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RAMP* Addition-1: "Expectations," February 19, 2000
Demonstration, for All-Cancers-Combined:
The Findings in RAMP Are in Line
with Reasonable Scientific Expectations.
A Response to Claims that the Findings
Are not in Line with Reasonable Expectations.
by John W. Gofman, M.D., Ph.D., and Egan O'Connor, Editor
* RAMP is a short name for the book, Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease, by John W. Gofman. Nov. 1999.
- Part 1. Purpose of This Communication
- Part 2. Per-Capita Population Dose: Proper Considerations
- Part 3. Risk per Unit of Dose: Proper Considerations
- Part 4. Demonstration for All-Cancers-Combined:
RAMP Falls Within Expectation
* Part 1. Purpose of This Communication
The new evidence in RAMP produces the estimates that medical radiation has been a necessary co-actor in over 50% of the United States death-rates from Cancer and from Ischemic Heart Disease during the 1940-1990 period (RAMP, p.21, p.490). The short list, of estimates of Fractional Causation by medical radiation, is as follows:
Year Percent Year Percent All-Cancers-Combined, males 1940 90% 1988 74% All-Cancers-Combined, females 1940 58% 1988 50% Ischemic Heart Disease, males 1950 79% 1993 63% Ischemic Heart Disese, females 1950 97% 1993 78%
Soon after publication of RAMP in mid-November 1999, we saw statements in the press to the effect that the new estimates for Cancer are not credible because they are too different from the prevailing opinion --- namely, that medical radiation is a negligible cause of today's cancer burden, and is not a cause at all of Ischemic Heart Disease.
Meanwhile, we had initiated peer-review of RAMP by sending the 699-page monograph to over a dozen experts who might be qualified to evaluate it. A few of them have expressed the same reservation: They have trouble believing RAMP's findings because the findings are so different from the prevailing opinion. The unspoken assumption is that the prevailing opinion reflects the range of reasonable, informed, scientific expectation.
Here, we will demonstrate that the prevailing opinion, with respect to xray-induced Cancer, does not reflect the range of reasonable, informed, scientific expectation. Using evidence completely independent from the input to RAMP, we will demonstrate that the new findings in RAMP, with respect to Cancer, fall within the range of reasonable, informed, scientific expectation.
With respect to Ischemic Heart Disease, the findings in RAMP also are consistent with reasonable expectations, in view of growing evidence from pathologists and cell biologists that mutations play a role in atherogenesis. Some evidence, not already mentioned in RAMP, will be described online at www.ratical.org/radiation/CNR/RMP/ soon.
We do not wish to leave the impression, however, that the validity of our new findings depends on their falling within the range of reasonable, informed scientific expectation. It often happens in science that genuine breakthroughs do not lie within anyone's expectations --- because expectations are faulty, and not informed well enough. The history of medical science contains many cases of ridicule and dismissal of valid new findings for years and decades (with great detriment to the population), simply because the new work fell far outside expectations. Two well-known physicians, separated by a over century, suffice to illustrate the point: Doctors Ignaz Semmelweis (childbed fever) and Barry Marshall (gastric ulcers).
* Part 2. Per-Capita Population Dose: Proper Considerations
The pre-RAMP way, of estimating the impact of medical radiation upon the cancer mortality rates, has been to estimate average dose (in rads) excluding radiation-therapy for Cancer, and then apply an estimate of risk per rad (cancer-production per rad). Rad and centi-Gray are two names for the same dose-unit.
The impact of medical xrays, upon the mortality rates from Cancer in a given year, depends biologically upon the xray-doses accumulated by the members of the population during their lifespans (RAMP, Chap.2, pp.49-50). Therefore, the population's average annual per capita population doses from many earlier decades has to be estimated, by anyone using this method. Failure to consider the many earlier decades is a fatal flaw in one of the low estimates of the xray's impact, already discussed in RAMP (Chap.67, p.500).
