Magic Bullets

By Grant Fjermedal

Originally published in 1984, Magic Bullets describes the most exciting development in cancer research: monoclonal antibodies, which can precisely seek out and destroy cancer cells while ignoring normal cells. This groundbreaking medical technology is finally coming into every day practice for the diagnosis and treatment of a range of diseases, including cancer. Magic Bullets, which reads like a hope-filled novel, provides an exciting look into the science and scientists behind the creation of this great advancement in medicine. For the first time in thirty-five years, this captivating journey has been re-released in digital format by the respected author and former Associated Press medical writer, Grant Fjermedal.

• Language: English
• Publisher: Andrew Gordon
• Release date: Jun 7, 2020
• ISBN: 9781393111917

Book preview

MAGIC BULLETS

THE BIRTH OF MONOCLONAL ANTIBODY THERAPIES

Grant Fjermedal

Copyright © 1984, 2020 by Grant Fjermedal.

All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording or by any information storage and retrieval system, without permission in writing from the author.

Publishing History

Original Hardback, Macmillan Publishing Company, 1984

35th Anniversary Ebook, Andrew Gordon, 2020

For Holly and Baby Cuyler with enduring love

"Many colorful characters populate Magic Bullets, from Dr. Order, whom the author presents as the ideal physician--highly competent and technically innovative but also deeply humane--to the rollicking band of beer-drinking geniuses or near-geniuses who do Hybritech's research and administration... This book is perhaps the most interesting exposition of how industrial innovation takes place since Tracy Kidder's The Soul of a New Machine looked at a computer company and won the Pulitzer Prize."

-The Wall Street Journal

CONTENTS

CONTENTS

FOREWORD

ACKNOWLEDGMENTS

1 A NIGHT AT THE OPERA

2 BACK TO THE MASTER

3 A PACKAGE DEAL

4 THE THREE SECRETS

5 BY THE WAY

6 CLOUDS

7 PLAYERS

8 PLACE AND TIME

9 THE BIG ROLL

10 TO TRY

11 A POSSIBLE SOURCE OF INCOME

12 THE SHARES AND EVERYTHING

13 THE ACCUMULATION OF KNOWLEDGE

14 SPECTAMUR AGENDO

15 CRY FOR JOY

EPILOGUE

FOREWORD

It’s been nearly 40 years since I was a very young science and medical writer working for the Associated Press out of its Seattle Bureau, and stumbled upon a report about using monoclonal antibodies to fight cancer cells. From my previous writings I understood the significance of finding a single antibody type that could attack cancer cells, and then cloning it to create massive amounts of cloned antibodies—hence the name monoclonal.

The idea was that if you could clone antibodies with a lock & key affinity for the surface antigens of specific tumor types, you could mass produce them and then release them to home in on the cancer cells, while leaving normal cells untouched. This would be the magic bullet science has so long sought.

Beyond using just bare monoclonal antibodies, scientists could use them as delivery trucks for carrying chemotherapy directly to the tumors. One approach is to split the toxin ricin in half and send the ricin A chain in one set of monoclonal dump trucks, and the ricin B chain in another set of monoclonal dump trucks. Alone, they would be harmless, but when the A chain and B chain were dumped into the tumor (figuratively speaking) they would recombine to destroy the cancer cells. 

And then there was Dr. Stanley Order a research physician in radiology at Johns Hopkins University who wanted to use polyclonal antibodies (multiple versions of cloned antibodies) as guided missiles with tiny radioactive warheads—each warhead being a bit of a radioactive isotope that only had a scatter of about half an inch, meaning that the tumor would be bombarded with radiation, but wouldn’t affect other tissue more than half an inch or so away.  

The significance of monoclonal and polyclonal antibodies was so great, and the science so intriguing that I left the Associated Press (a place I still recall fondly) and headed out to Johns Hopkins University, Harvard, and other research centers to explore this promising future—which after all these years is finally coming into fruition.  

Along the way, I was captivated by the massive humanity of Dr. Order. I knew he was brilliant, but what I admired most about him was how he carried his patients in his thoughts at all times. We would sometimes be driving to the hospital, or having long after-dinner conversations, and he would suddenly say: I’m worried about that tumor I saw today.  

Some years ago, a physician at Seattle’s Virginia Mason Hospital, a teaching arm of the University of Washington, told me that a dog-eared copy of my book was passed around amongst the interns and residents to read. Not so much about the science, but because of the beautiful humanity of Dr. Stanley Order. This, they were told, is what a physician should be.

