X-Rays, Cancer and Heart Disease

X-Rays, Cancer and Heart Disease
by John Gofman, M.D., Ph.D.

John Gofman, M.D., Ph.D., is one of the leading experts in the world in these issues. He is a nuclear physicist and a medical doctor.

The evidence presented in his book, Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease, strongly indicates that over 50% of the death-rate from cancer today, and over 60% of the death-rate from Ischemic Heart Disease today, are x-ray-induced.

The finding means that x-rays (including fluoroscopy and CT scans) have become a necessary co-actor — but not the only necessary co-actor — in causing most of the death-rate from cancer and from Ischemic Heart Disease (also called Coronary Heart Disease, and Coronary Artery Disease).

In multi-cause diseases such as cancer and ischemic heart disease, more than one necessary co-actor per fatal case is very likely. Absence of any necessary co-actor, by definition, prevents such cases. The concept of x-ray-induced cases means cases which would be absent in the absence of exposure to x-rays.

X-rays and other classes of ionizing radiation have been, for decades, a proven cause of virtually all types of mutations — especially structural chromosomal mutations (such as deletions, translocations, and rings), for which the doubling dose by x-rays is extremely low. Additionally, x-rays are an established cause of genomic instability, often a characteristic of the most aggressive cancers.

Not surprisingly, a host of epidemiologic studies have firmly established that x-rays and other classes of ionizing radiation are a cause of most varieties of human cancer. We have a high level of confidence that our findings, about the important causal role of medical radiation in both cancer and IHD, are correct.

Reduction of exposure to medical radiation can and will reduce mortality rates — from cancer with certainty, and with very great probability from Ischemic Heart Disease too.

Part 2. Some Key Facts about X-rays and Ionizing Radiation in General
Most physicians and other people appreciate the imaging capability of the x-ray, but — through no fault of their own — they are taught very little about the biological action of those x-rays which never reach the film or other imagereceptor.

Capacity To Commit Mayhem Among The Genetic Molecules
The biological damage from a medical x-ray procedure does not come directly from the x-ray photons. The damage comes from electrons, which those photons “kick” out of their normal atomic orbits within human tissues. Endowed with biologically unnatural energy by the photons, such electrons leave their atomic orbits and travel with high speed and high energy through their home cells and neighboring cells.

Each such electron gradually slows down, as it unloads portions of its biologically unnatural energy, at irregular intervals, onto various biological molecules along its primary track (path).

The molecular victims include, of course, chromosomal DNA, and the structural proteins of chromosomes, and water. Even though each energy-deposit transfers only a portion of the total energy of a high-speed high-energy electron, the single deposits very often have energies far exceeding any energy-transfer which occurs in a natural biochemical reaction. Such energy-deposits are more like grenades and small bombs.

The Free-Radical Fallacy
There is no doubt that, along the path of each high-speed high-energy electron described above, the energy-deposits produce various species of free radicals. Nonetheless, it is a demonstrated fallacy to assume equivalence between the biological potency of x-rays and the biological potency of the free radicals which are routinely produced by a cell’s own natural metabolism.

The uniquely violent and concentrated energy-transfers, resulting from x-rays, are simply absent in a cell’s natural biochemistry. As a result of these “grenades” and “small bombs,” both strands of opposing DNA can experience a level of mayhem far exceeding the damage, which metabolic free-radicals (and most other chemical species) generally inflict upon a comparable segment of the DNA double helix.

Ionizing Radiation: A Uniquely Potent Mutagen
The extra level of mayhem is what makes x-rays (and other types of ionizing radiation) uniquely potent mutagens. Cells cannot correctly repair every type of complex genetic damage, induced by ionizing radiation, and sometimes cells cannot repair such damage at all. Not all mutated cells die, of course. If they all died, there would be very little cancer and no inherited afflictions. Indeed, certain mutations confer a proliferative advantage on the mutated cells. Exposure to x-rays is a proven cause of genomic instability — a characteristic of many of the most aggressive cancers.

