ONE LAST CHANCE : Ovarian Cancer Is Killing Diane Hinton. Conventional Treatments Have Failed. Now Her Life Depends on an Experimental Therapy That Would Block the Action of a Deadly Gene.

DIANE HINTON HAS NO TIME TO WAIT PATIENTLY. OVARIAN cancer is killing her by inches. She knows a cure would be a miracle. But even a small miracle would do: just a treatment that would work, even temporarily, to shrink the tumors that have sprouted inside her abdomen during the past two years and defied an arsenal of conventional therapies. All she wants is more time--a year, even six months--to be with her husband and three young sons.

So early one summer morning, Diane and her husband, Scott, drive to Los Angeles from their home in Hanford, near Fresno. Diane is about to become one of the first women to test a radical new cancer therapy developed by researchers at UCLA that mobilizes biological defenses to halt tumor growth.

Diane, 31, sits cross-legged on a hospital bed in UCLA’s Clinical Research Center, waiting. She is in a quiet third-floor room within the university’s sprawling medical complex. Barely 5 feet tall and weighing about 85 pounds, Diane wears baggy black shorts and a print cotton top she bought in the children’s department. Illness has caused much of the flesh on her bones to waste away. But her face retains a haunting beauty, illuminated by enormous slate-blue eyes that blaze with a spirit that two surgeries and months of harrowing chemotherapy have been unable to extinguish.

Her husband, Scott, 33, with the dark hair and eyes of his Indian forebears, leans on the windowsill next to his wife’s bed and absently picks at the sleeve of his blue T-shirt. Behind him, hazy late-afternoon sunlight streams in through a window, bathing the beige and peach room in a warm glow that hints of eternal summer.

A tall man, with his shirt sleeves rolled up and tie loosened, saunters into the room. “Hi, I’m Denny Slamon,” he says, greeting the Hintons with the easy familiarity of a small-town mayor. Dennis Slamon is the physician-scientist who heads the research team that devised the new treatment. The Hintons have talked to Slamon on the telephone, but this is the first time they’ve met.

Facing Diane and Scott, Slamon leans his large frame against the bureau and explains what will happen in the next few days. He makes no promises: This is only the first phase of clinical trials designed to merely test whether the new treatment is toxic--nothing else. The treatment has reduced tumors in laboratory animals, but there’s no guarantee how it will behave in humans, he adds, nor is it known if it will have any side effects. It is a practiced speech Slamon obviously has given before; his only deviations are to answer the Hintons’ questions, which he does patiently.

After about half an hour, Slamon pauses, crosses his arms against his chest and studies Diane and Scott carefully. “You know,” he says finally, shaking his head, “I really don’t understand why people would voluntarily take a drug that might kill them. You two have some quality time left. Yet you’re giving us a week of that time. As far as I’m concerned, you’re the real heroes here.”

“We don’t feel like heroes,” Scott says.

“We feel this is my last chance,” Diane adds.

DIANE HINTON IS ONE OF 20 WOMEN--10 WITH BREAST CANCER and 10 with ovarian cancer--who have come to UCLA Medical Center this past spring and summer to participate in these clinical trials. For them, as for Diane, all other treatments have failed, and the time they have left is measured in weeks and months, not years. And like Diane, they are ordinary women, with husbands and children and jobs, who try to cope as best they can with the catastrophe that has taken over their lives.

They have volunteered to spend four days getting poked and prodded and having their insides photographed by the latest high-tech nuclear-imaging cameras in order to help advance medical science. Perhaps they can leave some kind of legacy, so that their daughters and other women will be spared the same fate. About one woman in nine will be stricken with breast cancer in her lifetime; this year alone, 175,000 American women will fall victim to breast cancer; another 20,000 will be afflicted with ovarian cancer. About 57,000 women will die of these cancers in 1991.

The treatment being tested is designed to halt the action of a deadly renegade gene known as an oncogene--one of thousands of genes packed into the two microscopically thin strands of DNA that are coiled inside the nucleus of each human cell. In the past decade, scientists discovered the existence of oncogenes, cancer-causing genes that send signals to healthy cells, prompting them suddenly to turn malignant. Experts now believe that oncogenes--about five dozen have been identified--may be the culprits in virtually all forms of cancer.

