Locked Away

The results are in. The ultrasound was conclusive. And despite my previously described hunch that our growing baby is a boy, she turned out to be a girl. We are, of course, ecstatic. A healthy baby and a girl to boot! As everyone tells us, girls are simply more fun.

As I was reading in my pregnancy book the other day, I came across an interesting bit of trivia about baby girls. At this point in my pregnancy (nearly 6 months in), our baby’s ovaries contain all the eggs she’ll have for her entire life. As I mentioned in a prior post, the fact that a female fetus develops her lifetime supply of eggs in utero represents a remarkable transgenerational link. In essence, half of the genetic material that makes up my growing baby already existed inside my mother when she was pregnant. And now, inside me, exists half of the genetic material that will become all of the grandchildren I will ever have. This is the kind of link that seems to mix science and spirituality, that reminds us that, though we are a mere cluster of cells, there’s a poetry to the language of biology and Life.

But after stumbling upon this factoid about our baby’s eggs, I was also struck by a sense that somewhere someone seemed to have his or her priorities mixed up. If our baby were born today, she would have a slim chance of surviving. Her intestines, cerebral blood vessels, and retinas are immature and not ready for life outside the womb. Worse still, the only shot her lungs would have at functioning is with the aid of extreme medical intervention. The order of it all seems crazy. My baby is equipped with everything she’ll need to reproduce decades in the future, yet she lacks the lung development to make it five minutes in the outside world. What was biology thinking?

Then I remembered two delightful popular science books I’d read recently, The Red Queen by Matt Ridley and Life Ascending by Nick Lane. Both described the Red Queen Hypothesis of the evolution of sex, which states that the reason so much of the animal kingdom reproduces sexually (rather than just making clones of itself) is to ‘outwit’ parasites. In short, if each generation of humans were the same as the next, parasites large and microbial could evolve to overtake us. By mixing up our genetic makeup through sexual reproduction, we make it harder for illnesses to wipe us out. Like the Red Queen from Lewis Carroll’s classic, we keep running in order to stay in the same place (which is one step ahead of parasites and disease).

Just as there are parasitic organisms and bacteria, one might say that there are parasitic genes. For example, mutations in the DNA of our own replicating cells can cause cancer, which is essentially a self-made, genetic parasite. Moreover, retroviruses like HIV are essentially bits of genetic material that invade our bodies and can insert themselves into the DNA of our cells. And the ultimate road to immortality for a parasitic gene would be to hitch a ride on the back of reproduction. Imagine what an easy life that would be! If a retrovirus could invade the eggs in the ovaries, it would be passed on from one generation to the next without doing one iota of work. It’s the holy grail of parasitic invasion – get thee to the ovaries! According to Matt Ridley in another of his books, The Origins of Virtue, the human germ line is segregated from the rest of the growing embryo by 56 days after fertilization. Within two months of conception, the cells that will give rise to all of the embryo’s eggs (or sperm, in males) are already cordoned off. They are kept safe until they are needed many years in the future.

So perhaps my little baby’s development isn’t as backwards as it seemed at first. Yes, lungs are important. But when you’ve got something of value to others, it makes practical sense to hurry up and lock it away.

How the Giraffe Didn’t Get His Long Neck

iStock_000009818096XSmallIt’s the early 19th century, before Darwin’s Origin of Species. Before Mendel’s peas and Watson and Crick’s double helix. Scientists are struggling with the big questions of inheritance and reproduction without the aid of modern scientific methods. In this vacuum of concrete information, odd theories gained traction – some based on racial or social agendas, others on intuition or supposition.

Lamarckism, or soft inheritance, was one of the more pervasive of these ideas. According to the theory, organisms can inherit acquired traits. In the days before Darwin’s evolutionary theory, Lamarckism helped explain why organisms were so well adapted to their environments. Take the example of the giraffe’s long neck. A giraffe of yore (when giraffes had shorter necks) had to stretch its neck to reach the luscious leaves further up on tree branches. All that stretching lengthened its neck a little, and this longer neck was passed on to its offspring, who in turn stretched their necks and sired offspring who could reach even higher and munch the choicest leaves. It went on like this until giraffes were tall enough that they didn’t have to strain to reach leaves anymore.