Unlike some other mutagens, x-rays have access to the genetic molecules of every internal organ, if the organ is within the x-ray beam. Within such organs, even a single high-speed high-energy electron, set into motion by an x-ray photon, has a chance (far from a certainty) of inducing the types of damage which defy repair. That is why there is no risk-free (no safe) dose-level.

There is widespread agreement that, by its very nature, ionizing radiation at any dose-level can induce particularly complex injuries to the genetic molecules. There is growing mainstream acknowledgment that cellular repair processes are fallible, or entirely absent, for various complex injuries to the genetic molecules.

The Very Low Doubling-Dose for X-ray-Induced Chromosomal Mutations
The inability of human cells, to repair correctly every type of radiation-induced chromosomal damage, has been demonstrated in nuclear workers (who received their extra low-dose radiation at minimal dose-rates) and in numerous studies of x-ray-irradiated human cells at low doses.

Besides demonstrating non-repair or imperfect repair, such studies have established that x-rays have an extremely low doubling-dose for structural chromosomal mutations. (The doubling dose of an effect is the dose which adds a frequency equal to the preexisting frequency of that effect.)

For instance, the doubling-dose for the dicentric mutation is in the dose range delivered by some common x-ray procedures, such as CT scans and fluoroscopy — i.e., in the dose range of 2 to 20 rads. The rad is a dose-unit which is identical to the centi-gray. We, and many others, prefer the simpler name: Rad.

X-rays are capable of causing virtually every known kind of mutation — from the very common types to the very complex types, from deletions of single nucleotides, to chromosomal deletions of every size and position, and chromosomal rearrangements of every type. When such mutations are not cell-lethal, they endure and accumulate with each additional exposure to x-rays or other ionizing radiation.

Medical X-rays as a Proven Cause of Human Cancer

Ionizing radiation is firmly established by epidemiologic evidence as a proven cause of almost every major type of human cancer. Some of the strongest evidence comes from the study of medical patients exposed to x-rays — even at minimal dose-levels per exposure.

Mounting mainstream evidence indicates that medical x-rays are 2 to 4 times more mutagenic than high-energy beta and gamma rays, per rad of exposure.

No Doubt about Benefits from Medical Radiation
Radiation was introduced into medicine almost immediately after discovery of the x-ray (by Wilhelm Roentgen) in 1895.

There is simply no doubt that the use of radiation in medicine has many benefits. The findings in this book provide no argument against medical radiation. The findings do provide a powerful argument for acquiring all the benefits of medical radiation with the use of much lower doses of radiation, in both diagnostic and interventional radiology. (Interventional radiology refers primarily, but not exclusively, to the use of fluoroscopy to acquire information during surgery and during placement of catheters, needles, and other devices.).

Within the professions of radiology and radiologic physics, there are mainstream experts who have shown how the dosage of x-rays in current practice could be cut by 50%, or by considerably more, in diagnostic and interventional radiology — without any loss of information and without eliminating a single procedure.

Role of Medical Radiation in Causing Cancer and IHD, Past and Present

This monograph has produced evidence with regard to two hypotheses.

Medical radiation is a highly important cause (probably the principal cause) of cancer mortality in the United States during the Twentieth Century. Medical radiation means, primarily but not exclusively, exposure by x-rays — including fluoroscopy and CT scans. (Hypothesis-1 is about causation of cancer, so it is silent about radiation-therapy used after a Cancer has been diagnosed.).

Medical radiation, received even at very low and moderate doses, is an important cause of death from Ischemic Heart Disease (IHD); the probable mechanism is radiation-induced mutations in the coronary arteries, resulting in dysfunctional clones (mini-tumors) of smooth muscle cells. (The kinds of damage to the heart and its vessels, observed from very high-dose radiation and reported for decades, seldom resemble the lesions of IHD).

