The Double-Edged Helix

In the delicate realm of biomedical research, those vigorous cervical cells from Baltimore are creating confusion and, possibly, disaster

Cervical cancer cells dividing. Credit: STEVE GSCHMEISSNER/Getty

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.

Walter Nelson-Rees's laboratory is the address where some 5000 of these cell lines reside: either deep frozen or still growing in three-man-high, stainlesssteel incubators, maintained just at body temperature and filled with chrome racks of culture bottles. Each culture bottle is about the shape of an old-fashioned cough syrup container, half-filled with a clear red solution, derived from calf fetuses, the color of weak cherry Kool-Aid. In some bottles, a faint whitish haze of human cells clings to the plastic sides; in others, the material has begun to peel, like dead skin, in wispy pale patches. Each bottle, regardless of appearance, contains the living cellular remnant of some more-or-less recently deceased medical J. Doe and a few from individuals still living.

"You can do with cells of humans," Nelson-Rees explains, "what you cannot do with humans themselves. While you can work with the whole animals in the laboratory, you really cannot work with humans that way." Good manners, at the very least, considering that most of the cells that leave Nelson-Rees's laboratory are bound for service in the National Cancer Institute's intense hunt for human cancer virus. Last year, in fact, Nelson-Rees sent out more than 2000 individual cultures, in a shipping process that is now as streamlined as that of frozen Kansas City fillets.

When shipped, cells can be sent either as living cells or as frozen samples. In the first instance, cells are transferred from their warm incubators to two broad stainless-steel cauldrons, the approximate size and shape of a tub washing machine. Each contains, halfhidden in the steamy, frigid vapors of liquid nitrogen, multiple stacks of tiny glass ampules, smaller than the last segment of a little finger, each numbered, each flame sealed and each containing a minute smear of flash-frozen human cells.

When its number is called, one of these ampules will be extracted from the nitrogen fog with tongs and placed into a styrofoam container the size of a shoebox, packed with dry ice, for airmail dispatch - along with a set of mimeographed instructions, reminiscent of those that arrive with mail-order rose bushes, recommending the nutrient mixture to prod one's newly thawed sample into maximum activity. While the recommended medium may vary slightly from culture to culture, it is always some blend of vitamins, amino acids, salts and related nutrients. "Basically," explains Walter Nelson-Rees, "body fluids."

One day in Walter Nelson-Rees's laboratory is enough to make clear just how easy it was for the young mother from Baltimore to travel the globe. Cancerous cells in the body show one notably lethal turn called metastasis, wherein a malignant cell detaches itself from the original tumor to travel, pell-mell, through the rest of the organism. Cancer cells cultured in the laboratory, by now, show a similar tendency toward propagation: cell lines are swapped, traded, forwarded, begged and borrowed among research institutions around the world.

The Tissue Culture Association has grown, since the Fifties, from less than 100 to 2000 members. The institutional sources of cells now range from NCI-supported facilities like Nelson-Rees's to commercial outfits with toll-free 800 numbers, from whom one can order, for about $25, a tiny glass vial of HeLa cells guaranteed to contain 100 square centimeters of cell surface area.

"But it's a very difficult business," sighs Walter Nelson-Rees, "to have things that are growing all the time. I'm not sending someone a dead product; it's an item that grows from day to day - even our frozen ampules, as soon as they are opened and placed into cultures, are dividing, and the potential for contamination is instant."

Even a single HeLa cell, accidentally introduced into another kind of culture, can conquer it altogether. And that is why, in lighter moments, Nelson-Rees refers to himself as the Ralph Nader of cell culture: his job is to insure the purity of any given cell line.

Each cell, cancerous or not, still contains specific genetic information - within the gene-packed chromosomes - that described the original organism. With certain exceedingly delicate biochemical techniques, Nelson-Rees can analyze that information and then surmise, rather exactly, what sort and sex of organism the cell might have come from in the first place - even if the original donor had been dead for decades.

Sometimes that news can be a surprise. A team of Russians, for example, shipped their American colleagues a set of assorted human tissue cultures thought to contain that golden fleece object of much recent cancer research: a human cancer virus. Not only, however, did the virus appear to be suspiciously like an already known virus, but the cell lines themselves turned out to be, one and all, HeLa - descendants, likely, of HeLa cells shipped to Russia years ago.

 While less complacent researchers might have tossed themselves off the roof of their medical building, the Russians took the news gracefully. And Nelson-Rees, suspecting that an increasing number of cell lines were no longer what they were supposed to be, redoubled his efforts at cell culture investigation. In life, the HeLa source had been black and female. Even as a single layer of cells in a tissue culture laboratory, she remains so. Nelson-Rees concentrated on, identifying the chromosomal markers peculiar to those two traits and, quite quickly, found enough of those markers--in cell cultures where they should not have been - to complete his Science paper.

Almost overnight, HeLa contamination became notorious. One lab, which had widely distributed a line of now-suspect human breast tumor cells, sent out a letter warning that their HBT-3 might, in truth, be HeLa. And even labs that had never worked with HeLa at all could not be certain that HeLa hadn't already visited under another name.

