Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes

by Moalem MD PhD, Sharon

  What could a seventeenth-century Italian doctor possibly have to say about twenty-first-century office life? Well let’s take a look at De Morbis to find out:

  The maladies that afflict the clerks…arise from three causes: First, constant sitting, secondly the incessant movement of the hand and always in the same direction, thirdly the strain on the mind from the effort not to disfigure the books by errors or cause loss to their employers when they add, subtract, or do other sums in arithmetic…Incessant driving of the pen over paper causes intense fatigue of the hand and the whole arm because of the continuous and almost tonic strain on the muscles and tendons, which in course of time results in failure of power in the right hand…14

  Yes, he pretty much nailed it, describing succinctly what we call today repetitive strain injuries.

  What Ramazzini recognized more than 300 years ago was that the process of doing the same thing over and over again is simply bad for us.

  And that brings us to the BNSF railroad. The company was founded in 1849 in the Midwestern United States and today has grown into one of the largest freight railways in North America, with lines cutting across 28 states and two Canadian provinces.

  It takes almost 40,000 workers to keep all those trains on the track. And as you can imagine, working on a railroad can be physically tough. That’s why it’s not surprising to find out that some of BNSF’s employees were occasionally taking disability leave because of work-related injuries. This, of course, can be extremely expensive for employers like BNSF, which prompted their management team to explore ways to keep costs down.

  Now, one good way to do this would have been to become even more vigilant about improving occupational health standards. They didn’t do that. Another way would be to ensure all workers are encouraged to take even more frequent breaks or rotate off from repetitive and injury-provoking activities. They didn’t do that either.

  Instead, they went after the genes of their employees.15

  You see, someone in BNSF management had apparently become interested in genetics upon learning that DNA might play a key role in determining whether a person is susceptible to the symptoms of tingling, weakness, and pain in the hands and fingers that we’ve come to identify as carpal tunnel syndrome.16 Soon, according to the U.S. Equal Employment Opportunity Commission, BNSF employees who filed claims for work-related injuries based on carpal tunnel were being forced to submit to having their blood drawn. The blood was then—without the employee’s knowledge or consent—allegedly tested for a DNA marker that would show whether the employee was genetically susceptible to wrist pain and injury.

  Purportedly, faced with the prospect of losing their jobs if they refused to be tested, most of the workers permitted their blood to be drawn. But at least one employee decided to fight back. Eventually there was a $2.2 million dollar settlement between BNSF and the Equal Employment Opportunity Commission, which took up the cause of the employees on the grounds that the testing violated the Americans with Disabilities Act.

  That was in the early 2000s. Today, U.S. federal law protects individuals from genetic discrimination in the workplace. The Genetic Information and Nondiscrimination Act, or GINA, was created to protect people from genetic discrimination in situations pertaining to employment and health insurance. Signed into law by President George W. Bush in 2008, the legislation that some called “the anti-Gattaca law” (rumor has it that some politicians were moved to support the measure after seeing the 1997 film about a genetically tiered future society) was heralded as a significant step forward in trying to predict and prevent some of the discrimination people might face as a result of genetic testing.

  Unfortunately, though, GINA provides no protection against discrimination in matters of life and disability insurance. This means that if you’ve inherited a genetic mutation, say in your BRCA1 gene, that could play a role in reducing your life expectancy or could make you more susceptible to disability, your insurance company can legally charge you more or outright deny you this type of coverage. This is why I always ask my patients to consider carefully what they might be getting themselves and their families into before they get any genetic testing or sequencing done that is not done anonymously. Because what we discover—while potentially vital for your health—can also become a disqualifying factor for disability and life insurance for you personally, your immediate family, and all your future genetic descendants.

  As genetic testing and sequencing becomes more routinely used in different aspects of medical care, from pediatrics to gerontology, we’ll have more information at our disposal to be able to link distinct health risks with our unique genetic inheritance.

  Obamacare is set to give many Americans better access to health care, but it might also inadvertently set them up for genetic discrimination. Thanks to a glaring loophole intentionally crafted into GINA, insurance companies have free reign to use that genetic information against us when they determine the premiums they will charge us for disability and life insurance.

  Here’s where things get even more frightening. These days, a potential insurance provider, or anyone else for that matter, doesn’t have to touch a single one of your cells to get a lot of information about your genetic inheritance.

  Among scientists like myself, it’s common practice to share genetic and sequencing data with other researchers while removing identifying information such as names and social security numbers. But what most of us have always seen as a relatively solid privacy protocol, an astute team of biomedical experts, ethicists, and computer scientists from Harvard, MIT, Baylor, and Tel Aviv University saw as a potential target to be hacked.