From Johns Hopkins I went to San Diego to spend time with the organic chemists at a biotech startup that were tackling the task of attaching the radioactive warhead (yttrium) to the cloned missiles. What a delightful batch of scientists and entrepreneurs I found there. Everyone was dedicated to creating the magic bullets that could save us all from the horrors of cancer. That was some decades ago. I was witnessing the birth of monoclonal antibodies, and all these years later they are more and more being applied to a wider array of medicine.  

May the progress continue. And I hope you enjoy this account of my journey through a world of science that was rich with humanity.

-Grant Fjermedal

ACKNOWLEDGMENTS

For three years I dwelled within the world of molecular biology and during this time I had superb guides. Among the dozens of scientists who generously made time to work with me were: Dr. Stanley Order of the Johns Hopkins Oncology Center; Dr. Cesar Milstein of Great Britain's Medical Research Council Laboratory of Molecular Biology in Cambridge; Dr. Robert Bast, Dr. Jerome Ritz, Dr. Steve Sallen, and Dr. Timothy Springer of the Harvard Medical School's Dana-Farber Cancer Institute; Dr. Ellen Vitetta of the University of Texas Health Sciences Center; Dr. Richard Miller of Becton Dickinson; Dr. Keith Yamamoto of the University of California at San Francisco; Dr. Hilary Koprowski of the Wistar Institute; plus a number of other researchers at Stanford, University of California at Los Angeles, the University of Washington, the Fred Hutchinson Cancer Research Center; as well as Dr. Jim Frincke's Organic Chemistry Group at Hybritech. Beyond this partial listing were many others who in seemingly countless ways helped me in my exploration of the creation of magic bullets. Closer to home, I had moral and pragmatic support from John Baunach, Geoff Reynolds, Elsie DeHart and a raft of family and friends to encourage me through this three-year effort. I am also grateful for the never-flagging enthusiasm and support provided by George Walsh and the rest of his team at Macmillan.

My deepest appreciation and thanks is given to the cancer patients who shared with me what they had seen as the specter of death had come near. Some are now departed, while others were granted an unexpected and eleventh-hour continuation of life through the treatment with magic bullets. In both cases, the proximity of death seemed to bestow upon these persons a special heroism in their fight for life and a wonderful eloquence for their love of life. If this book were to do no more than convey to the reader a sense for the wonder of life and the need for living each day as a special gift, then it would accomplish far more than I initially set out to do.

CHAPTER 1

A NIGHT AT THE OPERA

About 23 miles southeast of Baltimore, Maryland, in the rolling hills of Green Springs Valley, just a couple of miles up the road from the Vanderbilt farm, sitting at the end of Falling Leaf Court, sits a modest brick and wood home inside of which could be heard the nonrural sounds of a video game in progress. The game was called Astrosmash, and the object was for the player to launch ground-based missiles to blow apart asteroids, UFOs, and other invasive agents of disorder before they could land on Earth.

Dr. Stanley E. Order, whose full title is the Willard and Lillian Hackerman Professor of Oncology and Radiological Sciences, Professor of Environmental Health, Director of Radiation Oncology, the Johns Hopkins Oncology Center, and who also has been awarded two honorary doctor of sciences degrees, and who is on the boards of several peer review publications, was bouncing up and down on the edge of his chair, control button in his hands, screaming at the asteroids that were showering down as fast as he could blast them: Die! Die! Die! They're all cancer cells and we have to kill them! Die! Die! Die!

In this manner he was relaxing after having put in a twelve-hour day at Johns Hopkins, where he had done, in one sense, very much the same thing.

I had just flown in from Seattle, Washington, to spend a week at Johns Hopkins before going on to Harvard, Wistar, Stanford, and several other research centers that are developing new monoclonal and polyclonal antibody drugs that can seek out and destroy cancer cells with the precision of heat-seeking missiles. I was here to witness the first stages of the Astrosmashing of cancer.

The biological sciences, and especially cancer research, are in the beginnings of a revolution that may soon produce cancer cures so effective that the wide collection of diseases collectively called cancer may be finally brought under control. It is an exciting revolution and I was visiting some of the major fronts. Johns Hopkins was the first stop because several researchers had told me that the biggest front-line action to be seen was there, where Dr. Stanley Order, in a manner of speaking, is involved in hand-to-hand combat with cancer. His weapons are polyclonal antibodies, microscopic guided missiles that carry radioactive warheads through the bloodstream to the cancer cells. At the time of my visit, Dr. Order had already won more tumor remissions, more cancer victories for patients who had been declared terminal, than any other user of polyclonal or monoclonal antibodies in the world.

