"NASAL RADIUM IRRADIATION

& THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS--

A FAILURE OF PROCESS:

BAD SCIENCE

BAD MEDICINE

BAD ETHICS"

Testimony submitted to a Hearing of the

Senate Committee on Governmental Affairs

on

'Human Radiation Experiments'

Washington, DC

March 12, 1996

by

Stewart A. Farber, MSPH

Director

Radium Experiment Assessment Project

Introduction -

Nasal Radium Irradiation Human Radiation Experiments

The Advisory Committee on Human Radiation Experiments (ACHRE) issued a Final Report to the President on Oct. 3, 1995 after "reviewing" over 4,000 human radiation experiments, holding over a dozen public meetings in Washington, DC. and across the nation, and "studying" hundreds of thousands of pages of government documents at a cost of many tens of millions of dollars. The ACHRE Final Report recommendations stated that not a single group of experimental subjects who were still alive and might benefit from notice and medical follow-up should be provided such notice by the U.S. Government.

In the case of Nasal Radium Irradiation (NRI) Human Radiation Experiments performed on at least 7,613 military personnel by the Navy and Army Air Force, and over 500 children in NIH funded research carried out at Johns Hopkins, ACHRE by its own limited review found NRI to have the greatest likely excess cancer mortality of any experiments it examined. However the ACHRE decision to provide "no notification and medical follow-up for the purpose of protecting their health" for over 8,000 experimental NRI subjects represents bad science, bad medicine, and bad ethics. ACHRE actions on NRI represent a total failure of the process by which radiation risks should be evaluated and contradicts the Executive Order which established it.

The lack of notice and medical follow-up recommendations for NRI experimental subjects (both military veterans and children) was based on an incomplete and inaccurate review of NRI in the Final ACHRE Report. The gaps in the ACHRE review of NRI suggest that in the end, the ACHRE was guilty of hypocritical actions in regard to its mandate. The ACHRE members' actions suggest an attempt to avoid embarrassment and potential liability for their parent medical institutions on NRI, thus failing to properly serve the U.S. Government which had sought to promote an open and honest review of past practices in the hopes of closing out a "legacy of distrust".

However, in regard to NRI follow-up, other Governmental bureaucracies beside ACHRE such as the DOD and VA (see Skolnick, A, Medical News & Perspectives Editor: "government Is In No Rush To Study Thousands Of Veterans Who Received Nasal Radiation Therapy", Journal of the American Medical Association, Vol. 274, No. 11, pp. 858-859, Sept. 20, 1995) have also failed to act in a responsible manner in following up on NRI risk to exposed veterans treated either experimentally or subsequently into the 1960s in some cases as "standard medical practice".

This recent ACHRE failure to deal honestly and ethically with the facts of the NRI issue unfortunately calls the entire set of the committee's final recommendations to the President into question, since the ACHRE failure to act in the specific case of NRI is so blatant. If the ACHRE decisionmaking process on NRI could be so flawed, one has to question whether other findings and recommendations on risk or need for medical follow-up are accurate and/or defensible.

The ACHRE actions regarding NRI risk and follow-up raise questions as to the ACHRE committee itself doing something in the present which ACHRE press releases (see Oct. 3, 1995 ACHRE Press Release) had stated "... the Committee found deeply troubling" in regard to past practices by government officials and scientists, namely:

"managing the release of information to make sure that the public image of the nuclear enterprise would be positive. In some cases, this amounted to deception and withholding of the truth".

In regard to NRI human radiation experiments, ACHRE has failed in its mandate to:

"be fair, thorough, and unafraid to shine the light of truth on this hidden and poorly understood aspect of our nation's past....[and] to tell the full story to the American people."

This review provides details to document the following three major points:

1) NRI Human Radiation Experiments Would Never Have Addressed By ACHRE If It Had Not Been Forced To Do So By Scientists And Citizens Outside Of Government.

NRI was used experimentally on over 8,000 individuals, both in DOD research on military personnel and in NIH funded research on children at Johns Hopkins. After being forced to review NRI experimental use, NRI was found to have the greatest risk to health of any experiment examined for which people were still alive and might benefit from notice and follow-up.

2) The ACHRE Risk Analysis For NRI Is Flawed

In a complete error, ACHRE carried forward its calculated lifetime risk estimate for brain cancer alone, mistakenly stating (see p.843, Medical Notification and Follow-Up, Final Report) that "the lifetime risk of tumors to the central nervous system (brain), head, and neck is approximately 4.35/1000.." when by their own calculations (p. 355, Footnote o) the correct number for all cancers of the head and neck is 8.4/1000. Accordingly ACHRE's entire discussion and justification for no notice/no follow-up for NRI experimental subjects is based on an error by ACHRE and has to be revised.

ACHRE ignores in its recommendations published epidemiological evidence for elevated brain cancer rates (Relative Risk = 5.3, p =.01, lifetime risk = 8.8/1000) for children treated with the US protocol for nasal radium irradiation that exceed by more than a factor of two, ACHRE's calculated lifetime risk for brain cancer alone (4.35/1000 lifetime risk) and exceed ACHRE's calculated risk estimate (8.4/1000 lifetime risk) for all cancers of the head and neck based on ACHRE's simplistic 'bounding' calculation (see Final Report, Footnote o., p. 355, Ch. 7). .

ACHRE ignores epidemiological evidence for what was found to be "highly statistically significant" non-malignant health effects from NRI (Relative Risk =8.6, p<.00l) from research performed at Johns Hopkins in 1977-78.

3) ACHRE's Findings And Recommendations For "no Notice, No Follow-up" Related To NRI Are Without Merit Scientifically, Medically And Ethically. Due To ACHRE Error, Lifetime Risk Of Head And Neck Cancers Underestimate By Factor Of 1.9

ACHRE's entire discussion and rationalization of no notice/no follow-up for NRI experiments is based on an error by ACHRE staff in carrying forward their own risk estimates from Chapter 7 to Part IV, Addendum to Recommendation 4: Medical Notification and Follow-Up. The "... lifetime risk of tumors to the central nervous system (brain), head, and neck" is 8.4/1000 per ACHRE's calculations and not "approximately 4.35/1000.." as the Final Report states and ACHRE's recommendations on NRI have to be revised by the Interagency Working Group to reflect this error by the ACHRE staff carried over to the Final Report.

ACHRE's final recommendations on NRI raise the question of potential conflicts of interest on the part of some ACHRE committee members whose parent institutions had key roles in NRI experiments by the military and civilian sectors.

ACHRE's recommendations appear to be based on political considerations according to statements of an ACHRE committee member. ACHRE actions on NRI suggest decisions based on concern about financial liability for the medical establishment in general and some of the ACHRE members' parent medical institutions in particular

Discussion

Point 1 - ACHRE DID NOT WILLINGLY TAKE UP THE NRI ISSUE.

IF NOT PUSHED, IT WOULD HAVE IGNORED THE ISSUE

In early 1994, as a radiation risk assessment specialist, I began a personal effort to bring public attention to nasal radium irradiation, which I recognized as representing an important human biomedical radiation issue which had been largely overlooked and ignored by the medical and scientific community. In an earlier 1992 Letter-to-the-Editor to the New England Journal of Medicine ( see "Radium Exposure in U.S. Military Personnel", Farber, 1992), I had called for identification and medical surveillance of a group estimated at that time as numbering no fewer than 5,000 Navy submariners who through my research I had estimated to have received nasal radium irradiation on entering the Navy from 1945 into the 1960s. However, the response by the medical and scientific communities, as well as the response by 'responsible' Government bureaucracies, to this 1992 Letter-to-the-editor was totally underwhelming.

The 1992 NEJM Letter-to-the-Editor published my dose calculations, based on a "typical" Navy protocol of four 10 minute irradiations:. These 1992 published dose estimates are: Contact doses (treatments were bilateral) - 2000 Rad (20 Gy) to the nasopharynx; Dose at 1 cm depth in tissue - 206 Rem (2 Gy) gamma and 68 Rad (0.68 Gy) beta from each applicator.

A summary discussion of present knowledge and history regarding potential health effects from NRI treatments of children as practiced in the U.S. is included under Point 2 below, and has been presented in more detail elsewhere. [see Farber, 1994(a); Farber, (1994(b); Farber, 1995(a); Farber, 1995(b); Farber, 1995(c); Farber, 1995(d); and Farber, 1995(e)]

At the time of my 1992 published letter-to-the-editor, the Navy spokesperson reply position was that "the risks [of NRI on veterans] incurred were relatively small" but did not at that time dispute that at least 5,000 submariners received radium irradiation as trainees. Further the Navy claimed that the Navy irradiated patients had a "right to privacy" rather than a "right to know" they were potentially at risk and claimed an almost complete lack of patient-identification data and exposure data represented "practical impediments" to a follow-up study.

