The Double-Edged Helix

On a mild, rainy Thursday, early in February of 1951, an energetic young black woman, just 31, appeared for examination at the outpatient gynecologic clinic of Baltimore’s Johns Hopkins Hospital – a massive, copper-spired castle of brick, ten minutes’ walk east of downtown. That same day, 21 German war criminals, sentenced to die on the gallows, were spared in the most sweeping American clemency move since the cessation of hostilities.

At just about the same time the Germans received their clemency, the young woman received her death sentence, phrased in the precise language of the pathology lab: a tiny purplish lesion on her cervix, less than an inch in diameter, was cancer.

Her malignancy diagnosed, the patient would spend the remaining eight months of her life shuttling in and out of Johns Hopkins for treatment, to die there, finally, during the long humid days of late summer, leaving behind a soft-spoken husband, five children, a handful of photographs – and a tiny piece of her own flesh that by now, a quarter-century later, thrives and conquers in laboratories around the world.

The first time I heard about Helen Lane was the spring of 1974 in the men’s room of a San Francisco medical school library, where an odd, felt-pen scrawl over the urinal read “Helen Lane Lives!”

The observation was meaningless to me then, and I likely would have forgotten it altogether – except less than two months later I ran across Helen Lane again. This time it was in the prestigious pages of Science. Helen Lane was the topic of a brief, highly technical paper that immediately sent tremors through the whole structure of international medical research.

According to the paper, the oldest and most dependable line of human cells, dubbed HeLa, had suddenly been found to be not only old and dependable, but positively aggressive. These tiny human cells had surreptitiously spread from their own glass containers to infiltrate and subvert whole sets of other cell lines – altogether unbeknownst to the countless medical researchers who based their work on them.

HeLa, according to Science, is cell culture shorthand for Helen Lane, and Helen Lane is a big name in that arcane pursuit. Human tissue culture is essentially the art of convincing a glass-bound set of cells that it is in fact still safely ensconced within some warm body and thereby prompting its continued reproduction. That’s not an easy trick, but over the past 20 years, tissue culture has become a critical tool in medical research, allowing the scientist to observe all sorts of cellular processes – from virus infections to nutrition – without actually having to fool around with a whole live human being. And it started, really, with Helen Lane–a Baltimore woman now long dead, whose cancerous cervical cells performed so spectacularly in laboratory glassware that they became, almost overnight, one of the hottest items in experimental biomedicine.

Now, a quarter of a century later, HeLa also looks like a major problem. For, it develops, even a single HeLa cell transferred on a glass pipette by a careless technician can overgrow an entire precisely labeled colony of different cells and settle in, right at home. At that point, of course, that precise label becomes meaningless and thus, by now, some number of researchers who had thought all along that they were experimenting with kidney cells from Los Angeles or breast tumors from Vladivostok were in fact all working with identical versions of those vigorous cervical cells from Baltimore.

In the delicate realms of biomedical research that’s not exactly a minor error. It is closer, all in all, to disaster.

Just how disastrous, the Science paper wouldn’t even hint. How, I wondered, does this tissue culture business work? How did this HeLa cell become a monster amidst the Pyrex? What are the implications for research – and most of all, who was this Helen Lane?

That wet Baltimore February day when the young black woman first appeared at the Johns Hopkins clinic, a physician/researcher named George Gey and his wife, Margaret, in a small laboratory in the same building, were rapidly approaching the culmination of a quarter-century’s work in the techniques of growing human cells in glass. Gey – who died in 1970 – will likely be recognized someday as a significant figure in the medical history of the early 20th century. “Biology and medicine,” said one journal, a few months after his death, “are greatly indebted to George Gey, whose skill with the tissue culture technique made so much possible.”

Back in 1951, however, Gey was less lionized; he blew his own glassware, employed his wife and worked long hours to support his laboratory. His research had little funding – during most of Gey’s career the great war on cancer, which would put living human cells at a premium, was still well in the future.

In 1933 – after eight years of shoestring research–Gey had invented the “roller tube” – a device for cell culture which, by means of slow rotation, offers the developing cells more nutrition than was possible in the traditional hollow-ground depression of a glass microscope slide. While human cells had been cultured before Gey’s roller tube, it was a major step forward in simplifying what had previously been a spectacularly delicate, erratic operation.

Gey’s wife, Margaret, still has the first roller tube. “He blew the glass for it himself,” she says, “put the cells in and rolled it in an incubator overnight. And that was the breakthrough. Pretty soon bacteriologists were using it, and then . . . Oh my!”

But even the roller tube didn’t mark smooth sailing for the Geys. “We were lucky,” says Margaret Gey, “during the Depression to have $5000 a year to work with. We had to do everything from scratch. I painted our lab myself. These days people waste so much money.”

Almost 20 years after the first roller tube, the young Baltimore black woman walked into Johns Hopkins and eight days after that, the resident gynecologist passed onto the Geys a tiny bit of her ultimately fatal lesion – rescued, as it were, just before the first round of her radium treatments. Gey grew that tissue in his roller tube and after several weeks of mounting excitement, he realized that this time he had cultured something very special. Historical, even. “HeLa,” noted one journal, “with a generation time of about 24 hours, if allowed to grow uninhibited under optimum culture conditions, would have taken over the world by this time.”

HeLa’s contribution to modern medicine began immediately. The day before the young woman first visited the Baltimore clinic, 10,000 mothers marched against polio in New York City; three years later, the HeLa strain would take those mothers off the street permanently. Polio is caused by a virus and viruses require cells in which to grow. These indefatigable, undeflatable HeLa cells proved to be ideal hosts for polio virus – a pivotal development in the creation of a successful vaccine. And that was only the beginning. Within a few years, HeLa was in laboratories around the world. Why, one wonders, did the Geys keep at their tissue culturing for all those years when no one was paying any attention?

“Well,” says Margaret Gey, “that’s what everybody asked us. Why do you do it? It won’t get anyplace. But I believed in George and George kept saying that there’s a field in this – he could feel it coming!”

Dr. Gey was right. Ask, for example, Walter Nelson-Rees, the ebullient California cell geneticist whose terse Science paper, coauthored with colleagues Robert Flandermeyer and Paula Hawthorne, produced the first hard data that triggered the HeLa controversy. Nelson-Rees’s sole business is, in fact, the maintenance and distribution of life in glass. The business is, however, still sufficiently new that some mysteries remain. “I don’t think,” says Nelson-Rees, “that anyone really knows why one cell grows and another doesn’t.”

HeLa – while it is still human, reflecting the genetic makeup of its donor – is also cancerous, as are many other popular cell lines in the tissue culture business. Might this explain HeLa’s laboratory longevity? Nelson-Rees considers the possibility for a moment. “It’s really not that easy,” he shrugs finally, “even to grow tumor cells.”

Nelson-Rees, almost certainly, should know: in a small laboratory tucked away on Navy property just south of Berkeley, he runs a thorough reference library of human and other vertebrate cell lines for the National Cancer Institute.

Everyone on Nelson-Rees’s mailing list receives, annually, a thick computer-generated catalog that may well be one of the more exclusive mail-order services on the planet. The catalog describes, for example, the conditions surrounding the early demise of a 16-year-old Los Angeles male, and then offers, by number, a variety of cultured samples of those deceased teenaged tissues: lung, liver, heart or kidney.