Hacking Darwin Read online

  But to understand where we are going, we first need to take a step back to understand where we are coming from.

  For the first 2.5 billion years of life on earth, our single-cell ancestors reproduced clonally.* One bacterium, for example, would divide into two separate bacteria with the same genetics, and then the process would start over again. This was a great way to do things because you didn’t need to waste any time and energy finding a mate. All you had to do was find food and divide and your lineage could go on. The downside was that the clonal reproduction process created a lot of genetic consistency among the single-cell organisms in a given community, limiting the options available for natural selection compared to what would come later.

  This consistency, however, was not complete. Bacteria evolved a way to literally grab genes from other bacteria using microscopic harpoons we call pili.1 Still, while clonal reproduction helped bacteria pass on beneficial mutations, it also left some entire colonies at risk when dangers such as bacteria-infecting viruses arose because the cloned bacteria possessed too many of the same inadequacies in their defense mechanisms. Sexual reproduction changed that in a big way.

  Exact copies in biology are rarely exactly perfect. Although it is impossible to pinpoint the exact time, the fossil record suggests that about 1.2 billion years ago one of these simple organisms developed a strange mutation. Rather than just copy themselves or grab a few genes from other microorganisms, they somehow paired with other microbes to create offspring combining the DNA of both parents—et voilà, sex was born, dramatically expanding evolutionary possibilities.

  It took more energy to find a partner than it did to clone yourself—there were, by definition, no other potential suitors to contend with. Those on the lookout for optimal partners had to develop new, ever-better capabilities to attract the best mates and fight off competitors. But once a mate was secured, they could more fully and more randomly mix their genetics when procreating—a huge advantage.

  Organisms that reproduced sexually had more genetic losers that their clonal forebears, but they also had a far greater possibility of evolving genetic winners. With so many different models of sexually reproducing organisms being constantly generated, sexually reproducing species were able to adapt more quickly to changing circumstances, do a better job of fighting off intruders and finding food, and speed up the process of evolutionary change. As one of them, our entire evolutionary history is made of these often-random genetic mutations and variations creating a multitude of new traits, the most useful of which spread across our species. Armed with these differences, our ancestors competed for advantage with each other and the environment around us in a process Darwin called natural selection.

  Over time, the process of sexual reproduction itself faced evolutionary pressures to which different creatures responded in different ways. Some, like today’s salmon, released as many eggs as possible into the world in the hope that some of the eggs will encounter sperm. Releasing thousands of eggs into the holes at the bottom of rivers increased the odds that at least some of them might be fertilized by male sperm, but this approach also eliminated the possibility of parenting. No matter what you may think about your parents, parenting itself confers huge evolutionary advantages.

  Rather than sending out huge numbers of eggs, other organisms—our more recent ancestors included—kept the eggs inside the females until fertilization then gestated embryos inside their bodies. If sex were a game of roulette, creatures like salmon puts a chip on every number but creatures like us placed our chips on a few single numbers. By producing fewer offspring than other mammals and keeping them closer to home, our ancestors invested more in raising children, which meant that our kids can develop skills far beyond what a single salmon, hatched and on its own, could ever have.

  Sexual reproduction supercharged diversity, creating an ongoing evolutionary arms race. When the salmon won, they reproduced in big numbers but couldn’t by definition do anything to raise their kids who were already long gone. We, on the other hand, protected our helpless babies after birth, allowing their brains to keep growing, and nurtured them to provide new skills. Our nature created the evolutionary possibility of our nurture. When we won, we built civilization.

  Baked-in sex drives ensured that our ancestors kept sexually reproducing even if they didn’t understand, at least on a technical level, much of what was happening. Early civilizations attributed the magic of reproduction to the gods, but our inherently inquisitive brains were hardwired to keep searching for a deeper understanding of the world around us. For millennia, very slow progress was made in understanding our biology, but our knowledge expanded considerably with the advent of the philosophies and tools of the Scientific Revolution.

  In 1677, the happy Dutchman Antonie van Leeuwenhoek jumped out of bed. Inventor of a far better microscope than anything before, he had already, on his own, peered deeply into bodily fluids of blood, saliva, and tears. This time, however, he recruited his wife. After a sexual encounter, van Leeuwenhoek placed a bit of his ejaculate under his microscope and was amazed to see what he described as “seminal worms” wiggling around “like an eel swimming in water.”2 But what role, he wondered, did these wiggling worms play?

  A prominent view in Europe at the time, one that originated with the ancient Greeks, was that male semen contained homunculi, a name for tiny people waiting to start growing. The female body, according to this hypothesis, was like the soil in which a plant seed grows. An alternative belief was that female eggs contained the little mini-mes, whose growth was catalyzed by male semen. A third group of people, presumably mostly dimwits, believed life generated spontaneously like flies emerging from rancid meat.