These Hypotheses in Terms of Multi-Cause Diseases
Cancer and Ischemic Heart Disease are well established as multi-cause diseases. In efforts to prevent these multicause diseases, reduction or removal of any necessary co-actor is a central goal. The evidence in this book is that medical radiation has become a necessary co-actor in a high fraction of the U.S. mortality rates from both diseases. Fortunately, dosage from medical radiation is demonstrably reducible without eliminating a single procedure.

During the 1985-1990 period, the number of diagnostic medical x-ray examinations performed per year in the USA was approximately 200 million, excluding 100 million dental x-ray examinations and 6.8 million diagnostic nuclear medicine examinations.

The source of these estimates warns that 200 million could be an underestimate by up to sixty percent.

Not only is the number of annual examinations quite uncertain, but the average doses per examination — in actual practice, not measured with a dummy during ideal practice — vary sometimes by many-fold from one facility to another, even for patients of the same size. The variation by facility has been established by a few on-site surveys of selected facilities, because measurement and recording of x-ray doses are not required for actual procedures.

Fluoroscopy is a major source of x-ray dosage, because the x-ray beam stays “on” during
fluoroscopy. Such doses are rarely measured.

When fluoroscopic x-rays are used during common diagnostic examinations, the total dose delivered varies with the operator. When fluoroscopic x-rays are used during surgery and other nondiagnostic procedures, the total dose delivered varies both with the operator and the particular circumstances.

Our monograph is essentially the first, large prospective study on induction of fatal Ischemic Heart Disease by medical radiation. The results are stunning in their strength. Such strong dose-response relationships do not occur by accident.

Our Unified Model of Atherogenesis and Acute IHD Events
Our view (shared by many others) is that the plasma lipoproteins have no physiologic function in the intimal layer of the coronary arteries, and that under normal circumstances, their rate of entry and exit from the intimal layer is in balance. We propose that what disrupts this lifelong egress of lipoproteins from the intima — with the disruption occurring only at specific locations — are mutations acquired from medical radiation and from other mutagens.

In our Unified Model, some mutations acquired by smooth muscle cells render such cells dysfunctional and give such cells a proliferative advantage — so that they gradually replace competent smooth muscle cells at a localized patch of artery (a mini-tumor). And this patch of cells, unable to process lipoproteins correctly, becomes the site of chronic inflammation, resulting in construction of an atherosclerotic plaque — whose fibrous cap is sometimes too fragile to contain the highly thrombogenic lipid-core within the plaque.

A Personal Word: The X-ray Deserves Its Honored Place in Health
The finding, that radiation from medical procedures is a major cause of both Cancer and Ischemic Heart Disease, does not argue against the use of x-rays, CT scans, fluoroscopy, and radioisotopes in diagnostic and interventional radiology. Such uses also make very positive contributions to health. We deeply respect those contributions, and the men and women who achieve them.

This author is most definitely not “anti-x-ray” or “radio-phobic.” As a graduate student in physical chemistry, I worked very intimately with radiation, in the quest for the first three atomic-bombs. Subsequently, in medical school, I considered becoming a radiologist. In the late 1940s, I did nuclear medicine with patients having a variety of hematological disorders. In the 1960s, I did chemical elemental analysis of human blood by x-ray spectroscopy. In the early 1970s, our group at the Livermore National Laboratory induced genomic instability in human cells with gamma rays.

In short, I fully appreciate the benefits and insights (in medicine and other fields) which ionizing radiation makes possible.

But no one honors the x-ray by treating it casually or by failing to acknowledge that it is a uniquely potent mutagen. One honors the x-ray by taking it seriously.

While doses from diagnostic and interventional radiology are very low relative to doses used for cancer therapy, diagnostic and interventional x-ray doses today are far from negligible. The widely used CT scans, and the common diagnostic examinations which use fluoroscopy, and interventional fluoroscopy (e.g., during surgery), deliver some of the largest nontherapeutic doses of x-rays. In 1993, the United Nations Scientific Committee on the Effects of Atomic Radiation warned, appropriately, in its Annual Report:

“Although the doses from diagnostic x-ray examinations are generally relatively low, the magnitude of the practice makes for a significant radiological impact.”