Just beyond the Astrosmashing action on the television set, hanging above the fireplace and spanning the entire width of the room, was an iridescent blue and silver 374-pound, ll-foot-2-inch blue marlin. Covering much of the wall to the right of the fireplace were two sailfish, each measuring about 7 feet in length and each having a rectangular dorsal fin that extended about 18 inches in height and about 36 inches in length. If it were not for the whale of a blue marlin, the sailfish would be overwhelming giants. On the wall to the left of the fireplace was an 11-pound bone-fish. And placed all around these fish were framed photographs that chronicled past fishing expeditions.

But what caught my eye were some letters that had been allowed some space in one corner at the far end of the sailfish wall. One was from Dr. Baruj Benacerraf, a Nobel laureate with whom Dr. Order had once worked. Another was from newspaper columnist Art Buchwald, which read:

Dear Stanley—I'm impressed when you get written up in the Washington Post, the New York Times, and the New England Journal of Medicine. But I never thought you would make Parade magazine. That is the highest honor for any doctor to receive. I mean you are talking about 20 million people reading your story. What you don't realize is that you are going to be bombarded by every cancer patient in America now that they know your secrets. For God's sake, Stanley, please speak to me before you give any more interviews. You may know all there is to know about radiation oncology, but you are a babe in the woods when it comes to the media. How about an interview for Playboy?

Cheers, Art Buchwald

Buchwald was right on two counts: Dr. Order, who doesn't believe it proper for a doctor to have an unlisted number, has had his home as well as his office phone ringing off the hook. Some callers forget about the time zones, so the calls come at all hours. Others forget what day it is, so the calls come on weekends and holidays. Even when I ate Thanksgiving dinner with the Orders, he was called away from the table for such a call. Dr. Order spoke with the person for several minutes, too. As he later explained to me, These are concerned people who are either facing cancer themselves or trying to help someone who is.

Buchwald also was right about Dr. Order being a babe in the woods regarding the media. In actuality, he is a media veteran, his pioneering work in cancer having not gone unnoticed. But he is an unjaded and completely trusting veteran. He has retained the openness and vulnerability of Buchwald's babe in the woods.

Not only did he welcome my week's visit to his clinic, he suggested I forego the bleakness of downtown Baltimore hotels and stay with the family. While at the clinic, I was like a shadow, seeing every patient, sitting in on every meeting, making the rounds, listening to his side of the conversation for every incoming and outgoing telephone call. Yet whenever I would begin speaking with a patient or colleague, he would exit so as not to inhibit the exchange.

After a day in the clinic we would go to his home and then talk through dinner and well beyond until one or two in the morning, even though the alarms went off at six.

At the turn of the century there lived in Germany a brilliant researcher who was said to have lived on black cigars and distilled water. Dr. Paul Ehrlich, the father of immunobiology, spent much of his life developing his theories about the receptor sites that are found on the outside surfaces of cells. Today, the new antibody missiles are being targeted against such receptor sites on cancer cells.

The body's immune system is made up largely of white blood cells that circulate through the bloodstream looking for invaders to destroy. The white cells do this by looking at the receptor sites on the surfaces of all our cells. The receptor sites are like name tags that say either I belong or I don't belong. The receptor sites also are like keyholes, and when the receptor sites are on objects that don't belong—for example, a flu virus—the white blood cells respond by creating antibodies that can fit like keys into the receptor-site locks. This lock and key action enables the antibody to destroy the invader.

Dr. Ehrlich proposed that if the white cells could produce antibodies that could kill bacteria, they should be able to produce antibodies that could attack cancer cells. It was Dr. Ehrlich's dream to find ways of increasing the body's ability to produce the needed antibodies.

These antibodies would be magic bullets, a term he created on a raucous night train between Berlin and Frankfurt. He was returning from a triumphant conference at which he had blasted away the critics of his theory of receptor sites and antibody actions. It was in such a state of ecstasy that he spoke words that are astonishingly close to exactly what is happening today: The antibodies are magic bullets, which find their target by themselves, hence their astonishingly specific effect. ... In chemotherapy we can never count on such complete success and must therefore concentrate all our powers and abilities on making the aim as accurate as we can contrive, so as to strike at the parasites as hard and the body cells as lightly as possible.

