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Agent orange and its associated dioxin: assessment of a controversy
321
TXL02194
Book Review
_
Agrtzt Ortrtgc~ and Its Associated Dioxin: Assessment qf’u Controversy, A.L. Young and G.M. Reggiani (Eds.), Elsevier, Amsterdam, 1988, 344 pp. Price: Dfl. 250. ISBN o-444-80980-5. The topic of dioxin toxicology has been an interest of mine for over a decade. This excellent book about Agent Orange and dioxin provides a wonderful, but sometimes depressing review, combining critical elements of science, history. and human nature. It is written to be understood by an intelligent lay audience, but it has data, science. and meat enough to satisfy the knowledgeable expert. The stated purpose of the book is to try to lay the current Agent Orange controversy to rest. It is problematical whether this is at all possible, but the book is very useful in that it gathers so much of the available information into one source. People from all sides of the political spectrum will agree that the Vietnam War was one of the most destructively divisive events in the history of the United States. Driven by fears of service-related toxic injuries to Vietnam veterans. a recent fallout from the war has been the controversy over the medical consequences of the use of Agent Orange as a tactical defoliant. In the introductory chapter, the editors argue that the ‘overwhelming scientific data on the toxicology of chemical components in Agent Orange do not substantiate these claims (of injury)‘. However, ‘intense sympathetic coverage’ has been given by the news media to the complaints of the veterans. Large amounts of time, effort, and money have been spent in investigating the claims. The editors feel the controversy has been fueled by the dual controversies over the military use of herbicides, and about military service, itself. in Vietnam. From previously classified information, Chapter 2 provides an extensive description of the use of herbicides in Vietnam. The nomenclature and recipes for several different defoliant mixtures are described. The great difficulty in verifying the degree of any given individual’s exposure to these herbicides is also discussed. Hence, one of the most necessary ingredients for reliable epidemiological studies about the effects of Agent Orange exposure is not available. The third chapter is concerned with a historical overview of the Agent Orange controversy. The chapter is divided into two parts: the first, before we knew about dioxin as a contaminant in certain defoliants, and the second, after dioxin was discovered. The public was introduced to dioxin through the accident at Seveso, Italy. I remember the hysterical media coverage. This example is from the August 16, 1976, issue of Time magazine: ‘. . . Farmyard chickens dropped dead, wild birds fell from trees, mice and rats crawled out of their holes and died. One farmer saw his cat keel 037%4274~89~$3.50
(‘ 1989 Elsevier Science Publishers
B.V. (Biomedical
Division)
over. and Lvhen he went to pick up the body, the tail fell off. When the authoritlc\ dug the cat LIP for examination two days later. said the farmer, all that was left XI\ its skull’. Within u year, the Sekeso event was (un)popularircd in .lohn <;. FulIc~~‘\ T/X, Poi.s0/7 7‘l1rr/ FP// FUMJ~ 7‘11~%.I, (Random House. New York. 1977) which bccame available as ;t R~tkr’.~ Di,qc~.stcondensation. Young and Reggiani provide an extensive catalog ol‘dioxin-rclatcd industrial accidents and their toxicological sequelae. The Seveso accident is part of thih covcragc. The studies pcrformcd by the Vctcrans’ Administration. the EPA. and the Intcragency Work GI-OLIN of the federal government are reviewed. I-‘rom all of the documented human exposures. fl~c,.cj \\‘(J~‘ootil~\~ tlir.w cotlsisfc~lt :o.~-i~~ologic~ol /iiu//ii,q\ Chloracne usually occurred. there wcrc frequent liver disturbances. and there ~vas ;III occasional peripheral neuropathy. The third chapter also describes a change in the scientific perception of risk that occurred following the discovery that dioxins are everywhere and occur as natural phenomena resulting from ‘trace chemistries of fire’. Table 31 in the chapter dctailk the evolution of the risk perception: ‘I 970 1980
There Since detect place
is no such thing as a safe exposure to any amount of ;I carcinogen these chemicals are widespread in the environment and since WC’L;LI~ them down to very low levels. we must assume that lift no\% take\ in a minefield of risks from perhaps thousands of substances.‘
In no manner is the latter sentiment universally accepted. but it is coming to in more and more so. It follows that having developed in such a hostile envIronmen[. organisms must have developed biological protections against such toxic agents. 1hc public needs to bc educated about these newer. more balanced concepts. At the same time, the pendulum must not be allowed to swing too far toward the lack of attention to toxicological hazards. Chapter 4 is a review of the dioxin animal data. In addition. there IS a discussIon of the problems and ambiguities associated with carcinogcncsis data. The conseiI>uh is that much of dioxin cellular toxicity correlates with the ability to induct atylhydr-ocarbon hydroxylase activity. The possible consequences of this are described. Chapter 5 is a pivotal chapter in this book. It deals with the epidemiology ot.Agcn! Orange and dioxin. One of the things about which there is no doubt is that dioxin is one of the most toxic chemicals known. However. humans as a spoc~es are high;) resistant to its most alarming effects. ‘The traditional difliculties in transitioning flroi>; the animal laboratory to the human laboratory have been compounded bq the progressive array of special interest groups. media representation. legal action. congrebsional interest. and finally. legislative compensation.’ This chapter is a primer on the principles and problems associated with epidemiological research, and describes wh! science has been unable to answer questions of causality of human injury with dioxin One of the major critical problems is that in cases where there has been so much
323
media coverage.
