The Gene: An Intimate History. By Siddhartha Mukherjee. Scribner, New York, 2016. ISBN 978-1476733500. 592 pp. Hardcover, $32.00.
Nearly six years ago, I reviewed Siddhartha Mukherjee’s book The Emperor of All Maladies: A Biography of Cancer (SI, May/June 2011). It was hands-down one of the best books I have ever read on a medical topic. Now he’s done it again. His new book is titled The Gene: An Intimate History.
Mukherjee is a superb writer. Much of what I said about his first book applies equally to his second, so I will quote myself:
It is a unique combination of insightful history, cutting edge science reporting, and vivid stories about the individuals involved: the scientists, the activists, the doctors, and the patients. It is also the story of science itself: how the scientific method works…. Beautifully written and informative…. Reads like a detective story with an exciting plot.
He links this second book to his first by pointing out that cancer is an ultimate perversion of genetics and that studying cancer means also studying its obverse: normalcy. He gives the topic a human face by interspersing anecdotes from his own family’s struggles with mental illness and its connection to inherited genes. He sets out to tell the story of the birth, growth, and future of one of the most powerful and dangerous ideas in the history of science: the gene. He says it is one of three destabilizing ideas that have transformed science: the concept that irreducible units underlie matter (the atom), digitized information (the byte or bit), and biological information (the gene). He explains how the consequences of these ideas have transformed our thinking, our language, and our culture, politics, and society.
Mukherjee delves into the fascinating history of our early groping toward understanding inheritance. Pythagoras believed that information was carried only in the sperm, and the uterus only provided nourishment. The preformation theory held that sperm contained a miniature human. Lamarck believed that acquired characteristics could be inherited. Mendel was the first to discover dominant and recessive inheritance of traits, which meant that there must be inheritable units. His published research was ignored for decades, and only much later did those units come to be called genes.
The history of genetics was stained by the eugenic movement, which had dire consequences. In America, there were involuntary sterilizations of people who were thought to be defective but often weren’t. One such person who was sterilized against her will was Carrie Buck, the plaintiff in the Supreme Court Case on the topic, Buck v. Bell. In Nazi Germany, eugenic arguments were used to justify the murder of children, gypsies, Jews, and other politically undesirable groups.
The research of Mendel and others convinced scientists that there must be such a thing as a gene. Around 1900, they figured out that genes must be carried in the cell’s nucleus and narrowed it down to the chromosomes. Studies of fruit fly mutants and variants found that some traits were linked, so their genetic information must be located close to each other on the chromosome. But how was the information carried?
When DNA was first proposed, it was dismissed as a “stupid molecule” that couldn’t carry clever messages. It took a long series of ingenious experiments to reveal that DNA was the carrier of genetic information, and it was decades before the amino acid triplet code was discovered and the structure of the DNA molecule was revealed by Watson and Crick. Mukherjee tells the story step by step, experiment by experiment, with all the suspense and excitement of a detective story where the gradual accumulation of clues finally reveals the culprit. His use of language is delicious, noting for example that “Bread molds are scrappy, fierce creatures.”
As he relates discovery after discovery, the story gradually educates the reader about all the important concepts in genetics: introns, “junk” DNA, the function of RNA, how genes direct the embryo to form a human, recombinant DNA, gene sequencing, how proteins are manufactured, genotype vs. phenotype, transcription and reverse transcription, alleles, and epigenetics. He explains the “central dogma” that information moves from genes in DNA to messenger RNA to proteins, and then he explains why that overly simplistic theory has required several modifications.
He tells the complicated story of political restrictions on genetic experimentation and of the conflicts that troubled the Human Genome Project. He explains how genes carry a molecular clock that tells our evolutionary history and how gene analysis can reconstruct the movements of early human populations. He explains why the Mitochondrial Eve is the mother of us all. He tries to explain why most biological males have a Y chromosome. He throws a monkey wrench into racial discrimination by showing that there is more diversity within races than between races. He talks about genetic factors in homosexuality and transgender identity. He explains why epigenetics is on the verge of transforming into a dangerous idea that is being used to justify junk science and a new Lamarckism. He even speculates about how life itself began.
We have mapped the human genome and understand a lot about the genetic code, but we know virtually nothing about the genomic code, which governs how multiple genes at various sites on the human genome coordinate gene expression in space and time to build, maintain, and repair a human organism. We don’t understand the functions of noncoding tracts of DNA between the genes.
Tinkering with Genes
Understanding the genome was the first goal that inevitably led to a second goal: altering the genome. The hope was that we could outwit nature and take control of our own destiny, changing the course of human evolution. If we could identify genes that caused diseases, we ought to be able to fix the genes and eliminate diseases. We had eliminated smallpox from the world; now genetics offered the hope of eliminating everything from nearsightedness to cancer. We are still far from that goal, and it is looking more and more unrealistic, but some progress has been made.
Genetic analysis can identify couples who might want to avoid pregnancy because of a high likelihood of transmitting a serious genetic condition such as Huntington disease. Prenatal diagnosis can be used to guide selective abortion of fetuses with genetic diseases (and sometimes fetuses of the “wrong” sex!). Gene therapy is already possible, although some of the early experiments have gone awry due to incompetence, blunders, neglect, and gaps in knowledge. It is now possible to biopsy a human embryo and extract cells for pre-implantation genetic diagnosis without affecting the viability of the embryo. In 2014, a landmark study was published in The New England Journal of Medicine reporting the successful use of gene therapy to treat hemophilia. Thanks to CRISPR (see SI Special Report “CRISPR-Cas9: Not Just Another Scientific Revolution,” May/June 2016), we have the ability to cut out a defective gene and replace it with a normal one.
The new technologies offer exciting promises but give rise to ethical dilemmas. Should society allow the creation of “designer babies”? Who is to determine what is normal and what is not? What if a defective gene causes mental illness but also causes genius and creativity? Genes affect the expression of other genes; modifying genes could have unforeseen consequences.
The book is a cornucopia of delights that offers something for everyone. You can read it for its detective story and literary value. You can read it to get a basic education in genetics. You can read it to finally understand what epigenetics is really all about. You can read it for its explanation of cutting-edge science, for its tantalizing clues about where science is headed, and for a challenging view of the ethical dilemmas we will have to face as a society.
Mukherjee is a rare combination of scientist, storyteller, and educator. He is a truly gifted writer. I highly recommend both of his books, and I look forward to reading whatever he may write about in the future.