The oncogene targeted by the UCLA clinical trials triggers unchecked tumor growth in virulent forms of breast and ovarian cancer. The therapy uses a mouse antibody, developed by researchers at Genentech, a South San Francisco biotechnological firm, to neutralize the action of this oncogene. Laboratory mice are injected with the deadly human oncogene and they churn out an antibody to fight off the invader. Like a key in a lock, the antibody binds with the tumor cells and stops them from receiving substances needed for their growth.

The research being performed at UCLA is pushing back the frontiers of medical science. This therapy is part of a new generation of genetically engineered treatments in preliminary tests at top research centers around the country. In one way or another, all of these therapies capitalize on medical science’s understanding of how flaws in our DNA, the master molecule of heredity and regulator of the cells, can cause a host of inherited defects and chronic illnesses.

Several types of cancer--breast, ovarian, lung and melanoma--and a rare genetic disorder, adenosine deaminase (ADA) deficiency, are the targets of these research teams’ initial experiments. But within the next year, scientists plan to test treatments for renal, head, neck, prostate and pancreatic cancers, a number of forms of leukemia and a rare type of emphysema, as well as a strategy to aid in liver transplants.

Scientists are excited because these genetically derived treatments hold the promise of being the long-sought “magic bullets”--the precisely targeted therapies that zero in on where cell function goes awry at the first or second step. This explosion in clinical trials based on genetic science indicates, says W. French Anderson, a gene-therapy pioneer at the National Institutes of Health, that “after many years of thinking of gene therapy only as a way to treat a genetic disease, investigators have broadened their outlook considerably.”

On the immediate horizon, experts are confident that gene-therapy techniques will be used not only to cure classical genetic disorders but also to harness the body’s natural defenses to combat killers such as cancer, heart disease and AIDS. And in the distant future, it may be possible to reprogram our genes to slow our biological clocks and cure all the ills associated with aging. The ultimate hope is prevention, and the ability to intervene before the damage is done--inserting genes that guard against the onset of certain diseases or replacing defective genes that trigger chronic ailments--rather than treating an illness after it’s gone on a destructive rampage. Scientists compare it to the difference between stomping out an ember and trying to contain an already raging fire. Or, in the case of the highly toxic chemotherapies used to combat cancer, destroying so much healthy tissue in the process, it’s the pinpoint aim of a pistol instead of a bazooka blast.

The first attempt at gene therapy in humans was performed in 1980 by Martin Cline, a UCLA professor of medicine. In unsanctioned experiments in Israel and Italy, Cline removed bone-marrow tissue from two women stricken with beta-thalassemia, an often fatal blood disorder caused by a defective hemoglobin gene. The marrow cells were incubated in the laboratory with quantities of a functional hemoglobin gene and then inserted back into the patients. But the experiment failed because the genes did not function properly, and Cline was disciplined by the NIH and UCLA.

Only in the last decade has science advanced to the point that researchers have the biotechnological tools to splice genes into cells and deliver these fragments of DNA to their desired targets. And only in 1989 did the U.S. Food and Drug Administration approve the first experiment in which foreign genes, cloned from human tissue, were implanted into patients. More important, the public seems to be growing increasingly comfortable with the idea of scientists tinkering with our genes, quieting fears that we had crossed the threshold into a frightening Brave New World where we can play God by altering our DNA.

On May 22, 1989, in the first sanctioned gene-transfer experiment, an NIH team headed by Dr. Stephen Rosenberg, of the National Cancer Institute and including Dr. R. Michael Blaese, also of the NCI, and Anderson, of the National Heart, Lung and Blood Institute, inserted a foreign gene into a human patient. Ultimately, eight patients with advanced melanoma, a fatal form of skin cancer, received infusions of tumor-infiltrating lymphocytes (TIL), special white blood cells that the body’s immune system unleashes to fight cancer; a foreign marker gene was spliced into the TIL cells. Though the experiment had no therapeutic value, it was a key step in laying the groundwork for actual gene therapy. “It proved foreign genes could survive intact long enough to be useful for therapy without doing any damage to the patient,” Rosenberg says.