Despite the Navy's 1992 evasive and inaccurate response to the New England Journal of Medicine letter, I began a private effort in late-1993 following DOE revelations about human radiation experiments in general which led to an expanding base of knowledge about the numbers of veterans, dependents of veterans, and members of the public treated with and potentially affected by nasal radium irradiation. In early Jan. 1994, I was able to interest Sen. Joseph Lieberman (D-CT) in the nasal radium irradiation of Navy Submariners performed in Groton, CT by the Naval Medical Research Lab. On Jan. 18, 1994 Sen. Lieberman wrote a letter to Jesse Brown, Sec. of Veterans Affairs pointing out that:

"the submariners may not have been provided full disclosure about the potential health risks associated with this treatment. According to Mr. Farber, studies of groups having undergone similar procedures indicate excess... brain cancers (JNCI, 1982: Vol. 68: p. 3-8). He suggests that the Navy submariner population may also be at risk. Mr. Farber indicates that the government did not have in place a long term medical follow-up program and is not currently attempting to locate and evaluate the long term health of this group

On Jan. 25, 1994, Sen. Lieberman raised the radium nasal irradiation issue at a hearing of the Senate Governmental Affairs (Glenn) Committee on human radiation experiments. Sen. Lieberman was able to receive general commitments from the VA that it would "investigate" this issue and possibly notify exposed veterans about potential health problems associated with the treatments. To date, the VA has failed to provide any notice to any veterans on this issue, whether exposed experimentally or subsequently as "standard medical practice" from 1946 into the 1960s.

On July 1, 1994 I authored a News Release and a review (Appendix I, Estimate of Radium Nasal Irradiation Health Effects) regarding the initial use of NRI on Submariners in Groton, CT by the Navy and the Army Air Force on aviators at bases across the U.S. and in Europe (a total of 7,613 individuals) for a veteran group called the Submarine Survivors Group concerned about NRI. This review provided documentation that NRI was initially a "human radiation experiment" by the admission of Navy and Army ENTs involved in the experimental use of NRI. The level of potential risk [of excess brain cancer based on the only study of NRI brain cancer risk ever performed on NRI as the treatment was used in the U.S] was significant.

The July 1, 1994 press release by the Submarine Survivors Group which was FAXed to the ACHRE included quotes from a 1946 medical journal article (see Haines, 1946) which described that of 6,149 Navy trainees evaluated in this initial "study" at the Navy's Medical Research Laboratory in New London, CT during 1945-46, 732 experimental Navy subjects received a course (four ten minute irradiations on average-estimated, with a range of two to eight irradiations in each nostril) of radium irradiation. Navy Capt. Haines in his introduction to the cited report wrote:

"Merely another clinical study would not meet the need. In view of the fact that we had a rich source of material [Inserted Note: This is a reference to human subjects available for testing] , and since every condition necessary for rigid experimental control was available, we felt it possible to meet rigorous research criteria, and thus to provide a fairly definitive study on the causes, effects, prediction, and treatment of the disorder. The present report describes aerotitis media as it appears in submariners, and recounts the experiments by which we attempted to understand it and mitigate its effects." [Note: added emphasis not in original] (see Haines, 1946, p.347)

The analysis of risk presented in Appendix I to the July 1, 1994 News Release prompted Sen. Lieberman (D-CT) to organize a Senate Hearing of the Environment and Public Works Committee, Subcommittee on Clean Air and Nuclear Regulation on August 29, 1994. On July 20, 1994 Sen. Lieberman put out a Press Release regarding nasal irradiation with the heading: "Lieberman Urges President to Order Study of Radium Treatments - Senator Says New Evidence Describes Experimental Nature of Treatments; Data Indicates Abnormal Cancer Rate". This release states that:

"In a letter to President Bill Clinton, Sen. Lieberman says newly discovered documents [Insert: A press release dated July 1, 1994 which I authored for a veterans group and supplied to his office] describe radium treatments given to more than 7,000 military personnel ...as 'experimental' and one study states that people receiving the treatments may experience brain cancer at rates comparable to those of all cancers among Hiroshima and Nagasaki survivors".

Citing the 'disturbing new data,' Sen. Lieberman is urging the President to order an epidemiological study of those who received the radium treatments. Sen. Lieberman said the treatments should also be made part of the jurisdiction of the Human Radiation Interagency Working Group..." [emphasis added].

Despite the above July 1, 1994 News Release containing clear statements by Navy researchers published in 1946, and the letter by Sen. Lieberman to the President and his request that the ACHRE evaluate the strong evidence for NRI treatments of Navy submariners and Army Air Force aviators as subjects of a 'human radiation experiment" in July 1994, the ACHRE ignored the NRI issue until early March 1995, as reviewed below.

Following growing media coverage throughout 1994 on NRI due to my continuing efforts, as well as the efforts of several other private individuals who were potential victims of NRI related health effects, Sen. Lieberman held a U.S. Senate Hearing on this issue titled: "Assessing the Effects of Nasal Radium Treatments" . This Hearing was held before the Subcommittee on Clean Air and Nuclear Regulation of the Committee on Environment and Public Works of the US Senate (S. Hrg. 103-822) on August 29, 1994. At that hearing, I testified as a radiation risk assessment specialist in my role as a citizen/scientist working with various concerned veterans and members of the public. I presented written and oral testimony that regarding NRI health risks that based on current scientific knowledge and publicly available information as to the size of the exposed NRI cohorts that:

"the level of exposure, the likely health risk to each exposed individual, and the collective dose and risk -- because of the size of the irradiated military and civilian cohort basically dwarfed all radiation exposure issues which have come to light since the DOE biomedical experiments issue has ...presented itself." (p. 9, S. Hrg. 103-822 transcript)

"As you know, an advisory committee [ACHRE] was formed earlier this year, and ...Federal agencies were directed to follow-up per Executive Order 12891, on... records to identify any individuals who have been subjects for human radiation experiments....this [ACHRE] project...with a completion cost estimated ...at $24 million....[has] not turned up any population that has the scale and the potential impact on health of the radium [nasal irradiated] population... people have come forward....wanting proper health screening and evaluation, and .this has raised a very important public health issue." (p. 10, S. Hrg. 103-822 transcript)

On March 2, 1995, I called Stephen Klaidman, ACHRE Counsel and Director of Communications to find out what actions if any ACHRE had taken on the NRI Experimental Cohort information I had provided to ACHRE via FAX during July 1994 which backed up the information which Sen. Lieberman had used as the basis for his letter to the President and to ACHRE. After speaking with Mr. Klaidman and finding out that all information on NRI provided to ACHRE had been "put into a file and no action taken", I authored an 11 page letter to the ACHRE dated March 8, 1995, "RE: Nasopharyngeal Radium Experiments Performed by DOD on 7,613 Navy and Army Air Force Military Personnel during 1944-45". This letter included an Appendix I - "Estimation of Radium Nasal Irradiation Health Effects in Military Experimental Cohort" . The first paragraph of this March 8, 1995 letter to ACHRE states:

This letter is being written to reiterate my earlier communications with the Advisory Committee during July 1994, and to follow-up my discussions with you during the past week about the above issue not being handled in an ethical and responsible manner. In response to my recent calls to your office, on March 2, 1995 we discussed that to date the Advisory Committee has not seriously reviewed this issue as a human radiation experiment in its initial use by the Navy and Army Air Force. The facts of this issue have been clearly presented in numerous communications which I have directed to the Advisory Committee and other branches of government as noted below.

It was only after the ACHRE received his March 8, 1995 letter that ACHRE began to seriously review the NRI experimental issue under its Presidential mandate.

One fact is clear. Without pressure from a scientist outside of Government who was completely independent of the ACHRE staff and its hired consultants, the NRI experimental cohorts-- the only human radiation experiment which exceeded the ACHRE criterion for medical notification and follow-up (according to ACHRE's flawed risk analysis)-- would never have been reviewed by ACHRE as a human radiation experiment. On March 13, 1995, The Albuquerque Tribune, the newspaper which broke the Plutonium series in 1993 which led to DOE's Openness Initiative later that year, published a news article: "Committee ignoring radium tests on troops, physicist says". It mentioned that Stephen Klaidman, ACHRE Director of Communications, as saying that the committee "had to make choices" and his "best guess now is we will address it in some form in our final report." The NRI issue suddenly had too much visibility to ignore.

