How Do Genes Work?
On April 25, 1953, two young researchers at Cambridge University in England—James Watson and Francis Crick—published a paper in the journal Nature arguing that the structure of DNA consisted of two interlocking strands arranged in a double helix, something like a twisted chain ladder. In their proposed model each rung of the ladder consisted of a molecule called a base from one chain, paired with a complementary base from the other chain. As a result, if you pulled the chains apart, each of them could act as a template from which a new complementary partner could be created. In this manner, one molecule of DNA could turn into two. Watson and Crick’s article was brief and contained only one sentence that hinted at its implications: “It has not escaped our notice that the specific pairing we have postulated suggests a possible copying mechanism for the genetic material.”
Watson and Crick’s publication came almost exactly two years before Einstein’s death. Unlike Einstein’s general relativity, their work was neither a great conceptual leap nor an advance that would have been greatly delayed had they not gotten there first. But it did mark the beginning of a new era in biology, which allowed scientists to study the details of inheritance on the molecular level. No one knew where that investigation would lead, although Watson and Crick published a speculative paper about the meaning of their work a month later. In June the New York Times ran an article with the timid headline “Clue to Chemistry of Heredity Found,” along with a cautionary statement from famed Caltech chemist Linus Pauling that he “did not believe the problem of understanding molecular genetics had been finally solved.” Pauling—who the next year would win the first of his two Nobel Prizes—was right.
How complex is the mechanism of heredity? Today, some sixty years later, tremendous progress has been made, but thousands of scientists are still working out the details.
The idea of evolution goes back at least to the ancient Greeks, but what many consider the first coherent theory of the subject—involving the concept of inherited traits—was proposed around 1800, decades before Darwin, by the French scientist Jean-Baptiste Lamarck. According to Darwinian evolution, new traits, such as the giraffe’s long neck, arise through mutations, which make it possible that the traits of a child might not correspond to the traits of either parent. If, given the environment, that new trait turns out to provide an advantage, the child will thrive, reproduce, and pass the mutation on to subsequent generations. But Lamarck believed that animals’ traits are not limited to the effects of their heredity. He proposed that traits can change during an organism’s lifetime in order to allow it to best adapt to its environment, and that the organism’s newly developed traits can then be passed to the next generation. In this view, for example, if a giraffe were suddenly moved to an environment with taller trees, its neck might grow longer, in which case subsequent offspring could be born with longer necks. Today we call that process soft inheritance. It is not the way evolution normally operates, though recently scientists have discovered that such processes do occur, spawning a field called epigenetics, which I will return to later.
Both Darwinian and Lamarckian theories of evolution raise a crucial question: how are traits passed from parent to child? In 1865 Czech monk Gregor Mendel presented a paper showing that certain traits in peas, such as shape and color, are passed along in discrete packages we now call genes, but his work went unappreciated until the turn of the century. Meanwhile, the molecule we now call DNA was discovered in 1869 by Friedrich Miescher, a Swiss physician studying white blood cells he obtained from the pus in surgical bandages. Miescher didn’t know what the substance was good for, but he knew there was a lot of it—there is in fact enough DNA in almost every human cell to make a strand about six feet long.
The connection between genes and DNA didn’t get made until 1944. Before that, if there was one thing scientists were confident about, it was that DNA was not the molecule of heredity. That is because DNA seemed far too simple—it was known to be made of just four different components, called nucleotides. (Each nucleotide consists of a base, as I mentioned—one of four different types—plus two other small molecules, a sugar and a phosphate molecule, which we now know form the spine of the DNA.) Then in 1944, after many years of intricate experiments, a shy sixty-seven-year-old researcher named Oswald Avery and his colleagues showed that if DNA was extracted from dead bacteria and injected into a live strain, it caused permanent changes in the DNA and traits of the live strain, which were inherited by subsequent generations. Avery’s work inspired a search to discover the structure of that mystery molecule, culminating in Watson and Crick’s discovery of the double helix in 1953.
