THE GREAT SEARCH FOR CURES ON A NEW FRONTIER

IN the mushroom-clouded dawn of the Atomic Age, dark as it was with fresh dangers for the human race, there shone a ray of brilliant promise; the sudden abundance of radioactive elements gave medical researchers their most important new tools since the invention of the microscope. For five years now, physicians and biochemists have been learning to handle them.

How much progress have they made?

The short answer is that they have wrought no miracles. Atomic medicine has cured no disease that cannot be cured without it. But in five years there has been time to explore only a fraction of the new frontier--and meanwhile there have come discoveries in three directions that are worth cheering about:

TREATMENT: radioactive iodine, phosphorus and gold are effective in half a dozen diseases, though in no more.

DIAGNOSIS: radioisotopes of iodine, sodium and potassium have already proved helpful in appraising several disorders of body chemistry, e.g., in cases of heart and kidney disease, to help establish the kind of treatment the patient can stand. Other isotopes are helpful in locating brain tumors.

STUDY OF BODY FUNCTION: with "tracer" doses of dozens of radioactive elements, medical researchers are beginning to learn things they never knew before about how the body, sick. or well, performs some of its incredibly complex chemical processes. Biochemists will be busy for many years in this field. Eventually their knowledge should lead to better ways of treating a host of diseases, and probably to new ways of curing some.

Iodine Is Unique. So far, about the only evident cure that atomic medicine can claim is with radioactive iodine in severe cases of Graves's disease (overactivity of the thyroid gland). For these, it is as good as other drugs or surgery, and probably better. Until radioisotopes began to be made (in cyclotrons) in the '303, doctors were able to use only "external radiation"--X rays from an assortment of machines--or the closely related gamma rays given off by radium as it decays to lead. But the thyroid picks up any isotope of iodine in a greater concentration than any other part of the body by a factor of 100 or more t01. So radioactive iodine (known as iodine-131 from its atomic weight)*was the answer to the radiologists' dream: it supplied internal radiation in a highly selective way. As the iodine crowded into the^thyroid of a victim of

Graves's disease, its disintegrating atoms destroyed the-overactive tissue.

Nothing could have been neater--and nothing could have led to more disappointment. For, inevitably, researchers began to hunt for other elements which would localize equally well in a particular part of the body. They found none.

However, they found another valuable treatment use for radio-iodine. Cancer of the thyroid is not a common disease, and most cases do not yield to radio-iodine.

But 15% to 20% of the time, the thyroid-cancer colonies which spread through the body behave like little thyroid glands and pick up radio-iodine. Such a case was that of Norman Bennett.

Norman is a lanky boy of 13 who has been playing basketball this season at Madisonville (Ky.) Junior High, and hopes to play football next fall. Two years ago, despite surgery and X rays, Norman was wasting away with a spreading cancer of the thyroid. Then his doctor got him into the little (30-bed) hospital at Oak Ridge, Tenn., which is set aside for atomic medicine. There, Norman had an "atomic cocktail"--radioactive sodium iodide dissolved in water. The cancer colonies soaked up the iodine; from each radioactive atom, beta particles and gamma rays shot out to destroy cancerous cells. Norman goes back to Oak Ridge regularly for checkups, and sometimes he gets another radioactive drink. He eats well and has gained 30 pounds.

Doctors cannot be sure how much they have done for Norman Bennett and others in his plight. They will not talk about a "cure," or even a "fiveyear cure" or a "ten-year cure." But they are confident that they have done a lot of good.

The benefits of radio-iodine extend to patients with chronic, congestive heart disease and angina pectoris. If, as is common in such cases, the healthy thyroid's activity is too high for a damaged heart, then a dose of iodine-131 can be used instead of the surgeon's knife to reduce the gland. Two-thirds of the heart cripples so treated at Boston's Beth Israel Hospital show worthwhile improvement, and half of these are so much better that they can lead nearly normal lives. Equally gratifying, the treatment releases many patients from the agonizing "tight" pains of angina.