Subsequent to my sending the March 8, 1995 letter on NRI to Steve Klaidman, I sent a FAX to Dr. Faden, Chair of the ACHRE, on March 21, 1995, which stated in part:

Attached is a copy of a news story which ran 3/13/95 in the Albuquerque Tribune titled: "Committee ignoring radium tests on troops, physicist says" about a letter I sent dated 3/8/95 to the President's Advisory Committee on Human Radiation Experiments.

This 3/8/95 letter to the Advisory Committee, directed to Stephen Klaidman, points out the failure of the Advisory Committee to deal with the issue of experiments on 7,613 military personnel during 1944-45 involving nasal radium exposure. This issue suggests a hypocritical attitude by the Advisory Committee regarding its mission to investigate all human radiation experiments. Concerning radium experiments on military personnel in 1944-45, there is also a arguable conflict of interest between the Advisory Committee ignoring this issue, the Committee being chaired by a representative of Johns Hopkins University- School of Public Health, the past role of Johns Hopkins Hospital in training the Army and Navy doctors who performed the initial experiment (and popularizing the radium nasal irradiation procedure after W.W.II) and the current attempts by Johns Hopkins Hospital to put out self-serving, and scientifically inaccurate, press releases about the lack of evidence for harm from past radium irradiation practices (see The Sun for 2/19/95). Recent news quotes attributed to Dr. George Comstock, a Johns Hopkins epidemiologist who directs Hopkins' public health research center in Washington County, MD, and to Dr. Donald Proctor, the former Hopkins' physician who designed the monel metal encapsulated sealed radium nasal irradiator used in the Navy and Army Air Force experiments in 1944-45 are quite simply either false or extremely inaccurate vs. present knowledge about health effects of radium irradiation on health [emphasis added].

....You should review my Jan. 2, 1992 letter-to-the-editor of the New England Journal of Medicine: "Radium Exposure in US Military Personnel" which sought to pressure the Navy to establish a formal program for identification and medical surveillance of radium irradiated veterans. However, the Navy denied any responsibility in this matter in 1992 and has still, despite their testimony before the Senate subcommittee hearing in August 1994, failed to initiate any outreach and identification program.

I would greatly appreciate your reviewing the status of this issue with Stephen Klaidman and other members of the Advisory Committee. Please call me at your earliest convenience to discuss your thoughts on this issue.

No one from the ACHRE ever answered the above FAX sent to Dr. Faden. However, after my March 8, 1995 letter to ACHRE presented detailed scientific documentation of the facts, ACHRE was forced to stop ignoring what it ultimately judged to be the most significant human radiation experiment of any of the 4,000 "experiments" it reviewed for which people were still alive and might benefit from notification and follow-up. Subsequent to my March 8, 1995 letter FAXed to Stephen Klaidman that day, the ACHRE staff apparently began preparation of a Review Memo (5 pages plus 13 attachments totaling 126 pages) dated March 27, 1995, RE: Nasopharyngeal Radium Treatment" from the Advisory Committee Staff to the ACHRE as discussed below in the Section ACHRE Review and Discussion.

Although I had not seen it when I sent the above March 21, 1995 FAX to Dr. Faden, another news story had run on March 21, 1995 in the Tampa Tribune ("Panel reviews radium treatments") in which Stephen Klaidman, ACHRE spokesman said that a high-level Navy official also had indicated that NRI treatments [conducted by the military during WW II] should be considered experimental.

After speaking with Mr. Klaidman on March 22, I was told the source of this statement was an internal Navy memo which the ACHRE had in its files. I requested he FAX me a copy of this key memo for my review and it was FAXed to me on March 23. The Navy memo was from the Commanding Officer M.D. Curley,, Naval Submarine Medical Research Laboratory, Groton, CT, dated Feb. 23, 1994, To: Chief, Bureau of Medicine and Surgery, Washington, DC.

Subject: Human Radiation Research Review. This memo clearly stated that in response to a BUMED Directive to perform an "Assessment of whether command conducted or sponsored human radiation research":

NSMRL's predecessors (Medical Research Department of US Submarine Base, New London, CT: Medical Research Laboratory (MRL) participated in research evaluations of radium in the prevention and treatment of aerotitis media in submariners...and was carried out under Research Project X-434 (Sub. No. 90)...."No other human radiation research at NSMRL or its predecessors has been identified."

This Feb. 23, 1994 Navy memo was a direct statement by the Navy that it had carried out "human radiation experiments" during 1945-46 on at least 732 submariners under the definition of a human radiation experiment mandated by the Executive Order which established the ACHRE. However, this Navy memo of 1994 had been ignored by the ACHRE up to the time of my March 8, 1995 letter discussed above, and would likely have continued to be ignored, if ACHRE was not backed into a corner on the NRI issue. On April 6, 1995, I requested in an E-mail to Stephen Klaidman to check when the ACHRE received the Navy memo dated Feb. 23, 1994 given its significance. Mr. Klaidman responded that the Feb. 23, 1994 Navy memo admitting to a human radiation experiment was "not date stamped" and that: "Regrettably, I have not been able to find out when the Navy memo arrived. I'll keep trying." On several subsequent occasions, I requested Mr. Klaidman to check again on this point and was told there was no way to determine when this vital memo arrived which documented the Navy's written admission of having performed NRI experiments.

On Feb. 20, 1996 I was invited to participate on a panel on Medical Notice and Follow-Up to the ACHRE Final Report at a DOE sponsored Stakeholders Workshop on Feb. 26-27, 1996 in Washington. This workshop also reviewed how to access the ACHRE files sent to the National Archives. Following the workshop, I requested a copy of the Feb. 23, 1994 Navy memo in question directly from the Archives. In speaking with the Research Librarian an the National Archives, I was told every document the ACRHE sent to the Archives had an "Accessions Record" cover sheet which listed the "Accession Number" by which ACHRE filed and referenced any document and details as to how it was received and from whom it was received.

In the case of the Feb. 23, 1994 Navy memo, it was noted for ACHRE Accession Number DOD-022395-A, that the Navy memo was received on Feb. 23, 1995 by Stephen Klaidman himself. I spoke on at least three occasions with Mr. Klaidman after sending him my March 8, 1995 memo and was told the memo was not date stamped and that there was no way to determine how or when it was received. This was obviously not the case, and the ACHRE Chief Counsel was being less than candid in responding to my legitimate questions, since this was supposed to be an open process. It is unclear why Mr. Klaidman, Counselor to the Committee and Director of Communications was unwilling to reveal that he had personally received the key Navy memo dated Feb. 23, 1994 admitting to NRI being a human radiation experiment. Perhaps he was embarrased that ACHRE knew NRI was a DOD sponsored experiment and ACHRE had merely filed this information without acting on it. Only Mr. Klaidman can and should answer this question.

This issue assumes greater significance in that the Navy's Feb. 23, 1994 memo admitting to conducting a human radiation experiment was included in the ACHRE staff review memo dated March 27, 1995 (footer date April 7, 1995) as Reference 3. This March 27, 1995 ACHRE staff memo on NRI served as a basis for the final ACHRE Report discussion of NRI history and health effects with a few major exceptions, discussed below. However, while all DRAFT versions of the ACHRE Report's NRI discussion in Chapter 7 (up through Sept. 14, 1995) included mention and reference to the Navy's Feb. 23, 1994 memo to BUMED stating that NRI was a human radiation experiment, the final ACHRE report issued two weeks later suddenly dropped all mention of this Navy Memo.

One possible reason for this memo disappearing is that this key Feb. 23, 1994 Navy memo admitting to the DOD having carried out human radiation experiments on military personnel during 1945-46 was directly contradicted over 6 months after it was authored, in both written and oral testimony on Aug. 29, 1994 by the Deputy Surgeon General of the Navy and the Surgeon General of the Air Force at the Senate Subcommittee Hearing (S. Hrg.103-822) on "Assessing the Effects of Nasal Radium Treatments". In late Sept. 1995 , over 18 months after the Navy memo in question was written to BUMED, two other official Navy spokespersons at a CDC/VA sponsored Workshop: The Public Health Response to Nasal Radium Irradiation" held at Yale University also gave formal presentations containing false statements vs. the Feb. 23, 1994 Navy Memo on NRI intially being a Human Radiation Experiment. Was the Feb. 23, 1994 memo which was dropped from the final ACHRE report too embarrassing to DOD spokesman given that their public statements throughout 1994 (including sworn testimony before a Senate hearing) and 1995 were directly contradicted by the contents of its own internal 1994 memo? Did the ACHRE cave in to pressure by the DOD to delete mention of the Feb. 23, 1994 admission by the Navy that it performed human radiation experiments? How (and why) did this Navy memo suddenly disappear from the Final ACHRE Report? These questions deserve answers.