The question was not just academic curiosity. Careers had been built on the basis of human tissue culture research, papers written and published, grants and fellowships received - and now, abruptly, arose the possibility that the fundamental unit of study might not have been even vaguely what it was supposed to be. For some researcher, pushing 40, who had devoted ten years of his life to a series of lengthy and delicate experiments, each step built upon the results of the last, such news could be disaster.

And no one could really be certain. In the months that followed Nelson-Rees's paper, for example, it develops that at one prestigious American tissue culture depository, almost half of the established human cell lines now look suspiciously like HeLa. A curious paranoia spreads through laboratories worldwide: "HeLa," as Nelson-Rees points out, "by many other names can spell trouble."

Helen Lane left her marker chromosomes all over the laboratory, but in life, her trail was not so well blazed. I ask Margaret Gey if I could come to Baltimore to talk about the early days, and she demurs immediately. It's not, she says, really such a good idea.

Why?

"Oh," she says, "you know. There are always those who are jealous, of what you are and what you did, and so I want to be very, very careful..."

Dead end. And then, quite by chance, the next day I learn Helen Lane's real name. "You know," Walter Nelson-Rees is telling me, "that polio was defeated, primarily, because of the techniques that allowed one to study virus within the individual human cell - and much of that was due, initially, to the strain derived from Henrietta Lacks."

Beg pardon?

"Henrietta Lacks," he says. "That was her real name. I don't think anyone is quite sure how everybody got to calling her Helen Lane."

That afternoon I call Margaret Gey again. "Oh," she says, "I don't know. It was confused, by a publisher in Minneapolis. The name wasn't supposed to be revealed at all. It was just that somebody got confused."

A week later I am sitting on the seventh floor of the downtown Baltimore Holiday Inn. Through the thermopane picture window is a huge public clock in which the numerals have been replaced by the characters b-r-o-m-o-s-e-l-t-z-e-r; in my lap is a telephone, and the Baltimore White Pages. Halfway through the "Lacks" listings it becomes clear that just about everybody had known Henrietta. But over the two and a half decades of her laboratory existence, there have been separations, divorces, people have moved South, moved North, changed addresses, lost their telephones, and no one, finally, has really kept in touch.

"Henrietta Lacks?" one young male voice replies. "You mean Helen Lane?"

My God, I say, yes. This Lacks sounds unmistakably white. How, I wonder, did he know about Helen Lane?

"Well," he says, "I'm a medical student and we've just finished a course in medical genetics and..."

By afternoon, my luck takes a turn. And by dark, I am at the two-story brick house of Henrietta's oldest son, Lawrence. And across a narrow dining room table sits David Lacks - Henrietta's husband, still a widower, a medium-sized black man, for 20 years employed in the Baltimore shipyards. When, I wonder, did he learn about his wife's role in medical science?

"I don't know," he says slowly, touching one hand to his short graying hair and staring at the table. "Did they take it from her before she died or after she died?"

Before, I say, is what I read in the medical journals.

"Well then," he says, "the first I knowed about it was, she had that cancer, and they called me to come up there, 'cause she died. And they asked me to let them take samples and I decided not to let them do it. But then my cousins said it wouldn't hurt none, so I let them do it.

"They said it wouldn't disfigure her none, because it was all down in her womb, to begin with." He nods. "They said it was the fastest growing cancer they'd ever known, and they was suppose to tell me about it, to let me know, but I never did hear."

His son, Lawrence - a brawny railroad engineer, with a short Afro and a sleeveless undershirt - nods also. "First we heard," he says, "was about a month ago, a person called us on the phone and asked if we'd like to take a blood test. That's the first time we heard about it."

David Lacks agrees. "And I said, gonna be just like the last time, say they call and they don't. Then they sent me a book, sent me some letters, said it might be good for my children and grandchildren."

What book did they send?

Lacks looks at his son. "Where's that book?"

Lawrence sends his wife, Bobbette, up the stairs to find the book. "They said," says Lawrence, "they wanted to find out why it been living so long."

"Doctors all over the world," says Mr. Lacks, "is trying to figure out why these cells is living so long."

"This chromosome thing," Lawrence says. "They want to find out whether we inherited it."

Are the Lacks a healthy family?

"None of us slippin'," says Mr. Lacks, "far as I know."

"One baby girl died," Lawrence says. "Natural causes."

Bobbette appears at the foot of the stairs, bearing a thick medical textbook, and gives it to Lawrence.

Lawrence begins to page through. It is a text on medical genetics, authored by a professor at Johns Hopkins. "What page she's on?" asks Lawrence. Bobbette doesn't hear. Lawrence shakes his head, continues browsing. "Should be in this section," he says. After a moment, he calls again, more loudly: "Hey, Bobbette, you know what page she's on?"

"She's upstairs," says one of the kids.

"Go ask her what page Grandma's on."

"Page 15," Bobbette yells down the stairs.

Lawrence flips pages."There it is," he says.

"There she is," says Mr. Lacks. "That's her, right there."