But it was the second such experiment, conducted by a team headed by Anderson, assisted by Rosenberg and Blaese, that was considered the watershed. On Sept. 14, 1990, at the NIH, an i.v. tube was inserted into the arm of a 4-year-old girl suffering from ADA deficiency, a severe immune deficiency caused by the absence of the gene that regulates the production of an enzyme crucial to keeping the body’s immune cells functioning. The strategy was to insert copies of the gene in hopes that it would produce the enzyme.

The procedure itself was astonishingly routine and took less than half an hour, but it marked the dawn of a new era in medicine: the age of human gene therapy.

Since then, the girl has returned once a month for repeat infusions, and her immune function appears to be vastly improved; in fact, her parents report that when the entire family caught colds last winter, she got well faster than anyone else. A 9-year-old girl with the same condition was added to the trial last January, and Anderson expects to test this technique on two more patients soon.

Rosenberg’s team has gone a step further. Four patients with melanoma have received blood cells fortified with a gene that produces a tumor-necrosis factor, a lethal enzyme that is programmed to attack malignant tissue. They plan to treat another 50 patients within the next year. “Right now, we’re only looking at melanoma,” Rosenberg says. “But if this works, we can use it on other cancers.”

Slamon’s team at UCLA is taking a different approach, one that starves tumor cells of substances needed for growth. Current treatments for women with recurrent breast and ovarian cancer--such as radiation and chemotherapy--aren’t very effective; they kill normal, healthy tissue, and the side effects are nightmarish. “The appeal of this approach,” Slamon says, “is its precision, that it may be a more effective way to treat advanced cancers, and it appears to have no side effects.”

Similar therapies are being tested by a team headed by John Mendelsohn, chairman of medicine at New York’s Memorial Sloan-Kettering Cancer Center, which has developed an antibody that inhibits the action of an oncogene and tested it on 19 lung-cancer patients. At Georgetown University in Washington, a group headed by Marc Lippman, director of the Vincent T. Lombardi Cancer Center, has begun clinical trials with 11 patients with breast and other types of cancers using pentosan polysulfate, a carbohydrate that halts the action of another oncogene known to stimulate tumor growth.

But amid all of this scientific ferment, others sound a note of caution. In the next five to 10 years, these biologically derived treatments may become potent weapons in our therapeutic arsenal, used in combination with other therapies, says Bruce A. Chabner, director of the division of cancer treatment for the National Cancer Institute. “But they haven’t as yet proved to be any more effective than what’s currently available. They’re also too expensive and labor-intensive to produce to be used on a broad scale,” though costs may decrease as techniques are refined.

Others worry about the long-range consequences. “There’s a distinction between traditional pharmaceuticals and genetically engineered ones--a distinction that has been lost,” says Marc Lappe, a bioethics expert at the University of Illinois in Chicago. “We might be inadvertently making permanent alternations in the human genome. This is never considered in these protocols.”

But to Rosenberg, the benefits outweigh the risks. “Right now, we’re dealing with the basic biology of life itself, and we’re in the infancy of the development of these therapies. But last year 515,000 Americans died of cancer in spite of our best available treatments--that’s more Americans than died in all of Vietnam and World War II. So it’s obvious we need better ways to treat cancer, and we have to use every tool at our disposal.” What drives the Stephen Rosenbergs of this world are the Diane Hintons.

