The suspensions of Southam's and Mandel's licenses were stayed, leaving them both on one-year probation instead. And the case seemed to have little impact on Southam's professional standing: soon after the end of his probationary period, Southam was elected president of the American a.s.sociation for Cancer Research. But his case brought about one of the largest research oversight changes in the history of experimentation on humans.

Before the Board of Regents announced its decision, the negative press about Southam's work had gotten the attention of the NIH, which funded his research and required its investigators to get consent for all studies involving humans. In response to the Southam situation, the NIH investigated all their grantee inst.i.tutions and found that only nine out of fifty-two had any policy in place to protect the rights of research subjects. Only sixteen used consent forms. The NIH concluded: "In the setting in which the patient is involved in an experimental effort, the judgment of the investigator is not sufficient as a basis for reaching a conclusion concerning the ethical and moral set of questions in that relationship."

As a result of its investigation, the NIH said that to qualify for funding, all proposals for research on human subjects had to be approved by review boards-independent bodies made up of professionals and laypeople of diverse races, cla.s.ses, and backgrounds-to ensure that they met the NIH's ethics requirements, including detailed informed consent.

Scientists said medical research was doomed. In a letter to the editor of Science, one of them warned, "When we are prevented from attempting seemingly innocuous studies of cancer behavior in humans ... we may mark 1966 as the year in which all medical progress ceased."

Later that year, a Harvard anesthesiologist named Henry Beecher published a study in the New England Journal of Medicine showing that Southam's research was only one of hundreds of similarly unethical studies. Beecher published a detailed list of the twenty-two worst offenders, including researchers who'd injected children with hepat.i.tis and others who'd poisoned patients under anesthesia using carbon dioxide. Southam's study was included as example number 17.

Despite scientists' fears, the ethical crackdown didn't slow scientific progress. In fact, research flourished. And much of it involved HeLa.

CHAPTER 18

"Strangest Hybrid"

By the 1960s, scientists joked that HeLa cells were so robust that they could probably survive in sink drains or on doork.n.o.bs. They were everywhere. The general public could grow HeLa at home using instructions from a Scientific American do-it-yourself article, and both Russian and American scientists had managed to grow HeLa in s.p.a.ce.

Henrietta's cells went up in the second satellite ever in orbit, which was launched by the Russian s.p.a.ce program in 1960, and almost immediately afterward, NASA shot several vials of HeLa into s.p.a.ce in the Discoverer XVIII satellite. Researchers knew from simulated zero-gravity studies using animals that s.p.a.ce travel could cause cardiovascular changes, degradation of bone and muscle, and a loss of red blood cells. They also knew radiation levels were higher beyond the ozone layer. But they didn't know what effects any of this would have on humans: Would it cause cellular changes, or even cell death?

When the first humans went into orbit, Henrietta's cells went with them so researchers could study the effects of s.p.a.ce travel, as well as the nutritional needs of cells in s.p.a.ce, and how cancerous and noncancerous cells responded differently to zero gravity. What they found was disturbing: in mission after mission, noncancerous cells grew normally in orbit, but HeLa became more powerful, dividing faster with each trip.

And HeLa cells weren't the only ones behaving strangely. Since the start of the decade, researchers had been noticing two new things about all cultured cells. First, it seemed that all normal cells growing in culture eventually died or underwent spontaneous transformation and became cancerous. This phenomenon was exciting for researchers trying to understand the mechanisms of cancer, because it suggested that they might be able to study the moment a normal cell becomes malignant. But it was disturbing for those trying to use cell culture to develop medical therapies.

George Hyatt, a Navy doctor working with the National Cancer Inst.i.tute, had experienced this phenomenon firsthand. He'd cultured human skin cells for treating badly burned soldiers, then created a wound on a young volunteer officer's arm and smeared the cells across it, hoping they'd grow to form a new layer of skin. If it worked, it might mean doctors could use skin-cell transplants to treat wounds in the field. The cells did grow, but when Hyatt biopsied them a few weeks later, they were all cancerous. He panicked, removed the cells, and hadn't tried transplanting skin cells since.