A Shot of Phosphorus. After iodine, radioactive phosphorus is the isotope which has proved most useful in treatment. It seems to be as effective as any other means of combating two kinds of chronic leukemia (lymphatic and myeloid), and it is more convenient than others. It is useless against the acute leukemias of childhood.

Ten years ago a San Francisco shipping executive heard the bad news from his doctors: he had chronic lymphatic leukemia. X-ray treatment might have slowed down the disease enough to give the patient ten or even 20 years of useful life, but doctors have done the job more easily with an occasional injection of colorless fluid containing phosphorus-32.

The shipping man has his blood count checked regularly. About once a year the count shows that he needs another shot of atomic medicine. When he goes to a Gulf port on business, a local doctor watches his blood counts and reports back to San Francisco. If the white-cell count begins to go up ominously, there is still plenty of time for a dose of radiophosphorus to be flown to the Gulf Coast. The shipping man drives himself hard and feels fine.

If radiophosphorus is good for these leukemias, in which the white cells become predominant, it is even better for polycythemia vera, in which the red cells get too numerous. This is because the radioactive atoms act on the bone marrow, where both types of blood cells are made. If either red or white cells are increasing too fast, the radioactivity cuts down their birth rate. For simple polycythemia (uncomplicated by disease of the heart or lungs), radioactive phosphorus is the best medication known today. Some patients are still getting along well 15 years after beginning this treatment, and their number is growing daily.

Gold to Ease Pain. Ranking third among the isotopes used in the treatment of patients is radioactive gold. In a few U.S. medical centers, the gold is injected directly into the tumor mass in certain cases of cancer of the cervix or of the prostate gland. This work is still in its infancy; in the standard medical summary, "the results are encouraging but inconclusive." Far more widespread is the use of radiogold, with no thought of cure but _ simply to ease the pain and inconvenience of excess fluid formation in cancers of the chest or abdominal cavity.

A typical case is that of Mrs. H., a storekeeper's wife, who was bloated and miserable when she first went to the women's clinic of Manhattan's Memorial Hospital. She had had an ovarian cancer removed, but not soon enough: its colonies were spread around the lining of her abdominal cavity, causing it to fill rapidly with fluid. She had constant pain, cramps and constipation; she could not keep house, and had to be "tapped" regularly.

It got so the doctors had to drain off almost four quarts of fluid every ten days.

One day the doctors at Memorial drained off the fluid as usual, then injected ten cubic centimeters (two-thirds of a tablespoon) of purplish liquid containing 20 trillion particles of gold. It took a while for the doubly precious metal to work, and Mrs. H. soon had to be tapped again. But by then the radioactive gold had bombarded the cancer cells and checked their multiplication. For the first time in a year, Mrs. H. could enjoy a full meal.

She has had to be tapped only once in the last six months. Mrs. H. is up & around, taking care of her teen-age children. She is not cured, and she knows it. But life is infinitely easier.

Several other radioisotopes offer marked advantages in treating some of the less dramatic (and usually nonfatal) forms of cancer. Example: blotting paper soaks up a solution containing phosphorus-32; the paper can then be cut to the exact shape of a skin cancer and held in place with adhesive tape. In a few days the cancer is arrested. Strontium-go, on the end of a probe, has been found to be even better than phosphorus-32 for treating malignant growths of the eye.

Atoms for Diagnosis. In the long run, atomic medicine may prove to be more important as a tool kit to help doctors in diagnosis than as a shelf of cures. Already, radio-sodium is extremely valuable as a treatment gauge in certain types of kidney disease of which children are most often the victims. It is all very well to keep these little patients, with their puffy eyes, on a diet from which salt is rigorously excluded. But doctors need to be sure that they are not going too far: if the system is really salt-starved (and hence, sodium-starved), the patient may die of kidney failure. With a tiny injection of radio-sodium, which mixes with the rest of the sodium in the body so that the dilution can be computed with the aid of a Geiger counter, doctors can tell when the danger point is approaching. Every day a dozen happy children banging around the playroom of the hospital at Long Island's Brookhaven Laboratory give testimony to the success of this technique.