Roughly speaking, in modern parlance a gene is a region of an organism’s DNA that contains instructions for making a particular protein. Biologists say that the gene “codes for” the protein. The code, or recipe, is written using just four letters—A, C, G, and T, which stand for the four bases that make up DNA—but the recipe book is a long one, containing over three billion pairs of bases. When the recipe is used successfully to create the protein product, the gene is said to have been “expressed.” The proteins are all cooked up from a pantry of just twenty amino acids. Proteins constitute much of any organism’s physical structure, are involved in virtually every cell function, and control all the chemical processes inside the cell. Each of our bodies contains over a hundred thousand different proteins, including our hormones, enzymes, antibodies, and transport molecules such as hemoglobin.
The traits we inherit are determined by the proteins our bodies produce, which are in turn dictated by the recipes in our genes. The cookbook containing all those recipes is an opus of many volumes called the genome, the different volumes of which are called chromosomes. We all have distinct characteristics, some due to our environment and experiences, others arising from our heredity. Since each of us has a different heredity, my genome is different from yours. What, then, does it mean to speak of “the human genome”?
Our personal differences seem great to us. Some of us would rather shovel snow than listen to opera, while others can’t imagine a world without La traviata. Some propose marriage over a quiet picnic on the beach, others at a table next to a drunken rugby team at the Outback Steakhouse. But on the level of genes, what makes us alike is far, far greater than what makes us different: the genomes of any two human beings typically differ by only about one letter out of each thousand. They are virtually identical, like copies of the same book that differ only in their misprints.
The misprint metaphor is apt here: our genetic differences arose through mutations—random changes in the genetic letters—that occurred over the millennia. These mutations account for that part of human variability that is not due to differences in experience or environment, such as our differing blood types, hair and skin colors, and facial features, and perhaps even for why some of us can carry a tune, while the singing of others could be used to keep rats out of the basement.
All told, humans are now thought to have about twenty-three thousand genes. That’s fewer than a newt has, or a grape, which is bound to make those who believe that bigger is better a bit uncomfortable. That illustrates the dangers of oversimplified thinking, and indeed though I’ve given the big picture of how genes are connected to traits, it is important to keep in mind that it is a greatly simplified version. For example, each cell has not one, but two copies of the recipe book, since we receive one intact genome from each of our parents. When the recipes conflict, sometimes one prevails over the other, but at other times some sort of compromise is made, or a completely different protein is created. Also, many genes contribute recipes for more than one protein—almost half of our genes are spliced in order to produce multiple proteins, which is why we can have more than a hundred thousand proteins but just twenty-three thousand genes.
The effect of a gene also depends a great deal on what is called “gene regulation”—processes that determine whether the recipe dictated by the gene is actually carried out or, as we say, expressed. On the molecular level gene regulation occurs when certain chemicals interact with parts of the DNA molecule to inactivate a gene. As a result, for example, two identical twins—who by definition have the same DNA—can be strikingly different. In rodents called agouti mice one twin can be thin and brown, while the other is obese and yellow. Such obese yellow mice result from environmental effects. These mice occur occasionally in natural conditions, but when pregnant agouti mice are exposed to a chemical called bisphenol A, present in many plastic drink bottles, significantly more obese yellow mice are born. It was found that as a result of the exposure, the DNA of the offspring have less “methylation,” a process that turns off genes. This causes more than the usual amount of a certain protein to be produced, which in some mice has two disparate effects—one in the skin (blocking cells from making black pigment) and the other in the brain (affecting feeding behavior). Though giraffes don’t develop long necks by stretching toward trees, as Lamarck believed, the expression of genes—and hence the makeup of an individual—can, through gene regulation, be profoundly affected by the environment, and you don’t need chemical toxins to do it. Himalayan rabbits, for example, carry a gene required for the development of pigment. But the gene is inactive in temperatures above 95 degrees Fahrenheit, which is below the rabbits’ body temperature—except at their extremities, which are cooler. As a result, Himalayan rabbits are white, with black ears, nose tips, and feet.
Changes in traits that, like these, are due to mechanisms other than a change in the underlying DNA are called epigenetic. Because of gene regulation and epigenetic changes, there can be many characteristics within an organism (of any species) which did not arise at conception, but rather are a reflection of the interaction between the genome and the information in the organism’s environment, from its time in the womb onward through life. In a few cases these epigenetic changes have been observed to continue through many generations. These instances correspond to the Lamarckian view of evolution, in which traits that change within the lifetime of an individual can be passed on to that individual’s descendants.