The other unusual thing scientists had noticed about cells growing in culture was that once they transformed and became cancerous, they all behaved alike-dividing identically and producing exactly the same proteins and enzymes, even though they'd all produced different ones before becoming malignant. Lewis Coriell, a renowned cell culturist, thought he might have an explanation. He published a paper suggesting that perhaps "transformed" cells behaved the same not because they'd become cancerous, but because they'd been contaminated by something-most likely a virus or bacterium-that made them behave similarly. Almost as an aside, he pointed out one possibility that other researchers hadn't considered: all transformed cells seemed to behave identically to HeLa, he wrote, which could mean that HeLa was the contaminant.

Soon after his paper was published, Coriell and a few other top tissue culturists called an urgent meeting to talk about the state of their field, which they worried was becoming a disaster. They'd mastered the techniques of cell culture and simplified them to such a degree that, as one researcher put it, they'd "made it possible for even the rank amateur to grow a few cultures."

In recent years, using tissue samples from themselves, their families, and their patients, scientists had grown cells of all kinds-prostate cancer, appendix, foreskin, even bits of human cornea-often with surprising ease. Researchers were using that growing library of cells to make historic discoveries: that cigarettes caused lung cancer; how X-rays and certain chemicals transformed normal cells into malignant ones; why normal cells stopped growing and cancer cells didn't. And the National Cancer Inst.i.tute was using various cells, including HeLa, to screen more than thirty thousand chemicals and plant extracts, which would yield several of today's most widely used and effective chemotherapy drugs, including Vincristine and Taxol.

Despite the importance of this research, many scientists seemed cavalier about their cultures. Few kept clear records of which cells grew from which donors, and many mislabeled their cultures, if they labeled them at all. For scientists doing research that wasn't cell-specific, like investigating the effects of radiation on DNA, not knowing what kind of cell they were working on might not affect the outcome of their research. But if cells were contaminated or mislabeled in research that was cell-specific-as much research was-the results would be worthless. Regardless, the culturists who called the meeting said, precision was essential in science, and researchers should know what cells they were using, and whether they were contaminated.

According to Robert Stevenson, one of the scientists involved in the meeting, their goal was to keep the field from "degenerating into complete chaos." The group encouraged researchers to use protective measures, like working under hoods with suction that pulled air and potential contaminants into a filtration system. And they recommended that the NIH establish a reference collection of cells: a central bank where all cultures would be tested, cataloged, and stored under maximum security, using state-of-the-art sterile techniques. The NIH agreed, and formed a Cell Culture Collection Committee made up of tissue culturists, including William Scherer, Lew Coriell, and Robert Stevenson. Their mission was to establish a nonprofit federal cell bank at the American Type Culture Collection (ATCC), which had been distributing and monitoring the purity of bacteria, fungi, yeast, and viruses since 1925, but never cultured cells.

The scientists on the Collection Committee set out to create the Fort Knox of pure, uncontaminated cell culture. They transported cultures in locked suitcases and developed a list of criteria all cells had to meet before being banked: each had to be tested for any possible contamination, and they all had to come directly from the original source.

Cell number one in the ATCC's collection was the L-cell, the original immortal mouse cell line grown by Wilton Earle. For cell number two, the committee contacted Gey asking for a sample from the original HeLa culture. But in his initial excitement, Gey had given all of the original HeLa cells to other researchers and kept none for himself. He eventually tracked some down in the lab of William Scherer, who'd used some of the original HeLa sample in their polio research.

Initially the committee could only test samples for viral and bacterial contamination, but soon a few of its members developed a test for cross-species contamination, so they could determine whether cultures labeled as being from one animal type were actually from another. They quickly found that of ten cell lines thought to be from nine different species-including dog, pig, and duck-all but one were actually from primates. They promptly relabeled those cultures, and it seemed they'd gotten the situation under control without attracting any bad publicity.