It is often important for doctors to know how much water there is in a patient's body, especially if he has heart disease. Almost 20 years ago, Physicist George Hevesy worked out a way to use the stable isotope of hydrogen (deuterium or hydrogen-2) in heavy water for this purpose. But the technique is complicated and takes a long time. Now the University of California's Dr. John H. Lawrence, one of the first and most imaginative of the atomic medicine men, can do the job far faster with heavy-heavy water, the oxide of hydrogen3 or tritium.-The radiant atoms of tritium reveal themselves (to the Geiger or scintillation counter); from the dilution of tritium oxide, it is a simple matter to calculate the total amount of water in the body.

Facts for the Surgeon. No less important is the mass of red blood cells in the body. Some researchers hold that the "count" of red cells in a droplet of blood is not precise enough. Lawrence now gets a more accurate estimate by tagging the red cells with phosphorus. Then there is the question of blood volume; a surgeon needs to know how much blood may have been lost by injury before he undertakes an amputation, and then how much is lost during the operation. With iodine-131 or phosphorus-32 and a Geiger counter this too, is relatively easy. _ One of the most difficult problems facing cancer specialists and brain surgeons is the diagnosis and location of brain tumors. Now a team of doctors claims to have reached 95% accuracy in pinning down the tumor site with the aid of a dye tagged with iodine-131. Other doctors have not been able to get as good results so the search goes on. Boston's Dr. Abraham S. Freedberg is encouraged by the way radioactive rubidium (a rare trace element in the body) concentrates in the tumor more than in healthy brain tissue making the cancer easier to spot.

Paths for Pioneers. The medical pioneers, advancing behind thick lead shields and armed with radiation counters, are striking out along two main paths: i) experiments in actual treatment, where the benefit _of new discoveries may be felt by the patient tomorrow, and 2) fundamental research into the most deeply hidden details of the chemistry of the body and its every cell--the results of which may not be apparent for years. Prime examples of experimental treatments:

51 Bone cancers are hard to treat because if radioactive elements (such as calcium and phosphorus) settle in hard bone, they also affect the marrow and damage the blood-making cells. At Oak Ridge, doctors and radiologists have just eliminated gallium7 2 as unsuitable for treatment, largely because it takes too long to settle in the bone (and meanwhile loses most of its radioactivity). Next on their list is gallium-67.

Finally, in the most dramatic of all experiments in atomic medicine, Boston's Dr. William H. Sweet and Brookhaven's Dr. Lee E. Farr have developed something entirely new: internal, instantaneous radiation for treatment of brain tumors.

The first patient who received this treatment was almost unconscious when she went to Brookhaven. The woman could not talk and did not recognize her family. Into her bloodstream the doctors injected a solution containing boron, a common, stable element with an atomic weight of 10. But under neutron bombardment, boron-10 changes to an excited boron-11, which lives about one-hundredth of a trillionth of a second. In that infinitesimal fraction of time before it decays to stable lithium, it shoots out alpha particles.

When the boron had soaked through the woman's system, including the brain tumor that was killing her, the doctors placed her head near Brookhaven's high-flux pile. While the doctors watched from a platform, the pile operator threw the controls and a stream of neutrons from the pile shot through her skull, aimed at the tumor site. For 17 minutes the boron in the tumor was turned, atom by atom, into a source of instantaneous alpha radiation.

The patient lived only two months after the treatment, but in that interval she was up & about, talked almost normally, and enjoyed movies and baseball games. This epoch-making treatment has been used so far on only half a dozen patients. All that Drs. Sweet and Farr will say is that the results in the last two cases were most encouraging.

The Elementary Questions. It is in fundamental research that atomic medicine comes into its own. Here the frontiers of man's knowledge of how his body works, and how its every cell functions, are being extended day by day. To the men with their eyes on the future, the most elementary things, seemingly the simplest, are by far the most important. Certainly they have proved so far to be the most baffling.