It was a neat explanation that appealed to many 19th century scientists; even Darwin occasionally made use of it. But the theory had a nasty side as well. People applied it to humans and used it to explain differences between races or socioeconomic classes, calling the phenomenon degeneration. The mental and physical effects of years spent boozing and behaving badly would be passed down from father to son to grandson, each successively worse than his predecessor as the collective sum of each reckless lifetime added up. There was a technical term for the poor souls who wound up literally inheriting the sins of their fathers: degenerates. Certain scientists (or pseudoscientists) of the era, such as Benedict Morel and Cesare Lombroso, used the ideas of soft inheritance and degeneration to explain how violence, poverty, and criminality were heritable and could be categorized and studied.

Lamarckism, in the hands of Morel and others, offered a credible explanation of why the son of an alcoholic was more likely to be an alcoholic himself. But it did so by implying that the poor, the miserable, the suffering were inherently inferior to those with better, healthier (and probably wealthier) lifestyles. The poor were genetically degenerate, and they had no one to blame but themselves.

Thank god, thank god, Lamarckism and its corollary, degeneration, were debunked. By the 20th century, scientists knew that inheritance didn’t work that way. Our genetic information isn’t changed by what we do during our lifetimes. Besides, our sex cells are segregated from the other cells in our bodies. We don’t descend from our mothers, subject to all the stresses, strains, and yes, even boozing that their brains and bodies may have experienced. Instead, we descend from their ovaries. And thankfully, those things are well protected.

Only there’s a catch. In the last few decades, we’ve learned that while Lamarckism isn’t correct, it isn’t entirely wrong either. We’ve learned this through the field of epigenetics (literally, above genetics). This burgeoning field has helped us understand why the causes of so many heritable diseases still elude us, nearly a decade after we sequenced the human genome. Epigenetics adds untold complexity to an already complex genome. Some of its mechanisms are transient, others last a lifetime, but they all regulate gene expression and are necessary for normal growth and development. Thanks to them, females inactivate one of their X chromosomes (so women don’t get a double dose of proteins from that set of genes). Epigenetic mechanisms also oversee cellular differentiation, the process by which embryonic cells containing identical genetic material become skin cells, hepatocytes, neurons, and every other diverse cell type in the human body.

It now appears that epigenetic factors play an enormous role in human health. And what we do in our lives, the choices we make, affect our epigenome. Exposure to chemicals, stressors, or dietary changes can cause long-lasting tags to sit on our DNA or chromatin, controlling which genes are read and transcribed into proteins. For example, chronic cocaine use causes lasting epigenetic changes in the nucleus accumbens, a brain area linked to addiction. These changes boost plasticity and drug-related gene expression, which in turn probably contribute to the reinforcing effects of the drug.

But that’s not all. Epigenetic effects can span generations. No, the hardships of your parents’ lifetimes aren’t literally passed on to you in a cumulative fashion, giving you that longer neck or boozier disposition that Lamarckism might predict. Nonetheless, what your parents (and even your grandmother) did before you were born can be affecting your epigenome today.

It’s pretty wild stuff. Even if you’ve never met your maternal grandmother, even if she died long before your birth, her experiences and behavior could be affecting your health. First of all, the prenatal environment your mother experienced can have epigenetic effects on her that then propagate on to the next generation (you). Moreover, all the eggs a female will ever make have already formed in her ovaries by the time she’s born. They may not be mature, but they are there, DNA and all. I think that’s a pretty amazing transgenerational link. It means that half the strands of DNA that wound up becoming you were initially made inside your grandmother’s body. As science reveals the power of the prenatal environment, evidence is mounting that even what your grandmother ate during your mother’s gestational period and whether she suffered hardships like famine can alter your own risk for heart disease or diabetes.

Luckily, epigenetic gene regulation is softer and less absolute than its cousin Lamarckism. It is reversible and it can’t accumulate, generation upon generation, to create a degenerate class. The science of today is more humane than the old guys predicted, but it doesn’t let us off the hook. Epigenetics should remind us that we must be thoughtful in how we live. Our choices matter, for ourselves and for our offspring. We don’t yet understand how epigenetic mechanisms control our health and longevity, but that isn’t stopping our bodies from making us pay for what we do now.