SCOTT HINTON GUNS THE MOTOR OF HIS 16-FOOT SPEEDBOAT, and the craft bursts into noisy life. Diane and the three boys--James, 13, a dark and introspective adolescent; Joel, 11, freckle-faced and sensitive, and Joseph, 10, with blond hair, blue eyes and a killer smile--sway sideways as the boat lurches forward, bobbing across the waves on Lake Kaweah, a reservoir about 40 miles east of their home in Central California. The kids take turns water-skiing. Each one glides expertly across the water; their faces shine with happiness as Scott tows them back and forth across the lake. Then it’s Diane’s turn. She deftly skims the waves for about 15 minutes, bouncing like a delicate doll. But she firmly grips the line tethered to the boat, drawing on surprising reserves of strength. “For almost a year, our lives revolved around my cancer,” Diane says later, sinking back onto the seat cushions of the boat. “Now we’re trying to get back to some semblance of normalcy. I could sit around and snivel until I die. Or I can live until I die. I’ve decided to live.”

Diane and Scott live in Hanford, a prosperous farming town of about 30,000 with quaint antiques shops, clean streets and well-tended lawns. They enjoy small-town life: church barbecues and camping trips in the summer, dirt biking and skiing at Badger Pass in Yosemite during the winter.

The Hintons arrived in Hanford in 1983, mired in debt because the cafe they owned near Sacramento was a casualty of the 1982 recession. But they put down roots and flourished. Scott made decent money running his own construction company, while Diane kept the books and took care of the house and the kids. The Hintons were able to afford a pool and a hot tub in the back yard of their four-bedroom home, the boat and dirt bikes for Scott and the boys.

In early 1990, Diane started to experience some cramping and constipation. She thought it was a minor problem that could wait a couple of months until she went in for her annual gynecological examination. Her doctor felt a grapefruit-size mass in Diane’s abdomen. He thought it was a fibrous cyst and urged her to get it removed, though, he assured her, it was nothing to worry about. “What are the chances of its being cancer?” Scott had asked.

“It’s very unlikely,” answered the doctor, dismissively waving his hand. “This woman is 30 years old. Cancer would be doubtful.”

On Friday, April 20, 1990, Diane was wheeled into surgery. Twenty minutes later, her doctor burst through the doors of the operating room. “She has cancer, and it’s everywhere,” he told Scott, his face flushed and his eyes filled with tears. “I’m afraid your wife doesn’t have much of a future.”

Scott collapsed on the floor, sobbing. Diane remained in surgery for another four hours, and doctors performed a hysterectomy. All Scott could think was: How was he going to tell his wife she was dying?

Their family closed ranks. Diane’s mother and Scott’s mother, who are both named Joanne, took turns driving down from Sacramento--sometimes, they joked, they’d pass each other on the freeway--to help Scott and look after the kids while Diane received the chemotherapy treatments that left her incapacitated.

“The drugs destroy your mind,” says Diane, whose weight plummeted from 112 to 86 pounds. “I’d wake up in the morning thinking, ‘I’ve just got to get through this day.’ I’d lie there trying to find distractions. Some days, I couldn’t get out of bed.”

This went on for four punishing months. But Diane and Scott, who are deeply religious Missionary Baptists, did not doubt that they would beat this, and their faith sustained them. Diane’s “second-look” surgery, where doctors check the status of the cancer, was scheduled for Oct. 11. The Hintons were convinced they were about to put this nightmarish episode behind them. But doctors discovered her cancer was even worse--hundreds of new tumors had spread through her abdominal cavity. “The chemo had done nothing ,” Diane recalls. “Four months of my life down the drain, and it did no good. We were devastated.”

While Diane recovered from the surgery, Scott gathered his three sons around him. “Your mother is going to be all right for a while,” he told them. “But then she’ll get sicker and sicker, and she won’t get better.”

DENNIS SLAMON IS A MAN IN A HURRY. HE’S 6-FOOT-3, AND HIS long strides swallow up the hallway that leads to his cluttered laboratory, adjoining his cubbyhole of an office on the 11th floor of the Factor Health Sciences Building, a gleaming brick-and-smoked-glass structure that towers over the east end of the UCLA campus. This is Slamon’s turf, and he commands the bustling corridors like a benevolent, if exacting, paterfamilias. Even his wardrobe is dictated by expediency. He owns 20 or so long-sleeved dress shirts in the same style--10 in powder blue and 10 in white--several pairs of black or gray slacks and “a collection of maroon ties,” he explains with a toothy grin.