Point 2 - ACHRE Risk Analysis for NRI is Flawed - History of NRI Use is incomplete and Inaccurate

As noted in the Introduction to this testimony, the ACHRE values of calculated lifetime head and neck cancer vs. brain cancer alone used by ACHRE to discuss NRI medical notice and follow-up are simply wrong. In a complete error for its NRI risk estimates, ACHRE staff or consultants carried forward a calculated lifetime risk estimate for brain cancer alone, mistakenly stating (see p.843, Medical Notification and Follow-Up, Final Report) that "the lifetime risk of tumors to the central nervous system (brain), head, and neck is approximately 4.35/1000.." when by their own calculations (p. 355, Footnote o) the correct number for all cancers of the head and neck is 8.4/1000. Accordingly ACHRE's entire discussion and justification for no notice/no follow-up for NRI experimental subjects (both children and adults) is based on an error by ACHRE and has to be completely revised.

ACHRE Stated Medical Notification and Follow-Up Criteria

Part IV (p. 840) of the ACHRE Final Report notes that the ACHRE was supposed to consider the issue of notice to experimental subjects of "any potential health risk or the need for medical follow-up". Despite this mandate, the ACHRE quickly jumps to an unsupported statement that:

"The basic intent of this provision is not directed at subjects who have already died, or at subjects who have already become ill and been treated. It is primarily aimed at asymptomatic subjects who remain at significant risk for the development of radiation-induced cancers."

How any "potential health risk" per the Executive Order suddenly becomes narrowed down to "significant risk for development of radiation-induced cancer" is never explained or justified by ACHRE. In any case, the logic and the ethical hypocrisy of the above ACHRE statement is astounding. What ACHRE seems to be stating is that carried to the extreme, if a human radiation experiment were performed and every subject became ill (of course only from radiation induced cancer, since no other health problem by definition needs to be considered in ACHRE's judgment) in a few decades (and they were presumably treated, but one would never know since the individuals would never have been notified they faced an excess cancer risk) or died of radiation induced cancer before the facts of the matter were ever revealed to them, the Government is under no obligation to notify any individual of anything.

ACHRE's stated criteria (p. 841) for health creening required that: "The condition must have an asymptomatic period during which it can be detected by available screening methods." This notification criterion implies a prudent public health advisory to a broad group of people who are known to be potentially at risk of some known health effect (like brain cancer) from a known risk factor like NRI serves no useful purpose. Further, ACHRE, by excluding without justification any consideration of non-malignant health effects such as the NRI link to an 8.6 fold higher risk of Graves disorder [see Sandler, 1980] or thyrotoxicosis, avoided having to recognize that there is substantial benefit to advising NRI treated subjects of the potential health symptoms that might indicate preclinical forms of Graves such that the individual seek medical evaluation and avoid potential effects on the quality of their lives. It is well known that thyroid disorders such as Graves disease linked to NRI have numerous preclinical symptoms which can be easily detected by a low cost blood test. Failure to notify individuals who may be at risk is irresponsible and unethical. As an example of the potential benefit of screening [Note: I am not implying Mrs. Bush had NRI treatment] for an endocrine disorder linked to NRI, Barbara Bush was diagnosed in the late 1980s with a full clinical case of Graves disorder. Despite her having access to the best medical care in the world as the wife of a CIA director and Vice President, her pre-clincal Graves disorder went undiagnosed for many years. She wrote in her 1994 published authobiography that before she was diagnosed and treated for Graves disorder in 1988, she suffered long periods of unexplained and severe depression. Her severe depression led her to propose a divorce from President Bush and at times she even contemplated suicide because of the mood disorders clearly linked to her Graves condition. Once her Graves disorder was diagnosed and treated, her depression and other health problems linked to it quickly disappeared. The point is that had Mrs. Bush been a subject of NRI treatment, and knowing that NRI causes an 8.6 fold excess of Graves, should someone like Mrs. Bush be notified that NRI is a significant risk factor for Graves disorder? How can the ACHRE argue that it is justifiable to ignore sound epidemiologically data suggesting a non-malignant health problem exists related to NRI treatments and not move to provide people at risk proper medical screening, or even an advisory that certain general symptoms are clear signs of potential health problems known to be linked to Graves? ACHRE's actions on the NRI issue and their rationalizations are callous and perhaps even immoral.

The ACHRE actions and recommendations to provide no notice for non-malignant endpoints and to insist that no notice is warranted unless there is a screening test that has high specificity in an asymptomatic period is unethical and indefensible.

ACHRE stated that: "the criteria for consideration of active notification were set at 1/1000 future or remaining lifetime risk and an excess relative risk of greater than 10 percent (organ specific)". This one phrase actually contains four independent limiting criteria or "filters":

a) "1/1000"

b} "future remaining lifetime risk"

c) "cancer mortality only

d) "an excess relative risk greater than 10 percent (organ specific)",

each of which reduces the population of experimental subjects who might require active notification of health risk. Each of these arbitrary factors was clearly chosen to limit the probability any one test subject would have to be notified of any potential health effect. These separate limiting criteria were never justified and never compared to the risk criteria applied in any other kind of risk assessment or regulatory proceeding related to various health hazards. These notification criteria should have been justified by ACHRE in that we are dealing with what were in many cases secret, unethical experiments by the statements of the ACHRE itself. Experimental subjects were often not given anything like modern informed consent, a situation much different than that faced in many other regulatory proceedings. Accordingly, the arbitrary ACHRE notification criteria suggest that the ACHRE's medical notice and follow-up recommendations are disingenuous, even without examining the specific case of NRI, as is done below.

Examples of Incomplete or Inaccurate History on NRI Stated in ACHRE Report

The ACHRE discussion of the history and use of Nasopharyngeal Irradiation (p. 352-355) , Chapter 7, Part II is quite incomplete and in some aspects very inaccurate. A detailed review of the facts of this matter are beyond the scope of this review. However, a few points are presented below.

a) Achre Statement: For this treatment, intranasal radium applicators (sealed ampules containing radium salt) were inserted (at least three insertions per treatment cycle) into the nasopharyngeal area for twelve minute periods." (p. 352)

Known Facts of Matter: The ACHRE statement generally describes the use of the monel metal irradiator which began to be used for the first time at Johns Hopkins in 1944 after the Monel applicator was developed there for the Army, and in experimental Navy and Army programs in mid-1944. The 50 mg Monel applicators started out being used for about 6 min 40 seconds and then 8 min 30 seconds in the AAF experimental program in 1944-45. The Navy NRI experiments during 1945-46 initially used 10 min treatments during 1945-46. After WWII the standard duration of exposure for children, at least in Maryland and associated with Johns Hopkins became 12 minutes delivered 3 times, or more as needed. Dr. Donald Proctor, Prof. Emeritus, Johns Hopkins speaking at a CDC/VA sponsored workshop on NRI on Sept. 27, 1995 mentioned that the first commericial Monel metal applicator shipped to Johns Hopkins was received on May 24, 1944. Prior to this radium applicators sealed in brass (containing 250 mg or more of Radium) were used for up to 8 minutes in one sitting (delivering 2 gm-min per nostril in one treatment to each adenoid). Most commonly during the late 1930s and early 1940s Radon applicators (sometimes containing up to 1 Ci of Radon) were used in an extremely variable manner, delivering 2 to 3 gm-min radium equivalent to each nostril.

b) Achre Statement: In the early 1940s, 732 submariners were subjects of a controlled experiment...." (p. 352) Known Facts of Matter: The Navy experiment mentioned was actually conducted in 1945- 46 under Project X-434 (Sub. No.) " in New London, CT as mentioned in the Navy memo of Feb. 23, 1994 cited in drafts of the ACHRE Final Report, but which was dropped from mention in the Final ACHRE Report

c) Achre Statement: "In a 1945 journal article, it was noted that a controlled study was considered by the Army Air Forces, but rejected....." "As noted it does mention differences between various dose groups, implying an uncontrolled experimental comparison was made." (p. 352)

Known Facts of Matter: The 9/14/95 draft of the ACHRE Final Report mentioned about the Army Air Force (AAF) Aerotitis Media Control Program vs. the Navy experimental project: "Similar treatment was administered to 6,881 airmen". The number of airmen treated was dropped from the ACHRE Final Report sometime between the Sept. 14, 1995 Draft and the Final Report, apparently to minimize the number of veterans who appeared to be experimental subjects. The published journal article cited (Annals, 1945) is an incomplete history of the use of radium experimentally by the AAF. As one example, the Army's radium aerotitis control program was initiated in May 1944 following a high level meeting of Army and Navy officers, and Johns Hopkins Civilian medical consultants to the Secretary of War held at Westover Air Force Base (112th Air Force) in Massachusetts. A followup meeting was held at Westover Field on Jan. 11, 1945 at which progress in conducting the NRI research program was reviewed, since the Navy research on NRI was just getting started in early 1945. In a memo to the Navy Surgeon General dated Jan. 11, 1945 from a Capt. Adams of the Navy Department, it was mentioned that: "Out of 2393 [airmen] examined [at Westover] , 982 have received radium therapy, 799 were treated prophylactically, and 183 therapeutically... ....Statistical study is underway to evaluate this prophylactic work. All aviation personnel are screened and divided into two groups: (1) positive lymphoid tissue, and (2) negative lymphoid tissue. One half of the positive group receive irradiation and one-half do not......This study should result in a true evaluation of the efficacy of this therapy."