The search for a magic bullet continued for more than seven decades without fruition. When the break finally came, it arrived well hidden within the August 7, 1975, issue of the prestigious British scientific magazine Nature. The editors of Nature will probably go to their graves trying to explain why they didn't see the full significance of the report, which was to cause immediate waves of excitement and communications throughout the world of medical research.

The cover of the August 7 issue of Nature was dedicated to desert locusts. The featured articles were The origin of nucleic and of eukaryotic cells, Palaeolithic remains at the Hadar in the Afar region, and Integration of viral genomes.

Drs. Cesar Milstein and Georges Kohler, of Great Britain's Medical Research Council Laboratory of Molecular Biology in Cambridge, had offered their findings to Nature as an article, but instead it was relegated to the Letters to Nature section where it was preceded by letters on Defensive stoning by baboons, Tree remains in southern Penine peats, Evidence for visual functions mediated by anomalous projection in goldfish, and twelve other similarly esoteric, though I would think interesting, subjects. Upon reaching the sixteenth letter, the perhaps bleary-eyed reader would have come across the title Continuous cultures of fused cells secreting antibody of predefined specificity.

For any researcher who had ever contemplated a magic bullet, this title would have provided quite an adrenaline rush. It was the answer to Paul Ehrlich's dream. Here was a report on using cloning technology to create endless supplies of identical antibodies. This meant that if the right receptor-site locks could be identified on cancer cells, one could test to find the antibody keys that would fit into them. Then one could mass produce these cancer-killing antibodies using the continuous cultures of fused cells that were capable of secreting antibody of predefined specificity.

The letter described how Milstein and Kohler had created an immortal producer of monoclonal antibodies by fusing two mouse cells into one. It was a brilliant move in that they exploited one of the most deadly characteristics of a cancer cell: its immortality.

When a cell becomes cancerous, it becomes frozen in time and stops maturing. The normal aging process is somehow turned off. This is one of the reasons why cancer cells keep reproducing uncontrollably, first forming a primary tumor, and all too often shedding cancer cells to spread to other areas of the body to create metastatic tumors.

Milstein and Kohler took a mouse cancer cell and an antibody-producing mouse white blood cell and fused the two cells into one. The result was a basically endless supply of exactly the same antibodies. Because all of the millions and millions of future antibody progeny would be exact clones of the original clone, they are called monoclonal antibodies.

With some confidence, one could say that in the Western world today there doesn't exist a molecular biologist involved in cancer research who hasn't heard of the Milstein-Kohler work. If such a person does exist, it seems unlikely that he or she would step forward to announce such a distinction.

Yet the letter opened with understatement:

The manufacture of predefined specific antibodies by means of permanent tissue culture cell lines is of general interest.

And the letter closed with understatement:

Such cultures could be valuable for medical and industrial use.

Later, Dr. Milstein would tell me that he hesitated in even using this ending, and that in more than a hundred previous papers he had never contemplated such a statement.

The only question we had was that we felt it was a bit immodest, Dr. Milstein said. But we felt the case was so strong that it would be wrong on our part not to say something.

In speaking with others about the Milstein and Kohler work, I found them to be less reserved:

You may have what Paul Ehrlich predicted eighty years ago in the form of a magic bullet. We believe this is going to induce a revolution of what can be done therapeutically.

—Dr. Karl-Erik Hellstrom

Codirector of Tumor Immunology

Fred Hutchinson Cancer Research Center

Ehrlich would be in awe of what actually has been accomplished. On the basis of what's happened in science, he would have been extraordinarily pleased to see that the essence of what he felt about the specificity had come to pass, particularly with monoclonal antibodies. I think that a lot of the dreams of scientists are now appearing to be reality. What has happened has been so remarkable, the monoclonal antibodies coming up at the same time as recombinant DNA technology, that it's virtually a revolution in terms of what we can do in the research laboratory.

—Dr. Stanley Falkow

Chairman of Microbiology, Stanford University

Recipient of the Paul Ehrlich Science Award

I think that the effects of the monoclonal antibodies are only beginning to be seen. And it's a small beginning in terms of what is going to be done with them. But it already has really revolutionized many areas of research.

—Dr. Timothy Springer

Chief of the Laboratory of Immuno Chemistry

Dana-Farber Cancer Institute of Harvard Medical School

In the earliest days of monoclonal research it was hoped that cancer cells would be found to have receptor sites that were completely different from those found on normal cells. So far, such complete specificity hasn't been found, probably because cancer cells, after all, begin as normal cells.

