The Gene: Part Six–Epilogue

At the conference, the students are concerned about the dangers of such novel DNA fragments: if the wrong gene is introduced into the wrong organism, the experiment might unleash a biological or ecological catastrophe. But Berg’s interlocutors aren’t only worried about pathogens.

The experiment worked at first—but it was stymied by two unexpected effects.

As an animal ages, cells on the surface of its skin grow, die, and slough off.

A stem cell is somewhat akin to a grandfather that continues to produce children, grandchildren, and great-grandchildren, generation upon generation, without ever losing his own reproductive fecundity.

The viral genes might fall into a silent crevasse of the genome, never to be expressed.

These mice have substantially increased memory and superior cognitive function. They are the savants of the rodent world: they acquire memories faster, retain them longer, and learn new tasks nearly twice as fast as normal mice.

For a while, her doctors were mystified by her symptoms, attributing her periodic illnesses loosely to an underdeveloped immune system that would eventually mature. But when the symptoms refused to abate as Ashi turned three, she underwent a barrage of tests.

Known for its tough oversight, the advisory committee was the gatekeeper for all experiments that involved recombinant DNA (the committee was so notoriously obstreperous that researchers called getting its approval being “taken through the Rack”).

Once infected, the cells grew in petri dishes, forming lush outcroppings of new cells, and even newer cells.

To test whether targeted genetic alterations could be introduced into human cells, and whether these genes would confer normal function safely and effectively, he proposed a careful, uncontaminated trial—“clean, chaste gene therapy,” as he called it.

He found his son unrecognizable—comatose, swollen, bruised, yellowed with jaundice, with dozens of lines and catheters crisscrossing his body.

The litany of troubles uncovered in the OTC trial was not limited to that trial alone. In January 2000, when the FDA inspected twenty-eight other trials, nearly half of them required immediate remedial action.

The litany of troubles uncovered in the OTC trial was not limited to that trial alone. In January 2000, when the FDA inspected twenty-eight other trials, nearly half of them required immediate remedial action.

In science, there is a well-known aphorism that the most beautiful theory can be slayed by an ugly fact. In medicine, the same aphorism takes a somewhat different form: a beautiful therapy can be killed by an ugly trial.

Decades of careful studies on families had suggested that breast cancer came in two forms—sporadic and familial. In sporadic breast cancer, the illness appears in women without any family history.

Gene hunting devolves into a spot-the-odd-man-out game on a gigantic scale: by comparing the genetic sequences of all the closely related family members, a mutation that appears in the affected individual but not in the unaffected relatives can be found.

Gene sequencing was performed on these families. Since most parts of the genome are shared in any given family, only the putative culprit genes fell out as different.

During brain development, these synapses need to be pruned and reshaped, akin to the cutting and soldering of wires during the manufacture of a circuit-board.

Erika was utterly charming—modest, thoughtful, sober, mordantly funny.

The prophylactic treatments—mastectomy, hormonal therapy—all entail physical and psychological anguish and carry risks in their own right.

These interactions place powerful limits on genetic determinism: the eventual effects of these gene-environment intersections can never be reliably presaged by the genetics alone.

In India, parts of which are home to some of the most blatantly sexist subcultures in the world, attempts to use PGD to “diagnose” the gender of a child were reported as early as 1995.

Depraved dictators and predatory states are not an absolute requirement for eugenics.

It is a question that requires us to balance the desires of the individual—to carve out a life of happiness and achievement, without undue suffering—with the desires of a society that, in the short term, may be interested only in driving down the burden of disease and the expense of disability.

This was the rebirth of “positive eugenics.” Rather than eliminating humans carrying deleterious genes, scientists could envision correcting defective human genes, thereby making the genome a “bit better.”

It reminds us of the power of degeneracy in human biology: if only 5 percent of a clotting factor is sufficient to restore virtually all clotting function in human blood, then 95 percent of the protein must be superfluous—a buffer, or reservoir, possibly maintained in the human body as a backup in the event of a truly catastrophic bleed.

He knew of their propensity to fold up and die at the slightest provocation. He learned about their requirement for “nurse” cells to coddle them, their peculiar insistence on clumping together, and the translucent, refractive, hypnotic glow of the cells that transfixed him each time he saw them under a microscope.

An arcane microbial defense, devised by microbes, discovered by yogurt engineers, and reprogrammed by RNA biologists, has created a trapdoor to the transformative technology that geneticists had sought so longingly for decades: a method to achieve directed, efficient, and sequence-specific modification of the human genome.

This strategy is also intractable: once organized, the human embryo becomes fundamentally obdurate to gene modification.

But even with the new regulations, the NIH categorically prohibits two kinds of research on human ES cells.

“This reality means that germline manipulation would largely be justified by attempts to ‘improve ourselves,’” Francis Collins wrote to me. “That means that someone is empowered to decide what an ‘improvement’ is. Anyone contemplating such action should be aware of their hubris.”

Of the fifty-four embryos tested, only four were found to have the corrected gene inserted. More portentously, the system was found to have inaccuracies: in one-third of all the embryos tested, unintentional mutations in other genes were also introduced, including mutations in genes essential for normal development and survival.

The genome is also a testing ground for our fallibilities and desires, although reading it does not require understanding allegories or metaphors. What we read and write into our genome is our fallibilities, desires, and ambitions. It is human nature.

The task of writing that complete manifesto belongs to another generation, but perhaps we can scribe its opening salvos by recalling the scientific, philosophical, and moral lessons of this history...

Normalcy is the antithesis of evolution.

An epigenetic modifier may be designed to change the state of hundreds of genes with a single switch. The genome is replete with such nodes of intervention.

As we loosen the boundaries of this triangle (by changing the standards for “extraordinary suffering” or “justifiable interventions”), we need new biological, cultural, and social precepts to determine which genetic interventions may be permitted or constrained, and the circumstances in which these interventions become safe or permissible.

This self-fulfilling circle of logic is responsible for some of the most magnificent and evocative qualities in our species, but also some of the most reprehensible.

Geneticists and gene therapists around the world are currently exploring the possibility of changing the human genome with renewed verve and urgency—in part, because the current technologies have brought us to a precipice.

Infirmities might disappear, but so might vulnerability. Chance would become mitigated, but so, inevitably, would choice.

This vivisection of history—the partition of Partition—produced a strangely dissonant experience: the men and women of my father’s generation perceived themselves as unwitting participants in a natural experiment.

The Christian God, capable of inexplicable compassion and equally inexplicable wrath, was a more mercurial bookkeeper—but He too was the ultimate, if more inscrutable, arbiter of destiny.

Nineteenth- and twentieth-century medicine offered more secular conceptions of fate and choice.

But what is “natural”? I wonder. On one hand: variation, mutation, change, inconstancy, divisibility, flux. And on the other: constancy, permanence, indivisibility, fidelity.

Our genome has negotiated a fragile balance between counterpoised forces, pairing strand with opposing strand, mixing past and future, pitting memory against desire. It is the most human of all things that we possess. Its stewardship may be the ultimate test of knowledge and discernment for our species.