This is clearly a controlled biomedical experiment that was not described in the published journal article about the AAF Otitis Media that includes at least another 799 airmen. The format and content of the Annals, 1945 journal article is such that the entire 6,881 AAF personnel given radium therapy should have been carried by ACHRE as subjects of a human radiation experient in the Final ACHRE report.

d) Achre Statement: Adult military personnel who participated in trials of this procedure received significantly lower radiation exposures, did not attain our arbitrary 1/1000 criterion for risk....(p. 843)

Known Facts of Matter: According to a study of experimental use of radium on submariners [Haines, 1946], submariners treated in Project X-434 received from 2 to 8 bilateral treatments with a 50 mg. radium irradiator. The likely average number of irradiations is 4 bilateral irradiations. Each Navy experimental treatment lasted from 8 to 10 minutes in duration per side, or 32 to 40 minutes of radium exposure, delivered bilaterally. The average protocol for treatment of children studied by Sandler, 1982 was 3 twelve minute irradiations, or 36 minutes duration bilateral exposure. Thus submariners and children treated experimentally received approximately the same radiation dose and the only difference in long term risk is that related to differences in radiation relative risk (Risk/Rad) which the ACHRE consultants cite as being about a factor of 2. Given that the risk (overall head and neck cancers) derived by ACHRE for children based on a simplistic bounding calculation (8.4/1000), and ACHRE claimed (but undocumented) a factor of two relative risk for children over adults for cancers of the head and neck according to Dr. Webster, the derived ACHRE excess risk of cancer to the head and neck for submariners should be from 3.7/1000 to 4.7/1000 not less than 1/1000 as claimed in the ACHRE final report.

If the BEIR-V epidemiologically derived excess risk of brain cancer based on the Sandler, 1980 study is used [Brain cancer excess for NRI treated children = 1/7,400 per PY of follow-up times 65 years of remaining life = 8.8/1000 - see National Research Council, 1990] the excess brain cancer risk alone for submariners would be one-half of about 8.8/1000 x 50/65 to adjust for the 50 years of remaining life for a submariner treated at age 20 vs. 65 years of remaining life for a child treated at age 9 [as in the Sandler, 1982 study]. With these adjustments, this equates to an excess lifetime brain cancer risk of 3.4/1000 in NRI treated adults alone based on present epidemiological evidence for NRI irradiation risk as the procedure was performed in the US.

Similarly for the Army Air Force experimental aerotitis control program, the published report (Annals, 1945) notes that 1,562 Army Air Force aviators treated with NRI at Westover Field received a total of 5,065 NRI treatments, or an average of 3.24 bilateral treatments per aviator. At Westover, as at other AAF bases, bilateral irradiations were initially of 6 min 40 sec duration and after some 6 months were increased to 8 min 30 seconds based on input from Johns Hopkins researchers. Assuming an average NRI irradiation duration over the lifetime of the Westover experiment at the average of the above two durations, or 7.6 minutes, one can calculate the excess risk using ACHRE stated assumptions. As above, using the calculated ACHRE excess lifetime risk of cancer to the head and neck for children (8.4/1000), the lifetime risk of head and neck cancers for the 1,562 Westover airmen would be about 2.9/1000 not less than 1/1000 as claimed in the ACHRE final report. Using the BEIR-V summary of the Sandler, 1982 the excess lifetime brain cancer risk in treated AAF aviators would be 3.4/1000 in NRI as derived above for treated submariners based on present epidemiological evidence for NRI irradiation risk as the procedure was performed in the US.

As documented above, the ACHRE claim that: "Adult military personnel who participated in trials of this procedure received significantly lower radiation exposures, did not attain our arbitrary 1/1000 criterion for risk....(p. 843) is false for at least a total of 2,324 military personnel treated with NRI on an experimental basis (762 Submariners treated in New London by the Navy and 1,562 Aviators treated at Westover Field, by the Army Air Force).

e)Achre Statement: Nasopharyngeal irradiation, introduced by S. J. Crowe and J.W. Baylor of the Otological Research Laboratory at Johns Hopkins, was employed from 1924 on as a means of shrinking lymphoid tissue..." (p. 352)

Known Facts of Matter: The Otological Research Lab at Johns Hopkins was established in 1924 but the first use of x-rays and radium/radon to treat hypertrophied lymphoid tissue around the eustachian tubes did not occur until about 1929 (see Crowe, 1939)

Epidemiological Evidence for Excess Health Risks From NRI

There is only one long-term study directed at the overall effects of nasal radium irradiation on health as practiced in the US (Sandler, 1980). While this one small study (following only 667 individuals, average age at exposure = 8.8, average years from exposure to follow-up = 25 years) is certainly not definitive, it is the only study that reflects exposure protocols as used in the U.S. The U.S. NRI exposure protocol reported in the Sandler, 1980 study delivered average radiation doses of from four to six times that used in the European use of NRI (see Verduijn, 1989) and discussion below.

This (Sandler, 1980) epidemiological study of children treated with NRI was carried out by the Johns Hopkins University (JHU), School of Public Health in 1978-79 under a U.S Public Health Service, Bureau of Radiological Health grant. The purpose of this study was stated to "be part of the rationale used in the development of Agency [Public Health Service, Bureau of Radiological Health] decisions regarding risks." (see Matanoski, 1980). This study documented an excess of brain cancer ( 5.3 fold excess, p=0.01; based on 3 brain cancer deaths observed, 0.57 expected per analysis by the National Academy of Sciences in its BEIR-V Report, plus one cancer death from cancer of the soft palate, or 17 x expectation- see Sandler, 1982 and National Research Council, 1990).

The ACHRE report (p. 354) mentions the published study by Verduijn, 1989 "of cancer mortality risk for those individuals (mostly children) treated by nasopharyngeal irradiation ....in the Netherlands..Specifically, the finding of Sandler et. al [Sandler, 1982] of an excess of head and neck cancer was not found in this study group." While the March 27, 1995 ACHRE staff memo to the ACHRE clearly mentioned that the Verduijn study involved much smaller radiation doses on average (Radium equivalent: 1198 mg-min vs. 4,208 mg-min in the Sandler, 1982 study) this important fact was not mentioned in the ACHRE report. The average NRI dose delivered to children in the Sandler, 1982 study of U.S. NRI use was 3.5 times higher on average than that of Verduijn, 1989. This is because, in the Netherlands, physicians were much more conservative in using radium nasal applicators on children due to concern about potential harm. Specifically, in the Netherlands as reported in the Verduijn, 1989 paper, NRI therapy employed 25 mg Ra-226 monel irradiators vs. 50 mg in the US, children under 16 were treated for a shorter period of time (7 min for 4 treatments vs. 12 min for 3 treatments in the U.S.) and unilateral (one nostril) vs. bilateral (both nostrils) irradiation as in the U.S. The largest number of patients studied in the Verduijn, 1989 study were children under 16 ( almost 90%) who would have generally received total radium 'dosage' equal to 700 mg-min (7 min x 25 mg x 4 treatments) six times less than delivered in the U.S. as studied and reported by Sandler, 1982.

Accordingly, the Verduijn, 1989 study is a very important lower-dose point of reference as to the potential harm from NRI in children but it certainly does not contradict the Sandler, 1982 study as implied by the discussion in the ACHRE Final Report. ACHRE's not including any radium exposure information comparison for the two extant epidemiological studies on this matter, could only confuse and mislead anyone reading their discussion as to what is the present basis for concern about NRI as practiced in the US.

