That’s why obstetricians stress avoiding alcohol during pregnancy. For the most part it’s been assumed that when it comes to alcohol and pregnancy, there is no known safe level of exposure. On the other hand, though, we know that sometimes babies are born to mothers who drank alcohol during their pregnancies and those children appear virtually unscathed.
Why the difference? Because we are all genetically diverse—and particularly, it seems, as it relates to alcohol metabolism. Depending on what genes have been inherited by a mother—and what genes she and her partner have passed on to their child—the impact of alcohol on a fetus can be mildly toxic or like an incredibly potent straight-up poison.9 Given the uncertainties during this part of our children’s developmental journey, the best approach, in my opinion, is still to avoid drinking during pregnancy altogether.
That’s probably good advice for any questionable substance, including unhealthy foods, that a woman puts into her body during pregnancy, but it might be especially important when it comes to alcohol—and particularly during the first stages of development, when sober cilia, so to speak, are vitally important.
In a way, cilia are sort of like genetic conductors in a developmental orchestra. If you’ve ever watched an orchestral maestro at work, you know that it’s hard enough to make symphonic music when you’re sober. Just imagine trying to do it while you’re drunk. That’s why researchers have found that children of mothers who drank excessively during pregnancy may have many issues related to laterality, including difficulty hearing from their right ear and challenges interpreting speech, both functions that are generally processed on the left side of the brain.10
Instead of genetically directing the developmental orchestra through a spectacular performance of harmonies, melodies, and rhythm, malfunctioning cilia conduct performances that are more reminiscent of the work of Japanese composer Toru Takemitsu, whose often discordant compositions are fascinating to contemplate and study but can be hard to understand. And that’s the challenge with genetic diseases known as ciliopathies, which are caused when cilia fail to perform their normal functions.
To understand ciliopathies, it’s important to understand cilia and the genetics that are behind them. And to do that, first you must know that cilia are everywhere—and I mean absolutely everywhere. While you might never have heard of them, they’ve been looking out for you and your well-being since before you were born. Like a modified form of touch, some of your cells even use cilia to physically sense their way around their microscopic world.
However, there are other compelling examples of the importance of using touch to make sense of the world around us.
The American sculptor Michael Naranjo was blinded and lost the use of his right hand in a grenade attack when he was a 22-year-old soldier in Vietnam. While being treated at a hospital in Japan, Naranjo, who came from a family of artists in New Mexico, asked a nurse if she might find him a small piece of clay. A few days later she was able to fulfill his request, and Naranjo set out on an artistic journey that has taken him around the world.11 Many years later, he was even invited to the Galleria dell’Accademia in Florence, Italy, where a special scaffold was erected so that he could run his hands over the face of Michelangelo’s David. This is how Naranjo sees.
Like this amazing artist, our cells are physically blind and use their genetically encoded cilia as a means by which to sense the world around them. Even though cilia are so fundamental to our own lives, given their hidden microscopic size most of us don’t give them a second thought. What they lack in size, they more than compensate for in consequence.
Their impact on our lives begins very early—earlier even than the time that our cilia get to work stirring and sensing the embryonic fluids that make us who we are—because cilia also play a vital role in conception.
For starters, the tail of a sperm is a modified cilium known as a flagellum. If it doesn’t beat right, it won’t swim right, and if it doesn’t swim right, it won’t get to where it’s supposed to go. On the other side of the operation, cilia sit at the entrance to the fallopian tubes, where they beat faster during ovulation to create a strong current to usher in the egg from the ovary.
Our lungs are also considerably dependent on cilia to keep things physically tidy, and this is an important factor that helps oxygen move from the outside world into our bodies. Like concert revelers passing a crowd surfer across a sea of outstretched arms, our cilia also clear out mucus, dust, and microbes from our lungs. That’s a tough task even in the best of circumstances, but it’s made all the more difficult when we smoke, inhaling chemicals that can adversely affect cilia. Anytime you hear a smoker’s cough, you can say a little thank-you to your cilia—because that’s what we’d all sound like if those genetically driven little guys weren’t doing their jobs.
But you don’t have to be a smoker for this process to break down. All you have to do is inherit specific mutations in genes, such as DNAI1 and DNAH5, which cause cilia to misbehave. The genetic condition caused by mutations in these genes is known as primary ciliary dyskinesia or PCD. As we’re beginning to understand, more and more, most of what cilia are doing remains hidden to all of us. But when they’re not working well, the muscle and elastic tissue of the lungs eventually break down, resulting in difficulty breathing and swollen sinuses that block nasal drainage. All of these symptoms are the result of genetic conditions involving cilia that, for one reason or another, haven’t gotten the signal to beat the way they’re supposed to.
Some people with PCD also can have situs inversus, which, among other things, creates a great opportunity for senior physicians to have a field day with young doctors.