The son and grandson of Pennsylvania coal miners--his grandfather and two uncles were buried alive and rescued three times in cave-ins--and the first member of his family to attend college, Slamon slam-dunked his way through a combined MD and Ph.D. program at the University of Chicago in five years (it normally takes more than six years). Since coming to UCLA in 1979 as a post-doctoral fellow in oncology, he has raced up the ranks, in 1988 becoming director of clinical research for the Jonsson Comprehensive Cancer Center, an NIH research center at UCLA. Earlier this year he was named chief of the Division of Hematology-Oncology at the UCLA School of Medicine.

But the accomplishments he seems proudest of are those of his research team--a dedicated group of technicians, students, post-doctoral fellows and colleagues, some of whom have worked together since 1983. They’ve journeyed from a vague suspicion about the role played by a particular oncogene in promoting out-of-control growth in certain cancers to testing a treatment on patients--”from bench to bedside,” he says--in less than seven years. This is warp speed in scientific circles, where such a breakthrough can consume much of a medical career.

Their strategy was elegantly simple, rooted in established science. Scientists know certain genes either promote or stop cell growth. “So if cancer is an abnormality in growth,” Slamon explains, “then the logical place to look for problems is in genes that regulate growth. Our search started out as a fishing expedition, but we got lucky because we were fishing in rich waters.”

The actual medical detective work, though, was tedious; from start to finish, Slamon estimates it took half a million hours in the laboratory. The team’s first step was to use DNA probes to detect any aberrations in genes that govern cell growth in a series of human breast-, lung-, colon- and ovarian-cancer tumor samples. Probes are fragments of DNA that are produced using genetic-engineering techniques developed in the early 1970s. Because of the special properties of DNA--even tiny bits of DNA will attach themselves only to segments of DNA that have the same structure--a probe can be programmed to ferret out a specific gene. Once these microscopic scientific sleuths are unleashed in a petri dish, they home in on their identical twins like radar.

After nearly 18 months of peering at tumors through microscopes, Slamon’s team came up with a promising lead. “One of the things that jumped out at us was that, in breast cancer, a particular gene was altered, and the alteration was that multiple copies of it were made,” Slamon explains. “So the next question was: Does this mean anything? or was it just something that happens as part of the general disarray of a cancer cell? So we looked at the patient’s history. We discovered that patients with extra copies of this gene were more prone to an early relapse and more prone to a shortened survival. Once we saw that correlation, that set off alarm bells, and we knew we were onto something.” Later they found the same correlation in ovarian cancer.

These were heady but grueling days. It was not unusual for Slamon to spend the entire night at the laboratory, baby-sitting an experiment, or for his colleagues to work around the clock. “Dennis had a thriving lab in a very small space--about 600 feet--and the place was always packed,” recalls Michael S. Press, a pathologist at USC who has known Slamon since medical school and who has collaborated with him on several projects. “You practically had to take a number to get bench space--and if you left for a few minutes, someone would take your place. But there was a tremendous esprit de corps because we were doing valuable work.”

The congestion has eased, thanks to the addition of two more laboratories. But Slamon’s work hours are no more civilized--he rarely hits the freeway to his home in Woodland Hills before 10 at night, and he frequently works till midnight. Nailing down exactly why multiple copies of this gene--known as HER-2/ neu --can prompt tumor cells to behave so aggressively took four years. In May, 1989, Slamon’s group proved to the satisfaction of the scientific community that the HER-2/ neu oncogene is amplified (meaning that there are extra copies of the gene in the DNA of the tumor cell) in about 25% to 30% of human breast and ovarian cancers. Cancer patients with the HER-2/ neu amplification relapsed and died sooner than those without extra copies of this oncogene.

Based upon these findings, Slamon’s team moved on to formulating a treatment. The approach he devised stemmed from a simple premise. Each one of our genes has a different job and sends out a genetic signal (or code) that sparks a critical chain reaction. The HER-2/ neu gene, for example, codes for the production of a growth-factor receptor. These growth-factor receptors sit on the surface of the cell and receive signals like tiny antennae; they bond with growth factors, which are produced by another gene.

