Ahead of the Curve: David Baltimore's Life in Science

THREE: APPRENTICESHIPS

Three A P P R E N T I C E S H I P S Don't be afraid ofbeingfoolish. P H I L L I P S H A R P 1993 \obel laureate In medicme and p h ~ nologl THE EXPLOSIVE GROWTH O F molecular biology made the late 1950s both a great time and a chaotic time to become an apprentice molecular biologist . Baltimore could get involved in molecular biology immediately, but it was difficult to see how he could become a great scientist. The MIT graduate program in biology was rigidly structured, requiring students to learn oceans of knowledge during their first year in a series of biological problem-solving classes.Students quickly developed a chalkboard understanding of experimentation, learning to wield a battery of biochemical and genetic approaches for solving biological problems: identifying a gene that gives fruit flies white eyes or isolating a protein responsible for gluing sugars together. Baltimore and his classmatesvirtually memorized heaps of scientific papers written by the masters of molecular biology The rigid educational attitude of MIT was difficult to get used to after the more flexible structure of Swarthmore, but Baltimore adapted. In classes, the professors lectured on mutation rates, phage genetics, or enzyme biochemistry, drawing models on the board and explaining experiments in confident tones-and Baltimore interrupted. He blurted out aggressivequestions and challenged professors' interpretations of experiments. He refused to sit passively in a lecture hall and simply be indoctrinated. Science to him was not an immutable book of knowledge but a dynamic process, and if a professor mentioned a "scientific fact" in lecture that Bal- timore thought was flaccid or simpleminded, he pointed out its weaknesses and besieged it. Baltimore quickly earned a reputation as a bombastic student . One professor thirty years later privately recalled Baltimore as one of the brightest and most troublesome students he ever had: "Baltimore was a pain in the ass." His brilliant mind and blunt candor were a discomforting combination. He told one of his professors, "I can't attend your lectures, because they are terrible." Other professors privately agreed with him (and chortled behind closed doors), but his audacity shocked them. Yet although his manner could be abrasive and his arrogance was undeniable, his intelligence was difficult to ignore. In the words of Peter Medawar, winner of the 1960 Nobel Prize in medicine: "Humility is not a state of mind conducive to the advancement of learning." The most important biological concept David learned at MIT was the "Central Dogma," the flow chart of genetic information.Whimsically named by Francis Crick, the great sage of molecular biology, this principle is emblazoned in the minds of all molecular biology students: CDNA -RNA -Protein a 9 transcribe translate The CentralDogma of molecular biology. The Central Dogma states, first, that all cells use DNA to store their genetic information. For example, in humans, genetic information is passed from generation to generation in the form of double-stranded DNA. Human DNA is three billion nucleotides long. Written out as a continuous string of letters, the information in DNA necessary to describe the entire genetic blueprint of a person would fill five thousand books. That entire three-billion-nucleotide string of DNA is crammed into every individual cell in the human body. DNA is the genetic blueprint, but a blueprint by itself doesn't do anything . Human DNA is divided up into about fifty thousand genes. A simple way to think about this is to consider each gene a sentence in the code of life. It takes fifty thousand sentences to describe the human body plan. A P P R E N T I C E S H I P S 3 3 The remainder of the Central Dogma addresses the question: How does the cell get the information out of a gene in the DNA for use in the cell? This is a two-step process. First, an enzyme called RNA polymerase synthesizes ("transcribes,"in the scientificlexicon) RNA from the DNA. RNA is a polymer very similar to DNA, but less stable. Cells use RNA as the messenger molecule, a temporary replica of the gene. That RNA message of the gene is then "translated" into the protein, the final product, by molecular machines inside the cell, known as ribosomes, that read the RNA and synthesize the protein that the RNA contains instructions for. Why does it have to be so complicated to...