What, for instance, happens to a relatively simple compound such as sugar when it is taken into the body in food or drink? What goes wrong with sugar metabolism in the diabetic patient? At what point does the normal metabolic chain snap? Now, at last, biochemists hope to find out. At Manhattan's Memorial Hospital and elsewhere, they have built common sugars such as sucrose and dextrose with one or more atoms of radioactive carbon-14. As the tagged sugar goes through the system and eventually escapes, its progress can be clocked. Doctors already know that there is more to diabetes than the body's inability to "burn" sugar. With tracers, they expect to find that the trouble lies in the body's failure to do a good job converting what it gets from sugar into fats or protein.

Because carbon occurs in nearly all the thousands of chemicals in the body, carbon-14 is the most widely useful tag in the isotope catalogue. Sometimes the tag can be hung on easily in the laboratory; sometimes nature has to be called in to help with "biosynthesis." In a fifth-floor laboratory atop a pseudo-Gothic building on the University of Chicago campus, intense researchers are growing common foxglove--in Pyrex cylinders filled with radioactive carbon dioxide. They harvest the leaves and make radioactive digitalis.

Foxglove tea was an old wives' remedy for heart cripples hundreds of years ago; 170 years have passed since Withering gave the treatment medical respectability. Doctors know that digitalis goes to the heart, but they want to know how long it stays there and how it is broken down into other compounds. The Chicago team has found out that digitalis stays in the system much longer than had been thought; next, they hope to learn in far greater detail how it works, and how the body ultimately disposes of it. They are also growing radioactive belladonna to make radioactive atropine, and white poppies to give morphine an atomic kick.

In the last analysis, it is vastly more important to know what goes on in the body's individual cells than in the body as a whole. One noted cancer researcher says that there is properly no such thing as "cancer research"--only study of the life processes of cells. For, once the normal life processes are better understood, it should be but a step to find out wherein the life of a cancer cell differs from that of a normal cell, and another step or series of steps to find a way to eliminate the difference.

Throughout the U.S. (as in Canada and Britain and Western Europe), eager researchers are grasping for every usable tool they can find in the atomic kit. So far, of over a thousand known isotopes (many of them stable) of 98 elements, at least 60 radioactive forms have been tried in medicine and research. In the U.S., the Atomic Energy Commission is backing more than 300 research projects by private institutions in medicine and biochemistry, and there are many more, under security wraps, in AEC's own labs. And the nation's hospitals and universities themselves are sponsoring hundreds of projects.

The Elementary Precautions. Atomic medicine is far from the stage where a general practitioner down the block can look at a patient, reach into a lead-lined safe, pull out a shielded syringe and inject a radioactive isotope. Probably that stage will never be reached; even medically safe doses can be highly dangerous if carelessly handled. Wisely, the AEC has laid down strict rules to cover the distribution and use of its products. Before anyone may use an artificial radioisotope,*he must tell the AEC what he wants to use it for, how he intends to use it, what he hopes to show, and give evidence that nobody in his laboratory will be endangered. If the applicant wants to work on humans, he cannot get his radiant atoms until his answers to these questions have been considered by the AEC's Subcommittee on Human Applications of Isotopes (known affectionately in the trade as the "Subhuman Committee").

Under this setup, atomic research is going ahead more rapidly than any other line of medical investigation. Louisiana's Dr. Jason P. Sanders was not exaggerating much when he told fellow general practitioners last week: "Work in this field is moving so fast that if a doctor is up-to-date one week, he may be behind the next."

* The first radio-iodine used had an atomic weight of 128, but Dr. Joseph G. Hamilton, pioneering with it at the University of California complained that it lost its radioactivity too fast' Physicist Glenn Seaborg nodded, said-"I'll see what I can find." He found iodine-131 -Which is also believed to be the vital element in the H-bomb.*Thanks to the accident of prior discovery, radium has never been brought under similar control. Anyone can buy as much as he can afford and carry it home in his pocket. It might cost him $500,000 an ounce, but for a mere $3,000 he can get enough to burn through his pocket and flesh and well into his thigh bone.

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