Halfsies!

My husband spotted another one yesterday. A half-Indian, half-Caucasian blend. The woman had an Indian first and last name, but her features were more typical of a Persian ethnicity than either Indian or white. My husband overheard her describing her heritage and smiled. These days, with a half-Indian, half-white baby on the way, we’re hungry for examples of what our baby might look like. We’ve found a few examples among our acquaintances and some of my husband’s adorable nieces and nephews, not to mention the occasional Indian-Caucasian celebrity like Norah Jones. We think our baby will be beautiful and perfect, of course, although we’re doubtful that she’ll look very much like either one of us.

Many couples and parents-to-be are in the same position we are. In the United States, at least 1 in 7 marriages takes place between people of different races or ethnicities, and that proportion only seems to be increasing. It’s a remarkable statistic, particularly when you consider that interracial marriage was illegal in several states less than 50 years ago. (See the story of Loving Day for details on how these laws were finally overturned.) In keeping with the marriage rates, the number of American mixed race children is skyrocketing as well. It’s common to be, as a friend puts it, a “halfsie.” At least in urban areas like Los Angeles, being mixed race has lost the negative stigma it had decades ago and many young people celebrate their mixed heritages. Their unique combinations of facial and physical features can be worn with pride. But the mixture goes deeper than just the skin and eyes and hair.

At the level of DNA, all modern humans are shockingly similar to one another (and for that matter, to chimpanzees). However, over the hundreds of thousands of years of migrations to different climates and environments, we’ve accumulated a decent number of variant genes. Some of these differences emerged and hung around for no obvious reason, but others stuck because they were adaptive for the new climates and circumstances that different peoples found themselves in. Genes that regulate melanin production and determine skin color are a great example of this; peoples who stayed in Africa or settled in other locations closer to the Equator needed more protection from the sun while those who settled in sites closer to the poles may have benefited from lighter skin to absorb more of the sun’s scarce winter rays and stave off vitamin D deficiency.

In a very real way, the genetic variations endemic to different ethnic groups carry the history of their people and the environments and struggles that they faced. For instance, my husband’s Indian heritage puts him at risk for carrying a gene mutation that causes alpha thalassemia. If a person inherits two copies of this mutation (one from each parent), he or she will either die soon after birth or develop anemia. But inheriting one copy of the gene variant confers a handy benefit – it makes the individual less likely to catch malaria. (The same principle applies for beta thalassemia and sickle cell anemia found in other ethnic populations.) Meanwhile, my European heritage puts me at risk for carrying a genetic mutation linked to cystic fibrosis. Someone who inherits two copies of this gene will develop the debilitating respiratory symptoms of cystic fibrosis, but thanks to a handy molecular trick, those with only one copy may be less susceptible to dying from cholera or typhoid fever. As the theory goes, these potentially lethal mutations persist in their respective populations because they confer a targeted survival advantage.

Compared to babies born to two Indian or two Caucasian parents, our baby has a much lower risk of inheriting alpha thalassemia or cystic fibrosis, respectively, since these diseases require two copies of the mutation. But our child could potentially inherit one copy of each of these mutations, endowing her with some Suberbaby immunity benefits but also putting her children at risk for either disease (depending on the ethnicity of her spouse).

The rise in mixed race children will require changes down the road for genetic screening protocols. It will also challenge preconceived notions about appearance, ethnicity, and disease. But beyond these practical issues, there is something wonderful about this mixing of genetic variants and the many thousands of years of divergent world histories they represent. With the growth in air travel, communication, and the Internet, it’s become a common saying that the world is getting smaller. But Facebook and YouTube are only the beginning. Thanks to interracial marriage, we’ve shrunk the world to the size of a family. And now, in the form of our children’s DNA, it has been squeezed inside the nucleus of the tiny human cell.

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.

Grandparents’ Last Gift

My fiance’s grandmother passed away today. We will miss her very much. Her passing reminded me of my own grandparents, all of whom died a long time ago. It’s interesting and maybe in its own way poetic that one of the gifts our grandparents give us is our first experience with death. At least for most of us, our grandparents are the first people we truly knew and loved who died.

One of my grandmothers died before I was born, and one grandfather died when I was two, before I can remember. My other grandfather died when I was twelve. My father and I drove all day to reach his nursing home downstate, arriving in time to see the nurses wheel a body bag out of his room. Seeing his face in the casket was my first experience with death. Kissing his cheek at the service was the first time I touched a body devoid of life. I’ve done it more than once since then.

My last grandmother died when I was twenty-one. She died in home hospice care, slipping into a coma and passing away over the course of two days. Her breath and pulse were so faint that we couldn’t tell exactly when they stopped. The hospice nurse told us to watch her fingernails. When they turned blue, she was almost or already gone. I held her hand and watched them blue and when she was gone, I wasn’t as scared of death as I’d been before.

Unlike cultures elsewhere, and certainly, societies of the past, ours is stunningly sheltered from the realities of death. We don’t prepare the bodies of our loved ones for burial or witness their cremation. Their remains disappear and reappear as ashes or clean, well-dressed bodies in silk-lined caskets. Death isn’t something we’re comfortable talking about, even though it’s the one inevitability in our lives. Maybe it’s because the American culture is one of optimism, the make-lemonade-from-lemons mentality. But grandparents give us the gift of a quiet truth: that everything eventually ends, that our parents and spouses and our selves will pass, and that the world will continue without us.

Rest in peace, Shanti Bansal. We will keep you in our hearts and our memories.

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