I went through this hazing ritual once while I was a medical student. During an observed physical examination, one of our physician instructors asked me to “tap out the liver.” This a percussive technique that has been used for centuries by doctors to estimate the size of this vital organ—something that is crucial to know, even today after the advent of ultrasound. But the senior doctor conveniently didn’t mention before I started that this particular patient had situs inversus totalis, which means all of her major organs were on the side opposite of normal.
“Moalem, is there a problem?” the doctor asked as I fumbled around the patient’s abdomen, trying desperately to repeat what I had practiced so many times on friends, family, and patients while studying for my examinations.
“Well…I…um…”
“Come now, lad, just tap it out.”
“I am…I mean…it seems as though…um…”
At this point I was so flustered that I didn’t notice that the patient, who was in on the joke, was trying hard to control her laughter. She finally began laughing hysterically—a sign I at first took to mean that I must have been inadvertently tickling her abdomen as I searched for her seemingly absent liver. It wasn’t until everyone in the room began laughing as well that I realized that I was, in fact, the butt of the joke.
Now, looking back, I can easily say that this particular practical joke, while quite embarrassing at the time, was one of the most instructive lessons of my medical education. It taught me to always take a moment, before examining a patient, to clear my mind of any assumptions I might have.
Turning a physician’s mind into a medical tabula rasa isn’t easy. Some things we simply take for granted—especially if, as part of our medical training, we come to have certain clinical assumptions about human anatomy and physiology.
Indeed, this has become even more challenging as I have become a busier physician. But it has also become more important, because the closer we get to truly personalized medicine, the more critical it becomes for us to move beyond previous assumptions.
There are still some things, though, that we believe to be true for everyone. When it comes to our health, the genetics behind our cilia are unwaveringly important. Helping embryos decide where to form their internal organs isn’t all that cilia do. They are also involved in the proper internal structural form
ation of our kidneys, liver, and even the retinas of our eyes.12 Just like Naranjo’s hands running across a piece of marble, modified cilia even help facilitate proper bone formation as they help cells spatially orient themselves in three dimensions.
As it turns out, there’s almost no place in our bodies where cilia have not played a major role. And yet they still remain one of the most fundamentally under-studied structures we have.
Without genes that give us working cilia, we don’t have laterality. And without laterality, our internal organs and brain don’t form properly. This is why laterality is at the heart of life as we know it. As we’re about to see, laterality or sidedness has unspeakably deep genetic implications, ones that may be literally out of this world.
Sometimes, we just have to pick a side. I witnessed a comical real-world example of this a few years back while getting ready to cross a bridge that served as a border crossing point between Thailand and Laos. Thais drive on the left and Laotians drive on the right. When the border crossing opened on that morning there was a substantial bit of chaos and hilarity as drivers tried to figure out which side of the bridge they were supposed to cross on.
It’s like this deep within our bodies, too. Without choosing sides, we’d be quickly lost in a world of molecular and developmental chaos. Because of this, almost everything is set up in such a way that it is oriented to the left or to the right. And despite what the “righties” of the world would have you believe, our internal biochemistry seems to favor so-called “left-handed” molecular configurations.
Take the 20 different amino acids that work together to build millions of different proteinaceous combinations. At a very basic level, our bodies use amino acids as the material building blocks that give our bodies form and function. The specific order in which amino acids are strung together is dictated by information that is provided and translated from our genes. A change in one letter of DNA can change the amino acid that is used in making a protein and it can also completely change the protein’s ability to do its job. And, of course, that makes amino acids and the order in which they are put together extremely important.
Amino acids (save one exception—glycine) are chiral, which means there can be right-handed amino acids and left-handed amino acids. In fact, when we synthetically create them in a lab, we often can get an equal mix of righties and lefties.
Now, there’s nothing wrong with right-handed amino acids. They certainly can behave just like the left-handed ones. If you pile them up one atop the other like stackable chairs, they’re just as stable. But for some reason, biology on this planet seems to favor lefties.
Now, if you’re thinking that this is all beginning to sound just a little bit out of this world, you’re right on track with a theory being worked out by NASA scientists. And it is quite literally otherworldly.
After procuring a few fragments of a meteorite that fell on Tagish Lake in northwest Canada in the winter of 2000, NASA scientists mixed the samples in hot water. They then separated out the molecules bit by bit, using a technique called liquid-chromatography mass spectrometry, a common laboratory process for separating out individual molecules from a mess of other molecules.
Lo and behold, they found amino acids.
But the NASA folks didn’t get all starry-eyed there. They kept going. They started sorting the lefties from the righties. What they found was significantly more left-handed amino acids than right-handed ones.13 The implication, if the research holds up, is that the excess of left-handed amino acids we have here on Earth may have come from a galaxy far, far away. And that might mean that our little corner of the universe itself leans just a little to the left.
Let me let you in on one of the biggest secrets the supplement industry would rather you not know—some of the vitamins that you are buying and consuming are doing more harm than good. All thanks to handedness. Vitamin E is one such example of this. You might know it as an important antioxidant. Back in 1922, we called it tocopherol, from the Greek meaning “to bring child,” since one of the only things we knew about it then was that deficiency in this vitamin led to infertility in rats.