The union of the factor and receptor triggers the production of new cells. So it’s logical that if there are too many HER-2/ neu genes coding for the production of too many growth-factor receptors, an overproduction of cells will result. One way to halt this process is to block the union between factor and receptor, or in some way thwart the action of the receptor.

Knowing this, researchers at Genentech developed a series of antibodies that prevent this linkage. They injected mice with the substance produced by this oncogene, and the animals’ immune systems went into overdrive, churning out antibodies to ward off this foreign invader. Slamon’s team then identified which of the mouse antibodies was the most effective in inhibiting the action of the oncogene in human tumors. “Once we satisfied the FDA’s requirements,” Slamon said, “we were ready to go.”

Some scientists, however, believe that Slamon--and other researchers like him--are in too much of a hurry, and that such human trials may be premature. “Based on basic science established years ago, using one antibody only briefly reduces tumor growth. Two different antibodies are needed to be effective,” explains Mark I. Greene, a researcher at the University of Pennsylvania. He is hoping to have clinical trials under way early next year to test antibodies to combat pancreatic cancer.

“The risk here,” he continues, “is if the one-antibody approach doesn’t work, people get discouraged. So there’s no real reason to rush into this, especially when we know it’s not the most effective way.”

Greene’s criticisms reflect the divisions that exist in medical science between researchers who want every variable checked before going forward and physicians who are desperate to try anything that shows promise of easing their patients’ suffering.

DIANE AND SCOTT HINton lapsed into a deep depression after her second surgery. But slowly, they came to terms with their situation. If Diane was under a death sentence, they were going to enjoy the time she had left. Last January they took a lavish weeklong vacation, indulging their every whim at Disney World, and they began to have fun again.

Diane embarked on another round of chemotherapy, but again, it did nothing. “We made a conscious decision then not to have treatment,” she explains. “We knew the implications of that decision, but all these therapies were doing was making me sick.” Diane’s fate, they felt, was in God’s hands.

But Diane’s mother, Joanne Allen, refused to give up. In early April, a brief item in the business section of the Sacramento Bee caught her eye. Genentech was involved in an experimental test using antibodies for women with advanced breast and ovarian cancer. Galvanized, Allen grabbed the telephone. Two days and dozens of phone calls later, she got Dennis Slamon on the line.

He referred her to Dr. Beth Karlan, a gynecological oncologist and surgeon at Cedars Sinai Medical Center in Los Angeles. A former student of Slamon’s, Karlan was screening ovarian-cancer patients for the trials. Scott had Diane’s doctor send slides of Diane’s tumor to Karlan to see if Diane had the HER-2/ neu oncogene present.

And then they waited. After two months, the Hintons assumed that Diane hadn’t qualified for the trials.

At about 7 one Tuesday evening in late June, the phone rang. When Scott heard Karlan’s voice, he instinctively knew he was about to get the first bit of good news he had had in a year. “It’s Dr. Karlan,” Scott told Diane.

“ Yes! “ she cheered, thrusting two clenched fists over her head in jubilation.

ON A MORNING A WEEK later, Diane and Scott sit, chattering nervously, waiting. It is a little before noon when an orderly finally arrives with a wheelchair for Diane to escort her to her treatment. The Hintons’ excitement is palpable. Scott jokes with the orderly, and Diane beams with affection at her high-spirited husband as his raucous laugh echoes down the hushed hallway.

The elevator takes them down to one of the lower floors of the medical complex, and the orderly pilots them through the maze of tunnels connecting each building. Karlan is waiting for them outside a tiny, airless room cluttered with equipment, where she will insert a catheter--essentially a piece of plastic tubing--into Diane’ stomach. Later, the catheter will be used to channel the antibody to the tumors inside her abdominal cavity.