Non-malignant Endpoints Related To NRI

A paper was delivered of the Sandler, 1980 study results of the JHU study at a BRH Symposium on Biological Effects held on June 6-8, 1979. This paper examined a variety of health outcomes as well as malignancies. This symposium presentation and unpublished paper documented an 8.6 fold excess (p = <0.001) of thyrotoxicosis (Graves disorder) a non-malignant thyroid disorder normally considered autoimmune in origin. This significant excess of thyrotoxicosis according to the authors may be related to irradiation of the pituitary gland and hormonal (TSH imbalance) control of the thyroid. The JHU School of Public Health authors (see Sandler, 1980, p. 23) summarize their findings as follows:

"The results of the study of the chronic effects from irradiation of adenoids suggests a significant excess risk of head and neck cancers, especially brain tumors. The increased incidence of thyrotoxicosis in the exposed population may have resulted from hormonal imbalance secondary to pituitary gland irradiation and should receive further study." [emphasis added]

The findings of non-malignant endocrine effects (Graves disorder, or thyrotoxicosis at an 8.6 fold Relative Risk) were never followed up by JHU researchers (or any other epidemiologists apparently) since the evidence for non-malignant health effects presented at the BRH Symposium in June 1979 due to NRI were never published in any journal. The ACHRE totally ignored any discussion of epidemiological evidence for health effects other than cancer related to NRI despite non-cancerous endpoints having been clearly found in the Johns Hopkins research and reported in the Sandler, 1980 presentation.

Existing Epidemiological Data For NRI Effects on Brain Cancer Mortality

Of the various health effects discussed in Sandler, 1980, only the data for malignant effects noted ended up being published as Sandler, 1982 in the Journal of the National Cancer Institute. Further, the JNCI article in its introductory Abstract described the excess of brain cancer noted in this study as:

"...a slight excess of brain cancer occurred 15-20 years after radium treatment."

Subsequently the National Academy of Sciences in its BEIR-V report (see National Research Council, 1990, p-310-312) reviewed the Sandler, 1982 data presented in the JNCI and judged it as representing a 5.3 fold Relative Risk in brain cancer mortality. While a 5.3 fold Relative Risk for brain cancer mortality as judged by the National Academy of Sciences BEIR-V Report seems anything but a "slight excess", the above excerpt from the Lead Abstract is what was published in the JNCI Abstract on the JHU research.

With this lead in the published Abstract, one could see how someone scanning the medical literature might miss the import of results of the Sandler, 1982 paper. However, there is no excuse for the ACHRE misinterpreting or ignoring the results of this one study of NRI effects on health, since the actual findings, and its later review by the National Academy of Sciences in its BEIR-V report were clearly presented to them in my Press Release of July 1, 1994, my Senate testimony of August 29, 1994, and in my letter to the ACHRE of March 8, 1995. Instead the ACHRE and its consultants merely chose to ignore, with no sound basis, the epidemiological data which does exist for potential health effects from NRI as employed in the US for a significant excess of brain cancer (more than twice as high as the risk value used by the ACHRE in arriving at its recommendations not to notify NRI treated experimental subjects) as well as strong evidence of non-malignant health effects due to NRI.

The ACHRE report mentioned but failed to make use of the only epidemiological data (based on epidemiological research performed at Johns Hopkins in 1978-79) for excess cancers observed in studying NRI children treated with the irradiation protocol as used in the US. This Sandler, 1982 published study is the basis for a lifetime risk to a treated child for excess brain cancer mortality (8.8/1000) about twice as high as the excess cancer risk derived by ACHRE consultants who employed a bounding risk calculation with simplistic assumptions.

As the BEIR-V committee report states (see National Research Council, 1990, p 311):

"Similarly, 3 of 904 patients treated with radium implants in the nasopharynx and followed for an average of 25 years after treatment were observed to develop brain [fatal] tumors versus none in 2,021 controls; on the basis of an estimated average dose to the brain of 0.15 -0.4 Gy [ 15 Rem to 40 Rem ] and an expectation of 0.57 brain tumors, the excess in this series has been calculated to range from 3.4 +/- 2.4 to 9.0 +/- 6.4 cases/10,000 PYGy for doses of 0.4 Gy and 0.15 Gy, respectively "

The above BEIR-V cited risk factors for NRI both equate to 1 'excess' brain cancer death per 7,400 PY Person-Years (PY) of follow-up if one is assessing the effect of an 'average' protocol (three 12 minute or four 10 minute bilateral nasal irradiations by a 50 mg monel irradiator, and the estimated average dose is factored out) only on brain cancer excess risk. If one multiplies the expected remaining years of life on average (assumed to be 65, for the cohort studied by the Sandler, 1982 study: average age at treatment = 8.8)) times the 1/7400 'excess' brain cancer death per 7,400 PY of follow-up a lifetime excess brain cancer risk to an NRI treated child is calculated to be 8.8/1000.

The ACHRE consultants' review of present epidemiological evidence for NRI health effects was included as Attachment 10 to the March 27, 1995 ACHRE Memo, RE: Nasopharyngeal Radium Treatment (a Memo to Ron Neuman from E. W. Webster, dated Aug. 6, 1994, Subject: S. Farber investigation of Nasopharyngeal radium applicators for treatment of aerotitits in military personnel"). Dr. E. W. Webster, a consultant to ACHRE produced a review that contained major inaccuracies and significant gaps in the history of NRI use on experimentally treated veterans. Dr. Webster's review included several ad hominem insults toward me, and not just a review of the facts or claims as they were presented. Dr. Webster mistakenly states based on not having carefully read the Submarine Survivors Group Press Release of July 1, 1994 which ACHRE had asked him to review that:

"The comparison by Farber of the number of brain cancers in the Navy/Air Force personnel with the total Japanese A-bomb cancer cases is laughable. His projection is ruled out by the A-bomb survivor study." (See Webster, 1994 memo, p. 3)

I never compared the total number of brain cancers predicted in 7,661 veterans treated with NRI with all cancers found in studying the Japanese survivors of Hiroshima and Nagasaki. Rather, the July 1, 1994 Press Release issued on NRI risk to experimentally treated veterans also included a brief discussion of the then estimated overall NRI treated U.S. population (not experimentally treated with NRI, but treated after NRI became 'standard clinical practice' after WW. II which I conservatively estimated at that time as numbering about 250,000 individuals) as follows:

"Based on the BEIR-V Report risk estimates citing a research report by The Johns Hopkins University, School of Public Health published in the Journal of the National Cancer Institute (Sandler, 1982), nasal radium irradiation is not just equivalent to a domestic Nagasaki up the nose of at least 250,000 Americans but actually is likely to exceed the excess cancer mortality from all causes seen among both the Hiroshima and Nagasaki A-bomb survivors"

The above is a completely factual statement yet it was ridiculed as "laughable" by Dr. Webster as an ACHRE consultant. Dr. Webster failed to understand the point being made. Whether one finds my making a point about potential excess cancers in a domestic NRI treated population of 250,000 individuals exceeding all excess cancers at Hiroshima/Nagasaki as "laughable" depends a great deal on one's sense of humor. The basic and still valid point is that if the excess brain cancers alone predicted in NRI treated children per the Sandler, 1982 study as summarized by the National Academy of Sciences in its BEIR-V report in terms of a 5.3 fold Relative Risk (see National Research Council, 1990, p-310-312) are valid, it would equate to more excess brain cancer deaths for any size cohort of NRI treated children than there would be excess cancers of all sites predicted among an equal population of atomic bomb survivors of Hiroshima/Nagasaki followed for the same period of time. This is not an extrapolation, it is not hyperbole, it is a simple statement of the facts as we presently know them, using NAS risk factors for NRI and published excess cancers among Hiroshima/Nagasaki survivors.

The Press Release I prepared on July 1, 1994 on the NRI issue, quoted an estimate of 250,000 NRI clinically treated individuals in the general population. The CDC in Sept. 1995 released its first estimate that between 509,000 and 2,600,000 individuals received NRI treatments from 1945 to 1961 as "standard clinical practice". The "most likely" number of individuals in the general population treated with NRI is about 1,000,000 individuals (mostly children, average age about 9) about four times the 250,000 NRI treated individuals in the US carried in the July 1, 1994 Press Release. Overall, the "most likely" NRI treated population in the U.S. is about 12 times larger than the Hiroshima/Nagasaki Life Span Study cohort and the overall health effects may be proportionately larger.

The referenced review by Webster, and the dose calculations and risk assessments performed by Webster for both adults and children for the ACHRE became the basis for much of ACHRE's discussion of NRI in the Final Report which recommended no notice and no follow-up of any NRI treated experimental cohorts.

