The human face of gene therapy
Science is a difficult thing to communicate to nonscientists, now more than ever with familiar sciences such as biology, physics, chemistry and cybernetics morphing into new sciences, some of which exist beneath our line of sight, where the laws of nature hover between Newtonian and quantum mechanics.
Few scientists know how to make this world real to each other, let alone to the rest of us, and those who do are often reviled by their peers for popularizing something best left in the laboratory. Thus we laymen must rely on articulate mass media science writers to keep us abreast of subjects we left behind in our sophomore years. They master the language and complexity of new fields such as cyber-, bio- and nanotechnology and carry us with ease through the most arcane and baffling concepts. We are intrigued and empowered by their gift.
Jonathan Weiner, a Pulitzer Prize-winning writer-in-residence at Rockefeller University and former editor of the Sciences magazine, has been justly awarded for previous books about matters as diverse as the love life of fruit flies, the ever-evolving beaks of Galapagos finches and the future of the planet we occupy. Now he turns to medicine and recounts a desperate personal quest to cure an intractable orphan disease with untried, highly controversial gene treatments. The result is a captivating, suspenseful narrative, full of complex, fascinating characters and loads of pathos.
“His Brother’s Keeper: A Story From the Edge of Medicine” is a science drama involving the illness of one member of an amazing family. When Stephen Heywood, the second of three brothers, is diagnosed at 29 with amyotrophic lateral sclerosis, better known as Lou Gehrig’s disease, his older brother Jamie transforms himself overnight from a mechanical engineer to a genetic engineer in a desperate quest to save him.
ALS is a devastating, incurable neurological disorder that rapidly destroys the motor nerves of its victims. Their lives end in unimaginable agony and suffocation, generally, about two years after diagnosis. This is not something Jamie Heywood ever wants to watch.
As the story unfolds and Stephen’s condition worsens, Jamie is variously motivated by rage, ambition, curiosity, fame and profit to find a way to regenerate lost neurons somewhere in the fast-growing but still infant field of genetic medicine. But above all he is driven, at times into caffeinated frenzy, by a compulsive resolve to save his brother’s life.
When Stephen is diagnosed, Jamie leaves a lucrative career in La Jolla, Calif., and moves home to Boston where his brothers and their parents still live. Weiner follows him to become all but a member of the family. And what a family -- tight-knit, loving and defiantly loyal. Anyone would want to be part of it, most of all a solitary writer accustomed to lonely nights in motels, long rides in rented cars and impersonal interviews in neutral locations.
I envied Weiner being with the Heywoods, although as a fellow reporter I began to wonder how objective or dispassionate anyone could be when he stays overnight in their houses, parties at their cottage, joins them at church and drives thousands of miles up and down the East Coast with them, from Boston to New York to Baltimore, as they raise money and beseech molecular biologists, geneticists and clinical physicians to join their private war against ALS. Weiner admits, “I was hooked.” And I realized I would have been too.
The plot thickens when Weiner’s mother is diagnosed with a rare neurological disorder called Lewy Body dementia. I can imagine his editor asking whether the author and his mother needed to be injected into the drama that was engulfing the Heywood family.
But it turns out that Lewy Body is a condition that could be cured by some of the same treatments being considered for Stephen. So this additional drama works, and we join the Weiner family as Jon Weiner joins the Heywoods.
In the course of his research into the science behind the treatments, Weiner signs a can’t-write-about-it-for-three-years contract and joins another desperate voyage. A Caribbean cruise ship called the Galaxy sets sail from Miami. On board is a small group of geneticists and fertilization specialists who are dodging the glare of media, the judgment of bioethicists and the intrusion of government for a week at sea.
In safe international waters they discuss some of the more controversial and ethically challenged procedures emerging in their practice. The most riveting debate is over germ line engineering, which offers the ability to permanently alter the human genome in such a way as to breed a superhuman species that cannot interbreed with its genetically inferior ancestors.
Weiner witnesses an exchange any journalist would die for. And he returns to shore wondering whether this genetic manipulation is responsible medicine.
That sort of question, alongside the growing doubts among bioethicists about experimental procedures on consenting terminal patients, sends Jamie Heywood into a rage. “That’s just like totalitarianism,” he tells another reporter. “If we’ve gotten to the point where human beings aren’t capable of making decisions in their own best interests, then what kind of society do we believe in?” But this is not a simple decision, Jamie is soon to discover, for either Stephen or the dozens of scientists and physicians Jamie has recruited to his cause.
There are two interventions possible for Stephen. One injects healthy stem cells either into his spinal column or directly into his brain. The other infinitely more experimental and complex procedure involves a neurological vaccine made by inserting DNA into billions of viruses and injecting them into the patient in the hope that they will penetrate nerve cell walls, find their way to the nucleus and instruct it to produce a chemical that will block the cellular production of glutamate, an amino acid that in excess kills nerve cells -- the mechanism of ALS.
Stem cells had been tried on a few ALS patients in their endgame. Results were not encouraging. The vaccine was untried. Which was right for Stephen, the stem cells or the neurovaccine? Or was either treatment right for anyone?
Perplexed by that question, Weiner calls Arthur Caplan, the most widely quoted bioethicist in the country, a man whom I have known to answer his phone on the first ring. When he hears the question, Caplan does not hesitate to express an opinion looming in his practice about stem cells and gene therapy.
“My skepticism about all this is somewhere between unbounded and enormous,” he tells Weiner. Stem cell therapies, Caplan says, belong “on a five year plan, not a short term plan,” and adds, “the fact is you can be made more miserable -- even though it doesn’t seem possible -- by interventions.”
And therein lies the central question of this story and of regenerative medicine itself. How far can we go in experimentation, even with dying patients still competent to provide informed consent? The value of books like “His Brother’s Keeper” is that they force the healthy to address such questions while they are healthy, rather than waiting until they and their frantic family are driven by desperation to find a silver bullet. At that point they are at the mercy of medical cowboys like the geneticists on board the Galaxy who discussed practices and procedures they did not want us to know about until they had mastered them.
It’s not the first time this has happened in medicine. Nor will it be the last until we, the consumers of treatment, better understand what they are talking about. For that we can be grateful to writers like Jonathan Weiner.