In the USA until about 1970, fetal irradiation occurred during ~ 1 pregnancy per 14.

Every Benefit of Medical Radiation: Same Procedures, Lower Dose-Levels
The fact that ionizing radiation is a uniquely potent mutagen, and the finding that radiation from medical procedures is a major cause of both Cancer and Ischemic Heart Disease, clearly indicate that it would be appropriate in medicine to treat dosage of ionizing radiation at least as carefully as we treat dosage from potent medications. In the medical professions, we do not administer unmeasured doses of powerful pharmaceuticals, and we do not take a casual view of a 5-fold, 10-fold, even 20-fold elevation in dosage of such medications.

By contrast, in both the past and the present, unmeasured doses of x-rays are the rule — not the exception. When sampling has been done, in which actual measurements are taken, dosage has been found to vary from one facility to another by many-fold, for the same procedure for patients of the same size.

The reason for large variation is obvious from the list of numerous proven ways to reduce dosage. Facilities which apply all the measures can readily achieve average doses more than 5-fold lower than facilities which apply very few measures.

Certain Spinal X-rays: A Dramatic Demonstration
The potential for dose-reduction may far exceed 5-fold for some common x-ray exams. This has already been demonstrated for the spinal x-rays employed to monitor progress in treating idiopathic adolescent scoliosis, a lateral curvature of the spine. An estimated 5% of American children, or more, have this disorder. In a most responsible way, Dr. Joel Gray and coworkers at the Mayo Clinic developed radiologic techniques for scoliosis monitoring which can reduce measured x-ray dose to various organs as follows:

Abdominal exposure: 8-fold reduction.

Thyroid exposure: 20-fold reduction (with a back to front radiograph), and 100-fold reduction (with a lateral radiograph).

Breasts: 69-fold reduction (with a back to front radiograph), and 55-fold reduction (with a lateral radiograph).

They report, “These reductions in exposure were obtained without significant loss in the quality of the radiographs and in most instances, with an improvement in the over-all quality of the radiograph due to the more uniform exposure.

Mammography: A Model of Success
The importance of dose-reduction for the mammographic examination has been recognized, and such doses have been reduced by about a factor of ten in recent years. “Where there is a will, there is a way.” In certified mammography centers today, doses are routinely verified periodically, and measurements provide the feedback required, in order to achieve constant dose-reduction instead of upward creep.

The Benefits of Every Procedure — with Far Less Dose
Dose-reduction can be a truly safe measure. It is clear that average per patient doses from diagnostic and interventional radiology could be reduced by a great deal without reducing the medical benefits of the procedures in any way.

Radiography: Quality-assurance (dose-reduction by an average factor of 2), beam-collimation (by a factor up to 3), rare-earth screens (by a factor of 2 to 4), rare-earth filtration (by a factor of 2 to 4), use of carbon-fibre materials (by a factor of 2), gonadal shielding (by a factor of 2 to 10 for the gonads).

Digital Radiography: Decrease in contrast resolution, when such resolution is not needed (dose-reduction by a factor of 2 to 3), use of a pulsed system (by a factor of 2).

Fluoroscopy: Changes in the operator’s technique (dose-reduction by a factor of 2 to 10), variable aperture iris on TV camera (by a factor of 3), high and low dose-switching (by a factor of 1.5), acoustic signal related to dose-rate (by a factor of 1.3), use of a 105mm camera (by a factor of 4 to 5). Additional methods not specified in the list: Use of a circular beam-collimator when the image-receiver is circular, adoption of “freeze-frame” or “last-image-hold capability, and restraint in recording fluoroscopic images.

An Immense Opportunity: All Benefit, No Risk
The evidence in this monograph, on an age-adjusted basis, is that most fatal cases of Cancer and Ischemic Heart Disease would not happen as they do, in the absence of x-ray-induced mutations. We look forward to responses to our findings.

We have also presented findings, from outside sources, that average per patient radiation doses from diagnostic and interventional radiology could be reduced by a great deal, without reducing the medical benefits of the procedures in any way. The same procedures can be done at substantially lower dose-levels.