The media, it turned out, was far more interested in a bit of HeLa-related news that was almost as sensational as Alexis Carrel's immortal chicken heart. And it all started with cell s.e.x.

In 1960, French researchers had discovered that when cells were infected with certain viruses in culture, they clumped together and sometimes fused. When they fused, the genetic material from the two cells combined, as with sperm meeting egg. The technical name for this was somatic cell fusion, but some researchers called it "cell s.e.x." It was different from sperm-and-egg s.e.x in several important ways: somatic cells were cells of the body, like skin cells, and their union produced offspring every few hours. Perhaps most important, cell s.e.x was entirely controlled by researchers.

Genetically speaking, humans are terrible research subjects. We're genetically promiscuous-we mate with anyone we choose-and we don't take kindly to scientists telling us who to reproduce with. Plus, unlike plants and mice, it takes us decades to produce enough offspring to give scientists much meaningful data. Since the mid-1800s, scientists had studied genes by breeding plants and animals in specific ways-a smooth pea with a wrinkled one, a brown mouse with a white one-then breeding their offspring to see how genetic traits pa.s.sed from one generation to the next. But they couldn't study human genetics the same way. Cell s.e.x solved that problem, because it meant researchers could combine cells with any traits they wanted and study how those traits were pa.s.sed along.

In 1965 two British scientists, Henry Harris and John Watkins, took cell s.e.x an important step further. They fused HeLa cells with mouse cells and created the first human-animal hybrids-cells that contained equal amounts of DNA from Henrietta and a mouse. By doing this, they helped make it possible to study what genes do, and how they work.

In addition to the HeLa-mouse hybrid, Harris fused HeLa with chicken cells that had lost their ability to reproduce. His hunch was that when those deactivated chicken cells fused with HeLa, something inside HeLa would essentially turn the chicken cell back on. He was right. He didn't know how it worked yet, but his discovery showed that something in cells regulated genes. And if scientists could figure out how to turn disease genes off, they might be able to create a form of gene therapy.

Soon after Harris's HeLa-chicken study, a pair of researchers at New York University discovered that human-mouse hybrids lost their human chromosomes over time, leaving only the mouse chromosomes. This allowed scientists to begin mapping human genes to specific chromosomes by tracking the order in which genetic traits vanished. If a chromosome disappeared and production of a certain enzyme stopped, researchers knew the gene for that enzyme must be on the most recently vanished chromosome.

Scientists in laboratories throughout North America and Europe began fusing cells and using them to map genetic traits to specific chromosomes, creating a precursor to the human genome map we have today. They used hybrids to create the first monoclonal antibodies, special proteins later used to create cancer therapies like Herceptin, and to identify the blood groups that increased the safety of transfusions. They also used them to study the role of immunity in organ transplantation. Hybrids proved it was possible for DNA from two unrelated individuals, even of different species, to survive together inside cells without one rejecting the other, which meant the mechanism for rejecting transplanted organs had to be outside cells.

Scientists were ecstatic about hybrids, but throughout the United States and Britain, the public panicked as the media published one sensational headline after the next:

MAN-ANIMAL CELLS ARE BRED IN LAB ... THE NEXT STEP COULD BE TREE MEN ... SCIENTISTS CREATE MONSTERS

The Times of London called the HeLa-mouse cells the "strangest hybrid form of life ever seen in the lab-or out of it." A Washington Post editorial said, "We cannot afford any artificially induced mouse-men." It called the research "horrendous" and said the researchers should leave humans alone and "go back to their yeasts and fungi." One article ran with an image of a half-human, half-mouse creature with a long, scaly tail; another ran with a cartoon of a hippopotamus-woman reading the newspaper at a bus stop. The British press called the HeLa hybrids an "a.s.sault on life," and portrayed Harris as a mad scientist. And Harris didn't help the situation: he caused near-pandemonium when he appeared in a BBC doc.u.mentary saying that the eggs of man and ape could now be joined to create a "mape."

