DNA pioneers and their legacy

After read “DNA pioneers and their legacy” (U. Lagerkvist 1998 Yale University Press, New Haven, CT), summarizing, discussing, and evaluating.

In the account of the origins of modern molecular biology, the lives of pioneering scientists in the field of nucleic acid research, and the discovery of DNA, Ulf Lagerkvist speaks not only to scientists but also to students and general readers with an interest in science.

The author, whose career in the nucleic acid field began in the late 1940s, recreates historical episodes from the nineteenth and early twentieth centuries and introduces for a modern audience the scientists whose discoveries revolutionized the field of biology. Lagerkvist believes that knowledge of these pioneers as professionals and as human beings may help us see modern problems in a new light and appreciate the greatness of the researchers who contributed to the foundations of molecular biology and biochemistry.

The stated goal of Professor Lagerkvist’s book is to keep alive the legacy of scientists who devoted their lives to the field of molecular biology more than a century ago. His focus is on DNA, its discovery, structure, replication and role as the primary genetic material.

He wants the new generation of researchers to remember the contributions made by these early pioneers and not just their names mentioned briefly in textbooks, if at all. In bringing recognition to these investigators, he says, ‘these pioneers may teach us a useful lesson in humility and make us realize the truth of the old saying that if we can see as far as we do, it is because we stand on the shoulders of giants.’ I agree totally with Professor Lagerkvist on this point.

The book also explores early research into general problems of the chemistry of biological materials. Lagerkvist vividly describes the research of such influential scientists as Albrecht Kossel, another early leading figure; Emil Fischer, who received the Nobel Prize in 1902 for his work on carbohydrates and purines and was regarded as the foremost chemist of his time; P. A. Levene, known for his discoveries concerning the structure of nucleotides and the way these nucleic acid building blocks are linked to one another; and Oswald T. Avery, often considered the grandfather of molecular genetics.

Among scientific pioneers was the nineteenth-century biochemist Friedrich Miescher, discoverer of nuclein, the material now known as DNA. It would be appropriate to speculate on Friedrich Miescher’s scientific achievements in more details, for his work can serve excellent example of the way scientific conception was developing in the period of initiation of a new science branch.

It may be of interest to recall, for a moment, the general situation of contemporary medicine when Miescher took up his medical studies. The basic sciences of medicine – anatomy, pathology, physiology, and biochemistry – had made enormous progress. When scientifically based clinical research slowly emerged in the first decades of the nineteenth century, however, the practice of medicine was in a state of bankruptcy. Not only was the intellectual framework, based on the body humors that had ruled medical thinking for two millennia, in chaos and disintegration, but even venesection (bloodletting), the unshakable foundation of all therapy, was being questioned.

Miescher had originally intended to study lymphocytes, but he soon realized that it would be impossible to get enough of these cells. Encouraged by Hoppe-Seyler, he instead focussed on leucocytes, known to be the main cellular constituent of the laudable pus that could be obtained fresh every day from used bandages in the nearby hospital. The trick was to wash the cells without damaging them.

To this end Friedrich tried various salt solutions, but the cells swelled and gave rise to a highly viscous porridge that was impossible to handle. In hindsight it is easy to see that this occurred because he extracted high-molecular-weight DNA from damaged cells. Eventually he hit on a dilute solution of sodium sulfate as the best way to rinse well-preserved cells from the bandages. After filtration to get rid of tissue fibres, the cells were left to sediment to the bottom of the beaker; laboratory centrifuges were nonexistent in those days. When examined in the microscope, the leucocytes seemed intact and showed no sign of damage.

His first task was to isolate undamaged nuclei free of cytoplasm. This had never been accomplished before and only after long hours of hard work did Miescher come up with reasonable quantities of nuclei in good condition. He tried several methods, but his final procedure was as follows. Miescher first treated the cells with warm alcohol to remove lipids, then digested away the proteins of the cytoplasm with the proteolytic enzyme pepsin. What he used was not a pure preparation of crystalline pepsin, as would be used today; nothing comparable was available. Instead, he extracted pig’s stomach with dilute hydrochloric acid, which gave him an active but highly impure enzyme that he used for his digestions.

The pepsin treatment solubilized the cytoplasm and left the cell nuclei behind as greyish precipitate… He subjected his purified nuclei to the same alkaline extraction procedure he had previously used with the whole cells, and on acidification he again obtained a precipitate. Obviously this material must have come from the nucleus, and he therefore named it nuclein.

Using elementary analysis, one of the few methods available to characterize an unknown compound Miescher found that his new substance contained 14 percent nitrogen, 3 percent phosphorus, and 2 percent sulfur. Its comparatively high phosphorus content and its resistance to digestion with pepsin suggested that the substance was not a protein. (At the same time, its appreciable content of sulfur immediately indicates to us today that his preparation did contain substantial amounts of proteins.)

The book also observes the Molecular Genetics. The discovery of the structure of DNA was one of the biggest discoveries in the history of biology, because the structure of DNA is so important to the way it does its job. This puzzle was solved by the scientists James Watson and Francis Crick, and has shaped our understanding of genetics ever since. DNA, or deoxyribonucleic acid, contains deoxyribose (a sugar), phosphate groups, and nitrogen bases, all linked in a long chain or strand. In cells, two separate strands of DNA are joined together by hydrogen bonds and twisted into a double helix. Because strands of DNA are so long, they are packed very tightly into chromosomes so they fit inside the nucleus of a cell.

The structure of DNA is very special, because it allows a DNA strand to store information. There are four different nitrogen bases  (building blocks) that appear along a DNA strand: guanine (G), adenine (A), thymine (T), cytosine (C). The order of these bases along a strand of DNA can be read by the cell like a cod, making sentences called genes. The cell reads these coded messages on the chromosomes in its nucleus, and knows what kinds of proteins to make and what to do with them.

I found this an unchallenging read, designed to inspire young researchers to enter the field. Crucially, for me, Lagerkvist’s internalist account is untouched by the more critical approach to the growth of scientific knowledge that comes from historians, philosophers and sociologists.

REFERENCE:

1. “DNA pioneers and their legacy”, U. Lagerkvist 1998 Yale University Press, New Haven, CT