2a. A Reasonable Dose-Estimate for 1950 (USA)
Appendix-K in RAMP uses data, from the professional medical journals at mid-century, to make an estimate of the population's per-capita average xray dose per year in 1950, from non-therapeutic diagnostic medical xrays. That estimate is 0.654 rad of whole-body internal-organ dose per year (RAMP, p.614). The estimate necessarily incorporates many approximations, all of which are explicitly stated in Appendix-K, which shows step-by-step how the estimate was made. The per-capita estimate of 0.654 rad/year is shown (RAMP p.612, p.616) to be consistent with a low frequency of xray procedures before age 30.
If anyone insists that the estimate of 0.654 rad/year is too high for 1950, such a person needs to present a case why a lower estimate would be more credible, scientifically. Instead, the feed-back so far is that our estimate may be a reasonable approximation for 1950.
2b. A Reasonable Dose-Estimate for the 1900-1950 Period
And what about the population's average per-capita xray dose per year between the years 1900 and 1950? Although the xray was introduced into medicine as early as 1896, it is fair to estimate that the population's per-capita dose was still essentially zero in the year 1900. Usage of xrays grew very rapidly between 1900 and 1950, as fully documented throughout Gofman 1995/96, and also in Evens 1995.
Starting with a per-capita dosage of zero in 1900 and ending with 0.654 rad during 1950, we can reasonably approximate that average per-capita dose was 0.3 rad per year during the 1900-1950 period. This may even be an underestimate, because doses per procedure in the early decades (when reddening of the skin was the only "dose-meter") were almost certainly higher than in 1950, when doses could be far better controlled.
2c. A Reasonable Dose-Estimate for the 1950-2000 Period
And what about the population's average per-capita xray dose per year between the years 1950 and 2000? Doses were (and are) rarely measured, even though xrays have been a proven mutagen and carcinogen for decades. Xrays are almost singular in that respect, for physicians pay careful attention to dosage and its reduction, when they administer other agents with potentially fatal side-effects.
Even the number of procedures administered per year in the USA is very uncertain (RAMP, Chap.2, p.33). The UNSCEAR 1993 report notes that the number could be 60% higher than the estimate it uses (UNSCEAR 1993, p.229).
In short, the evidence is absent for making a reasonable estimate of per-capita dose today in the USA.
How much has per-capita dose really declined since 1950? Several post-1950 forces clearly operate to reduce doses, but several others clearly operate to increase doses. Both kinds of forces are examined in RAMP, Chap.2, pp.34-37. The net effect upon the population's per-capita dose is just unknown and unknowable. The per-capita figure of 0.04 rad/year from diagnostic xrays, commonly used in "pie-charts," is a guesstimate provided by a radiation industry which has a clear self-interest in providing low estimates. And 0.04 rad does not even include fluoroscopy used during surgery --- a major source of exposure.
For the sake of the demonstration which follows (Part 4), we will make the extreme approximation that the average per-capita dose from xrays in the year 2000 will be zero. Because we are using the reasonable approximation of 0.654 rad/year for 1950, we can approximate that 0.3 rad/year is the population's average per-capita xray dose each year during the 1950-2000 period. This will clearly be an underestimate, because the year-2000 population dose is nowhere near zero and must be well above 0.04 rad/year.
2d. A Conservative Dose-Estimate for the Century, 1900-2000
On the basis of Parts 2a, 2b, and 2c, and in the absence of contrary evidence, we consider a scientifically reasonable approximation to be as follows: In the USA during the Twentieth Century (1900-2000), 0.3 rad per year has been the population's annual average per-capita whole-body internal-organ dose from medical xrays.
It is certainly worth noting that this approximation is consistent with another estimate, based on completely different data. We refer to the estimate of annual xray dose to the breasts, developed in Chapters 8 through 23 in Gofman 1995/96, for the 1920-1960 period. That estimate works out to be about 0.42 rad/year (Gofman 1995/96, Col.T, p.267).