Karlan, 34, is like a ray of sunshine in these claustrophobic corridors. With her thousand-kilowatt smile, luminous hazel eyes and iridescent-gold, three-inch heels, she exudes a soothing glow. “How are you today?” she asks as Diane clambers onto a gurney and is prepped for the procedure.

Slamon dashes in, a stethoscope around his neck. He glances at Karlan’s elegant beige pants suit--Karlan’s sartorial splendor is legendary--and can’t resist cracking wise. “Dr. Karlan likes making a fashion statement when she comes out of the operating room,” he says, rocking back on his heels and grinning like a mischievous schoolboy. The Harvard-educated Karlan blushes as she snaps on a pair of surgical gloves.

But beneath the banter, it is obvious that Karlan and particularly Slamon are even more excited than the Hintons. The clinical trial represents the culmination of years of work, and there is an expectant charge in the air. Once the catheter is inserted, Diane is transported by gurney to the Nuclear Medicine Department two floors down, with an entourage trailing behind that includes Slamon, Karlan, another doctor, two nurses, Scott and a reporter.

First, Diane will be injected with a tiny, 100-milligram dose of the antibody, followed by a chaser of technesium sulfur colloid isotope, which emits radioactive signals so the doctors can see whether the antibody is being distributed throughout the abdomen. For all the cutting-edge technology used to devise this mouse antibody and to monitor its course throughout the body during the clinical trials, administering the antibody itself is as unremarkable as a blood transfusion.

“I’ll do the infusion,” Slamon says with a proprietary air, gingerly cradling in his hands the plastic pouch containing the precious fluid. The moment of truth has arrived. Scott leans over the gurney, his face suffused with love, and gives his wife a quick kiss for luck. And then, in a flash, it is done: Slamon attaches the pouch to an i.v. stand and plugs the i.v. tube into the catheter.

Forty-five minutes later, the pouch is drained and Diane is shuttled to another room. There, an imaging camera is positioned over Diane’s waist so it can detect the radioactive “footprints” of the technesium-laced antibody flooding throughout her abdomen, which shows up on the computer screen as tiny white dots.

Afterward, Diane is injected with a specially prepared radioactive isotope, by which iodine-131 molecules are chemically attached to the antibodies. “Right now, we’re using the iodine-131 isotope merely to follow the antibody through the body (once it leaves the abdomen and enters the bloodstream) and see where it is going,” Slamon explains. “But in the future, it could be another therapeutic approach, and we may use antibodies with a radioactive isotope attached to radiate tumors.”

Because the iodine piggybacks onto the antibody, and therefore can home in on the cancerous cells, iodine in bigger doses could be used as a lethal payload to kill tumors. The appeal of this approach is that it attacks tumors with far more precision than conventional radiation treatments, where healthy tissue is destroyed along with the malignancies.

“I’m going to glow in the dark,” Diane jokes as she is injected with another radioactive substance--this time a fluorine-18 isotope that measures the metabolic activity of her tumors. Diane stoically spends the next four hours lying inside a PET scanner, which takes fluorine-enhanced electronic photographs of her tumors. These will be compared with later PET scans to determine whether, in fact, the antibody has stopped or curtailed the tumors’ action.

It is early evening before all the tests to record the data needed for these clinical trials are finally completed. Diane is wheeled back to her room at about 7. It is after 8 when she is given another infusion of what the doctors believe may be a therapeutic dose of the antibody. (The first few women in the trials received only small doses of the antibody because they were testing for toxicity; but now that it’s clear that the antibody is safe at the lower level, researchers are upping the dosages they administer to women in the trials to determine how much can safely be tolerated.)

Then, suddenly, one of the nurses grabs Slamon as he is coming down the hallway to check on Diane. “The mouse antibody,” the nurse gasps. “She’s had a bizarre reaction to the mouse antibody.” Slamon’s face turns ashen as he hurries into the room. He doesn’t see Diane right away because Scott and a nurse are standing around her bed.

When Scott and the nurse step aside, Slamon sees Diane sitting up in bed--wearing a huge mouse mask.

Everyone, including Slamon, dissolves into laughter. As Diane pulls off the mask, she confesses, “I’ve been planning this for days.”