We find vitamin E in a variety of the foods we eat, including leafy vegetables. And yes, it’s known as a protectant for the membranes of cells from the chemical onslaught of oxidation, sort of like a rust prevention treatment that might protect the underside of your car from the ravages of weather and road salt. But that’s not all it does. We’ve also learned that it can dramatically change the expression of certain genes, including those associated with cell division—something that must happen millions of times a day to sustain our lives.14
Where does the vitamin E used in supplements come from? Vitamin E, like most commercially available supplements today, is made artificially in chemical factories.
The form of vitamin E often found in supplements is alpha-tocopherol, which itself can come in eight different forms, called stereoisomers—only one of which is actually found in the natural foods we eat. And for many decades we’ve known that, in high doses, alpha-tocopherol brings down the levels of the naturally occurring gamma-tocopherol found in our diets.15 In other words, the artificial capsule version can counteract one of the naturally ubiquitous forms of vitamin E.
In light of that, might I suggest that you skip the little capsules and cartoon-shaped tablets and instead eat foods that are rich in vitamin E, like certain nuts, apricots, spinach, and taro. Nature, as it turns out, is usually a pretty good arbiter of the types of vitamin E variants we actually need.
Taking our vitamins by eating sensible meals is beneficial in another way. It makes it a lot harder to go way beyond what is reasonable and prudent when it comes to vitamin intake.
And, at this point, I probably don’t even need to mention the fact that your specific genotype can have a significant impact on how you metabolize individual vitamins. In fact, a recent study has even identified three different genetic variations that impact how men respond to vitamin E supplementation.16
But the key for most of us is simple equability, in which the equilibrium of our bodies, our lives, and even our universe is dependent on just the right amount of imbalance.
In this way our genes help us choose between left and right. We owe our lives and the normal development of our brains to this well-orchestrated balance of laterality. Without having the right genes being turned on at just the right moment, we’d all be mixed up inside and out, from our spleens to our fingertips.
* You might not be as good at it as you think—research has shown that cell phone users are generally as bad as intoxicated drivers when they get behind the wheel of a car.
* A meta-analysis is a study that combines the results of many similarly designed studies to increase the statistical power and thus the accuracy of the results.
Chapter 8
We’re All X-Men
What Sherpas, Sword Swallowers, and Genetically Doped Athletes Teach Us about Ourselves
There’s a Coca-Cola machine on the top of Mount Fuji.
That’s about all I can recall from my time at the summit of Japan’s tallest mountain.
Unfortunately, there’s plenty else that I remember from the climb itself, which I began at dusk in the Land of the Rising Sun. It takes most people about six hours to reach the summit, and those who travel at night (as I did, in anticipation of getting to the top with plenty of time to spare to watch the sunrise) are advised to build in plenty of extra time.
But I was young, healthy, and confident that I’d be leaving everyone else in that big, beautiful mountain’s volcanic dust. I planned to stop along the way at one of the crowded mountain rest-huts for a hot bowl of udon noodle soup and maybe a quick power nap, then continue on to take the summit in time to create a proud and beautiful memory.
Man, was I delusional.
Getting to my intended resting spot was the easy part, though it did take me quite a bit longer than I’d imagined it would. The higher I got, the slower I went. My legs weren’t ti
red, but my mind was. I knew I’d slept a good eight hours the night before, but I told myself that it must have been a fitful sleep, perhaps owing to my excitement over this much-awaited climb.
Yes, I thought, that must have been it.
Nonetheless, I was determined to reach the summit before daybreak. I skipped my intended inemuri—that’s what the Japanese call a power nap—slurped down my bowl of udon, filled my metal thermos with hot green tea, and hit the mountain trail.
And then, like a karate master, the mountain hit back. Hard.
I spent most of the rest of the climb fighting rain, then sleet, then pellets of hail. But the weather wasn’t the biggest problem—not by far.
My head was pounding. I was nauseated and light-headed. The world was spinning. Imagine the worst hangover you’ve ever experienced—this was worse than that. I doubled over on the side of the trail, not able to continue and at a complete loss for what to do next.
My mind simply refused to work.
And then, to my rescue, came an elderly Japanese woman. I’d first met her at the base of the mountain a few hours earlier when she’d asked me to help steady her as she tried to get into some oversized foul weather gear. She had proudly pointed to both her hips and left knee, letting me know that she had recently been “upgraded” with stainless steel and titanium implants. Because of this, I had been certain she wouldn’t get even halfway up the mountain. In fact, to be honest, given the weather and the difficulty of the climb, I had been more than a little worried about her.
Now, here I was, being helped by a woman close to the age of 90 who was gracefully hobbling up the side of a mountain with the aid of two canes. She stopped to take my pack and helped me to my feet.
I was pretty sure that nothing could be more humiliating. But I was wrong. Much to my own dismay, as well as to the dismay of those around me, I then learned firsthand just how much flatulence human beings are capable of producing.
Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes Page 14