  Plugging short segments of seemingly anonymous information into recreational genealogy websites (the users of which are increasingly including genetic information as a way to track down long-lost family members), the researchers were able to easily identify the anonymous patients’ family groups. And with just a little additional data that’s commonly included in shared samples—age and state of residence, for instance—they were able to triangulate the precise identity of many individuals.17

  This can also work the other way around. Do you have a family member who has survived cancer? Did they keep a blog? Facebook it? Tweet about it? Social media’s not just a great way to keep in touch with our loved ones—it’s also a potentially very deep and rich source of information for genetic cyber sleuths. Already, more than a third of employers say they’ve used information found on social media sites such as Facebook to eliminate job seekers from the applicant pool.18 With employer-based health-care costs in the United States rising ever skyward, companies might feel justified in making a social media health status sweep a regular, if secretive, part of their hiring practices.

  Using just your name and the millions of genealogy records publicly available on the Web, an inquisitive and resourceful person—someone considering hiring, dating, or marrying you, perhaps—could come to know more about you than you might even know about yourself.19 And if you just happen to be that resourceful and inquisitive person and there was a much easier way for you to access someone’s genetic information without them ever knowing, how far would you go? What I’m asking you is this: Would you be willing to hack someone’s genome?

  ***

  I was trying to hail a cab when my phone vibrated to let me know that a new e-mail had arrived. It was from a friend of mine, a young professional named David who was recently engaged. His fiancée, Lisa, was a fashion photographer who was also living in New York City. I had the pleasure of meeting her just a few weeks prior to their official engagement, at her first solo photography exhibit in a gallery in SoHo.

  David e-mailed that night to ask if I was free to chat as he had a few questions he wanted to ask me about genetic testing. This is a common request I get from friends and family who are looking for advice in this rapidly evolving field. David had mentioned that he was looking forward to starting a family with Lisa once they got married, and I assumed that he wanted to take advant
age of expanded prenatal genetic testing possibilities. These “gene panels” can be used to see if you and your partner carry mutations in hundreds of genes. This type of testing can provide couples with a genetic snapshot of their genetic compatibilities. We all carry around a handful of recessive mutations. On their own they are mostly harmless, but if you and your partner share the same misbehaving gene, that’s a recipe for potential parental genetic disaster. Many more couples are taking advantage of screening hundreds of genes before starting down the road to parenthood. And it’s easy to do: Just spit into a small vial, drop it into the mail, and wait for the results.

  Given the fact that most of our mutations aren’t in the same genes as our partners’, though, this type of genetic incompatibility is often avoided. But as I quickly came to discover, after finally getting into an available cab and giving David a call, prenatal testing was not what he was after. Instead, he wanted to know whether he could hack his fiancée’s genome without her knowledge.

  David’s concerns arose after his fiancée, who was adopted when she was very young, was reunited with her biological father. Lisa had tracked her father down in anticipation of inviting him to their wedding. A coffeehouse conversation had revealed that her biological mother had passed away after suffering from a slew of symptoms that sounded a lot like Huntington’s disease, a fatal genetically inherited neurodegenerative disorder.

  In someone who has Huntington’s disease the nerve cells in the brain slowly degenerate. There’s no cure for Huntington’s, and the path to death is paved with a loss of muscle coordination, psychiatric problems, and eventually cognitive decline and death.

  Complicating matters, though, was the fact that David’s fiancée wasn’t interested in getting genetically tested herself.

  “But,” he said, “if I could just get you a piece of her hair, or something like her toothbrush, that’s all it would take, right? We could check, right? I mean, she wouldn’t even have to know. I understand this is crazy. But…it would be so much easier if I knew what I was up against.”

  What he was asking me to facilitate was ethically problematic at best and, in a lot of countries, downright illegal.20 Rather than expressing my complete disapproval outright and declining his request, leaving him to his own devices, I thought it best to invite him out for a drink. David said he needed to run a few errands after work and would be free later. We agreed to meet at 10 p.m. I was looking forward to uncovering what would have led David to consider behaving so uncharacteristically.

  It was one of those exasperatingly hot and humid August evenings in Manhattan when most people seek shelter in an air-conditioned dwelling or, if they can, leave the city. As I got out of my cab and ducked into the bar, I was really glad to get a reprieve from the humidity.

  I found two free stools at the bar, sat down and ordered. Watching the bartender expertly prepare and pour my muddled mojito, I thought about David and decided to call Kelly. She’s a social worker and friend, who has a lot of experience counseling and working with the partners of people newly diagnosed with a terminal illness.

  “Try to identify some of the underlying fears and expectations associated with getting married to someone who might be harboring the gene for a fatal inherited condition,” Kelly said. “Then figure out what kind of discussions they’ve already had. Most of us are scared to be vulnerable—especially in front of our partners—but if he hasn’t expressed his fears to her, neither of them can have an honest conversation about what this means for their future, their relationship, and what to do next.”

  A few minutes later, David walked into the bar. Not surprisingly, he wasn’t interested in having a conversation about applied medical ethics. What he wanted was simply to be heard.