Who Am I Again?


Thanks to a recent kerfuffle over the Earth’s precession and its effect on our astrological signs, many people have spent this week questioning their personality traits. I went from being a life-long Gemini (changeable, duplicitous) to a possible Taurus (stubborn, steady), neither of which I think describe me. I’ve never believed in astrological signs, but many people do, and this week must have been a confusing one for them.

The whole thing got me thinking about how we look outward for explanations and definitions of our inner selves. No one has a better vantage point than we do to observe our own personal thoughts, feelings, attitudes, and behaviors. How funny that we once looked to the stars in order to understand ourselves! Those of us who consider ourselves scientific and modern are no better. Although we scoff at sun signs and palm readings, increasingly we are turning to our brains and our DNA for answers that they simply can’t give.

In the 1800’s, the Phrenological Fowlers (later Fowlers and Wells) founded a nationwide industry on reading people’s personalities based on the bumps on their heads. They published extensively and sent emissaries to small towns throughout the U.S. so that, for a small fee, the masses might come to know themselves better. The company and its methods were an unrivaled success. America was obsessed with phrenology. Sometime in the 1860’s, a curious Mark Twain visited Fowler’s office under an assumed name. Fowler read his head and said that his skull dipped in at a particular point where it should have bulged out – a sure sign that Twain, the preeminent American humorist, utterly lacked a sense of humor.

Nowadays, many still look to their brains for answers. When I used to scan participants in fMRI experiments, they would often ask what I could tell them about their brains. I couldn’t tell them anything; all the analysis took place later, back at the lab. But as a frequent subject in pilot experiments for my own and colleagues’ studies, I’ve had unfettered access to data from my own brain. I know that I have a large and robust fusiform face area (a region thought to be critical for face recognition) and a rather dinky visual word form area (implicated in identifying letters of the alphabet.) What does that mean, when I am an avid reader and often embarrass myself with my poor ability to recognize faces?

While people still look to the stars and to brains (if not skulls) in order to understand themselves, the next big thing has arrived. The age of personal genomics is upon us and countless startups out there are eager to swap a check and a swab of our cells for a glimpse into our futures and ourselves. I have to admit, I fantasize sometimes about having my genome read. I would love the chance to pour through details about my ancestral line or learn what type of diseases I am predisposed to developing. But the biggest draw is to learn about myself. What forms of the anxiety genes do I have? What about genes linked to mental illness, intelligence, novelty-seeking? As a scientist, I know that complex traits are determined by a mixture of environment and numerous genes, many of which we haven’t yet discovered. Beyond that, epigenetic factors influence the expression of our genes in ways we don’t yet understand. Yet I still find myself wishing someone would hand me that printout with the secrets to myself.

The cognitive scientist Steven Pinker wrote a wonderful essay wading through his results when his own genome was sequenced. In it, he struggles with the discrepancies. His genome says he should be sensitive to bitter flavors, yet he enjoys beer, broccoli, and brussels sprouts. His genome says he has a high risk of baldness, yet he is known for his thick mane of overflowing, curly hair. Other results he believes or would like to believe. What is a person seeking direction and self-wisdom to do?

So at the end of this astrologically confusing week, I find myself at a loss. Why do we crave external guidance to help us understand our internal selves? It may be because we are less static and more changeable than we like to believe. As I alluded to in my post about our potential to do evil, psychology experiments (and history) have shown that human beings are heavily influenced by their circumstances. Because we are adaptable, we behave very differently depending on who we are with and what we are doing. Although the adaptability may be advantageous, I suspect it unsettles us. We want to believe we have a solid, stable identity, and we will look to mystics or scientists – anyone who can give us that assurance. I know who I am and who I always will be.

The hard (but in its own way beautiful) truth is that we are each a complex and contradictory landscape of traits, behaviors, and passions. Be wary of those who try to describe you with a handful of paltry adjectives. Know thyself. Or keep trying, anyway. It should take at least a lifetime.

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