Today, mores along with technological advances like cars, airplanes, and even the Internet impel and allow us to seek mates from a much wider variety of gene pools than ever before.
In 2013, an instance of an incestuous family showed the horrible toll of inbreeding (as well as pedophilia) in stark relief. Given the pseudonym “the Colt family,” four generations of close family members were discovered living together in the Australian wilderness. Incest among brothers and sisters, parents and children, and even an instance of a grandparent and a grandchild—had led to catastrophic illness, mental impairment, and even a rare genetic condition that caused the death of a three-month-old. A teacher at the local primary school was reported to have overheard one of the Colt children say to another child in the playground, “My sister is pregnant and we don’t know which of my brothers is the father.” The statement led to the discovery of these dozens of family members of varying ages living together on an impoverished commune. The family had been so isolated that several teenagers did not speak properly, and none of the children had any practical understanding of hygiene. The repeated occurrence of mental disorders and physical deformities among the children seemed in equal parts due to a lack of proper treatment and to a multitude of rare, recessive genetic conditions caused by incestuous relationships.
Cases like the Colt family, as well as extensive studies on inbreeding in other species, offer fairly damning evidence that it is to our benefit that we mate outside of our familial gene pool. However, historically, we haven’t always known this to be the case. Marriage between cousins was the rule far more often than the exception even in this country less than two hundred years ago. Even today, religious and cultural groups make a point of choosing mates from within their ranks.
Some statistics show that, worldwide, people are most likely to marry someone who lives within a twenty-mile radius of their home—or the length of a bike ride. But with the ubiquity of cars and airplanes, once-segregated groups have access to gene pools from great distances away. Today the Ashkenazi gene pool, like so many others, enjoys far more diversity. However, for people who have given birth to sick children, perhaps even for my family, the damage was already done. But it can be undone.
Benjy Stacy is believed to be the last blue person in his family. Met-H is a recessive condition, which means that in order to pass the gene, Benjy’s partner would also have to have the gene. It is possible that after Benjy, the recessive trait for blue skin will just silently exist among his ancestors, unable to express, unable to turn anyone else’s skin blue. Until one day when two carriers of the gene for met-H, now possibly distant relatives, mate. Then once again a blue person will be born.
The other possibility is that Benjy Stacy won’t pass his blue gene. Neither will any of his relatives, both close and distant. In that case, the gene for blue skin will simply die out as naturally as it came to be.
There remain, of course, groups of people who prize religious or ethnic homogeneity, and I understand that there can be a richness to maintaining and cultivating a shared history and customs. However, I have grown skeptical about it being in our best interests to breed like with like. Genetically, there is some stark evidence that suggests we’re stronger and better off when we mix it up.
Twenty-Eight
I became fascinated with the BRCA1 variant and Angelina Jolie when her first article appeared in the New York Times, on May 14, 2013, largely because I had just spent a year mulling over my own preventive treatment. Preventive treatments usually come up when healthy people want to stay healthy and a genetic variant indicates that they might not.
Angelina’s mother was diagnosed in her early forties with a deadly ovarian cancer caused by a gene variant called the BRCA1, commonly pronounced “BRAH-kah.” The BRCA gene comes in two varieties, 1 and 2, and likely more will be flagged before this book goes to print. Both BRCA1 and 2 are actually stabilizing forces in genetic material. When they contain variations like Angelina’s, however, they destabilize cells, which can lead to cancer. The information in Angelina’s DNA from the BRCA1 is repeated in every cell of her body, over and over, in upward of thirty-seven trillion BRCA1 genes.
The name BRCA itself simply combines the first two letters of the words “breast” and “cancer.” BR-CA. But it doesn’t just mean “breast cancer.” BRCA also elevates the risk for cancers of the ovaries and fallopian tubes. It also leads to greater risk of peritoneal cancer, which is cancer in the lining of the abdomen and the lining surrounding abdominal organs. In men, the BRCA genes increase the chance of prostate cancer.