  In the eighteenth century, the brilliant Italian Catholic priest and polymath Lazzaro “Magnifico” Spallanzani crafted an ingenious experiment to test his hypothesis about procreation. Sewing tiny frog pants out of taffeta, he made it impossible for male frogs to pass their “fluids” to the females. Every young person learns this in sex ed today, but in the eighteenth century it was big news that female frogs could not get pregnant when the male sperm was filtered by the pants. When Spallanzani artificially inseminated the female frogs with male frog sperm, the females became pregnant. Sperm, it was now clear, was an essential component of the semen needed to make the females pregnant.3 Magnifico! It took an additional century before scientists figured out that both the male and the female sex cells contribute equally to the fertilized egg.

  Drawing of the homunculus by Dutch physicist Nicolas Hartsoeker in 1694.

  Learning more about how humans are made then merged with another realization our ancestors had intuitively sensed but never fully understood—the science of heredity.

  For millennia, our ancestors must have had an inkling about how heredity works. Every time a tall man and a tall woman had a tall child, they received a clue. When a tall man and a tall woman had a short child, they probably got a little confused and, perhaps, the man cast a wary eye at the short, vivacious Casanova living one cave over. Our ancestors used this limited knowledge of heredity to start changing the world around them.

  Our nomadic hunter-gatherer ancestors, for example, began noticing that some of the wolves picking through their garbage were friendlier than others. Starting around fifteen thousand years ago, probably in Central Asia, they started breeding those friendlier wolves with each other, eventually creating dogs. Unadulterated by humans, nature on its own devices probably would not have morphed a proud wolf into a yapping Chihuahua, but our ancestors pushed the creation of an entirely new subspecies.

  The same human-led domestication process transformed plants. After the vast ice sheets receded almost twelve thousand years ago, our ancestors started replanting particularly useful plants they’d plucked from the wild.4 Long before Monsanto started genetically engineering seeds, our human ancestors noticed that a few particular plants did something different and more desirable than the others being grown. They figured out that if they plante
d seeds from these plants, the next generation would more often do the same great thing. Over the coming millennia, this selective breeding process was used to turn wild plants into what we know today as wheat, barley, and peas from the Middle East, rice and millet from China, and squash and corn from Mexico. As humans all around the globe either figured out animal and plant domestication on their own or were exposed to it by others, we increasingly pondered the nature of heredity.

  Our ancestors knew how to do heredity but had very little understanding of how it was actually working. For millennia, great human thinkers like Hippocrates and Aristotle in ancient Greece, Charaka in India, and Abu al-Qasim al-Zahrawi and Judah Halevi in Islamic Spain hypothesized about human heredity, but no one had gotten things quite right.

  In 1831, an English gentleman explorer with a deep curiosity finagled his way onto a five-year survey voyage along the coasts of Africa, South America, Australia, and New Zealand. A keen observer of detail, Charles Darwin studied his environment carefully, collected huge numbers of specimens, and took meticulous notes. Returning to England in 1836, he spent the next twenty-three years obsessively mulling over his findings and piecing together a powerful hypothesis about how organisms evolve. Darwin recognized his theory would shock Christian morality, so he wanted to be certain he was right before publishing his work. When he learned that a competitor with ideas dangerously close to his own was about to go public, Darwin finally published On the Origin of Species by Means of Natural Selection in 1859.

  In his masterpiece, Darwin described his theory that all life is related and that species evolve because small changes in heritable traits compete in a process he called natural selection. Over time, a species with traits conferring specific advantages in a given environment thrive and reproduce more than those with less advantageous configurations. If the environment changes, the different traits face different selective pressures in the never-ending process of adaptation and evolution. A highly advantageous trait in one environment might become a liability in another, and vice versa. Darwin was spot-on in his theory of evolution but knew little about how heredity actually worked on a molecular level. It took another genius to unlock that mystery.

  At the time Darwin’s great work was published, an obscure Augustinian friar, Gregor Mendel, was devoting his free time, analytical mind, and careful record keeping to figuring out how traits were passed across generations.

  The brilliant son of a peasant farmer, Mendel joined the Augustinian St. Thomas Monastery in Brno (in the modern-day Czech Republic) in 1843. Immediately, he took an active interest in the work already being carried out by other monks trying to better understand how traits were passed on in sheep. Recognizing Mendel’s abilities, the abbot sent young Gregor to study physics, chemistry, and zoology at the University of Vienna. After returning from his studies, Mendel convinced the abbot to give him free reign to carry out even more ambitious experiments. Breeding over ten thousand pea plants of twenty-two different varieties between 1856 and 1863, he meticulously recorded how various traits were passed from parent plants to their offspring and painstakingly deduced the laws of heredity that mostly hold true today.

  First, Mendel confirmed, each inherited trait is defined by a pair of genes, where one gene is provided by each parent. Second, each trait is determined independent of other traits by the two genes for that trait. Third, if a gene pair has two different genes for the same trait, one form of these genes will always be dominant. Mendel published his revolutionary findings in his seminal 1866 study, “Experiments in Plant Hybridization,” and then…nothing happened. Few scientists knew of the paper, which was originally published in the little-read Proceedings of the Natural History Society of Brünn. Mendel’s incredible work was, for the moment, lost.