But researchers say absolute specificity won't be needed. The changes a cell goes through in becoming cancerous can greatly increase the populations of receptor sites on a tumor cell's surface. Suppose a cancer cell has 10,000 of a certain type of receptor site for each such receptor site found on a normal cell. Monoclonal antibodies could be made so that it would take several hits to affect a cell. The occasional hits on normal cells would be inconsequential compared to the dense bombardment being received by the cancer cells.

By using the monoclonal antibodies as guided missiles, researchers have several choices in selecting a warhead. The first choice is that of the bare missile. A second option is to attach a radioactive isotope to provide exquisitely specific radiation therapy. A third option is to create a chemical warhead by having the missiles deliver chemotherapy, something that would again allow a far more precise delivery than the shotgun approach available today.

I think basically all you have to do is look at what people are using now for chemotherapy to say My God, almost anything is better, because these treatments are so awful. If you find anything that is more specific, even if it has certain side effects, I mean right now you are throwing things into the body that kill almost any multiplying cell. Let's say that we develop some monoclonal antibody targeted reagents that kill the target cells plus one out of ten of some other kind of cell in the body, and say that causes certain side effects. You're a lot better off probably than with the things that are thrown into your body now that cause your hair to fall out and immobilize your immune system and God knows what else. Things look very hopeful at this point, and I think everybody is proceeding on that basis. My feeling is that this whole field is in its infancy, that we've just barely scratched the surface.

—Dr. John Collier

Professor of Microbiology

University of California, Los Angeles

It seems quite reasonable to believe that with enough effort you could find these specific antibodies that could really provide sort of a magic bullet, if you will, to treat a number of different kinds of cancer. We have a lot of work to do, but our hope is that now we've got this exquisitely explicit and specific recognition system whereby the monoclonal antibody fits like a key into a lock on a cell and sticks there. Then, whether the antibody carries a chemotherapeutic drug or a radioactive element, you can explode the cell.

            That's an exquisitely specific system, and the antibodies can recognize a particular protein out of many millions of similar proteins and just attach to that one specific one. So I guess that's why people are excited about it. The possibilities are there for helping to destroy many of the tumors which have so far been resistant to treatments of other kinds.

—Dr. Steve Larson

Professor of Medicine

Laboratory of Medicine and Radiology

Nuclear Medicine Section

University of Washington

Going from lab to lab, from researcher to researcher, there seems to be a tremendous excitement in the air, as if the conquest of cancer and a good many other developments were drawing very near.

Everybody feels it coming, but we don't know when. I think you'd be crazy not to see that. There's a lot of enthusiasm, and it's as if everybody sees what's on the blackboard and sees what has to be done. . . . It's like somebody gave you a very, very magic lamp and said that you sort of sit there and know you can have anything you want, and you just have to do it, and that's how everyone feels.

            It's early. I mean you are talking to people in the first five years of this discovery, which is very early in science. It probably will take five years before people believe most of it. So it's quite early, but there's no question that this is a major finding. The discovery of monoclonals is going to revolutionize virtually every field in biology within ten years. But we have to get there before everybody is willing to say; Well, we've done it.

—Dr. Ellen Vitetta

Professor of Microbiology

University of Texas Health Sciences Center

It was against this backdrop that I was visiting Johns Hopkins.

One thing working in cancer research and in clinical medicine has taught Dr. Order is to enjoy each day and each minute of that day. In his words, We are all preterminal. So in retrospect, I shouldn't have been surprised when I walked into my office one day a few weeks prior to my departure and found a telephone message from Dr. Order suggesting that I arrive early enough Monday evening to go with him and his wife, Mary, to the Baltimore Opera.

I drove directly to the Baltimore Lyric Theater after renting a car at the airport. I was a bit nervous about recognizing Dr. Order in the crowd, as I had met him only once before, and that was in 1982 when I drove him around Seattle after he presented a paper on his work at the Thirteenth International Cancer Congress, an eight-day marathon held only once every four years.

My fears were put to rest though when I saw Dr. Order bobbing down the street with Mary. Dr. Order has a stocky build and reddish brown hair that he wears long at the back, Isaac Asimov style. He has a strong, 4-by-4 version of a young Bob Hope face, one of the most expressive I have encountered. Seemingly, no one could smile more broadly or laugh more heartily. If one were to attach a laugh meter to his lapel it would max out before the end of any day. Yet, on other occasions, it would seem that no one could ever look more determined or pensive. His face has the kind of cartoonish flexibility that is probably born of the never-ending emotional roller coaster ride that is part of caring for and trying to save cancer patients.