After her mother’s death at the age of fifty-six, Angelina became very public in her own battle with the BRCA1 gene, which she learned she had inherited from her mother, just as I had inherited my own bad gene from my father. It made me feel close to her. You know, me and Ange.
There are very few treatments for genetic conditions, like chest percussions for cystic-fibrosis patients and tapping for my family’s illness. Today, prophylactic amputation, a procedure popularized by Angelina herself, has become a way to treat a possible, impending deadly illness. In May of 2013, Angelina Jolie had her healthy breasts removed. On March 24, 2015, she followed it up by having her healthy ovaries removed. She wrote about both in op-eds for the Times. If the cancer is most likely to form in her breasts or ovaries, she wrote, the simplest solution would be to remove the susceptible body parts. What many fail to realize is that although the chances of developing cancer might decrease by so many percentage points, you risk suffering from the side effects of these surgeries. It’s a tough choice. Since these treatments are new, we lack long-term understanding of their impact.
In the summer of 2011, I was married and finally on Aaron’s health insurance policy, so I took myself to a doctor who specialized in gastrointestinal conditions to examine the poppable varices in my digestive tract. I presented him with my MRI from the Seidman lab study, and he promptly passed me on to gastroenterologist Dr. Samuel Sigal at NYU, with a wry, “Wow, he’s gonna love you . . .”
I brought Dr. Sigal, a renowned liver specialist and one of the top liver-transplant surgeons in the world, my father’s medical chart and a story about my cousin Valerie. Unfortunately, the illness I was trying to describe was several generations along from patient zero and there were only fourteen people who had contracted it. This makes it difficult to explain to even the smartest people in the medical community. By all accounts, our gene continued to disregard our expectations with the curveball it threw us by involving our livers and its seeming disregard for our two X chromosomes.
Dr. Sigal’s nurse practitioner was quick to tell me that reading my MRI made it almost impossible to believe that I could look so healthy sitting here in his office.
“You should look like you’re dying,” he said, with a big smile. “I mean, if I was only looking at your MRI, I’d say you needed a liver transplant, ASAP.”
I don’t think I replied. “Thanks” just didn’t feel appropriate.
* * *
I knew that I wanted to stay a few steps ahead of the game. I took on the quest for answers with gusto. Dr. Sigal felt that I should consider a treatment called a “transjugular intrahepatic portosystemic shunt,” or TIPS. Both my father and my cousin Valerie had undergone TIPS procedures. Val’s was by all accounts successful. My father’s had been a failure.
Dr. Kricket also agreed that a TIPS was something to consider. It was a minimally invasive procedure in which a radiologist tried to prop open my almost-nonexistent portal vein. The biggest complication—a swelling in the brain called “encephalopathy”—could be caused by a buildup of toxins in the blood. A shunted portal vein might also lead to a subtle but chronic state of confusion, or as Dr. Sigal put it, I could “lose my edge.” I was gently reassured that this probably wouldn’t happen to me because my liver seemed otherwise healthy.
Out of the gate, I liked Dr. Sigal and the radiologist he worked with, Dr. Hearns Charles, so much, so quickly, that I felt confiden
t about putting myself in their hands and trusting their expertise. But many hospitals in the New York City system are overwhelmed with patients. My doctors took special interest in my case, thanks to its rarity, but they needed bite-sized answers they could tackle in the simplest way possible. I was far from simple. At that point, exactly two people worldwide had had a liver that looked like mine and shared my gene: my father and my cousin Valerie. Val underwent a successful TIPS procedure before her “mushy spleen” removal. With her portal vein open, the gastric varices throughout her digestive tract shrank. In my father’s case, the shunt had simply clotted with stagnant blood and closed. So, based on the limited experience our family gene had with this procedure, the success rate was 50 percent. However, when considering statistics, I also had to factor in that ten years after her TIPS, Val had had a catastrophic stroke. Was her TIPS related to this? Did the 50 percent success rate come with an enormous, unattractive caveat? There was no reason to think it did, but given how little we knew, there was also no reason to think it didn’t.
