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Arsenic and cancer
CORRESPONDENCE
Arsenic
und
cancer
To the Editor: Opportunity to comment here on the paper, ((Asthma, arsenic, and cancer,” by Novey and is most welcome and seems timely for many reasons. For about 11 years I have studied the history of arsenic and how it got its awesome reputation. This is recounted in part in Fed. PTOC. 26: 194, 1967, and in Nutrition Rev. 18: 129, 1960. 1 note the author credited me with a “complete refutation for the theory of carcinogenesis by arsenic,” and this is what I indeed sought to do. Each point was as well documented as time and space permitted. Mine was not a categorical rejection. It had t,aken me countless hours of painstaking literature search to make sure that there is no real basis to associate arsenic with cause of cancer. After all, Fowler’s solution came into use in 1786, and millions must have been so treated. As Sir Ernest Kennaway, the dean of cancer research who never subscribed to the idea, once noted, the small number of cancer cases said to stem from Fowler’s solution seemed to argue against rather than for its carcinogenicity. Applying Gertrude Stein’s neat statistic, “a difference to be a difference must make a diff’erence,” one just doesn’t find for sure that Fowler’s solution “made a difference.” Surprisingly, one does find that some of Hutchinson’s and Neubauer’s (cited by Novey and Martel) cases were not definitely known to have been treated with an arsenical. As Kennaway remarked, Hutchinson “rode the idea with a loose rein.” Neubauer, who came to England after the mar, partly through Kennaway’s efforts, began with the premise that “arsenical cancer” existed. So do Novey and Martel, based on one patient. An important point perhaps and one which seems often missed is that exposure to carcinogenic hydrocarbons do produce the type cancers assigned to arsenic. This I reviewed (see above). Most important is the growing evidence that even inorganic arsenitcs may have value against cancer in animals (Milner, Arch. Environ. Health 18: 8, 19G9). A retrospective study, as Novey and Martel suggest, of asthmatic patients on the Gay t,reatment could be instructive, even though the time element is discouraging. Most needed are animal models by which to relate arsenic effects to man. Using sensitized guinea pigs, one group found that arsenic protected against anaphylaxis, apparently by preventing histamine and SRS-A release (Funderburk et al., European J. Pharmacol. 5: 203, 1969). This seems a fine lead on how As3 may act enzymatically. Although there is very little arsenic in tissues, some is always to be found. Thus, we need t,o know just what good, if any, the 700,000 odd atoms of As in each red blood cell may do there. The so-called tonic and alterative effects of arsenic have been mooted for centuries. So have allegations that the element either causes or cures cancer. I’ve come to realize that, especially for As, it’s not what people don’t know that delays progress, but what they know that isn’t so. What, for instance, if arsenicals actually inhibit cancer9 From what I have gathered, arsenicals do appear to have some small protective value against tumors. The close relation between arsenic and phosphorus should be explored in the positive sense, i.e., how arsenate stimulates phosphorylations. The role of arsenite may be sought in its relation to -SH groups or more likely its relation to S-Se-S groups in enzymes. On the positive side also, one might study populations where the As level in water is unusually high, as in Lane County, Oregon, and Churchill County, Nevada. If well enough done, such studies might provide medicine and agriculture with answers the whole world needs on safe uses of arsenicals. As I see it, the myth of arsenic cancer has slowed research progress for 150 years. This has led to unscientific regulations regarding uses of arsenicals in most countries. Now only medical scientists and oncologists can free research to pin down the truth about this amazingly elusive but ubiquitous element. Dmglas 77. Frost, Ph.D. Rrattleboro, Pt. Martel
320
Arsenic
und
cancer
To the Editor: Opportunity to comment here on the paper, ((Asthma, arsenic, and cancer,” by Novey and is most welcome and seems timely for many reasons. For about 11 years I have studied the history of arsenic and how it got its awesome reputation. This is recounted in part in Fed. PTOC. 26: 194, 1967, and in Nutrition Rev. 18: 129, 1960. 1 note the author credited me with a “complete refutation for the theory of carcinogenesis by arsenic,” and this is what I indeed sought to do. Each point was as well documented as time and space permitted. Mine was not a categorical rejection. It had t,aken me countless hours of painstaking literature search to make sure that there is no real basis to associate arsenic with cause of cancer. After all, Fowler’s solution came into use in 1786, and millions must have been so treated. As Sir Ernest Kennaway, the dean of cancer research who never subscribed to the idea, once noted, the small number of cancer cases said to stem from Fowler’s solution seemed to argue against rather than for its carcinogenicity. Applying Gertrude Stein’s neat statistic, “a difference to be a difference must make a diff’erence,” one just doesn’t find for sure that Fowler’s solution “made a difference.” Surprisingly, one does find that some of Hutchinson’s and Neubauer’s (cited by Novey and Martel) cases were not definitely known to have been treated with an arsenical. As Kennaway remarked, Hutchinson “rode the idea with a loose rein.” Neubauer, who came to England after the mar, partly through Kennaway’s efforts, began with the premise that “arsenical cancer” existed. So do Novey and Martel, based on one patient. An important point perhaps and one which seems often missed is that exposure to carcinogenic hydrocarbons do produce the type cancers assigned to arsenic. This I reviewed (see above). Most important is the growing evidence that even inorganic arsenitcs may have value against cancer in animals (Milner, Arch. Environ. Health 18: 8, 19G9). A retrospective study, as Novey and Martel suggest, of asthmatic patients on the Gay t,reatment could be instructive, even though the time element is discouraging. Most needed are animal models by which to relate arsenic effects to man. Using sensitized guinea pigs, one group found that arsenic protected against anaphylaxis, apparently by preventing histamine and SRS-A release (Funderburk et al., European J. Pharmacol. 5: 203, 1969). This seems a fine lead on how As3 may act enzymatically. Although there is very little arsenic in tissues, some is always to be found. Thus, we need t,o know just what good, if any, the 700,000 odd atoms of As in each red blood cell may do there. The so-called tonic and alterative effects of arsenic have been mooted for centuries. So have allegations that the element either causes or cures cancer. I’ve come to realize that, especially for As, it’s not what people don’t know that delays progress, but what they know that isn’t so. What, for instance, if arsenicals actually inhibit cancer9 From what I have gathered, arsenicals do appear to have some small protective value against tumors. The close relation between arsenic and phosphorus should be explored in the positive sense, i.e., how arsenate stimulates phosphorylations. The role of arsenite may be sought in its relation to -SH groups or more likely its relation to S-Se-S groups in enzymes. On the positive side also, one might study populations where the As level in water is unusually high, as in Lane County, Oregon, and Churchill County, Nevada. If well enough done, such studies might provide medicine and agriculture with answers the whole world needs on safe uses of arsenicals. As I see it, the myth of arsenic cancer has slowed research progress for 150 years. This has led to unscientific regulations regarding uses of arsenicals in most countries. Now only medical scientists and oncologists can free research to pin down the truth about this amazingly elusive but ubiquitous element. Dmglas 77. Frost, Ph.D. Rrattleboro, Pt. Martel
320