human body as a backup in the event of a truly catastrophic bleed. If the same principle holds for other genetic diseases caused by single genes—for cystic fibrosis, say—then gene therapy might be vastly more tractable than had previously been imagined. Even the inefficient delivery of a therapeutic gene to a small subset of cells might be sufficient to treat an otherwise fatal disease.
But what about that perennial fantasy of human genetics, the alteration of genes in reproductive cells to create permanently amended human genomes—“germ-line gene therapy”? What about the creation of the “post-humans” or “trans-humans”—i.e., human embryos with permanently modified genomes? By the early 1990s, the challenge of permanent human genome engineering had been reduced to three scientific hurdles. Each of these had once seemed like an impossible scientific challenge, but each is on the verge of being solved. The most remarkable fact about human genomic engineering today is not how far out of reach it is, but how perilously, tantalizingly near.
The first challenge was the establishment of a reliable human embryonic stem cell. ES cells are stem cells derived from the inner pith of early embryos. They live in transit between cells and organisms: they can be grown and manipulated like a cell line in the lab, but are also capable of forming all the tissue layers of a living embryo. The alteration of the genome of an ES cell is thus a convenient stepping-stone to the permanent alteration of an organism’s genome: if the genome of an ES cell can be changed intentionally, then that genetic change can potentially be introduced into an embryo, into all organs formed within the embryo, and thus into an organism. The genetic modification of ES cells is the rather narrow pass through which every fantasy of germ-line genomic engineering has to travel.
In the late 1990s, James Thomson, an embryologist in Wisconsin, began to experiment with human embryos to derive stem cells from them. Although mouse ES cells had been known since the late 1970s, dozens of attempts to find human analogues had failed. Thomson traced these failures to two factors: bad seed and bad soil. The starting material for the establishment of human stem cells was often of poor quality, and the conditions for their growth were suboptimal. As a graduate student in the 1980s, Thomson had studied mouse ES cells intensively. Like a hothouse gardener capable of coaxing exotic plants to live and propagate outside their natural environments, Thomson had gradually learned the many eccentricities of ES cells. They were temperamental, volatile, and fussy. 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.
In 1991, having moved to the Wisconsin Regional Primate Center, Thomson began to derive ES cells from monkeys. He plucked a six-day-old embryo from a pregnant rhesus monkey, then let the embryo grow in a petri dish. Six days later, he peeled away the outer layer of the embryo, as if skinning a cellular fruit, and extracted single cells from the pith of the inner cell mass. As with mouse cells, he learned to culture these cells in nests of nurse cells that could supply crucial growth factors; without these nurse cells, the ES cells died. In 1996, convinced that he could try his technique on humans, he asked the regulatory boards at the University of Wisconsin to allow him to create human ES cells.
But mouse and monkey embryos had been easy to find. Where might a scientist find freshly fertilized human embryos? Thomson stumbled on an obvious resource: IVF clinics. By the late 1990s, in vitro fertilization had become a common treatment for various forms of human infertility. To perform IVF, eggs are harvested from a woman after ovulation. A typical harvest yields multiple eggs—sometimes up to ten or twelve—and these eggs are fertilized by a man’s sperm in a petri dish. The embryos are then grown briefly in an incubator before being implanted back into the uterus.
But not all IVF embryos are implanted. Implanting more than three embryos is unusual and unsafe, and the spare embryos are typically discarded (or rarely, implanted into other women’s bodies, who carry such embryos as “surrogate” mothers). In 1996, having obtained permission from the University of Wisconsin, Thomson obtained thirty-six embryos from IVF clinics. Fourteen of them grew