“Life’s Greatest Secret: The Race to Crack the Genetic Code,” by Matthew Cobb, Basic Books, NY, 2015. This 434-page hardback tells of the molecular biology/biochemistry research that discovered genes and how they work to create proteins. The author reviews the various phases of the research naming researchers and describing the many discussions that took place along the way. It is noticeable that the research tends to be inbred with a handful of universities doing most of the work. Outsiders contributed significant findings but their work was often discounted or ignored.
Gregor Mendel’s study to pea genetics in 1865 is the start of the story. His research was published but largely ignored until rediscovered in 1900. He showed that characteristics are inherited and passed down from generation to generation with aspects contributed by both parents and some dominant. In 1912, Morgan’s fly studies at Columbia found that certain factors were inherited together suggesting their genes were near each other on the chromosomes. The nature of genes was unknown. In 1926, Muller found that xrays resulted in mutations. Genes were thought to be proteins. Nucleic acids were nearly identical and irrelevant.
MacLeod and Avery at Rockefeller Institute Hospital in New York made an important discovery in 1940. Working with pneumococcal pneumonia bacteria they were able to isolate a white precipitate that could transform rough or smooth colonies from one form to the other. It was active at very low levels and proved to be DNA. The scientific community held to the protein idea and ignored their work.
Watson and Crick’s discovery of the double helix of DNA has been told before. It was at Kings College where Rosalind Franklin had x-ray crystallography data but somehow failed to interpret them as a helix. Cobb tells more about the personalities involved. Watson, Crick and her boss received a Nobel Prize for their discovery but Franklin had died of ovarian cancer.
Replication of DNA was demonstrated in 1958. Under Seymour Benzer, two students Meselson and Stahl, made DNA with heavy nitrogen by growing E coli and then in regular nitrogen. They showed that regular nitrogen was incorporated in stages.
Next came the question of how four nucleotides in DNA became proteins made of twenty amino acids. In 1961, Matthaei and Nirenberg at National Institutes of Health made proteins from synthetic RNA containing all uracils. Using radioactive amino acids they showed that poly(U) coded for phenylalanine. Others copied their method to learn the three nucleotide code for all 20 amino acids.
The book then turns to more recent developments. PCR (polymerase chain reaction) developed in the 1980s made it possible to amplify DNA rapidly providing larger samples for investigation. Faster methods were developed for gene sequencing. Sequencing the human genome was undertaken by two groups. Work begun by the International Human Genome Sequencing Consortium led by Jim Watson was too slow. Celera Corp took up the project with a plan to protect the information as intellectual property and charge for its use. Completion was announced in 2000. Faster technology makes possible sequencing the DNA of many species. The data provides ancestry information. It also allows DNA fingerprinting of individuals.
Technology now allows inserting genes in other species. Valuable drugs such as insulin or human growth hormone can now be made by fermentation of e coli or excreted in goats milk. Recombinant DNA technology has now been improved with Crispr technology. In 2014, many crops including soybeans, corn, sugar beets, and cotton are now genetically modified. Roundup Ready Soybeans resist the herbicide Roundup making it possible to spray for weeds after they sprout (rather than preemergent herbicides used earlier). Plants can make their own natural insecticides. Cobb explores the possible misuses of the technology to create new diseases or insert toxic genes in organisms.
This book will be of greatest interest to those considering a career in molecular biology or biochemistry. It names major institutions in the field and implies admission to top departments is important for a successful career. Cobb’s writing is highly readable and not overly technical. He includes illustrations and an appendix of technical terms. Photos. References. Index.