Ponder & Thrive's Key Ideas from The Gene
by Siddhartha Mukherjee

In about 500 BC, ancient Greek philosophers like Hippocrates and Pythagoras believed fathers held the answers to heredity. They thought that men’s semen floated around their bodies and collected the essence of their bodies, from their height to physical strength to hair color. That essence would condense into a person in the womb. They also thought that if a person’s body changed, that fluid would record and pass on those changes - so a weightlifting daddy would make a muscular baby.

A few hundred years later in around 300 BC, Aristotle pointed out that some kids also look like their moms and grandmas, and that traits like grey hair showed up after somebody made kids, but still made it into the next generation. He introduced the idea that it might be instructions that are passed along instead of a physical template, a blueprint rather than bricks. But he did stick to the idea that info got captured by semen and menses floating around the body.

Father of surgery Al-Zahrawi wrote an enormous encyclopedia on medicine around 1000. He also wrote the first detailed record we have of a hereditary disease, which is an illness that is passed along in a family. Now we know that disease - a clotting disorder called hemophilia - is more common in men than in women because it’s linked to the X chromosome. If one of a woman’s X chromosomes has the hemophilia mutation, she has a backup and will avoid most of the symptoms. But if she passes that mutated copy to her son, he will have hemophilia. Colorblindness is another sex linked trait.

When Antonie van Leeuwenhoek vastly improved the microscope in the 1600s and observed living cells for the first time, humanity started to understand we are made up of tiny parts. And then we jumped to the conclusion that we’re so complex that the only way we could make something as complicated as a baby human was if it was already put together and just needed to grow. This miniature human was called a homonculus, and scientists thought it was fully pre-formed inside either a sperm cell or an egg cell, and needed just a womb to grow in or a sperm to jump-start.

In the 1800s, Charles Darwin had big ideas about how species evolved when natural selection killed off members with bad traits. But he didn’t have a good grasp on how those traits were passed along from parent to child. What he put forth was similar to Hippocrates’s idea - that body parts emit particles that affect eggs and sperm. He called them gemmules, thinking that better body parts produced better gemmules, and that each parents gemmules would blend in a baby. But his theory of evolution kind of needed inherited traits to be stable, unchanging units.

Gregor Mendel a 19th century monk bred generations of pea plants and meticulously kept track of each plant’s traits from size to color to seed shape. He observed that parental traits didn’t blend together in a baby pea plant, but appeared and disappeared with mathematical precision. This could have been a breakthrough, demonstrating to the scientific world that traits were passed on in stable units of information, but everyone ignored his work. He even wrote to a scientist he admired for advice, who thought his experiment was dumb and told him to switch plant.

It took scientists a long time from the discovery of cells to understand which parts of a cell do what. But as microscope technology improved and researchers learned how to stain specific structures within the cell, they started to put the puzzle together. In the early 1900s, several scientists including Theodor Boveri and Walter Sutton watched cells duplicate and discovered chromosomes. Finally, they had linked Mendel’s mathematics about traits to a physical structure in a cell. Further experiments showed that it was DNA in the chromosome, not proteins, that actually carried the genetic code.

To really understand how something works, you have to know what it looks like. Many scientists got almost all the way there but fell short. One figured out the bases stacked flat on top of each other like coins, another almost figured out how the bases paired together, but no one put all the pieces together until the 1950s when James Watson and Francis Crick used data from Rosalin Franklin and other scientists to unveil the elegant double helix. This discovery allowed researchers the first glimpse of how our traits are physically coded in our DNA.

Knowing the general shape of DNA is good, but until scientists could read the code, they couldn’t make a lot of progress in understanding how our genes affect our health and lives. At first, it was slow. One of the first published DNA sequences was just 24 base pairs long and took the team two full years in the 1970s. But by the late 1980s, computers could read 1000 base pairs a day. Once they could read the sequence of a gene, scientists still had to figure out what it does.

In the early 1990s, the international community came together to sequence the entire human genome, all 3 billion base pairs. Techniques for computerized gene sequencing got faster and faster and they finished in 2003. Over the last 20 years, the cost of sequencing a genome has dropped from more than $100 million to just $1,000. And now, scientists are learning to quickly and accurately change DNA, perhaps in the future allowing them to cure many genetic disorders.