Reader’s Digest, November 1980

Issac Djerassi’s All-Out War Against Cancer

In 1969, Marie Killilea was told by her doctors that she had a recurrence of lung cancer and had only three months to live. On referral, she went to Mercy Catholic Medical Center in Philadelphia for treatment by Dr. Isaac Djerassi. He prescribed a totally new treatment: huge doses of Methotrexate, a powerful drug. In eight months, every trace of Mrs. Killilea’s cancer was gone. Today she remains cancer free.

In Philadelphia, one year after Mrs. Killilea’s frightening diagnosis, Kimberly Ann Brennan, age three, developed a giant tumor that wrapped itself around her heart and collapsed both her lungs. Then the tumor, diagnosed as lymphosarcoma, spread to her brain. Dr. Djerassi also treated her with high-dose Methotrexate. Hers was the first case on record in which anyone has survived a wide-spread lymphosarcoma involving the brain.

Fifty-five year old Isaac Djerassi, winner of American Medicine’s highest honor, the Albert Lasker Award, has pioneered new treatments for several of the most virulent forms of cancer. Physicians all over America send him their toughest cancer cases. A small (five feet, three inches tall), boyish-looking man with unruly brown )hair and intense dark eyes, Djerassi has spent all of his adult life seeking answers to the riddles of cancer. He is fiercely determined to reduce its terrible toll: roughly 4oo,ooo deaths in the United States this year.

Target: Leukemia. Djerassi, born in Sofia, Bulgaria, the son of a wealthy Jewish merchant, was almost lost to the world in 1943, when the Nazis began transporting Bulgarian Jews to extermination camps. Isaac and his family, shipped to a rail depot from which they were to be sent to gas chambers, were spared only when thousands of Bulgarians bravely defied the Nazi occupation forces and protested the deportations.

After the war, Djerassi graduated from an Israeli medical school, and in 1954 came to Children's Hospital Medical Center in Boston to do research in his specialties, hematology and oncology. But his greatest concern-and challenge-was to somehow find a way to attack leukemia.

Most leukemic patients were bleeding to death then, and nothing could be done for them. At Children's Hospital, Djerassi perfected a technique using massive transfusions of platelets from cancer-free donors to halt tile hemorrhaging. (Platelets, one of three main components of our blood, counteract bleeding.)

Albert J. Roy, a physiologist who was Djerassi's chief assistant, remembers the first time they administered platelets: "The kids' bleeding stopped right before our eyes," he says. Today, platelet transfusions are standard therapy for leukemia and other blood diseases.

Djerassi was also one of the first to demonstrate that transfusions of white cells, which battle infection, could help cancer patients. In fact, he invented the first practical machine for collecting white cells by filtration from the blood of healthy people.

"Fooling" Cancer. The platelets and white cells provided some protection for leukemic victims, but they still died agonizing deaths. There was not yet a cure. So after he moved to the Children's Hospital of Philadelphia in 1960, Djerassi turned to Methotrexate, one of the oldest anti-cancer drugs. Basically, Methotrexate is a chemically deranged version of folic acid, a vitamin required by all body cells in order to multiply. If cancer cells could be "fooled" into absorbing Methotrexate instead of the real vitamin, they would starve to death.

The drug had been tried before on children with leukemia, but had only short-lived effects; not enough penetrated the leukemia cells. Working with ten leukemic children on whom standard doses had been ineffective, Djerassi did something different: he administered massive doses, 20 to 30 times the normal quantity, by dripping the drug continuously into the bloodstream.

While all ten children had immediate remissions, Djerassi feared the risk of side effects-among them mouth ulcers, hair loss, severe nausea, and bone-marrow damage from the huge doses of Methotrexate on a daily basis. As usual, he went a revolutionary route. He gave the children 100 to 200 times the normal dosage, but only for one or two days. Four weeks later, he administered the same dose. "That way I produced results that were many times greater than if I'd given the same amount of Methotrexate in small, divided doses throughout the entire period."

To protect against side effects, Djerassi devised a "rescue" technique. He followed up each Methotrexate treatment with another drug, Citrovorum factor, which is an antidote to the harsh effects of the Methotrexate. Subsequently, Djerassi created a new method for administering Citrovorum factor that enables him to tell exactIv how much of it a patient needs to offset the Methotrexate dripping into his veins. He continuously monitors the amount of Methotrexate remaining in the blood and matches it precisely with citrovorum factor before the critical 36th hour when the patient's bone marrow starts to sufter crucial damage. Djerassi has used this chemotherapy approach in cancer treatment without the usual side effects.

The results of the high-dose Methotrexate treatment were astounding: 80 percent of the advanced leukemia patients who received it were alive after 30 months-at a time when virtually all other such patients died within 14 months. In 1975, Djerassi reported that 70 percent of his patients with lymphocytic leukemia - the most common kind in children-had passed a crucial five-year survival period, beyond which cures are most likely.

New Frontiers. Moving to Philadelphia's prestigious Mercy Catholic Medical Center in 1969, Djerassi continued to test high-dose Methotrexate on other forms of cancer, including lymphosarcoma, which invades the lymph glands. When childhood lymphosarcoma is widespread, the average length of survival is only 6 to I2 months. Djerassi achieved a 5o-percent five-year survival rate!