If others deny these dose estimates, they first need to produce the quality of evidence and work produced in Appendix-K and Chapter 2 of RAMP, and in Chapters 8-23 of Gofman 1995/96. Simple repetition of unexamined dose-guesstimates from the radiation industry would be irresponsible, if such dose-guesstimates are invoked to dismiss the findings in RAMP.
* Part 3. Risk per Unit of Dose: Proper Considerations
In the USA and internationlly, almost all risk-per-rad estimates are based heavily or even exclusively on study of the Japanese A-Bomb Survivors (for example, BEIR 1990, p.162, and UNSCEAR 1988, p.490). In about 1980, the governments of the USA and Japan (who control the A-Bomb Database, which is managed by the Radiation Effects Research Foundation in Hiroshima) undertook a re-assessment of the doses delivered by the bombs. By 1986, they had agreed that almost all of the human exposure came from very high-energy gamma radiation, and only a negligible amount from neutrons. Soon, some experts asserted that the 1986 judgment was all wrong, and that the dose was overwhelmingly from neutrons --- a view which has not yet prevailed.
So when we discuss whether the findings in RAMP fall within informed expectations, we necessarily refer to expectations based on the nearly universally-used premise that the A-Bomb Survivors received their doses from very high-energy gamma rays.
3a. Xrays 3-Fold More Mutagenic per Unit of Dose than Bomb Radiation
There is good evidence from cell-studies, micro-dosimetric evidence, and from track-analysis, that medical xrays are about 2 to 4 times more mutagenic than gamma radiation. Chapter 2 of RAMP presents the details and references from the professional literature (pp.46-48). A 3-fold estimate, of greater mutagenicity for medical xrays than for gamma exposure from the A-Bombs, most certainly falls within the range of reasonable opinion. Therefore, it is not reasonable to apply per-rad risk estimates from the A-Bomb Study to medical xrays, without multiplying the risk by 3.
3b. Another Factor of 3 in Per-Rad Risk
What is the range of reasonable opinion about the per-rad risk for solid cancers among the A-Bomb Survivors? We will compare the estimate for instantaneous exposure from the BEIR 1990 Report and the comparable estimate from Gofman 1990, which is 3-fold higher.
The BEIR 1990 Report was published several months before Gofman 1990, and did not discuss the Gofman 1990 analysis. Gofman 1990 did discuss the BEIR 1990 analysis.
It deserves emphasis that exposures from xrays are received acutely (all at once), not gradually over weeks and months. By contrast, exposure by nuclear pollutants occurs gradually. Government agencies routinely assert that the per-rad harm will be much less from slow exposure than from the instant exposure at Hiroshima and Nagasaki. Indeed, the BEIR 1990 Report (p.6, p.23) claims a factor of "two or more" lower for slow exposure. The UNSCEAR 1988 Report (p.491) claims a factor of five "in typical situations." Persons calculating expectations from medical radiation must assure themselves that they are employing a per-risk value published for acute exposure, not for slow exposure. The Gofman 1990 estimate applies to both acute and slow exposure.
3c. Nature of the 3-Fold Disparity, BEIR versus Gofman
The 1990 BEIR and Gofman estimates will be compared in terms of radiation-induced deaths from solid Cancers, among 10,000 persons each exposed to one rad of bomb radiation. Leukemia, which accounts for less than 4% of all cancer deaths in the USA, is excluded in both estimates.
From BEIR 1990, p.172. BEIR's Table 4-2 is for Excess Cancer Mortality, Lifetime Risks per 100,000 Exposed Persons from a Single Exposure to 10 Rems (0.1 Sv). Entries are excess deaths from solid Cancers. To make those entries correct for 10,000 persons each exposed to 1.0 rem (rad), we must divide each entry by 100. Thus, we take an average of the male value (6.60) and the female value (7.30), which is 6.95. Then we multiply 6.95 by 1.23, which yields 8.55 extra cancer deaths. The factor of 1.23 for under-ascertainment in the A-Bomb Study was used in the previous BEIR Report (1980, p.196) and in the 1988 Report by RERF, which is the Radiation Effects Research Foundation (Shimizu 1988, p.41, pp.49-50). The factor was provided by, and applied by, what would be regarded as "mainstream" analysts funded by the U.S. and Japanese governments. Bottom line: The BEIR-1990 estimate is 8.55 extra cancer deaths per 10,000 persons, each exposed to 1.0 rad of bomb-radiation.
