove residual cotton fibers, he allowed the cells to settle at the bottom of a beaker. Examination in the microscope indicated that the cells were intact and free of contaminating materials. By this simple method, Miescher obtained large enough quantities of the cells for analysis (Fig. 1.1).

Figure 1.1 Friedrich Miescher (1844–95).

One of the first experiments Miescher carried out with the isolated white blood cells was to treat them with gastric juice (we now know that gastric juice contains an enzyme, pepsin, which digests protein). Today, one would simply buy pepsin from one of the many companies that produce the enzyme. However, Miescher had to obtain the gastric juice himself by extracting the juice from pigs’ stomachs. As observed in the microscope, the treatment of the white blood cells with the gastric juice dissolved the cytoplasm of the cell, leaving only a fine gray precipitate consisting of shrunken nuclei. Since the material was isolated from nuclei, he called it “nuclein.”

Nuclein had one property that was typical of proteins; it dissolved in mild alkali and could be precipitated with cold acid. However, when Miescher subjected nuclein to elementary analysis, one of the few chemical tests available at the time, it revealed a weight composition that was different from any cell component known at that time: 14% nitrogen (N), 2% sulfur (S), and 6% phosphorus (P). The high phosphorus content was particularly noteworthy since proteins lack that element.

When a scientist, or for that matter anyone, is confronted with an unexpected finding, one has the choice of ignoring it and moving on, or trying to explain it. Miescher was shy, but he did not lack self-confidence. He did what any good experimental scientist would do—he repeated the experiment, following the exact procedure he had written in his notebook. When he achieved the same results, he must have had a eureka moment, realizing that he had made an important discovery—nuclein was a novel material present in the nucleus of white blood cells.

The final studies on nuclein in Tübingen were made in the summer of 1869, after which Miescher returned to Basel in his native Switzerland to write a manuscript on his research. The manuscript, dated “Basel, October 1869,” was sent to his mentor Hoppe-Seyler, who was skeptical about the rather revolutionary findings of a beginner, especially the unprecedented high concentration of phosphorus. Accordingly, he decided to repeat the experiments himself, and he published Miescher’s paper “Über die chemische Zusammensetzung der Eiter-zellen” (On the Chemical Composition of Pus Cells) in 1871 only after he had v...

Table of contents

• Cover
• Title page
• Table of Contents
• Copyright
• Dedication
• Preface
• Acknowledgments
• Prologue
• Chapter 1: The Beginning
• Chapter 2: Chemistry of DNA
• Chapter 3: DNA Is the Genetic Material
• Chapter 4: DNA in Three Dimensions: The Double-Helix
• Chapter 5: Duplicating DNA
• Chapter 6: From Genes to Enzymes
• Chapter 7: Cracking the Genetic Code
• Chapter 8: DNA Sequencing and PCR
• Chapter 9: Jumping Genes
• Chapter 10: Genetic Engineering
• Chapter 11: The Human Genome
• Chapter 12: Human Microbiome: We Are Not Alone
• Chapter 13: Contribution of Microbes to the Health of Humans, Animals, and Plants
• Chapter 14: Origin of Nucleic Acids and the First Cells
• Chapter 15: Evolution: From Darwin to the Hologenome Concept
• Chapter 16: DNA and Cancer
• Chapter 17: DNA, Aging, and Death
• Appendix: Nobel Prizes Awarded for Nucleic Acid Research
• Glossary of Scientific Terms
• Selected Bibliography
• Index