Harris and Watkins wrote letters to editors complaining they'd been quoted out of context, their story sensationalized to "distort, misrepresent and terrify." They a.s.sured the public that they were just creating cells, not "trying to produce centaurs." But it didn't help. A public survey about their research was overwhelmingly negative, calling it pointless and dangerous, an example of "men trying to be G.o.ds." And the PR problem for cell culture was only going to get worse from there.

CHAPTER 19

"The Most Critical Time on This Earth Is Now"

When Deborah was a junior in high school, at the age of sixteen, she got pregnant with her first child. Bobbette cried when she found out. Deborah stopped going to school and Bobbette said, "Don't get too comfortable cause you're goin to graduate." Deborah yelled right back, saying she couldn't go to school all big and pregnant.

"That don't matter," Bobbette said, "you're goin to that special girls school where all the pregnant girls have big bellies just like you."

Deborah refused, but Bobbette filled out the application for her and dragged her there for her first day of cla.s.s. On November 10, 1966, Deborah gave birth to Alfred Jr., who she named after his father, Alfred "Cheetah" Carter, the boy Galen had once been jealous of. Each morning, Bobbette made Deborah's lunch, got her to school, then took care of Alfred all day and most of the night so Deborah could go to cla.s.s and study. When Deborah graduated, Bobbette made her get her first job-whether Deborah liked it or not, Bobbette was going to help her and that baby.

Deborah's older brothers were doing fine on their own. Lawrence went into business for himself, opening a convenience store in the bas.e.m.e.nt of an old townhouse; Sonny had graduated from high school, joined the air force, and grown into a handsome ladies' man. He did some running around, but pretty much stayed out of trouble. Their younger brother, Joe, was another story.

Authority didn't agree with Joe. He argued with teachers and brawled with other students. He dropped out of school in the seventh grade and ended up in court for "a.s.sault by striking" right after his seventeenth birthday. He joined the military at eighteen, but his anger and att.i.tude got him in even more trouble there. He fought his superiors and other soldiers. Sometimes he ended up in the hospital, but more often than not, his fighting landed him in solitary confinement, a dark hole with dirt walls ominously similar to the bas.e.m.e.nt where Ethel once locked him as a child. He preferred being in the hole because it meant no one would bother him. As soon as they let him out, he'd fight another soldier or get belligerent with an officer and they'd throw him back in. He spent nine months in the service, most of it sitting in the hole, growing angrier and angrier. After multiple psychiatric evaluations and treatments, Joe was discharged for an inability to adjust emotionally to military life.

His family had hoped the military would help control his rage and teach him some discipline and respect for authority. Instead, he came out of the military angrier than ever.

A week or so after Joe got home from the military, a tall, skinny neighborhood kid named Ivy walked up to him with a knife and asked if he wanted to start something. Most people wouldn't have done that. At nineteen, Joe was at least four inches shorter than Ivy and only 155 pounds, but people in the neighborhood called him Crazy Joe because he seemed to enjoy violence. Ivy didn't care. He'd been drinking heavily and shooting heroin for years, and he was covered in scars from fighting. He told Joe he was going to kill him.

Joe ignored Ivy the first time. Then, about three months later, on September 12, 1970, Joe was walking down an East Baltimore street with his friend June. It was Sat.u.r.day night, they'd been drinking, and they'd just started talking up a group of young girls when three other men walked up the street toward them. One of those men was Eldridge Lee Ivy.

When Ivy saw Joe and June talking to the girls, he yelled, saying one of them was his cousin, and they'd better stop messing with her.

"I'm tired of your junk," June yelled back.

The two started arguing, and when Ivy threatened to punch June in the face, Joe jumped between them, calmly telling Ivy he would do no such thing.