‘respondent
bias to the exposure
circumstance
may well exceed the
correction capacity.. ‘. The next two chapters describe the literature and concerns linking Agent Orange exposure in Vietnam to development of soft tissue sarcoma. Concerns with toxic injury to war veterans have been expressed not only in the United States. but also in Australia. Chapter 7 deals with the Australian Royal Commission’s inquiry into dioxin’s cancer causality. In particular, the publications of the Swedish investigators, Olav Axelson and Lennart Hardell (whose studies have been the major ones used to imply a connection between Agent Orange and soft tissue sarcoma), were reviewed. In a very uncompromising manner, these studies were concluded to prove no causal association because of . . absence of replication, the absence of specific outcome (i.e.. 12 types of soft tissue sarcoma. non-Hodgkin’s malignant lymphoma and Hodgkin‘s disease). admitted information bias. the presence of significant confounding factors. the unreliability of the exposure data.. ‘. The book reports similar conclusions about these studies from recent United States litigations. Chapter 9 deals with the political dimensions of the Agent Orange controversy, and Chapter IO provides a social assessment of the problem. The latter chapter is constructed upon the concepts that we are too frequently calling upon epidemiology ‘to investigate questions that may not be answerable’, and that ‘society must deal scparately with the social and scientific problems associated with Agent Orange’. Chapters I I. 12. 13, and I4 are extensive case studies covering dioxin episodes and responses to those episodes in Missouri, Seveso. Michigan, and Australia. The chapter on Seveso is useful, given the notoriety of the incident. The Michigan story is also instructive. Following a history of failure of the legislature and public universities in Michigan to respond effectively and appropriately to a large polybrominated biphenyl exposure incident in cattle, their recent ability to respond to a dioxin scare was laudable. In Chapter 14. the Australian Royal Commission is extolled as an excellent example of how a judiciary can deal with such complex issues. There is no question in my mind that we owe much freedom in the United States to the continued existence of free and skeptical news media. Recent political events certainly confirm this. Given human nature, however, a balance must be maintained between freedom and license, one of the most difficult problems that faces a free society. The following paragraph from the concluding chapter, perhaps. is a good summary of the history and problems
associated
with Agent Orange
and dioxin:
‘Emotional role-playing by the national news media has had tragic consequcnccs for the American and Australian people in a number of ways. It has undermined national unity and morale by promoting unfounded fears of a cancer epidemic. of increases in the number of children born with defects, and misguided ideas of a ‘risk-free’ society. The loss of perspective in this issue has led to irresponsible and unwarranted action. e.g., prohibition or restriction of the use of herbicides in
agriculture. But, perhaps the most serious consequence of the intense media campaign has been its negative impact on Vietnam veterans. many of whom have ken led to believe that Agent Orange and dioxin adversely afTecLed their health and the lives of their children. The emotional impact of this fear campaign on the veteran and his family has been sevcrc.’
Division
Alan B. C’ombs, Ph.1). of Pharmacology and Toxicolog College of Pharmacy The University of Texas at Austin Austin, TX 787 I? IJ.S.A.