From Gofman 1990, Chapter 16, Table C. The comparable Gofman estimate is 26 extra cancer deaths per 10,000 persons, each exposed to 1.0 rad of bomb-radiation. This value is (26 / 8.55), or 3-fold higher than the BEIR-1990 estimate.
3d. The Main Reasons for the 3-Fold Disparity
The main reasons for the 3-fold disparity in per-rad risk estimates, from ostensibly the same data, can be summarized as follows:
o (1) BEIR-1990 (p.168) discarded the observations from the 1950-1955 follow-up, except for Breast Cancer;
o (2) BEIR-1990 (p.165) discarded the observations in the two highest dose-groups;
o (3) BEIR-1990 (p.165) discarded observations beyond age 75;
o (4) BEIR-1990 (p.200) made no use of its own finding that the dose-response in the A-Bomb Survivors is supralinear in both the old and new dosimetries, even below 35 rads in the latest report from RERF (Pierce 1996, pp.9-10).
In short, the BEIR-1990 analysts discarded evidence right and left, whereas Gofman used the evidence as the evidence presented itself. Gofman's approach is far less likely to suffer from subjective preconceptions. Objective analysts must regard the per-rad risk estimates from Gofman 1990 as being at least as credible as the BEIR-1990 estimates.
So, anyone who uses the A-Bomb Study, to assess "expectations" from medical radiation, must use the full range of reasonable results from the A-Bomb Study (sometimes called "the Japanese experience" in the literature) --- and not use only the low end of the range from BEIR-1990.
The BEIR 1990 Report (pp.46-47), referring to non-A-Bomb studies, acknowledges that "A number of low-dose studies have reported risks [per dose-unit] that are substantially in excess of those estimated in the present report ... Although such studies do not provide sufficient statistical precision to contribute to the risk estimation per se, they do raise legitimate questions about the validity of the currently accepted estimates."
* Part 4. Demonstration for All-Cancers-Combined:
RAMP Falls Within Expectation
Here, we use the considerations explained in Parts 2 and 3 to demonstrate that RAMP's finding of high Fractional Causation of Cancer, by medical xrays, falls within the range of reasonable expectation. Conventional analyses apply "the Japanese experience" to other nations (e.g., the USA). Because we are showing what expectations flow from conventional analysis, we, too, will apply "the Japanese experience" below.
4a. What Is the Expected Fractional Causation, by Medical Xrays, in 1940?
Question: What average accumulated xray dose per capita would be required to account for 100% of the 1940 cancer burden (USA)?
Answer: In 1940, about 11% of all deaths were from Cancer, or 1,100 cancer deaths per 10,000 total deaths. This is the same as 1,100 cancer deaths per 10,000 population of exposed persons, because everyone who died in 1940 was exposed to the average accumulated per capita dose (by definition).
If 1 rad of bomb radiation per person produces
~ 26fatal radiation-induced Cancers per 10,000 exposed persons (from Part 3c above, the Gofman estimate), then 1,100 cancer deaths per 10,000 deaths would require an average per capita accumulated dose of ~ 42rads of bomb-radiation: (1,100 cancers / 26 cancers per rad).
But xrays are about 3-times more mutagenic than bomb-radiation (from Part 3a, above). Therefore, the same result would require an accumulated per-capita dose of only 14 rads from medical xrays.
And Part 2 provides a reasonable estimate of annual per-capita population dose from 1900 to 1940: 0.3 rad per year. So, in 40 years, those who die in 1940 have each accumulated about 12 rads. And 12/14 equals 0.86, or 86% of the dose which would cause 100% of the 1940 cancer burden.