THREE DAYS LATER, ALL the tests to monitor the antibody in Diane’s body have been completed. Diane and Scott leave the hospital and return home to pick up the threads of their life. They will be back for a follow-up in a month. But even if the treatment has no effect, it has given them something they thought they had lost forever: hope.

It will be several more weeks before the first phase of these clinical trials are completed, and months more before all the data are assessed. It won’t be until early 1992 that Slamon’s team gears up for the next, expanded phase of the trials, which will measure the effectiveness of this therapy in several dozen patients (patients in the initial trials will be included in later tests, which will encompass more patients). Some of the testing will be done at Memorial Sloan-Kettering in New York City and perhaps at other cancer-research centers in order to handle the larger volume of patients.

Satisfying the FDA’s requirements for testing a new treatment is expensive and time-consuming. The first phase of these particular trials, for example, cost nearly $1 million ($150,000 came from an NIH grant, $800,000 was provided by Revlon, and the remainder came from an assortment of funding sources). This therapy will go through two more expanded trials--the third phase may encompass several hundred patients--to determine whether it actually works. If all goes extremely well--which rarely happens--the treatment will then wind its way through the often Byzantine FDA review process and could be approved for general-public use by 1994.

The competition to be among the first to devise new approaches to treatment is fierce. And the political infighting that goes on in the jockeying for grants--particularly for research on “women’s diseases” such as breast and ovarian cancer, which are notoriously underfunded--often seems more like roller derby than civilized rivalry among highly educated professionals.

But Dennis Slamon seems to keep up this frenetic pace without breaking a sweat. Having powerful friends helps. Like Brandon Tartikoff, former chairman of NBC Entertainment and the current head of Paramount Pictures. Through a circuitous set of circumstances, Tartikoff, who was stricken with Hodgkin’s disease, a form of lymphatic cancer, became Slamon’s patient more than a decade ago.

Over the years, Tartikoff’s wife, Lilly, asked Slamon repeatedly if she could raise funds to help advance his work. “I made that commitment after he saved Brandon’s life,” says Lilly Tartikoff. “That day when Dennis said Brandon was going to be fine, I felt I wanted to give something back.”

Slamon was reluctant to take advantage of their relationship--until three years ago, when Lilly Tartikoff delivered an ultimatum. She was going to do something for cancer research--with him or without him. He finally relented.

She immediately swung into action. She buttonholed Ronald Perelman, chairman of Revlon, and persuaded him to donate $2.4 million over three years to establish the Revlon/ UCLA Women’s Cancer Research Program. She also organized a benefit to raise money and to publicize the Revlon program. The first affair netted more than $300,000, and the benefit is now an annual event.

It is an early Friday evening in August, the end of a long day at the end of a long week, but Slamon is in an expansive mood. He will turn 43 in a few days, and he plans to celebrate his birthday fishing for salmon off the coast of Alaska. He relaxes in his sparsely furnished office, where the only personal touches are the compact-disc player perched on the windowsill and the collection of CDs--soft jazz, classical music and show tunes--Slamon listens to when he is alone.

“I think I could be successful in private practice,” he says, in a rare moment of reflection. “But here you get an idea about something and the leads start to pay off. I can’t imagine a return greater than that--and this isn’t altruism or dedication.”

Looking to the future, he’s optimistic. Even if the treatment fails, plenty has been learned already. These experiments can only deepen science’s understanding of cancer’s biological mechanisms.

Diane Hinton has subsequently undergone another surgery to remove her tumors. There are indications that chemotherapy, which earlier failed to kill the tumors, may now be working. Doctors believe she may live at least another year, but Slamon won’t speculate on whether the antibody has altered Diane’s reaction to the chemotherapy--or whether she has found her miracle. Nor will he reveal the results of the first phase of the clinical trials until they are presented at scientific meetings, which should occur in the next three or four months.

But he can’t hide his excitement about the discoveries being made in his and other laboratories. “There’s more here-- lots more,” he says. “This is only the beginning.”