POINT 3 - ACHRE no notice/no follow-up Recommendations on NRI Experimental Cohorts without merit

The ACHRE justification of no notice/no follow-up for any living group of experimental subjects has been widely criticized by many citizens and scientists who have followed the ACHRE process. This review provides documentation that the manner in which the ACHRE handled its review of Nasal Radium Irradiation (NRI) Human Radiation Experiments in particular in the Final Report represents a clear and gross failure of the ACHRE to meet its obligations under Executive Order #12891 of Jan. 15, 1994. ACHRE's actions in the case of NRI experiments represents a failure of process to deal with a real risk to group of over 8,000 NRI experimental subjects who have a right to know they were part of several different NRI human radiation experiments funded by the DOD and NIH.

A recent feature review article: "The Verdict: No Harm, No Foul" from The Bulletin of the Atomic Scientists for Jan/Feb 1996 provides a good overview of the ACHRE final report and gives prominent mention to the Radium Experiment Assessment Project which I have organized on behalf of NRI treated individuals. As noted on p. 35 of the Bulletin feature article:

"The [ACHRE] concluded that to be eligible for medical notification from the government, a person must have an increased lifetime risk of dying from radiation-induced cancer of more than one in 1,000.....[Only] One group exceeded this level of risk.

Part IV (Addendum to Rec. 4: Medical Notification And Follow-Up") of the ACHRE Final Report:

"For the children who received nasopharyngeal radium treatments, the Advisory Committee has estimated that the lifetime risk of tumors to the central nervous system (brain), head, and neck regions is approximately 4.35/1,000 [NOTE: See discussion below as to this being the ACHRE lifetime risk for brain cancer alone due to an error by ACHRE]....However, at greatest risk are the brain, and head, and neck tissues, for which there is neither an accepted nor recommended screening procedure. Thus, while the subjects in these experiments meet the Advisory committee's arbitrary 1/1,000 criterion for consideration for notification and medical follow-up, the utility of such a program has not been demonstrated, ...Therefore, the Advisory Committee does not recommend notification and medical follow-up of children or adults in this group of experiments."

Between half a million and 2.3 million schoolchildren throughout the country, according to the Centers for Disease Control and Prevention, were part of nasal radium experiments or received these treatments between 1945 and 1965 for ear and adenoid infection [emphasis added]...Using these numbers, Stewart Farber, a consulting scientist and organizer of the Radium Experiment Assessment Project, concluded that between 2,368 and 10,241 people would die of cancer from this exposure."

How did the ACHRE reach its decision not to notify over 8,000 experimentally treated NRI veterans and children?

As mentioned above, the supposed technical basis, and almost all text for the ACHRE Final Report discussion of NRI came largely from the March 27, 1995 memo from the ACHRE staff to the Advisory Committee on Human Radiation Experiments "RE: Nasopharyngeal Radium Treatment", dated March 27, 1995, a 5 page memo plus 13 Attachments. This memo was described by the ACHRE staff as a "capsule description of the issue as Staff presently understands it" for a planned discussion of NRI treatments by the ACHRE at the April 1995 Committee public meeting in response to my letter to ACHRE of March 8, 1995. This public discussion never occurred because the ACHRE tabled discussion of NRI at several subsequent meetings for unexplained reasons.

However, this March 27 ACHRE memo, with two major exceptions, became the source of the final text of the review of nasopharyngeal irradiation published in the Final ACHRE report. The first exception was the deletion of any mention of the Feb. 23, 1994 Navy memo discussed under Point 1 admitting that initial use of NRI on submariners was a human radiation experiment. The second exception was a deleted statement by Dr. Eli Glatstein, one of 14 members of the ACHRE. Dr. Glatstien was the most experienced radiation oncologist on the ACHRE (formerly Chief of Staff of Radiation Oncology at NCI/NIH) and at the time Chair of the Department of Radiation Oncology, University of Texas, Southwestern Medical Center at Dallas. The March 27, 1995 ACHRE memo states that: "According to Dr. Eli Glatstein, medical monitoring of military personnel given nasopharyngeal radium treatments is a must:

"I think there is no question that these individuals need to be monitored. I am not sure we can 'protect their health', but they should be monitored to see if there is any substantive problem that results from their exposure."

However, this unambiguous statement by Dr. Eli Glatstein was conspicuously absent from the Final ACHRE Report. The reasons for Dr. Glatstein's views having been excluded are discussed below in the section: "lack Of Notice To NRI Experimental Subjects - A Political Decision?"

Further, in early September, I received a DRAFT copy of the ACHRE Final Report on September 1, 1995 when it was FAXed to me by Dr. Duncan Thomas, another member of the ACHRE. Dr. Thomas had asked me to review the NRI discussion and to: "Please send a copy of any comments to ...the ACHRE office". After briefly reviewing the Sept. 1, 1995 draft sections on NRI, I told Dr. Thomas that the methodology employed by the ACHRE consultants in calculating the average dose and risk of the NRI procedure on children was meaningless. At that time ACHRE's consultant had calculated an excess lifetime cancer risk to the head and neck as 1.2/1000 which still exceeded their arbitrary criterion for notice of 1/1000. When I told Dr. Thomas of some of my criticisms of the reports shortcomings on NRI, in particular the dose calculation and risk, he asked if I could just try and "clean it up" by offering some constructive suggestions for wording. I told Dr. Thomas, that I had brought the technical facts of the NRI issue to the attention of the ACHRE and it was not my job to clean up the mess they had created in their review and in large part dismissal of the information I had presented. I was not an ACHRE consultant but a public health scientist trying to see that an important public health issue get the attention it deserves. Apparently my criticisms of the ACHRE consultant's dose calculations and risk methodology had some impact because the risks of NRI were significantly revised upward before the Final Report was issued on Oct. 3, 1995.

due To ACHRE Error, Lifetime Risk Of Head And Neck Cancers Underestimate By Factor Of 1.9

However, it appears that the ACHRE juggled so many assumptions in trying to modify their discussion of the NRI excess lifetime "head and neck" and "brain cancer excess risk" and "organ specific relative risk" between Sept. 1, 1995 and the Final Report, and their discussion of NRI was scattered over so many sections of their unindexed Final Report that they confused even themselves. As noted in the Introduction to this testimony, the ACHRE Final Report discussion of NRI "head and neck lifetime cancer risk", vs. "brain cancer risk" is totally in error. By mistake, ACHRE carried forward its calculated lifetime risk estimate for brain cancer alone, mistakenly stating (see p.843, Medical Notification and Follow-Up, Final Report) that "the lifetime risk of tumors to the central nervous system (brain), head, and neck is approximately 4.35/1000.." when by their own calculations (p. 355, Footnote o) the correct number for all cancers of the head and neck is 8.4/1000. Accordingly ACHRE's entire discussion and justification for no notice/no follow-up for NRI experimental subjects is based on a transcription error by ACHRE and has to be revised upward by a factor of 1.93. The Table below attempts to summarize the lifetime cancer factors since this is a key point in the final recommendations put forward by ACHRE about NRI.

Table 1

Calculated Lifetime Risk of Cancer due to NRI Treatment in Children (ACHRE Calculations vs. Epidemiological Data For U.S. Protocol)

ACHRE's entire discussion and rationalization of no notice/no follow-up for NRI experiments is based on an error by ACHRE staff in carrying forward their own risk estimates from Chapter 7 to Part IV, Addendum to Recommendation 4: Medical Notification and Follow-Up (See Table 1 above). The ACHRE stated "... lifetime risk of tumors to the central nervous system (brain), head, and neck" is 8.4/1000 per ACHRE's calculations and not "approximately 4.35/1000.." as the Final Report states. Accordingly, ACHRE's recommendations on NRI have to be revised by the Interagency Working Group to reflect this error by the ACHRE staff carried over to the Final Report. The ratio of 8.4/4.35 = 1.93 is the multiplier by which any of the "lifetime risk of tumors to the central nervous system (brain), head, and neck regions" listed in the Final ACHRE report (see p. 842-843) must be adjusted. As noted in the earlier discussion, it appears that at least 8,000 NRI treated veterans and children treated experimentally need to be provided medical notice and follow-up based on the above corrected risk estimates.

LACK OF NOTICE TO NRI EXPERIMENTAL SUBJECTS - A POLITICAL DECISION?