  But when other scientists exploring the nature of heredity in 1900 stumbled upon tattered copies of Mendel’s great paper, the seed of the genetic age was replanted. Ten years later, American biologist Thomas Hunt Morgan proved that the genes Mendel described are organized in structures of molecules called chromosomes. Over the coming decades, scientists showed how genetics worked across scores of different organisms. Mendelian genetics became the vehicle underpinning all of life. Combined with Darwinian evolution, it provided the essential keys needed to unlock and then transform all of biology, including our own.

  All genetic code is made up of very long strands of deoxyribonucleic acid, or DNA, which provides instructions to cells for making proteins. Sexually reproducing species like ours have two paired strands of DNA in the nucleus of nearly all of our cells (our red blood cells don’t have nuclei), one from our mother and one from our father. If we were a cake, each of our parents would contribute about half of each ingredient.

  But rather than being made up of flour, sugar, and baking soda, our DNA is made up of four different types of molecules called nucleotides. These nucleotide “bases” are named guanine, adenine, thymine, and cytosine, but each is more commonly referred to by its first letter: G, A, T, or C. The G’s, A’s, T’s, and C’s are strung together like trains on two sets of parallel tracks, just touching each other. The order of the trains, the sequences of the DNA we call genes, creates a unique set of instructions that are delivered by messengers called ribonucleic acid, or RNA, to the cells for making proteins. Proteins are the real actors in our cells that carry out whatever task has been assigned to them—like becoming a specified type of cell, structuring and regulating our tissues and organs, carrying oxygen, generating biochemical reactions, and growing.

  Our human genes are then normally packaged together into twenty-three pairs of DNA strands in our cells—our chromosomes—with each chromosome directing a specific set of functions in our bodies. Humans have about 21,000 genes and 3.2 billion base pairs—points on the genome, the complete set of genes in our bodies—where G’s pair with C’s and A’s pair with T’s.

  The genes that impact us the most are those providing instructions to our cells to create proteins, but nearly 99 percent of the total DNA does not code for proteins at all. These noncoding genes used to be called junk DNA because scientists thought they had no significant biological function. Today we can think of noncoding genes like football players standing on the sideline giving encouragement, tips, and direction to their teammates on the field. These noncoding genes play an important role directing the creation of certain RNA molecules that carry instructions from our genes outside the nucleus and in regulating how the protein-coding genes are expressed.

  Each of our cells that has a nucleus contains the blueprint for our whole body, but the result would be chaos if every cell were trying to create the whole person. Instead, our genetic DNA is regulated by a process called epigenetics for determining which genes are expressed. A skin cell, for example, contains the blueprint of a liver cell and every other type of cell, but the epigenetic “marks” tell the skin cells to produce skin. In our football team analogy, each player has the entire game plan but only needs to fulfill his or her particular function when instructed to do so.5

  That’s why the single cell of our original fertilized egg can grow into such complicated beings as ourselves. This first cell contains the instructions to generate all the different types of cells, but the cells then begin to specialize in different ways to perform their particular functions. These specialized cells, however, are not independent actors but differentiated parts of an interconnected cellular ecosystem. And just like our organs collaborate with each other within the system of our body, our genes influence each other within the dynamic system of our genome.

  This all sounds very complicated, and it is. That’s why it’s taken hundreds of years to understand how the system works, and we’re still only just beginning. But having a recipe and understanding the language of the instructions and the nature of the ingredients is a pretty critical start when baking a cake. Once scientists recognized that genes were the alphabet of the language of life, they still needed to figure out what the letters were saying to be able to
read the book. The DNA double helix was the manual made up of letters, but what did the letters say?

  Reading the human genome in any significant way was far too difficult for humans alone but not, ultimately, for humans paired with machines. In the mid-1970s, Cambridge scientists Frederick Sanger and Alan Coulson invented an ingenious way to run an electric current through a gel to break up a cell’s genome; staining the fragments and sorting the different nucleo-tides based on length and streaming the gel through a specially designed camera to read the genetic patterns. This first-generation genome sequencing process was slow and expensive but a gargantuan step forward.

  By figuring out how to automate this process and better read the flashes of light passing through the DNA “letters,” researchers like Lee Hood and Lloyd Smith massively increased both the speed and efficacy of genome sequencing and laid the foundation for another big step forward. When, in 1988, the U.S. National Institutes of Health launched a major initiative to supercharge development of the next generation of these DNA sequencing machines, the stage was set for an even more ambitious initiative to sequence the entire genome.6

  The Human Genome Project, an audacious, U.S.-led international effort to sequence and map the first human genome, cost 2.7 billion dollars and took thirteen years by the time it was completed in 2003. By then, a private company led by science entrepreneur Craig Venter had pioneered an alternative approach of sequencing the human genome that was less comprehensive but far faster than the government-led effort. Together, these initiatives were truly a giant leap for humankind, and the steps have kept advancing. The launch of companies like San Diego–based Illumina and China’s BGI-Shenzhen have turned genome sequencing into a competitive, fast-growing, multibillion-dollar global industry. Next-generation nanopore sequencers that electrically push DNA through tiny holes in proteins to read their contents like ticker tape have the potential to revolutionize gene sequencing even more.7