Document 5kX3yQDkdeNdZroG3LKeD8oM8

N ovem ber 23, 1964 H arriet L. Hardy, M .D . M assachusetts Institute of Technology O ccupational M edical Service C a m b r id g e , M a s s a c h u s e tts 39 Dear H arriet: Red Johnstone was kind enough to let m e in on his recen t co rresp o n d en ce with you o v e r C alcium disodium EDTA, and I am im pelled to q u a rre l with you, gently, about one part of your viewpoint concerning the useful ness of this chelating agent. A s you know, I am not m uch im p ressed by its ability to alleviate sym ptom s of intoxication, but I am p re p a re d to u se it and to advocate its use for the accelerated elim ination of lead from the soft tissu e s and, indirectly, from the skeleton if and when it is ad m in is tered properly. This applies especially in the case of infants and sm all children, whose danger is great because of their excessive body burden and the freq u en t a c c e ssib ility of fu rth er lead to be absorbed from th eir environm ent. In m y view , how ever, on the b a sis of a v e ry co n sid erab le am ount of ev i ) dance, the provocative u se of the agent for diagnostic purposes is i r r a tional and fraught with e r r o r . I have n e v e r seen any evidence that inorganic lead is d istrib u ted in an e rra tic m an n er in the tissu e s of the hum an body. In fact, the p a tte rn of the d istrib u tio n of lead, a s we and o th ers have seen it {see the Oak Ridge data of Dr. Tipton and her colleagues), is so consistant that th e re are no grounds, so far as I know, for the belief that it changes significantly (except, p e rh a p s, in re sp o n se to chelate th e ra p y ). If th is 'is tru e , the o ro p e r m ethod of d eterm in in g the body b u rd en of lead, is that of establishing the concentration of lead in one or m o re of the m ain tissu e s, and from this calculating the body burden o r in appraising its relativ e m agnitude, as com pared with the norm al lead content of the body. O ur experim ental work has provided the basis from such calculation or appraisal. Now, when the chelating agent is ad m in istered , an unpredictable resp o n se, both in tim e and in quantity, is found to o ccu r, on the p art of the ra te of the u r i n a r y e x c r e tio n . We h a v e no r e a l in f o r m a tio n on w hich to a p p r a i s e it, quantitatively, fo r we do not know, in b iochem ical te rm s at the c e llu la r point, in v ario u s tis s u e s , ju st what o c c u rs. T h erefo re it is p o ssib le only to give statem en t to a ru le of thum b for the in te rp re ta tio n of the re s u lt, and the in terp retatio n is ju st as likely to be wrong as to be right. This is, H a r r i e t L . Hardy, M. D. - () - N o v e m b e r 3, 1964 indeed, a poor b asis for any in terp retatio n of the am ount of lead in the soft tis su e s as a whole, and for deciding what, if any h a z a rd , is entailed th erein . A s a diagnostic procedure this is em p iricism at its w orst, for it is e m p iricism based on a false physiological p re m ise. By all odds, the best way to find out the g eneral o rd e r of m agnitude of the body burden, and its significance ion the purely p rag m atic b a sis of what can be o b se rv e d to be tneyc&nsequences of too g reat a body burden), ia to nee to it that the m etabolism of lead in the body is not d istu rb ed by any known th erap eu tic agent, and then to m e a su re p re c ise ly (and repeatedly if n e c e s sa ry ) the lead content of the blood. (That of the urine has too m uch physiological v ariab ility to be depended upon. ) If the l a t t e r is high, in te r m e d ia te o r low when th e blood is in e q u ilib riu m with the o th e r tis s u e s (i. e. u n d istu rb e d m e ta b o lis m ), the body burden is, in g en eral co rresp o n d en ce, high, in term ed iate o r low. T his is sound physiology, so fa r a s anyone now know s. If th e re a r e ex cep tions, they have not com e to light nor been in te rp re te d . I do not hold that th ere are not exceptions, but I have never seen them , and I have certainly looked lo n g e r and m o re c a re fu lly than h a s anyone who has w ritte n on the subject. I know that my view of this m a tte r is not shared by all of the clin ician s, including, vociferously, som e of o u r F ren ch colleagues. H ow ever they have not provided evidence, but only vigorously expressed opinions. I have no hesitation in ex p ressin g m yself to you with som ew hat corresponding vigor. This has come to be a fairly im portant m a tte r in com pensation m edicine, in which I have been involved not infrequently. This, featu re of the m a tte r is troublesom e, of co u rse, but of m uch m ore im p o rtan ce is this is s u e a s it r e la te s to a p e rs o n who se e k s m e d ic a l c a r e and a d v ic e . It is m ost distu rb in g to a m an who h as been exposed to lead without illn e s s o r a fte r re c o v ery from illn e ss, to be led to su sp ect that the u ltim ate effects of his exposure a re unpredictable, and that he has the potentialities of sequestering potentially dangerous quantities of lead in certain of his soft tis s u e s . There is not the slightest evidence now that this is tru e , and I hope that we shall not contribute to this kind of apprehension, u n le ss, indeed, we shouLd find it n e c e s s a ry , in clin ical ex p erien ce, to guard a g ain st undue optim ism , concerning the outcom e of unusual cases of pium bism . With kind regards. Sincerely, R o b e r t A . K e h o e , M. D, RAK ef cc: R. T. Johnstone, M .D . (blind)