Does the Public Need a Denial, “For Its Own Good” ?
One type of response to this monograph may be that the findings need to be denied immediately (without
examination), lest the public refuse to accept the benefits of x-ray procedures.

This type of response, insulting to the public, would not be consistent with reality. In reality, the public accepts a host of dangerous medications and procedures, in exchange for their demonstrable benefits — sometimes, for undemonstrated benefits. Very few people will forego the obvious benefits from diagnostic and interventional radiology, just because such procedures confer a risk of subsequent Cancer and IHD.

The only change will probably be that people will demand that the same degree of care, now exercised with respect to dosage of potent medications, be exercised with respect to dosage of radiation from each procedure. They will want to avoid a dose-level of, say, ten rads — if the same information could be acquired with one rad. They do not deserve”one useful part of information, and nine unnecessary parts of extra risk of Cancer and IHD.” Patients will want more measurements, and fewer assumptions, about the doses delivered. But they will not reject the procedures themselves.

The “Advocacy Issue” and the Hippocratic Oath
It is very often said that, if scientists advocate any action based on their findings, they undermine their scientific credibility. If such scientists stand to benefit financially from the actions they advocate, such suspicion occurs naturally. But even in such circumstances, if their work is presented in a way which anyone can replicate, it should be impossible for their advocacy to diminish the scientific credibility of their work.

Our findings are not encumbered either by financial interests or by any barriers to replication. The findings stand on their own, whether or not we advocate any action.

I have spent a lifetime studying the causes of Ischemic Heart Disease, and then Cancer, in order to help prevent such diseases. So it would be pure hypocrisy for me to feign a lack of interest in any preventive action which would be both safe and benign. And when sources, completely independent from me, set forth their findings that such action is readily feasible — namely, significant dose-reduction in diagnostic and interventional radiology — it would be worse than silly for me to pretend that I have no idea what action should occur.

After all, as a physician, I took the Hippocratic Oath: “First, do no harm.” Silence would contribute to the harm of millions of people. Why Wait? What Is the Purpose?

Although it is commonly assumed that radiation doses are “negligible” from modern medical procedures, the assumption is definitely mistaken.

An estimated 35% to 50% of some higher-dose diagnostic procedures are currently received by patients below age 45 — when the carcinogenic impact per dose-unit is probably stronger than it is after age 65 or so.

In diagnostic and interventional radiology, dose-reduction would be wholly safe, quite inexpensive, and guaranteed beneficial — because induction of Cancer by ionizing radiation has been an established fact for decades.

A Mountain of Solid Evidence That Each Dose Matters
The fact, that x-ray doses are so seldom measured, reflects the false assumption that such doses do not matter. This monograph has presented a mountain of solid evidence that they do matter, enormously.

And each bit of additional dose matters, because any x-ray photon may be the one which sets in motion the highspeed high-energy electron which causes a carcinogenic or atherogenic mutation. Such mutations rarely disappear. The higher their accumulated number in a population, the higher will be the population’s mortality-rates from radiation-induced Cancer and Ischemic Heart Disease.

The x-ray is a proven mutagen and a proven cause of Cancer, and the evidence in this book strongly indicates that it is also a very important cause of Cancer and a very important atherogen. From the existing evidence, it is clear that average per patient doses from diagnostic and interventional radiology could be reduced by a great deal without reducing the medical benefits of the procedures in any way.

A Prudent Position from Which No One Loses, Everyone Gains
Whether diseases are common or rare, a prime reason for studying their causation is prevention. Cancer and Ischemic Heart Disease, combined, accounted for 45% of all deaths in the USA during 1993.

If we in the medical professions take the position, that we should not press for reducing doses from medical radiation until every question has been perfectly answered, then we can never undo the harm inflicted during the waiting period, upon tens of millions of patients every year.