TXL02194
Book Review
_
Agrtzt Ortrtgc~ and Its Associated Dioxin: Assessment qf’u Controversy, A.L. Young and G.M. Reggiani (Eds.), Elsevier, Amsterdam, 1988, 344 pp. Price: Dfl. 250. ISBN o-444-80980-5. The topic of dioxin toxicology has been an interest of mine for over a decade. This excellent book about Agent Orange and dioxin provides a wonderful, but sometimes depressing review, combining critical elements of science, history. and human nature. It is written to be understood by an intelligent lay audience, but it has data, science. and meat enough to satisfy the knowledgeable expert. The stated purpose of the book is to try to lay the current Agent Orange controversy to rest. It is problematical whether this is at all possible, but the book is very useful in that it gathers so much of the available information into one source. People from all sides of the political spectrum will agree that the Vietnam War was one of the most destructively divisive events in the history of the United States. Driven by fears of service-related toxic injuries to Vietnam veterans. a recent fallout from the war has been the controversy over the medical consequences of the use of Agent Orange as a tactical defoliant. In the introductory chapter, the editors argue that the ‘overwhelming scientific data on the toxicology of chemical components in Agent Orange do not substantiate these claims (of injury)‘. However, ‘intense sympathetic coverage’ has been given by the news media to the complaints of the veterans. Large amounts of time, effort, and money have been spent in investigating the claims. The editors feel the controversy has been fueled by the dual controversies over the military use of herbicides, and about military service, itself. in Vietnam. From previously classified information, Chapter 2 provides an extensive description of the use of herbicides in Vietnam. The nomenclature and recipes for several different defoliant mixtures are described. The great difficulty in verifying the degree of any given individual’s exposure to these herbicides is also discussed. Hence, one of the most necessary ingredients for reliable epidemiological studies about the effects of Agent Orange exposure is not available. The third chapter is concerned with a historical overview of the Agent Orange controversy. The chapter is divided into two parts: the first, before we knew about dioxin as a contaminant in certain defoliants, and the second, after dioxin was discovered. The public was introduced to dioxin through the accident at Seveso, Italy. I remember the hysterical media coverage. This example is from the August 16, 1976, issue of Time magazine: ‘. . . Farmyard chickens dropped dead, wild birds fell from trees, mice and rats crawled out of their holes and died. One farmer saw his cat keel 037%4274~89~$3.50
(‘ 1989 Elsevier Science Publishers
B.V. (Biomedical
Division)
over. and Lvhen he went to pick up the body, the tail fell off. When the authoritlc\ dug the cat LIP for examination two days later. said the farmer, all that was left XI\ its skull’. Within u year, the Sekeso event was (un)popularircd in .lohn <;. FulIc~~‘\ T/X, Poi.s0/7 7‘l1rr/ FP// FUMJ~ 7‘11~%.I, (Random House. New York. 1977) which bccame available as ;t R~tkr’.~ Di,qc~.stcondensation. Young and Reggiani provide an extensive catalog ol‘dioxin-rclatcd industrial accidents and their toxicological sequelae. The Seveso accident is part of thih covcragc. The studies pcrformcd by the Vctcrans’ Administration. the EPA. and the Intcragency Work GI-OLIN of the federal government are reviewed. I-‘rom all of the documented human exposures. fl~c,.cj \\‘(J~‘ootil~\~ tlir.w cotlsisfc~lt :o.~-i~~ologic~ol /iiu//ii,q\ Chloracne usually occurred. there wcrc frequent liver disturbances. and there ~vas ;III occasional peripheral neuropathy. The third chapter also describes a change in the scientific perception of risk that occurred following the discovery that dioxins are everywhere and occur as natural phenomena resulting from ‘trace chemistries of fire’. Table 31 in the chapter dctailk the evolution of the risk perception: ‘I 970 1980
There Since detect place
is no such thing as a safe exposure to any amount of ;I carcinogen these chemicals are widespread in the environment and since WC’L;LI~ them down to very low levels. we must assume that lift no\% take\ in a minefield of risks from perhaps thousands of substances.‘
In no manner is the latter sentiment universally accepted. but it is coming to in more and more so. It follows that having developed in such a hostile envIronmen[. organisms must have developed biological protections against such toxic agents. 1hc public needs to bc educated about these newer. more balanced concepts. At the same time, the pendulum must not be allowed to swing too far toward the lack of attention to toxicological hazards. Chapter 4 is a review of the dioxin animal data. In addition. there IS a discussIon of the problems and ambiguities associated with carcinogcncsis data. The conseiI>uh is that much of dioxin cellular toxicity correlates with the ability to induct atylhydr-ocarbon hydroxylase activity. The possible consequences of this are described. Chapter 5 is a pivotal chapter in this book. It deals with the epidemiology ot.Agcn! Orange and dioxin. One of the things about which there is no doubt is that dioxin is one of the most toxic chemicals known. However. humans as a spoc~es are high;) resistant to its most alarming effects. ‘The traditional difliculties in transitioning flroi>; the animal laboratory to the human laboratory have been compounded bq the progressive array of special interest groups. media representation. legal action. congrebsional interest. and finally. legislative compensation.’ This chapter is a primer on the principles and problems associated with epidemiological research, and describes wh! science has been unable to answer questions of causality of human injury with dioxin One of the major critical problems is that in cases where there has been so much
323
media coverage.
