Mapping My Genome Starts a Search for DNA Answers I May Not Want to Know
On the fourth floor of a red brick medical building in Boston’s South End is an office where few want to go -- where people get a frequently unwelcome glimpse of their future through a careful reading of their DNA.
My chair faces Aubrey Milunsky, co-director of Boston University School of Medicine’s Center for Human Genetics. Women have been told here they’re harboring breast cancer genes. Men have learned they may develop incurable Huntington’s disease. Parents have been informed their child may die before they do.
Why, Milunsky asked during that visit in May, was I thinking about getting all my DNA decoded, a procedure that would give me a complete transcript of the instructions for making and operating my heart, lungs, liver, kidneys, skin, and brain? A 53-year-old father of two, I run a mile every day and play tennis three times a week. I most likely have decades of health in front of me. Yet hidden among the letters of the genetic code may be flaws that foretell horrible lethal diseases that he’s seen hundreds of times before.
“Why would you want to know that?” asked Milunsky, the author of “Your Genes, Your Health: A Critical Family Guide That Could Save Your Life” (Oxford University Press, 2011). “Why would you want to do that to yourself and your family? Why cast a blanket of gloom and doom over them? What good does it do you to have such dire information when there’s nothing you can do about it? I wouldn’t recommend it.”
While gene testing is useful for people who have documented risk or symptoms of disease and want to take action, the whole genome is currently a landscape filled with vague signposts pointing toward cancer, Parkinson’s disease, and other conditions that may or may not arise in my future, Milunsky warned. I might also discover that I’m fated to develop a degenerative nervous-system disorder, or may have passed genes linked to breast cancer on to my children.
I started thinking about this step 11 years ago in a press briefing in Cambridge, Massachusetts, on genome sequencing at the Whitehead Institute, a Massachusetts Institute of Technology-affiliated research center. I learned that the genetic material being analyzed there was from several people, and most of it came from one anonymous volunteer from Buffalo, New York -- my hometown.
I wished that volunteer had been me.
A decade ago, sequencing a single human genome took the combined efforts of laboratories and companies around the world. While the genome today remains at the frontier of biology and medicine, it’s rapidly becoming accessible to thousands, if not millions of people.
Days, Not Years
Companies are offering new products that can sequence genomes in days, rather than years. Doctors are preparing to use the technology to tailor cancer treatment, diagnose sick children, and track outbreaks of dangerous diseases in hospitals. Having my genome sequenced would offer glimpses of the biomedicine of the decades to come, and give me some insight into my ancestry. I wanted to take a look.
By the end of 2010, about 3,000 people had their full genomes sequenced since 2001, the year the U.S. National Institutes of Health published the first draft of the human genome at a cost of about $2.3 billion. Over that time, the cost to transcribe an individual’s genome has plummeted to about $4,000, and will drop to $1,000 by the end of the year, according to sequencer makers. While the first genome took 11 years to sequence, virtually anyone today can have their own decoded in a few weeks or months. The science journal Nature estimated that by the end of last year, the number of sequenced genomes rose to about 30,000.
At these prices, the cost of deciphering your entire genome is rapidly approaching that of a 10-speed bike. A study from the nonprofit Mitre Corp., a Defense Department advisory group, recommended that all military personnel have their full genomes sequenced because of the comprehensive health information it provides. The North Atlantic nation of the Faroe Islands has announced a program to sequence the genomes of all 50,000 citizens. Genome sequencing at birth may become as routine as cutting the umbilical cord, according to Jay Flatley, president of sequencer-maker Illumina Inc. (ILMN)
Sequencing the genes of tumor cells can save lives. Differences between normal tissue and cancers can tell doctors which treatments are most likely to work. Routine sequencing of the genomes of cancer cells is “definitely a direction we’re moving towards,” said Bert Vogelstein, an oncologist at Johns Hopkins Medical Institute in Baltimore.
Analyzing cancer DNA will constitute the largest clinical application of genomic-sequencing technology, according to Clifford Reid, chief executive officer of Complete Genomics Inc. (GNOM)
Personal Genome Project
There are other potential benefits. Anyone may be at some risk of hypertrophic cardiomyopathy, an often-silent, dangerous enlargement of the heart that can strike and kill young athletes out of the blue. People who have had their genomes sequenced can see whether they have these genetic risks, and might want cardiac imaging or preventive treatment, said George Church, a Harvard Medical School genetics professor who has spent his career pushing sequencing technology forward.