By contrast, if we take the prudent position that dose-reduction should become a high priority without delay (and if humans do not start exposing themselves to some other potent mutagen), the evidence in this monograph indicates that we will prevent much of the future mortality from Cancer and Ischemic Heart Disease, without causing any adverse effects on health. No one loses, everyone gains.

Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease

Dr. Gofman’s credentials are astounding. Not only does he have a Ph.D. in nuclear and physical chemistry, but he is also a medical doctor. While a graduate student at U.C. Berkeley, Gofman earned his Ph.D. (1943) in nuclear/physical chemistry, with his dissertation on the discovery of Pa-232, U-232, Pa-233, and U-233, the proof that U-233 is fissionable by slow and fast neutrons, and discovery of the 4n + 1 radioactive series. His faculty advisor was Glenn T. Seaborg (who became Chairman of the Atomic Energy Commission, 1961-1971).

Post-doctorally, Gofman continued research related to the first atomic bombs, particularly the chemistry of plutonium, at a time when the world’s total supply was less than 0.25 milligram. He shares patents #2,671,251 and #2,912,302 on two processes for separating plutonium from the uranium and fission products of irradiated nuclear fuel.

After the plutonium work, Gofman completed medical school (1946) at UCSF. In 1947, following his internship in Internal Medicine, Gofman joined the faculty at U.C. Berkeley (Division of Medical Physics), where he began his research on lipoproteins and Coronary Heart Disease at the Donner Laboratory.

In 1954, Gofman received the Modern Medicine Award for outstanding contributions to heart disease research. In 1965, he received the Lyman Duff Lectureship Award of the American Heart Association, for his research in atherosclerosis and Coronary Heart Disease. In 1972, he shared the Stouffer Prize for outstanding contributions to research in arteriosclerosis. In 1974, the American College of Cardiology selected him as one of twenty-five leading researchers in cardiology of the past quarter-century.

Meanwhile, in the early 1960s, the Atomic Energy Commission (AEC) asked Gofman to establish a Biomedical Research Division at the AEC’s Livermore National Laboratory, for the purpose of evaluating the health effects of all types of nuclear activities.

From 1963-1965, Gofman served as the division’s first director and concurrently as an Associate Director of the full laboratory. Then he stepped down from the administrative activities in order to have more time for his own laboratory research on Cancer and chromosomes (the Boveri Hypothesis), on radiation-induced chromosomal mutations and genomic instability, and for his analytical work on the epidemiologic data from the Japanese atomic-bomb survivors and other irradiated human populations.

By 1969, Gofman and a Livermore colleague, Dr. Arthur R. Tamplin, had concluded that human exposure to ionizing radiation was much more serious than previously recognized.

Because of this finding, Gofman and Tamplin spoke out publicly against two AEC programs which they had
previously accepted. One was Project Plowshare, a program to explode hundreds or thousands of underground nuclear bombs in the Rocky Mountains in order to liberate (radioactive) natural gas, and to use nuclear explosives also to excavate harbors and canals. The second was the plan to license about 1,000 commercial nuclear power plants (USA) as quickly as possible. In 1970, Gofman and Tamplin proposed a 5-year moratorium on that activity.

The AEC was not pleased. Seaborg recounts some of the heated conversations among the Commissioners in his book, The Atomic Energy Commission under Nixon: Adjusting to Troubled Times (1993). By 1973, Livermore de-funded Gofman’s laboratory research on chromosomes and Cancer. He returned to teaching full-time at U.C. Berkeley, until choosing an early and active “retirement” in order to concentrate fully on pro-bono research into human health-effects from radiation.

His 1981, 1985, 1990, 1994, and 1995/96 books present a series of findings. His 1990 book includes his proof, “by any reasonable standard of biomedical proof,” that there is no threshold level (no harmless dose) of ionizing radiation with respect to radiation mutagenesis and carcinogenesis — a conclusion supported in 1995 by a government-funded radiation committee. His 1995/96 book provides evidence that medical radiation is a necessary cofactor in about 75% of the recent and current Breast Cancer incidence (USA), a conclusion doubted but not at all refuted by several peer reviewers.