Another complication to the simple picture is that only 1 or 2 percent of the genome corresponds to the genes I described above, the recipes for proteins. The rest was mislabeled “junk DNA” by scientists before anyone understood its purpose, but it has since been discovered that most of this “intergenic” or “noncoding” DNA—terms now preferred by scientists—does indeed serve an important function. About half of it stabilizes the structure of the chromosome, which is a strand of DNA packaged in a protein. Other sequences define where genes begin and end, something like the capital letter and period that play the same role in language. Sequences called pseudogenes are copies of normal genes that contain a defect that prevents their expression as proteins. They used to be thought of as vestigial—perhaps the only true “junk” in our genome—but a breakthrough in 2010 indicated that they may play an important epigenetic role, keeping their normal gene sisters from becoming deactivated.
If this all seems complicated, that’s good, because living things are complicated. In computer programming a “kludge” is an ad hoc and perhaps clever but inelegant alteration to a program to accomplish some added purpose, or maybe to fix a bug. A program with many kludges can be complex and difficult for an outsider to decipher. But kludges are how evolution operates. For example, our ancestors needed a tail and we still have the gene for making one; rather than neatly excising it when the need for the tail disappeared, natural selection just turned the gene off.
Although the general ideas of science can often be described succinctly, there is an awesome complexity to biological systems that doesn’t come through in such accounts. One might describe the hippocampus as a tiny structure deep in the brain that plays an important role in emotion and long-term memory, and as far as it goes that is quite accurate; but the standard textbook on the hippocampus is several inches thick. Another recent work, an academic article reviewing research on the interneurons—just one type of nerve cell in another part of the brain called the hypothalamus—was over a hundred pages long and cited seven hundred intricate experiments. Few of us would have the patience or the ability to digest such publications, but fortunately for the human body of knowledge, there are those among us, shaped by who knows what interplay between their genome and their environment, who consider them compelling reading.
Being human, we often hope for simple links, like an easy correspondence between a single gene and a trait or a disease, and scientists sometimes find them—as in cystic fibrosis and sickle-cell anemia. Deepak’s metaphysics is always free to offer easy but vague answers and unsupported statements such as “You can’t start from a meaningless cosmos and get to the rich meaning of human life” or “Human life is embedded in the domain beyond space-time,” but science must give answers that are true, as determined by experiment, and the truth is rarely simple.
The richness of life comes from its complexity. It is a great gift that one can live and love and function as a being, the cooperative effort of thousands of trillions of cells, intricately and elaborately organized. And yet amidst all life’s complexity one can still find unity. I said above that it is only 0.1 percent of our genes that differentiate one human from another. The gene difference between a person and a chimpanzee is only about fifteen times that—we share 98.5 percent of our genes with those primate cousins. And we share over 90 percent with mice, and 60 percent with the lowly fruit fly. There seems to be integrity to life on Earth, resulting from its common basis, the molecule of DNA.
We are all here—from the grape to the fruit fly to the human—carrying our DNA forward. Every creature on Earth is a unique expression of it. But unique as each one is, all organisms share the same evolutionary mandate: to promulgate their own special version of that extraordinary molecule that—in 1869, in the guise of a being called Friedrich Miescher—made the discovery of its own existence.
From a spiritual perspective, my role isn’t to argue against Leonard’s fine account of how genes have evolved into the rich complexity that they display today. In all the great questions that face us, science is our best means of describing physical events. But spiritually speaking, genes exist to do more than provide a recipe book for life. Let’s see what that “more” is, which contains many surprises.
I attach great importance to the small number of human genes, but it takes a bit of discussion to show why. As the Human Genome Project was nearing completion in 2003, bets were informally placed. Would it turn out that we possess 80,000 genes, or 120,000? It was assumed, as the most advanced species on the planet, that our complexity required far more genes than any other species. What a shock, then, when the number came in at between 20,000 and 25,000, about the same number as a chicken or a lowly worm like the nematode. Corn had more genes, which was baffling. We experienced a minor version of the shock that hit the Victorians when Darwin revealed that Homo sapiens, like all mammals, was descended from fish.
In both cases the shock proved highly productive. As Leonard has described so well, inheritance is far more flexible than anyone ever supposed fifty or even twenty years ago. At that time we were getting to the point where “my genes made me do it” was turning into a universal explanation: my genes made me overeat, caused my depression, reduced my sex drive, made me suicidal, or made me a believer in God. The code of life was being interpreted like a code of law. Cells are not fixed structures, however; they are fluid, changing, and dynamic. They respond to thoughts and feelings; they adapt to the environment with all the unpredictability of a person. For anyone who values life’s rich possibilities, that’s very good news.
