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opinion | jim kozubek

Would you edit your genes?

Advances in gene therapy come with ethical and medical dilemmas

Jameson Golliday’s father, Rob, held him during a gene therapy procedure. Jameson was born with no immune system, commonly called Bubble Boy disease.
Jameson Golliday’s father, Rob, held him during a gene therapy procedure. Jameson was born with no immune system, commonly called Bubble Boy disease.Jennifer Golliday photo

By July, the swelter of summer was upon us. I felt locked into the crucible of Boston, so I headed West by highway. The roads were lined with milkweed and purple violets; the sky opened up, and rain clouds coasted in the distance. And then, I was there. I met Jameson Golliday, a blue-eyed boy, age 2, on a small patch of lawn in Bloomington, Ill.

Jamie has a rare disease called X-SCID, or Bubble Boy disease, which means he was born with no immune system. But last year he had his cells edited to add a gene called IL-2. During our visit, Jamie played in the dirt, picking up sticks and rocks and handing them to me. “It was scary in some aspects,” his mom, Jennifer Golliday, said of the treatment. “I was willing to risk it.” He now has a small army of T-cells, and no longer wears a mask. By early afternoon, he asked to hold my hand.

David Vetter was perhaps the most famous Bubble Boy. He traveled to a movie theater to see “Return of the Jedi’’ in a transport carrier. NASA built him a space suit. It was to no avail. He died in 1984 at age 12. Jamie is skirting that fate, thanks to advances in gene therapy.


In the past two decades, doctors have used viruses as tiny pilots to travel to the genome to install good copies of working genes. That has allowed them to treat enzyme deficiency disorders such as adrenoleukodystrophy and metachromatic dystrophy. And major hospitals have reported jaw-dropping success using gene therapy to cure leukemia and lymphoma. All of this is promising, but gene therapy has its risks, both medically and ethically. Jesse Gelsinger, 18, died in gene therapy in 1999, when viruses used to treat him touched off a massive immune reaction, called a “cytokine storm.” And big problems exist if a newly installed gene lands smack dab in a cell cycle gene, tripping the cycle and leading to uncontrolled cell growth: cancer.

A decade ago, 20 X-SCIDs patients were treated with gene therapy and five got leukemia, including one who died. David A. Williams, a chief at Children’s Hospital Boston, working with Christopher Baum, made alterations, which he thinks make the treatment safer, meaning no cancer side-effects. “I want to be very cautious about that,” he told me.


Time will tell. But the field is moving forward because of incremental gains. It’s due to Sangamo Bioscience’s work to improve tiny molecular scissors, called zinc finger nucleases, which can make precise edits; it’s due to Carl June’s work at Penn to culture T-cells so they’re high-functioning when returned to the body. Investors are now cottoning to the technology. Cambridge-based Bluebird Bio Inc. this spring completed an IPO at $17 a share, and since then its stock has doubled to around $35 a share.

Treatment of dangerously ill children remains contentious due to risks, but we’ve seen victories. Emily Whitehead, age 8, had leukemia that exhausted options at Children’s Hospital of Philadelphia, until gene therapy thrust it into full remission. Thank you, modern medicine. That was one of your best moments.

And then, there are futurists who want to perfect their genome. If you think you can boost your fitness, I say, go ahead. Throw caution to the wind. I’m not terribly interested in you. Besides, besting the human design would be strikingly difficult to achieve. Stuart Kauffman got it right in “The Origins of Order’’ when he wrote that “evolution is not just chance caught on the wing.” It is “not just tinkering of the ad hoc, of bricolage, of contraption. It is emergent order honored and honed by selection.”

The most difficult thinking about gene therapy involves normally healthy people who have mutations that are highly predictive of a disease. Geneticists call this penetrance. It includes people who have the repeats of the motif CAG in a single gene and are almost certain to get Huntington’s disease, or those with mutations in the PDK gene family, which almost certainly cause polycystic kidney disease. It’s the actress Angelina Jolie, who in the film “Tomb Raider’’ fought off a six-armed guardian statue, armed mercenaries, and a robot named SIMON. But it was a typo in a molecule that put her at the greatest danger. Carrying mutations in BRCA1 puts a woman’s risk at up to 80 percent for obtaining breast cancer.


And so, there’s the rub. We’d surely accept some risk to edit the genes of a dangerously ill child; but do you edit motifs in genes that are merely likely to cause a disease?

Consider the 1994 case Katskee v. Blue Cross Blue Shield of Nebraska. Sidnie Katskee had her ovaries removed as a precaution against cancer. Her mother and aunt died of ovarian cancer with diagnoses at 47 and 48 years. The insurer refused to pay, saying it was not “medically necessary.” A trial judge ruled for the insurer, saying Katskee did not have a “bodily illness or disease,” but the Supreme Court of Nebraska reversed the decision and ruled in Katskee’s favor. Boston University bioethicist George Annas wrote at the time that “the new genetics” will likely blur the distinction between prevention and treatment, since spotting a mutation that causes a disease is close to spotting the disease. But he cautioned that treatments based on a predisposition might be cost prohibitive and, after all, “we will all die of something.”


The Food and Drug Administration is expected to approve the first gene therapy drug in three to five years. For at least a decade, those treatments will be restricted to blood and immune system cells. But within our lifetime we may be asked if we want to change our genes. I’m not so sure I would edit my genes if they merely predict a disease. But I think people should have the choice.

Jim Kozubek, a science writer and computational biologist, lives in Cambridge. He is writing a book about gene therapy and genetic engineering in humans.