‘respondent
bias to the exposure
circumstance
may well exceed the
correction capacity.. ‘. The next two chapters describe the literature and concerns linking Agent Orange exposure in Vietnam to development of soft tissue sarcoma. Concerns with toxic injury to war veterans have been expressed not only in the United States. but also in Australia. Chapter 7 deals with the Australian Royal Commission’s inquiry into dioxin’s cancer causality. In particular, the publications of the Swedish investigators, Olav Axelson and Lennart Hardell (whose studies have been the major ones used to imply a connection between Agent Orange and soft tissue sarcoma), were reviewed. In a very uncompromising manner, these studies were concluded to prove no causal association because of . . absence of replication, the absence of specific outcome (i.e.. 12 types of soft tissue sarcoma. non-Hodgkin’s malignant lymphoma and Hodgkin‘s disease). admitted information bias. the presence of significant confounding factors. the unreliability of the exposure data.. ‘. The book reports similar conclusions about these studies from recent United States litigations. Chapter 9 deals with the political dimensions of the Agent Orange controversy, and Chapter IO provides a social assessment of the problem. The latter chapter is constructed upon the concepts that we are too frequently calling upon epidemiology ‘to investigate questions that may not be answerable’, and that ‘society must deal scparately with the social and scientific problems associated with Agent Orange’. Chapters I I. 12. 13, and I4 are extensive case studies covering dioxin episodes and responses to those episodes in Missouri, Seveso. Michigan, and Australia. The chapter on Seveso is useful, given the notoriety of the incident. The Michigan story is also instructive. Following a history of failure of the legislature and public universities in Michigan to respond effectively and appropriately to a large polybrominated biphenyl exposure incident in cattle, their recent ability to respond to a dioxin scare was laudable. In Chapter 14. the Australian Royal Commission is extolled as an excellent example of how a judiciary can deal with such complex issues. There is no question in my mind that we owe much freedom in the United States to the continued existence of free and skeptical news media. Recent political events certainly confirm this. Given human nature, however, a balance must be maintained between freedom and license, one of the most difficult problems that faces a free society. The following paragraph from the concluding chapter, perhaps. is a good summary of the history and problems
associated
with Agent Orange
and dioxin:
‘Emotional role-playing by the national news media has had tragic consequcnccs for the American and Australian people in a number of ways. It has undermined national unity and morale by promoting unfounded fears of a cancer epidemic. of increases in the number of children born with defects, and misguided ideas of a ‘risk-free’ society. The loss of perspective in this issue has led to irresponsible and unwarranted action. e.g., prohibition or restriction of the use of herbicides in
agriculture. But, perhaps the most serious consequence of the intense media campaign has been its negative impact on Vietnam veterans. many of whom have ken led to believe that Agent Orange and dioxin adversely afTecLed their health and the lives of their children. The emotional impact of this fear campaign on the veteran and his family has been sevcrc.’
Division
Alan B. C’ombs, Ph.1). of Pharmacology and Toxicolog College of Pharmacy The University of Texas at Austin Austin, TX 787 I? IJ.S.A.