If shunting my blocked portal vein meant that I could lose my edge, not shunting it meant I wouldn’t. I felt healthy and well. Attempting a procedure that could make me sick seemed counterintuitive. But just like a young Angelina Jolie responded to the possibility of dying of breast or ovarian cancer, I was motivated by the possibility of bleeding out my blood supply through my mouth. For now, though, as Dr. Charles, my trusty radiologist, put it, we’d start with a few simple tests.
* * *
I was awake as three arguably attractive men stood over me talking about whether or not they should shave my groin. Just the right side.
I was being prepped for a liver biopsy. This was my second test in two months. Dr. Sigal had already performed an endoscopy, in which—while I was under anesthesia—a little camera traveled down my throat and into my stomach looking for varices along my digestive tract. The results contained the phrase “nothing too alarming,” which is a mixed bag when you are looking at something that is one puke away from a scene out of Alien.
The doctors decided to forgo the shave and forge ahead through my jugular vein, in my neck. A wire threaded through my heart and into my liver would allow Dr. Charles to grab a tiny piece of liver for testing. I told Dr. Charles that I was under deadline and needed to work later that day, so I didn’t want to be medicated. He laughed and gave me one of those “okays” that really mean “you’re crazy.”
There was no deadline, just an overwhelming need to feel every minute of this. To imagine that I was doing it for my father, my sister, my grandmother, and all of my cousins. As I lay on the table, wide-awake, a local anesthesia was applied to the point of entry. I stared at the machines beeping around me. I felt the wire as it snaked through my chest. The bright lights hurt my eyes, which refused to close.
My bravery immediately dissolved. “Dr. Charles!” I called very softly and carefully. A nearby nurse leaned down to look at me.
“Do you want to pick the music?” she asked.
The distraction worked. I forgot to say “give me drugs.” Instead, I found myself experiencing a moment of social awkwardness. Did I want to pick the music? I hadn’t noticed the music. But, sure. Except my brain was blank. What tunes best fit the mood of the moment? What was at once uplifting, calming, and also not entirely uncool?
“R.E.M.,” I said. It surprised all of us.
Now, with what felt like a clothes hanger between my shoulder blades I could hear Dr. Charles mumbling, then calling out, “Can you page someone to . . . help me over here with . . . here, take this . . . I need someone to . . .”
I closed my eyes.
“Buy the sky and sell the sky, and tell the sky, and tell the sky fall on me . . .” R.E.M. sang on. “This one goes out to the one I love. This one goes out to the one I’ve left behind . . .”
Shut up, R.E.M.
Dr. Charles pulled out the wire.
My liver, he told me, was, and I quote, “gorgeous.”
“What this means,” he went on, “is that I don’t know.” He wanted me to have another procedure, called an “angiogram,” which checks blood pressure in my liver. For that one, they would definitely have to shave my groin.
Twenty-Nine
Although it’s redundant to say it, my blood tests continued to come back clean, and my liver was gorgeous, but everyone was still confused. I had begun taking a whole host of new pills designed to lower the blood pressure in my abdomen. I went off my birth control after a discussion with my gynecologist, who agreed that my fragile blood vessels didn’t need to be further compromised by hormones, although it was clear she didn’t entirely understand what the hell I was talking about and was more likely nodding blankly.
Aaron and I had decided to hold off on the conversation about children for the time being. We were told that blood supply during pregnancy increases by half, and my veins were already very delicate. I might be able to carry a child to term, if we decided that’s what we wanted, once we had a better understanding of my physiology. Meanwhile, we bought condoms.
My third test, the angiogram, was slightly more invasive than the first two; during it, Dr. Charles inflated a balloon in my liver in order to test my abdominal blood pressures. Three months after the anesthesia-free liver biopsy, Aaron accompanied me to the hospital. I immediately asked for drugs. All the drugs. Every drug. I did not want to hear R.E.M. and I didn’t want to feel wires. Before the procedure, I had to pee into a cup for a pregnancy test.
