I sat clutching my wife’s hand, nodding, listening, and trying to breathe.
“Your life expectancy hasn’t changed,” said my doctor, Harvard Medical School geneticist Joseph Thakuria, trying to reassure me.
That, I thought, is the good news.
I may get Alzheimer’s disease, I was told after getting my DNA analyzed. I could suffer the consequences of an abnormal blood clot in my heart or my brain. Or perhaps I’ll suffer from a disease called primary myelofibrosis that’s caused by an overactive bone marrow. All of these were possible outcomes, based on my genetic profile. In each case, the test only gives an increased risk for disease, not a definitive diagnosis. In a few, Alzheimer’s for instance, there’s nothing I can do anyway.
And the price tag to find out more answers kept rising.
“The sequencing of average, healthy adults is less informative than people had hoped it would be,” said Robert Handin, a Harvard Medical School doctor who does genetic testing. “We’re going through information overload. Everyone gets all this data and no one knows what to do with it. What do you do with a mutation that might increase your risk of some disease that you might not get for 20 or 30 years?”
I wanted to know. In September, Thakuria took a blood sample from me that was used to sequence all my DNA. In January, he and Harvard University’s Personal Genome Project told me I have a gene mutation called JAK2 V617F that’s associated with “cancer-like” blood disorders called myeloproliferative neoplasms.
Most people who have these disorders get relatively mild disease. Yet some, like an Indiana firefighter I spoke with, become very sick. He developed a severe case of primary myelofibrosis, a scarring of the bone marrow, underwent a bone marrow transplant and almost died.
There were other revelations. I have one copy of a gene variant called APOE4 that increases my risk of Alzheimer’s disease. I don’t have a gene that’s known to cause a shaking disorder, called benign essential tremor, that’s common in my father’s family. That doesn’t mean I won’t get the condition, however; other unknown genes may cause the same malady.
Since writing about my own DNA in January, I’ve spoken or e-mailed with hundreds of readers and almost no one wants to go through what I’ve experienced. About 90 percent of those who e-mailed or spoken with me, including doctors and scientists, said that under no circumstances would they want to have their DNA analyzed. There’s already plenty to worry about, they said.
Yet mapping the genome is becoming a standard tool of medical care. Faster, cheaper DNA sequencing is becoming routine for investigating the cases of children with unknown inherited diseases. Cancer hospitals are analyzing large chunks of tumor genomes to design safer, more effective treatments. The Faroe Islands in the North Atlantic Ocean have announced a plan to sequence all 50,000 citizens for use in regular patient care.
I am a healthy, tennis-playing 54-year-old man in the prime of life. When I volunteered last year to have scientists from the Personal Genome Project decipher my DNA, I prepared for months to pass through a door to greater understanding.
My medical odyssey cost almost $12,000. My employer and insurer picked up all but $200 in co-payments. That isn’t the case with all insurers, according to many patients and insurance companies.
Costs can climb even higher. I found that some people with diseases associated with my mutation can have enlarged spleens and low energy, and can be helped with a drug from Incyte Corp. called Jakafi. The treatment from the Wilmington, Delaware-based company costs about $80,000 year. It doesn’t correct the problem. It shrinks the spleen and restores some energy.
Insurance companies are terrified of people like me -- that our pursuit of answers will spiral into more tests and drugs driving medical costs ever higher. UnitedHealth Group Inc., the biggest U.S. insurer, said in March that DNA testing costs in the U.S. would grow five times over the next decade to $25 billion, and the value of many probes still hasn’t been proven.
The mutation my screening uncovered, JAK2 V617F, increases blood cell production and can lead to diseases -- most notably primary myelofibrosis -- that involve an overactive bone marrow and overproduction of blood cells. One of the conditions tied to my mutation is called thrombocytosis. It’s an excess of platelets, the sticky cells that circulate in the bloodstream and contribute to clotting. High platelet counts raise the risk of blood clots that can cut off circulation to the lungs, heart, brain and other vital organs.
It turned out I had been walking around with this danger -- unknowingly -- for a long time. In 2009, I was playing indoor doubles with some friends on a January evening when I began feeling pain on my left side. By midnight, I was on my way to the emergency room, sure I was having a heart attack. Doctors at the ER never found out exactly what caused all that pain.
Almost four years later, armed with an analysis of my DNA, Harvard’s Thakuria set to work connecting the dots. He noted my platelet count at the time was twice the high end of the normal range. He ran another blood test on the spot: the platelet count was high again. While otherwise healthy, I was genetically disposed to a higher risk of blood clots, he concluded.
As we sat together in the bright, cool examination room, he warned me about the risks. Study after study in hundreds of patients showed an increased risk of clotting, sometimes in the legs, sometimes in the gut and organs, and sometimes in the brain, where they can cause real damage.
Thakuria suggested my elevated clotting risk could be taken care of with one daily baby aspirin.
Slightly rumpled in rolled-up sleeves and a tie, he seemed delighted that my genetic test had explained a medical mystery:
“You may be the first person ever to be diagnosed with a disease based on their genome in this way,” he said. “I’m starting to think that this technology can really help lots of people.”
I left his office feeling a little stunned. One day I was healthy; the next I had a blood disorder. The idea took a little getting used to.
My insurer paid Thakuria $517 for my visit.
While I began taking my baby aspirin, I scheduled a meeting with Martin Reese, co-founder and chief executive officer of Omicia Inc., a closely held company based in Emeryville, California, that makes software for analyzing genomes.