Conclusion: These ballpark figures demonstrate that evidence prior to RAMP means that we and other analysts should have expected that in the neighborhood of 86% --- not 1% --- of the 1940 cancer mortality-rates would be due to medical xrays. And RAMP, using completely independent data and methods, produces the estimates of 90% for males, 58% for females (Part 1, above), whose average is 74%.
4b. What Is the Expected Fractional Causation, by Medical Xrays, in 1990?
Question: What average accumulated xray dose per capita would be required to account for 100% of the 1990 cancer burden (USA)?
Answer: In 1990, about 22% of all deaths were from Cancer, or 2,200 cancer deaths per 10,000 total deaths. This is the same as 2,200 cancer deaths per 10,000 population of exposed persons, because everyone who died in 1990 was exposed to the average accumulated per capita dose (by definition).
If 1 rad of bomb-radiation per person produces about 26 fatal radiation-induced Cancers per 10,000 exposed persons (from Part 3c above, the Gofman estimate), then 2,200 radiation-induced cancer deaths per 10,000 deaths would require an average per capita accumulated dose of
~ 85rads of bomb-radiation: (2,200 cancers / 26 cancers per rad).
But xrays are about 3-times more mutagenic than bomb-radiation (from Part 3a, above). Therefore, the same result would require an accumulated per-capita dose of only 28 rads from medical xrays.
And Part 2 provides a reasonable estimate of annual per-capita population dose during the Twentieth Century: 0.3 rad per year, and it might be appreciably higher. So, in
~ 65years of lifespan, people accumulate (65 years * 0.3 rad/yr), or ~ 19.5medical rads. And 19.5 rads divided by 28 rads equals 0.70, or 70% of the dose which would cause 100% of the 1990 cancer burden.
Conclusion: These ballpark figures demonstrate that evidence prior to RAMP means that we and other analysts should have expected that in the neighborhood of 70% --- not 1% --- of the 1990 cancer mortality-rates would be due to medical xrays. And RAMP, using completely independent data and methods, produces the estimates of 74% for males, 50% for females (Part 1, above), whose average is 62%.
4c. Consistency: Powerful Support for Both Old and New Findings
The amazing consistency, of findings from the old type of approach (using the Gofman per-rad risk) and from the new approach out of RAMP, provides powerful support for the validity both of the prior findings (Parts 2 and 3, above) and of the new findings.
The consistency also provides a powerful refutation of hasty claims that the new findings fall outside of reasonable expectations. We believe most objective analysts will agree that the input from Parts 2 and 3, into the demonstrations here in Parts 4a and 4b, falls within the range of reasonable scientific opinion. "Reasonable in, Reasonable out."
If consistency were lacking, between the old and new ways of evaluating the impact of medical xrays, then we would have far more confidence in the new method of RAMP than in the old method illustrated above. Eight reasons for this confidence are summarized in RAMP (pp.14-15). One of them is that the old method depends on very uncertain estimates of doses in rads and of risk/rad, whereas the method in RAMP does not depend on either of those very uncertain inputs (RAMP, p.15, p.501). It is the undisputed uncertainty, about accumulated dose and risk/rad, which causes us to marvel that the estimates in Parts 4a and 4b are so consistent with the estimates produced by RAMP from completely independent input.
We do not fault anyone for being surprised by the new findings about the immense impact of medical radiation upon cancer and IHD mortality. We were, too, as they presented themselves. But expressing surprise would be very different from asserting, mistakenly, that the findings are not scientifically credible because they fall outside the range of reasonable expectation. Parts 2, 3, and 4 show that the new findings for xray-induced Cancer fall within the range of reasonable and informed scientific expectation.
4d. And Where Is the Middle of the Pre-RAMP Range?
If people use the other end of the range for per-rad risk (Part 3c), the percentages in Parts 4a and 4b would each be 3-fold lower. This would mean a pre-RAMP expectation for 1940 in the neighborhood of 28% instead of 86% due to medical xrays, and for 1990 in the neighborhood of 23% instead of 70% due to medical xrays. These fractions due to medical xrays (28% and 23%) still would be very important shares of the cancer mortality-rate --- far too high to disregard.