I couldn’t pee. I sat in the bathroom for over an hour, feeling like my bladder was a dud. Finally, I appealed to the nursing staff, telling them I didn’t believe I could be pregnant. I used protection religiously. They took pity on me and let me out of the bathroom.
Two important things were true that day: (1) The blood pressures in my liver, according to Dr. Charles, “didn’t make any sense.” And (2) I was pregnant.
* * *
The amount of radiation that Dr. Charles used during the angiogram was not something you want to subject a human embryo to unless you want it to incur superpowers. So at that point, there was very little chance that the one inside me had survived. I went by myself to the high-risk ob-gyn appointment Dr. Sigal recommended, because I was so certain there was no possibility of a viable embryo that I didn’t think Aaron needed to come.
At the ob-gyn, however, I learned that the embryo had made it, although we wouldn’t know for sure whether or not it would be able to shoot spiderwebs from its wrists until its genes were tested. There were other concerns. If I carried the fetus to term, there was a 25 percent chance I would die from a bleed out caused by one or more of the collateral pathways from the blockage in my liver. What was worse, there was an even greater risk that I would have to deliver early in order to save me or the baby. Possibly very early. An early delivery might mean a life of illness for our unborn child.
And yet I knew right then that I wanted to keep it. I was thirty-seven years old. This fetus had survived a microwaving. I suddenly realized I was supposed to have this baby. The doctor told me about a procedure whereby at the tenth week, I could have the genome of my fetus read to make sure it didn’t have my bad gene and hadn’t been fried into an evil leprechaun.
This procedure, called “chorionic villus sampling,” or CVS, was briefly the go-to for genetic testing in the unborn. Before that, there was the slightly riskier amniocentesis, where amniotic fluid is extracted from the placenta for study. Today, a simple blood test called a “first trimester screen” doesn’t go anywhere near the fetus. It simply uses a mother’s blood for evaluation. In 2012, however, the first trimester screen wasn’t being widely used. Looking forward to the CVS, I was certain, if this baby didn’t have the gene, I was going to have it regardless of my own physical impairments.
Aaron was less convinced. I could see his point. I’d already leveled him with the admission that carrying meant I had a 25 percent chance of dying, that I could deliver early and have a very sick child, that th
ere was nothing that wasn’t dangerous about my plan. He agreed to wait at least until after the CVS to argue it with me. I scheduled my appointment for the earliest possible date.
The day before the CVS, on October 29, 2012, Hurricane Sandy hit. NYU, where my CVS was scheduled, was flooded, with twelve feet of water filling its elevator shafts. The entire hospital was thrown into chaos. I couldn’t reach anyone. News reports showed doctors and nurses carrying newborns on oxygen to waiting ambulances for transfer to other locations. Three days after my appointment, I came to a decision. I would try to get myself in for a CVS anywhere, but if I failed by the end of the day, I would abort. I could not risk giving birth to a baby who carried this gene.
I remembered asking my sister how she would have felt during her own unplanned pregnancy if she ended up standing over the bed of a dying child who was filling with chyle and slowly starving—knowing what we know. The numbers I called referred me to other numbers. I was offered appointments weeks away. I cried during one call. I begged during another.
By day’s end, I still didn’t have an appointment for a CVS. So I made an appointment for something else.
Thirty
“So, if I have the TIPS, can I have a baby?” I asked Dr. Sigal, after recounting the harrowing month we had endured since my angiogram. After the storm, Dr. Sigal had moved his office to another part of Manhattan.
“Yes. Absolutely,” he responded.
He went back over the risks of the TIPS. I might experience encephalopathy. If I did, I could expect to feel irrationally angry and lose my sense of time. Generally, I could expect to occasionally seem out of it. The doctors assured me that the procedure could be reversed. I loved not having to commit to things.
The Family Gene Page 17