When schoolchildren are taught about the double helix, the example used over and over is that there is a gene for blue eyes, another for blond hair, and yet another for freckles. This gives the impression that one gene equals one trait, but that is the exception, not the rule. I mentioned before how frustrating it was for geneticists to discover that what should be a simple link to how tall a child will grow has turned out to be a complex, dynamic process involving not just twenty different genes but a host of outside factors from the environment. Alzheimer’s or cancer seems to involve even more genes.
As a result of this murkiness, geneticists eager to fulfill the promise of DNA to improve human life are redoubling their efforts. Since that’s also a spiritual goal, how can the two join forces? One way is to quickly get past chemical determinism. The public is still being told that there might be a “criminal gene,” for example, that explains antisocial behavior. There’s speculation that such a gene could even be offered as a defense in court, and it wouldn’t be a big step to propose that antisocial genes could be removed through some kind of medical procedure, say, for the good of the criminal and society as a whole. But as genetics is being forced to abandon the simplistic notion of finding a single gene to fit every disorder, there is an opening for spirituality, which stands for free will, consciousness, creativity, and personal transformation—the opposite of chemical determinism. We should celebrate being released from our genetic shackles, while at the same time seeking more insight into how genes relate to consciousness.
DNA is treated by biologists like any other chemical sequence, but its behavior breaks the rules of mere objects. It spontaneously divides itself in half, turning into two identical versions of itself. It encodes life but also death, since there’s a gene for cancer that must be triggered for malignancies to develop. Why in the world would evolution retain such a gene when its whole purpose is to sustain life? And at an even more basic level, how do genes make inanimate chemicals like hydrogen, carbon, and oxygen come to life?
Tracing these issues back to the genome is a feature of materialism. Instead of flying in the face of facts, the spiritual perspective calls for expanded facts. Without them, we can’t hope to solve, for example, how DNA deals with time. Genes precisely time their actions years or decades in advance. Baby teeth, puberty, menstruation, male-pattern baldness, the onset of menopause—all these appear on a timetable; the same may also apply to cancer, which is largely a disease of old age. How does a chemical keep track of time? I asked a cell biologist that question and he pointed to telomeres, genetic material that caps the ends of genes like a dangling tail. (We previously touched on them in discussing the nature of time.) Telomeres bring a genetic word to a stop, the way that a period brings this sentence to a stop. But telomeres degrade over time, and aging could be based on their growing shorter and shorter, leading to cellular degradation and higher risk of harmful mutations.
But if the telomere really is like a clock, where did it get its sense of timing? Rocks are worn down by wind and rain, but that doesn’t make them clocks. Besides, how can telomeres lead to the harmful effects of aging and also to the beneficial effects of losing your baby teeth and passing into puberty? Even more mysteriously, DNA coordinates many different clocks simultaneously, since the timings of the processes I mentioned are very different from one another. Menopause obeys a clock that takes decades to unfold, while the steady production of enzymes in a cell takes a few hundredths of a second, red blood corpuscles follow a life cycle of a few months, and so on.
The reader will see where this is going. Genes don’t behave like ordinary things, because they serve consciousness. Timing requires a mind, and leaving mind out of the equation fatally flaws any genetic theory. To a materialist, the thought of mind outside the body is outlandish, but there is simply too much that mindless, random chemical reactions cannot explain. At bottom, a deep spiritual issue is at stake: free will versus determinism. At first, determinism was just physical, but lately it has been invoked to rule human behavior, too; whether you’re acting criminally, depressed, or awed before God, the argument is the same: if genes cause X, and you cannot change the genes that you’re born with, then X is here to stay.
Everyday experience belies this logic; none of us feels controlled by the nucleus of our cells. Leonard allows for environmental influence on our genes. I would make it a decisive factor. Identical twins offer a good test case. They are born with the same genes, but as life progresses, twins make different choices and go through different experiences. One twin may run away with the circus while the other joins a convent. One may become an alcoholic while the other becomes a vegan. By age seventy, the expression of their genes will be completely different from the perfect match they displayed at birth. In other words, the chromosomes haven’t altered, but the genes that got triggered, along with the products they produce in the tissues, have widely diverged. The escape route from chemical determinism was always there, waiting to be used.