  As the evening progressed, I was reminded that not knowing is sometimes much more complicated and painful than knowing. Having been friends with David for many years, it was obvious to me that he was experiencing a lot of emotional pain, not to mention shock. He felt that the person he wanted to spend his life with was keeping a secret inside of her that she didn’t want to let out.

  I tried my best to just sit, listen, and answer only the questions that I actually had answers for, which, to be honest, weren’t many. As the night progressed, I heard about the surprise discovery that Lisa’s biological father was alive and living not too far from them in upstate New York. I heard of the painful revelation that her mother had passed away young, leaving so many unanswered questions. I heard about the frustration David felt toward Lisa’s seeming ambivalence and staunch resistance to being tested.

  “I don’t get why she doesn’t want to know,” he kept saying.

  In this digital age, David already knew a lot about Huntington’s disease. He’d learned that, unlike other conditions that are caused by specific single letter mutations, the genetics behind Huntington’s disease could be compared to a scratched record that keeps skipping. People with this devastating neurological condition have, in a gene called HTT, a longer than normal stretch of three nucleotides—cytosine, adenine, and guanine—that repeat themselves over and over again.

  We all inherit a certain number of these repeats, but when someone has a gene that has 40 or more, they almost always develop Huntington’s disease. The more repeats, the earlier the disease develops. If there are more than 60 repeats, the affected person might develop symptoms of Huntington’s as early as the age of two.

  It’s not exactly clear why, but most people who develop Huntington’s very young have acquired the gene from their father. But even in the case of those who get it from their mothers, the repeats generally increase from one generation to the next. We call this type of change in genetic inheritance anticipation.

  From our conversation, it seemed that David had a pretty good handle on all of this material, including the way in which the disease was passed down. And because all you need is one copy of the HTT gene with a greater than normal number of repeats, he knew that if Lisa’s mother was affected, Lisa had a 50 percent chance of inheriting Huntington’s disease. And if that was the case, given the mechanism of anticipation, she would likely start showing symptoms at a younger age than her mother did when she first got sick.

  And most of all, he knew that, if she did have it, he wasn’t going to get to grow old with her. Instead, he would have to watch her personality change as the disease remodeled her brain, slowly disassembling her mind. Would he have the emotional, mental, and physical strength to properly care for her needs?

  “But I can do this,” he said. “Look, I know testing her for Huntington’s without her consent is wrong. But I just wish I knew what we’re up against. It’s the not knowing that’s killing me. Why can’t she just get herself tested? Maybe having an answer either way would make us live our lives differently… but ultimately, I guess, the choice to test is hers to make.”

  And that was it. David ended the conversation abruptly. I asked for the check and got ready to face a hot and sticky cab ride home.

  I’d really love to tell you that there’s a happy ending to this story.

  I wish I could say that they’re living a fabulous life together in a trendy neighborhood in Brooklyn, just like they’d planned. And that David found the strength to approach Lisa one more time and she agreed to undergo testing.

  And more than anything, I’d love to tell you that Lisa tested negative for Huntington’s disease.

  But genetic stories are like the rest of life. Sometimes they’re incredibly beautiful and other times they’re terribly painful. And sometimes they’re somewhere in between.

  The truth is that David and Lisa didn’t get married as planned. She’s still wearing his ring, and they’re still madly in love—maddening as love and life can sometimes be. For his part, David is still trying to come to terms with Lisa’s reluctance and resistance to knowing what lies ahead for both of them. For her part, Lisa has been in touch with a counselor who specializes in helping families affected by Huntington’s disease, though as of this writi
ng, she hadn’t made any decisions about whether to be screened.

  As the cost of genetic testing continues to plummet and as it continues to get easier to do, we’ll face more of these situations—and for many more conditions. To hack or not to hack a genome is going to be the question we’ll increasingly be faced with. And we’re not always going to have the ethical sophistication and experience to deal with the implications of that question.

  As we enter more fully into this brave new world, our relationships will be tested, and our lives will change. And as we’re about to see, so will our bodies.

  ***

  Angelina Jolie knew her odds were not good.

  The Academy Award–winning actress had watched—feeling helpless despite all her status and fame—as her mother lost a years-long battle with cancer. Wanting to ensure she would be able to continue being there for her own partner and their children, she underwent genetic testing that revealed a mutation in her BRCA1 gene.

  In most women, a BRCA1 mutation can mean about a 65 percent chance of developing breast cancer. That’s because BRCA1 belongs to a group of genes that, when functional, suppress tumors from forming by dialing down any rapid or uncalled-for growth.

  But that’s not all the BRCA1 gene can do. It can also work in concert with a slew of other genes to repair damaged DNA.

  So far, we’ve talked a lot about how many of our behaviors can change the expression of our genes through mechanisms like epigenetics. What you may not be aware of, though, is that many of the things you do on a daily basis can actually physically damage your DNA. And unbeknownst to you, you’ve likely been abusing your genome for years.

  In fact, if there were a governmental agency called the Department of Genetic Protective Services, it would have removed your genes long ago to protect them from you.