But the greatest achievement of Djerassi's technique has been with osteogenic sarcoma-a deadly bone cancer whose victims until a few years ago had a survival rate of only 20 percent. By the time the pain in a patient's sore arm or leg is diagnosed correctly, the odds are four to one that the cancer has already spread. Amputating the arm or leg can save the patient from the pain and discomfort of the primary tumor, but in eight out of ten cases new tumors appear, usually in the lung, within a year of diagnosis. And in such cases, death is practically certain.

Early in I971, Djerassi flew to Boston's Children's Hospital, where Dr. Norman Jaffe (now at M.D. Anderson Hospital in Houston) was trying Djerassi's Methotrexate treatment on a boy with osteogenic sarcoma. Djerassi could scarcely believe his eyes when shown the child's X rays. The tumors had disappeared. Collaborating over the next several months, he and Jaffe perfected the application of high-dose Methotrexate to this disease. Recently, Jaffe reported a projected five-year survival rate of more than 60 percent.

Djerassi's move to Mercy Catholic gave him a welcome opportunity to treat a broader range of cancer patients. He has tripled the life expectancy of patients with inoperable cancer of the pancreas. His breastcancer patients are surviving twice as long as most breast-cancer patients elsewhere. He is getting remissions in eight out of ten cases of lung cancer, and his patients are living two to three times as long-depending on the type of disease-as those at other hospitals. His use of high-dose Methotrexate treatment is achieving remissions for more than one out of every two cases of bladder cancer, and is doing even better for deadly head and neck cancers.

Djerassi has also pioneered in immunotherapy-marshaling the body's own defenses to fight cancer. He was among the first to inject lymphokines, medium-sized molecules produced by the body's immune cells, into human patients systemically. This has proved to be one of the most promising fields of cancer research.

Patient Comes First. Although Djerassi spends half his time in his research laboratories, he is above all a physician. "With Djerassi, first comes the patient, last comes the patient," says dermatologist Dr. Edmund Klein, who discovered an immunological treatment for skin cancer. "He'll do nothing to advance science unless it helps the patient."

For this reason, Djerassi has no use for the traditional technique of medical research: the controlled study. This is an experiment in which a physician demonstrates the effectiveness of an experimental drug by administering it to only half his patients, while he gives the others a placebo, a useless, inert substance. "If you have enough confidence in an experimental drug to try it on a cancer patient," Djerassi argues, "you have an obligation to use it on every cancer patient who can possibly benefit from it so long as they can handle its side effects, and no other treatment is available." Typically, Djerassi won't try a new experimental drug on a cancer patient unless he is dealing with a terminal case beyond help by conventional means.

"We play it by ear most of the time," Djerassi says. "No fixed formulas, or what doctors have come to call protocols, apply to all circumstances.'' If the patient needs help quickly and he appears well enough to take a strong treatment, Djerassi will give it to him. "If he is not well enough, we use something else, less hazardous, even though less effective. I will use anything that, in my judgment, is best for this patient at this particular moment. Naturally, this is very unscientific, but I am in no hurry to prove anything. I don't need statistics-I need living patients."

When Djerassi moved to Mercy. Catholic, he also developed a "minicenter" that provides the most advanced cancer therapy as well as well as research facilities. His intensive-care area, blood-platelet bank, blood donor center and laboratories are open 24 hours a day, if necessary, seven days a week. "Crises arise quickly in cancer," Djerassi says. "If a patient needs a transfusion of platelets, we can't wait until morning. The patient may be dead."

In as much as Djerassi's minicenter is small and does only applied research, its expenses for treating cancer patients are much lower than those of the big, comprehensive cancer centers. Two years ago Djerassi proposed that the government underwrite the establishment of 200 such minicenters in community hospitals in all 50 states. They would deliver the latest therapy to cancer victims in smaller cities that have no access to a major cancer center. Djerassi estimates they could care for 6o,ooo cancer patients who need special treatment each year. Annual underwriting costs would average $200,000 to $400,000 per minicenter.

Despite hearty support on Capitol Hill, progress to implement the program has been slow. Djerassi is fuming about the delay. "People are dying of cancer who can be saved," he states.

Totally dedicated, Djerassi lives with crises day in, day out. Reaching his office at the minicenter between 9 and 9:30 a.m. every day, he gets reports from his staff on the status of every patient and tears off to see those in trouble. On the way back to his office, patients cluster around him with questions. He always stops to talk to them. "They need the contact even more than the answers,'' he says. Skipping lunch, he starts laboratory experiments that will keep his research associates busy until late at night. Djerassi finally leaves about 7:45 or 8 p.m., but insists his staff call him at home whenever any patient has difficulties. Two or three nights a week, he races back to the hospital in the wee hours to help some patient over a crisis.

Tributes to Djerassi flow in from around the world. Frank J. Rauscher, Jr., senior vice-president for research of the American Cancer Society, describes him as a "remarkable scientist and dedicated physician who has made monumental contributions to the fight against cancer." Perhaps, though, one of his cancer patients put it best when a friend asked if she was frightened. "No," she replied. "I have Dr. Djerassi."

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