Church is the leader of the Personal Genome Project, a Harvard-based effort to obtain genetic and medical information from thousands of individuals and better understand the links between genes and health. He had his own genome sequenced and made his medical information public on a website.
Earlier this year, I called Church and told him I was thinking about having my genome sequenced. He agreed to cooperate, saying that having a reporter’s DNA analyzed would help demystify the process for the public and stimulate discussion about risks and benefits. (Bloomberg LP donated $7,000 to Church’s lab, about what it would cost to have my genome sequenced by a private company at that time.)
Could Be Cloned
I began spending my evenings reading through and filling out study registration materials. The consent information listed outlandish-sounding risks: If I made my genome public, it would be possible for someone to synthesize my DNA and plant it at a crime scene. I could be cloned. There was an all-capitals warning that none of the information obtained by having my genome sequenced should be used to make medical decisions.
That doesn’t mean that the information isn’t useful, Church told me in a meeting in his office in August. Any suggestion of genetic illness that arises from the results can be confirmed with approved medical tests. People who have the ApoE4 gene that raises the risk of Alzheimer’s disease may want to protect their families finances with long-term care insurance; those with genes that protect against Alzheimer’s may want to skip the insurance and save the premiums. Sequencing can detect signs of hidden genetic risks, such as those that cause cystic fibrosis, which may affect couples’ decisions about having children.
“There is all kinds of value locked up in the genome,” Church said. “The cost of getting it out is falling, but it’s already a bargain.”
Seeing how Church had thrived after sequencing gave me confidence. I’m a worrier, the kind of person who wakes up at 2 a.m. and can’t banish thoughts. I worry about my children, my job, my forehand, the home that needs repairing.
Yet there was something about genome sequencing that overshadowed the worry. It reminded me of the excitement I felt one winter in Buffalo when I realized the snow was so deep outside our house that I could climb out my bedroom window and jump off the porch roof. My mother happened to glance out from our living room just in time to see me flying through the air, and then watched me run upstairs to do it again. Exploring my genome gave me the same exhilaration. While there were risks, it was an entree to a new kind of understanding.
I had a number of motives, but they all essentially boil down to the difference between my two grandfathers. My maternal grandfather John died of cancer at 60, when I was two years old. My mother talks about him so much -- his kindness, his sense of humor, his love of ketchup sandwiches -- that I still feel close to him.
As for my father’s father, Grampa Frank, I can still see his face. I followed him into the frigid Pacific Ocean waters of La Jolla, California, when he was in his 70s. In that same decade of his life, he drove from San Diego to visit our family in Buffalo, where he showered my siblings and me with magical gifts: Buffalo nickels, hotel pens and soaps, tiny calendars, fishing lures.
Born in a generation when a man’s average life expectancy was about 46 years, Grampa Frank smoked thousands of cigarettes and lived to 82. His sister, Marie, lived alone in Washington’s DuPont Circle area from the end of World War II through the Reagan administration, finally dying at age 92 after a near- lifetime of smoking. Their brother, Lucian, died at 88.
Which grandfather’s genes did I get? Those of John, whose family has been affected frequently by thyroid disease and arthritis; or Frank’s, whose relatives have been beset by nervous-system illness?
Genome sequencing might give the answers to those questions -- and it might not, Denise Lautenbach, a genetic counselor at Harvard-affiliated Brigham & Women’s Hospital in Boston, told me in August. While there are no guarantees, the brain cancer my grandfather John died from was unlikely to be inherited, since no one else in the family appeared to have suffered from something similar, she said. On the other hand, I probably had a 50 percent chance of inheriting a disorder that caused my Grampa Frank’s hand to shake.
As to the other conditions that might run in my family -- depression, thyroid problems that can lead to obesity, cancer, varicose veins -- those may or may not be explained by genes, Lautenbach said.
“They’re all common conditions, and they appear to run in families,” she said. “But families have lots of things in common besides genes. They often eat the same diets, are exposed to the same chemicals and environmental conditions.”