A fuzzy photograph of Henrietta Lacks appears as a numbered plate. She is posed against a brick wall: stocky, well-dressed, hand on hip, smiling broadly into the camera. She looks like a very healthy woman.

"Well," says her husband, "you're right. Didn't have a sick day in her life until she went to the hospital. Then she came home, but she'd always be getting worse, and she'd go back to the hospital."

Was Mrs. Lacks a religious woman?

"She was Catholic," says Mr. Lacks. "About like any other. She had ups and downs - everybody's got ups and downs."

"What I was wondering," says Lawrence, "was about these cells. Is there something different about these cells? They say they're stronger, they're taking over - is that bad or good? Does that mean, if we get sick, we'll live longer? I mean," he says, "they say only the strong survive...."

Did the doctors ever take the blood?

Lawrence nods. "A couple tubes from each of us," he says. Blood was even taken by special arrangement from one relation housed at the Maryland State Correctional Institute.

That, Lawrence says, was only a few weeks before. And they haven't been back in touch?

"Nope."

"They sent me a book, they sent me a letter," says Mr. Lacks, "but that's all. The only time the doctors call is when they want something."

Did Mr. Lacks ever meet George Gey, I wonder?

"I met him at the hospital," Mr. Lacks says. "He told me, these things take time, he told me he'd let me know what happened. But it's been so long now, he's died!"

We talk a bit more and then, on the way out to the icy sidewalk, we pause in the living room, where Mr. Lacks takes a picture from an end table. It is a photograph of himself and Henrietta, both in Sunday best, and shot, he says, just when they arrived in Baltimore from Virginia, in 1943. The young couple gaze sedately into the camera, but something about the picture looks exceedingly unnatural.

"I said send it back," says Lawrence, looking over my shoulder. The picture, he explains, has been restored and tinted, from a tattered 2x3 original. The process cost $50, says Lawrence, "and you only get one print, in a little cardboard folder."

David Lacks is still studying the photo. "The legs are okay," he says. "But it's the face." He shakes his head. "They didn't get the face right at all."

Just about exactly a year after I left the Lacks house, I heard about Henrietta one last time. She was in Science again, in another paper authored by Nelson-Rees and Flandermeyer. "HeLa Cultures Defined," read the title, and accompanying the brief text was a two-page table describing a whole spectrum of established cell lines - from breast cancer to the marrow of a human sternum, originated everywhere from Maryland to the Soviet Union - all of which looked, rather distinctly, to be HeLa.

I telephone Walter Nelson-Rees once again. "I said at one time," he sighs, "that I hoped I'd never have to look another HeLa in the face, but I'm afraid now that as long as cell culture continues, there will be chances for contamination."

No one, Nelson-Rees says, really knows how much the cell line mixup will affect existing research. If only the general process of cancer is one's interest, then the change may not be significant. But if one's work is tied to some specific type of cell - and the subject cells turn out to be HeLa - then chances are that one is in trouble.

"Many recent publications," says Nelson-Rees, "now include statements like, 'The patient from whom such-and-such a cell was derived is Caucasian, a male...' and so on. These are things that did not happen two years ago. But it will take time for everybody to make sense out of the methods."

Nelson-Rees's private worry, he confides, is that other human cell cultures - younger than HeLa - may one day grow so adapted to the laboratory that they will become contaminators too. And so his task is unending. "This morning," he says, "I've just been presented with a huge big box of cells from another laboratory, which need to be looked at. Sometimes people think that such work must be very routine. But somehow each and every one seems to be a whole new entity."

We hang up and I call the Lackses, to tell them that Henrietta is in the journals again. Bobbette answers. "Those doctors," she says, "never did get in touch. We haven't heard a thing."

I tell her about Nelson-Rees's new paper, and that I've also learned what the doctors finally did with the Lacks blood. Each sample was minutely analyzed, in order to backtrack genetically from the chromosomes of Henrietta's husband and children and thus determine Henrietta's own genetics.

"An elegant piece of work," Walter Nelson-Rees had called it. "By simple Aristotelian class logic and pure applied genetics, you can speculate, to a remarkable extent, as to what Henrietta Lacks was."

The results - an intricate and almost incomprehensible chart listing the genetic markers of the whole Lacks family - will be used worldwide in something of a laboratory manhunt to track down renegade HeLa cultures. The cell that helped beat polio and has since figured in everything from drug research to cancer work is on the wanted list, and the charge is interfering with the orderly progress of science. Just how much interference no one can still quite say. Those most affected, certainly, are also the most quiet. One recent book on cancer speculated with the single word "catastrophic." "An elegant piece of work," Nelson-Rees had called the elaborate genetic fingerprinting of the Lacks blood, a piece that, a week later, would appear in Science.

"Can you buy that on the newsstand?" Bobbette asks.

I say I'm not sure, but I could send a copy. And then I ask to talk to David Lacks, for one more question.

"No," Mr. Lacks says, after a moment's silence. "If it had all happened at first, I would have felt bad. But by now," he says, "you know, I've pretty much forgot about it."