Shortly after receiving the Sept. 1, 1995 ACHRE Draft Final Report, I reviewed its recommendation for no notice and no follow-up of any NRI treated cohorts with the American Brain Tumor Coalition in Chicago. I sought their expert medical opinion on whether the ACHRE recommendations in the face of a finding of elevated brain cancer risk for NRI treated individuals were defensible. The ABTA had its Medical Advisor and Board Member, Dr. Lorraine Marin, a radiation oncologist who trained under Dr. Glatstein (when he was Chief of Staff of Radiation Oncology at NIH/NCI during the 1980s) call me. Dr. Marin and I had a long conversation in mid- September 1995 and discussed the ACHRE recommendations as they existed at that time. After I reviewed the ACHRE draft findings with Dr. Marin, she asked me in disbelief to review who were the medical members of the ACHRE. She expressed surprise an expert panel would recommend no notice and no follow-up given the facts of the NRI situation. She recommended that I call Dr. Glatstein and ask him to reconsider the recommendations that were out in draft form because if they were issued as they were presently worded, the North American Brain Tumor Coalition would likely eventually criticize the findings as not being based on sound medical and scientific knowledge.

I called Dr. Glatstein on Sept. 18, 1995 and told him of my discussion with Dr. Marin and her advice that we discuss the pending ACHRE Recommendations on NRI. Dr. Glatstein and I first reviewed the quote which was attributed to him noted in the March 27, 1995 ACHRE Staff memo (..."medical montoring of military personnel given nasopharyngeal radium experimental treatments is a must...", see p. 20 above) He told me the ACHRE staff memo quoted him accurately and that this was his expert opinion. When I asked him why none of this expert opinion was mentioned in the final ACHRE Draft, he said he was "outvoted" by the other 13 ACHRE Committee members 13-1. I then asked him what was the basis for all other members of ACHRE voting against him given that he clearly as the most experienced Radiation Oncologist and Physician member of the ACHRE.

Dr. Glatstein candidly responded, as to basis, that the other 13 ACHRE committee members did not return a recommendation to notify this many individuals of risk [over 8,000 NRI experimental subjects] because:

"it was not salable in today's political environment". [emphasis added].

I was totally amazed by Dr. Glatstein's candor as well as incredulous as to the failure of process documented by this admission regarding ACHRE and its mandate. I remember telling Dr. Glatstein that his statement was shocking and that the ACHRE process was supposed to bring medicine, science, and ethics to bare on righting past wrongs about radiation experiments carried out by the U.S. Government. I asked him why given his written quote about the need for monitoring of NRI exposed experimental subjects mentioned in the March 27, 1995 ACHRE memo, he did not feel the obligation to file a minority report. Dr. Glatstein's responded as follows:

"Mr. Farber, you have to remember the ACHRE committee members were appointed by the President and it's not considered polite to make waves."

I closed my conversation with Dr. Glatstein on Sept. 18, by mentioning that Dr. Marin of the North American Brain Tumor Coalition had indicated that if the ACHRE did not change its recommendations not to notify individuals who might be at risk of brain cancer of the need for medical follow-up, the North American Brain Tumor Coalition would likely (based on Dr. Marin's general comments to me) eventually issue a criticism of the ACHRE findings. Dr. Glatstein's replied: "that we probably deserve it".

Subsequent to the above discussion with Dr. Glatstein, Dr. Marin was quoted in a news article which appeared the day after the ACHRE Final Report was issued [see The (Baltimore) Sun, October 4, 1995, "Treatment linked to cancer risk - Hopkins pioneered method - But U.S. board recommends against notification"] in which she says that people who know they had the [NRI] treatment should tell their physicians so a closer examination of the head and neck area can be done during checkups. However, without any kind of general advisory by the Federal Government through DOD, VA, or CDC to at risk individuals, consisting of an accurate statement advising NRI treated individuals they are at risk, and notifying them of symptoms that might be related to conditions potentially linked to NRI, how are these individuals going to know they are at risk? The U.S. Government clearly has unmet obligations to experimentally treated NRI cohorts reviewed by the ACHRE.

In addition the American Brain Tumor Association and the National Brain Tumor Foundation are on record that many brain tumors, if caught early, are curable? [emphasis added] [see New York Times, July 5, 1995, "Brain Tumors: More Curable But More Numerous" by Jane E. Brody].

CONCLUSIONS

The facts as they are presently known indicate that the decision making process engaged in by ACHRE in the case of NRI risk and notification recommendations was a fraud. Decisions appear to have been made in advance of an honest review of the facts of each experiment that led to the process being corrupted. ACHRE's actions (and its omissions) on the NRI issue clearly document bad science, bad medicine, and bad ethics at work.

The cited reasons for ACHRE's decision for no notice/no follow-up of the NRI cohorts are found on examination to be either irrelevant or incorrect. The reasons for this failure of process are beyond the scope of this review. However, information as it presently exists suggests an effort to misrepresent, ignore, or even suppress information on the issue.

This review has also documented that for NRI experiments, ACHRE made major technical errors in using its own limited lifetime cancer risk estimates and carried forward incorrect values from Chapter 7 to the Addendum to Recommendation 4: Medical Notification and Follow-Up. All "lifetime risk of tumors to the central nervous system (brain), head, and neck" used by ACHRE must be increased from 4.35/1000 to 8.4/1000. These errors in lifetime risk factors invalidate the recommendations made by ACHRE regarding medical notification. ACHRE's recommendations on NRI have to be completely rewritten because of their error.

A Press Release issued by the ACHRE on Oct. 3, 1995 include statements by Dr. Ruth Faden, chair of the committee that stated:

"governmental officials kept the truth about the [past] experiments from the subjects and their families, as well as the public.....What most troubled the Committee was the lack of respect for the American people that seemed to permeate the conduct of research....It is clear that federal officials involved in radiation research were managing the release of information to make sure that the public image of the nuclear enterprise would be positive. In some cases, this amounted to deception and withholding of the truth, which the Committee found deeply troubling."

However, the above general criticisms of past failures by U.S. Government bureaucrats or medical institutions involved in government sponsored human radiation related research raised by the ACHRE chairperson could just as well be said of today's behavior of the ACHRE and its consultants in regard to its review and recommendations related to NRI. The ACHRE failure to recommend medical notice or medical follow-up of experimental cohorts of NRI treated individuals to a large degree discredit the entire DOE Openness Initiative and the mandate of the Executive Order which organized ACHRE.

The Openness initiative begun by DOE Sec. Hazel O'Leary in late-1993 has provided unprecedented declassification of records and access by the public to information throughout the Government. However, after selectively sifting through these documents, the ACHRE appears to have been unable to make some hard decisions and some embarrassing recommendations, perhaps because of biases by the committee members based on fears of adverse publicity or financial liability for their parent medical institutions. ACHRE actions on NRI do not appear to be so much a blatant cover-up by the U.S. Government (although pressure from the DOD may have led the ACHRE to delete certain references to incriminating Navy memos and Air Force NRI experimental scope from the Final Report) but a failure of the private individuals who made up the ACHRE.

Makeup of the ACHRE Panel - Deficient

The ACHRE did not include a single citizen stakeholder for any human radiation experimental cohort(s). The ACHRE also failed to include any independent scientists or physicians without institutional allegiances potentially compromised by their parent organization's past involvement in human radiation experiments. Accordingly, it was all too easy for the ACHRE to gloss over any experiments that could impact the medical establishment given the collegial makeup of the ACHRE.

The above review indicates that the Federal government has failed to meet its obligations regarding the identification and medical surveillance of NRI experimentally treated military and civilian cohorts . The Interagency Working Group must review and correct the errors made by ACHRE in regard to NRI risks and the Medical Notice and Follow-Up recommendations. Under the ethical format established by the ACHRE Final Report, over 8,000 NRI subjects are likely to deserve a formal written apology from the U.S. Government and financial compensation to the experimental subjects or their surviving family members.

At a bare minimum, the DOD, VA, and CDC owe more than 8,000 experimental subjects an accurate, comprehensive advisory of potential health risks. The DOD and VA have got to cease putting out inaccurate statements about the history of NRI and the status of veteran service records documenting NRI exposure. Those individuals who display symptoms that may be broadly linked to NRI experimental use should be provided proper examinations by either the VA or private physicians, as appropriate at Government expense. These actions are long overdue.

Any further failure by the U.S. Government to act on the NRI experimental issue highlights the deficiencies in ACHRE intent and indicts the entire process by which radiation risks to individuals exposed as a result of government sponsored experimentation was supposed to have been handled. The blatant errors on NRI made by ACHRE must be promptly corrected, in order that ACHRE actions are not to make a complete mockery of its mandate and its obligations to the U.S. Government.

Quality Control Review Needed On Final ACHRE Report

Lastly, as a quality control measure, a cross section of key findings and recommendations of the ACHRE must be reviewed by impartial third parties to determine if any other substantial technical and judgment errors similar to those which invalidate the NRI decisionmaking process, affected any other human radiation experimental issues reviewed by the ACHRE.

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