Genome sequencing can unearth serious, life-altering information that requires individuals to take action, or at least consider doing so. In June 2010, Life Technologies Corp. (LIFE) CEO Greg Lucier spent a weekend in his Carlsbad, California, offices as 10 experts from his company detailed the results from sequencing his genome. Life makes sequencing equipment and supplies, and Lucier had decided, like me, to give it a road test.
Lucier found that he’s a carrier of the BRCA1 gene that increases the risk of breast and ovarian cancer. He told his wife he thought she ought to be tested for the gene, which would help determine whether their daughter might be affected. His wife refused.
“She said, ‘I don’t have breast cancer and no one in my family has ever had breast cancer.’ So she’s not going to be tested for the gene. But when my daughter gets older I’m going to suggest that she have regular mammograms.”
What if your employer knew you had a high genetic risk of disease? Could you lose your health insurance? A public outcry erupted in the 1990s when it came to light that the Burlington Northern & Santa Fe Railroad had begun genetic testing on 125 employees’ blood without their consent. Employees were concerned that the company was trying to cut bills for repetitive stress injuries by showing that some employees had inherited the condition, recalls Democratic Representative Louise Slaughter from Rochester, New York. The case fueled distrust of DNA testing, she said.
“People were avoiding genetic tests because they were afraid of losing their health coverage,” Slaughter said.
In 2008, after 13 years of debate, President George W. Bush signed the Genetic Information Nondiscrimination Act, which Slaughter sponsored. The law specifically forbids health insurers from using genomic data to deny service to individuals.
Losing health insurance because of genetic testing is no longer a concern since the GINA law was passed, said Sharon Terry, president of the Genetic Alliance advocacy group. Still, the law doesn’t apply to some small-business employees, nor to members of the military. It also doesn’t cover long-term insurance against the costs of nursing-home care.
Initially I was attracted by the chance to take part in an experiment at the frontiers of science. But Milunsky’s warnings kept ringing in my ears: How much do you really want to know? What if you discover a genetic flaw that not only affects you, but your family.
I decided to talk to members of my family. In the months leading up to my sequencing, I spoke with my siblings, parents, children and wife individually to make sure they could air any feelings or fears about making my genome public. It was bound to reveal disease risks, and they might have similar susceptibility. I’m one of seven children, so it took a few days.
‘Under a Microscope’
My youngest sister Rosemary, a psychologist in Kansas City, didn’t object to my plan, though she was concerned about my state of mind. She recalled undergoing fetal testing for genetic disease before the births of her first two boys. By the time she was ready to have the third, she was sure she didn’t need to be retested. Suppose her third child had shown signs of Down syndrome? There are worse things, and she wouldn’t have changed her mind about having the baby in any case, she said.
“I don’t want to be tested, scrutinized, put under a microscope if I don’t have to be,” she said. “Maybe you’d rather just enjoy life up to the point where you absolutely have to face reality.”
After years of listening to my dinner-table talks about the promise of genetics, my wife and my two children weren’t surprised to hear that I wanted to write about my genome.
“If there’s something I should be concerned about, I’d rather know about it,” my 19-year-old daughter Hanna said. “Maybe we can do something, maybe not, but it’s better to know.”
On a sunny September day, I walked into Church’s lab to give samples for sequencing. Two of Church’s collaborators on the Personal Genome Project watched as Joe Thakuria, a Harvard clinical geneticist, pushed a needle into the crook of my left arm, and an IV tube zipped full of my blood. Afterwards, I spit about a dozen times into a saliva collection tube, from which DNA will also be purified. Samples were shipped the same day by FedEx to begin the process of sequencing, and my results were expected back in a few months.
I told my parents of my decision. My mother keeps track of all the families’ illnesses -- the gain and loss of weight, trips to the hospital for ailments real and imagined. She began speculating about which of our family traits might be inherited, and from whom. My father, a retired English professor from whom I inherited the gene for writing, if one exists, was thrilled.
“We’re delighted you’re doing this,” he told me over the phone, as if I’d told him we were having another child. “We can’t wait to see what comes out of it.”
(The sequencing results of reporter John Lauerman will be detailed later in this series.)
To contact the reporter on this story: John Lauerman in Boston at firstname.lastname@example.org