Moreover, the middle of the informed pre-RAMP expectation-range for 1940 would be in the neighborhood of 57%. And for 1990, the middle of the informed pre-RAMP expectation-range would be in the neighborhood of 46%.
4e. The Pre-RAMP Era Is Past
Now, the pre-RAMP era is past. RAMP provides completely independent data, analyzed by a completely independent method. The RAMP databases are unbiased with respect to radiation, and they are immensely large (statistically powerful) --- far more powerful than the A-Bomb Database. The data in RAMP are the kind of data beloved by objective analysts. And what does RAMP say about which region is correct in the pre-RAMP range of expectation?
RAMP produces spectacularly strong dose-responses which support the higher end of the range of informed pre-RAMP expectation.
The stakes for human health are very high. The findings in RAMP point to a safe and demonstrably feasible way to prevent countless fatal cases of Cancer and Ischemic Heart Disease: Just achieve the benefits of medical xray procedures with much lower doses per procedure. No flimsy basis for dismissing this opportunity should be tolerable.References
- BEIR 1980. Committee on the Biological Effects of Ionizing Radiation, The Effects on Populations of Exposure to Low Levels of Ionizing Radiation (also known of the BEIR-3 Report). (National Academy Press, Washington DC 20418).
- BEIR 1990. Committee on the Biological Effects of Ionizing Radiation, Health Effects of Exposure to Low Levels of Ionizing Radiation (also known as the BEIR-5 Report). National Research Council. Under contract from the federal government's Office of Science and Technology. 421 pages. ISBN 0-309-03995-9. (National Academy Press, Washington DC 20418.)
- Evens 1995. Ronald G. Evens, "Roentgen Retrospective: One Hundred Years of a Revolutionary Technology," J. American Med. Assn. Vol.274, No.11: 912-916. Sept. 20, 1995.
- Gofman 1990. John W. Gofman, Radiation-Induced Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages. ISBN 0-932682-89-8. (Committee for Nuclear Responsibility, San Francisco.)
- Gofman 1995/96. John W. Gofman, Preventing Breast Cancer: The Story of a Major, Proven, Preventable Cause of This Disease. First edition (1995), 339 pages. Second edition (1996), 422 pages. ISBN (second edition) 0-932682-96-0. (Committee for Nuclear Responsibility, San Francisco 94142.)
- Gofman 1999. John W. Gofman, Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease: Dose-Response Studies with Physicians per 100,000 Population. 699 pages. ISBN 0-932682-97-9 (hardcover edition); ISBN 0-932682-98-7 (softcover edition). (Committee for Nuclear Responsibility, San Francisco.)
- Pierce 1996. Donald A. Pierce + Yukiko Shimizu + Dale L. Preston + 2 co-workers at RERF, "Studies of the Mortality of Atomic Bomb Survivors. Report 12, Part 1. Cancer: 1950-1990," Radiation Research Vol.146: 1-27.
- RAMP (Radiation from Medical Procedures). Please see Gofman 1999.
- Shimizu 1988. Yukiko Shimizu + Hiroo Kato + William J. Schull, Lifespan Study Report 11, Part 2. Cancer Mortality in the Years 1950-85 Based on the Recently Revised Doses (DS86). 102 pages. Technical Report RERF TR-5-88. (Radiation Effects Research Foundation, Hiroshima.)
- UNSCEAR 1988. United Nations Scientific Committee on the Effects of Atomic Radiation, Sources, Effects and Risks of Ionizing Radiation. 647 pages. ISBN 92-1-142143-8. (United Nations, New York City.)
- UNSCEAR 1993. United Nations Scientific Committee on the Effects of Atomic Radiation, Sources and Effects of Ionizing Radiation: UNSCEAR 1993 Report to the General Assembly, with Scientific Annexes. 922 pages. ISBN 92-1-142200-0. (United Nations, New York City.)
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