Genes have no effect until they are switched on; they remain mute, as it were. When they do speak, a lifetime of experiences shapes the words expressed, even though the starting point is the same alphabet. Genes don’t tell our story; they give us the letters to tell our own story, and that genetic expression can be positive or negative. If twin A habitually lives with low sleep, high stress, a bad diet, and no exercise, such a lifestyle is likely to lead to drastic outcomes compared to those for twin B, who has chosen the opposite lifestyle. Studies in positive lifestyle choices by Dr. Dean Ornish and his research team have shown that more than four hundred genes change their expression in a positive way if someone practices the well-known preventive measures of diet, exercise, stress management, and good sleep.
In a word, the tables have been turned. Where genes used to take responsibility off our shoulders for the things we don’t like about ourselves, now they have become the servants of the choices we make. “Soft inheritance” is happening every second, as your cells adapt to the instructions you give them. For decades we’ve known that depressed people are at higher risk for disease, as are lonely people, the recently widowed, and executives who have been forced out of their jobs. The body can’t respond to such traumas without genes being involved, but back when genes were considered fixed, permanent, and unchangeable, no one thought much about the connection between the environment and DNA. (“Environment” in this case is a broad term to cover any outside influence on a cell.) Now doctors routinely warn pregnant mothers that they put their fetuses at risk by smoking and drinking, for instance, since we know that toxic chemicals in the bloodstream degrade the environment of an unborn child.
The next step was to show that toxic behavior can have the same effect. For a long time it was assumed that embryos develop automatically from the blueprint of the DNA inherited from their parents. As long as the fetus received the right nutrients in the womb, the theory went, the blueprint would unfold stage by stage until a baby was born. But as Professor Pathik Wadhwa, a specialist in obstetrics and behavioral science at the University of California, Irvine, puts it, “This view has more or less been completely turned upside down.… At each stage of development, the [fetus] uses cues from its environment to decide how best to construct itself within the parameters of its genes.”
Suddenly we find that we can add a new chapter to autopoiesis, or self-creation. The unborn embryo is part of a complex feedback loop, assessing the present to create a future for itself. DNA does the same thing. It takes cues from a person’s thoughts, moods, diet, and stress levels (to simplify the thousands of chemical signals coming into a cell at any given moment), and based on those cues, it expresses itself. A stressed-out mother passes on higher stress hormones to the fetus. Premature birth is then a risk; so is much else. Professor Wadhwa continues, “The fetus builds itself permanently to deal with this kind of high-stress environment, and once it’s born may be at greater risk for a whole bunch of stress-related pathologies.”
Where does that leave us? Our knowledge of medicine and biology has been shaken to the core. Genes do not control themselves. They are controlled by the entire mind-body system: in others words, we aren’t pawns but masters of our genes, which respond to everything we think and do. The signals from the epigene, the sheath of proteins that surrounds our DNA, are capable of causing thirty thousand different expressions from a single gene. The program of life is dynamic, constantly changing, and under our influence insofar as we make good or bad choices.
More and more, researchers are realizing that genes are more like rheostats than like on-off switches. Areas of “junk DNA” are vitally important, as Leonard touches upon, since they decide which genes to turn on, how much activity a gene expresses, when the activity occurs, and how it relates to thousands of other genes. But as we now know, these genes don’t control themselves. No one can tell the final story of the gene until it includes the way in which we metabolize experience. The epigene shows us that even invisible things like stress turn into bodily processes; whatever you feel, every cell in your body also feels. None of this comes as a surprise to those of us who work in the realm of spirituality. The very basis of the spiritual worldview is that everything is entangled and interconnected; one process diversifies into thousands of specific processes without losing its wholeness.
I find myself deeply moved when I reread some lines from the great Bengali poet, Rabindranath Tagore, as he addresses his creator. “Time is endless in your hands, my Lord. There is none to count your minutes. Days and nights pass. You know how to wait. Your centuries follow each other perfecting a wild flower.” I don’t read these words theistically, based on the existence of the God of any particular faith. What moves me is the patience and intricate workings of cosmic intelligence, which moves through us in order to create us, as life unfolds from within itself.