The opera was Mozart's Cosi Fan Tutte, an opera buffa of masquerading lovers testing the fidelity of their young maidens. However, it lacked the intellectual aura of Magic Flute, and I wasn't overly surprised when I thought I detected some snoring coming from the gentleman to my right, the fellow in the green polyester sport coat with the Johns Hopkins tie. Whatever his level of concentration may have been in the waning of the first act, Dr. Order sprang into action with the first sound of applause and deftly guided Mary and me to the lobby and became third in line for champagne.

Mary Order is a delightful woman with terrific skin that doesn't require makeup, elegant cheekbones, and long brown hair worn parted in the middle. Her clean and classic looks, combined with a wild, broad-brimmed maroon hat, made her seem so young that my first impression was that Stan had been chasing nurses. High school sweethearts, they have been married for twenty-six years.

The only time Mary ever saw her husband administer polyclonal drugs to a patient was on a Walter Cronkite television science special in 1981. She is so completely without pretension that I found myself asking her, Do you realize the stature of your husband?

Dr. Order, returning with three miniature bottles of champagne, answered on her behalf, About 5-foot-7. Then, bringing our attention back to the opera, Dr. Order looked at Mary and gravely pronounced: It's that horrible woman again isn't it.

It seems thirteen months prior, in the very same opera house, the diva in question had clomped about the stage as such a clumsy Carmen that her performance constituted an affront to that opera that was beyond the realm of forget and forgive.

It was annoying. It was infuriating! Dr. Order said as he began to mimic her walk as he hobbled about in the lobby cooing in a wretched falsetto. As Mary and I laughed at his impression he became more adamant in his denunciations. "As a Carmen, she was about as sexy as a truck with a flat tire. I could never understand why people would want to boo or throw things at the stage until I saw her do Carmen. But Dr. Order found a bright spot, Tonight, as a clumsy maid, she looks appropriate."

Cancer is a tough disease to work with. It apparently begins when just a single cell becomes transformed from normal to cancerous. Whether the cause of this transformation is a carcinogen in the food we eat or in the air we breathe, or whether it is a virus or a genetic time bomb, the result is the same: One cell becomes immortal and loses all regard for its neighbors.

The cell keeps dividing, and each new cell that is created keeps dividing, for they all inherit the same warped genetic information that makes them immortal and oblivious to the needs of the normal cells around them. At first, the rapidly dividing cancer cells are usually restricted to a single location, the primary tumor.

A tumor is just a mass of cells, and that mass by itself is often times no big deal, unless it is pressing against sensitive tissue. This is why a benign tumor can coexist peacefully within the body. But if the tumor is malignant, it can send invasive fingers into vital organs, or it can shed cancer cells that spread to distant parts of the body to create metastatic tumors that can invade vital structures or organs in the new locations.

So it isn't the presence of the tumor so much as it is the invasiveness and metastasis of active tumors. These characteristics also prove to be the greatest hurdles to our conventional therapies. As medicine is practiced today, there are basically three ways in which cancer is treated: cut it out, burn it out, or poison it.

Surgery is effective if the tumor hasn't wrapped itself around vital organs to the point where removal is impossible and if the tumor hasn't metastasized, as there is no way a surgeon can chase down widely dispersed metastatic cells.

Radiation can be extremely effective with some types of cancer, such as Hodgkin's disease, but the problem is how to get a lethal dosage of radiation to a tumor without wiping out too many normal cells. By using computerized positioning of the radiation equipment, the radiation is shot through the body from several different angles, with all of the beams intersecting in the tumor. But there are several limitations, one being that radiation cannot be used effectively against the seedling metastatic tumors that are too small to image and target.

Another limitation is that the effects of radiation are cumulative, meaning that during the course of a lifetime only so much radiation can be delivered to any part of the body, no matter how long the interval between treatments. So if a tumor reappears in an area that has already received the maximum dosage, there is nothing further the radiation oncologist can do.

Poisoning the tumor is the goal of chemotherapy, but the problem so far has been that chemotherapy works with such a broad and harsh hand that the normal cells take a terrible beating. In rigorous chemotherapy a patient is often taken to the very limits of death in hopes that the normal cells can somehow endure long enough for the cancer cells to be killed off. Unfortunately, this usually isn't the case, and except with some rather rare types of cancer, chemotherapy by itself often doesn't offer much more than agony and false hope.

One area in which chemotherapy can be beneficial is when used in conjunction with radiation therapy;