I asked him to run my genome through his software, so that I could get a second opinion on my DNA. To analyze my genome using the software would normally cost from $500 to $1,000; a consultation to discuss the results $1,000 to $2,000 more.
Reese’s analysis raised more alarm bells. He said I had a mutation in a gene linked to Huntington’s disease, the lethal neurological condition that killed Woody Guthrie. He quickly added that the mutation I had wasn’t a dangerous one. I learned I also have mutations that might affect how I react to drugs, such as beta-blockers that are used to treat high blood pressure. He warned me that any findings should be carefully checked with a doctor.
It was the JAK2 finding -- that I had a gene mutation that increases blood cell production -- that continued to be most worrisome. I flew to San Mateo, California, to attend a meeting sponsored by the MPN Research Foundation. There, patients with rare disorders like mine can meet and talk with the doctors who study them.
The first speaker was Ruben Mesa, a specialist on blood at the Mayo Clinic, and he confirmed my worst fears. While I’d been diagnosed with probably the least serious of JAK2 disorders, thrombocytosis, I remained at risk for the most dangerous -- myelofibrosis. The bone marrow condition robs patients of needed blood and can be fatal. Mesa said myelofibrosis was part of the “natural progression” of my condition.
My feelings of foreboding grew worse. I met Sam Klepper, a patient with the same JAK2 mutation as mine. Klepper is a workaholic and a workout fanatic who used to run triathlons. About 10 years ago, his doctor told him his red blood cell levels were twice normal -- it was similar to my high platelet counts, and linked to the same DNA mutation. His doctor began removing blood regularly to control the counts.
Klepper, 47, was doing sit-ups one day when he noticed discomfort in his upper abdomen. It was his spleen, which was growing to abnormal size as his red blood cell counts grew. Three years ago, on his daughter’s birthday, his spleen grew so big it had to be removed. He later developed high platelet counts and had to change treatments.
“I’m just keeping my fingers crossed,” he told me. “I’ve learned to live with and manage my disease.”
My visit to California filled my head with doubt. I thought again about Jakafi, the $80,000 drug. Would that help?
Back in Boston, I nervously waited for an appointment with David Kuter, a specialist in blood disorders like mine at Massachusetts General Hospital in Boston and Harvard. I told him about my experiences at the San Mateo meeting. What are the chances I would get worse?
Kuter listened and, just as soon as I had finished speaking, dismissed my concerns.
JAK2, my defective gene, is “not big-leagues in terms of your health or wealth in the future,” he announced. There was little doubt that I had thrombocytosis, Kuter said. The “thermostat on my bone marrow” had been turned up, as he put it, and I was making too many platelets, and probably had been for a few years.
“You’ve had this for at least four years now and there’s nothing else going on,” Kuter said. I could feel my wife, Judi, relax her grip on my hand as he spoke.
Kuter then asked whether blind spots ever appear in my vision.
I jerked back in my chair. For about 10 years, I had been experiencing these blind spots, called scotomas, with increasing regularity. They were sometimes large and rimmed by a flashing band, and a little frightening. They often appeared when I was playing tennis, and none of the doctors or eye specialists I’d spoken with seemed to know why I had them.
Scotomas are often caused by small clots in the blood supply to the eye or brain, Kuter said. Thrombocytosis was probably the cause of them.
Likewise, the unexplained kidney pain I’d experienced playing tennis in 2009 that drove me to the emergency room may have also been caused by a stray clot, he said. The pain could have been the result of a clot that blocked blood flow through the kidney or the adrenal gland, which sits atop the kidney.
“It can be very painful,” he said.
His recommendation: the one baby aspirin I was already taking. He predicted the scotomas would stop. The same tiny pill would probably be enough to prevent strokes, heart attacks, dangerous clotting in my legs and more pain around my kidneys, he said.
I don’t need Jakafi, the $80,000 drug, and it’s unlikely that I ever will, Kuter said.
“We’ve identified about 5,200 patients with essential thrombocytosis over the past 40 years,” he said cheerily. “I can count on two hands the number of patients who had something bad happen who were on aspirin. People aren’t dropping dead in the streets from this.”
So that was the end to all this: calm down and take a daily aspirin. For my meeting and the tests, Kuter charged my insurance $1,460.
A few weeks later, I met with my regular internist for my annual checkup. We had met several times as we sorted through what my DNA results meant, at a cost of $2,100 including lab tests. After we talked about my health for a few minutes, she pushed her chair back. Knowing what I know now, she asked, would I do it all again?
“Yes,” I replied without hesitating, the exam-room johnny still tied around my neck. “Before I was sequenced, I didn’t know I had this clotting disorder. Now I do, and since I began taking baby aspirin, I haven’t had a single scotoma. I could be saving myself from all kinds of serious potential illnesses, maybe a stroke or a heart attack.”
My optimism was tempered with a dose of reality from the scientist who set in motion my medical journey -- George Church, the Harvard scientist who oversaw my sequencing. This month, I attended a conference where he was the keynote speaker. He asked how many of the 250 people in the audience had put their complete DNA under the microscope. Five or six raised their hands, including me.
Church showed a slide with a list of names of people across the U.S. who had been tested, then diagnosed and treated for conditions such as cancer, diabetes, and Crohn’s disease. He considered these names successes, proof of the benefits of widespread genetic testing.
When I talked with Church afterwards, he said he probably should also have a slide of “failures,” people who potentially receive false information, or feel so devastated by what they learn that they do something rash and take unnecessary or unhelpful measures.
My name wouldn’t be on either slide, he said. There was still more to be learned from my genome.
“I don’t consider your case finished,” he said. “It’s not over.”