LSD and Chromosomes
^^^^^^^^^^^^^^^^^^^^
an excerpt from The Natural Mind
by Andrew Weil

pp. 44-46:

Retrospective studies are risky ways of framing hypotheses; they are fraught
with logical traps known to the ancients, and it is remarkable that men of
science still fall for them.

The saga of LSD and chromosomes is a case in point, for much of the evidence
was of this retrospective sort.  The initial hypothesis, first reported in
1967, was based on the observation that LSD users seemed to have a higher
frequency of broken chromosomes in certain white blood cells (lymphocytes)
than "normal" persons (1).  The _New England Journal of Medicine_ gave this
observation great prominence in an editorial titled, "Radiomimetic Effects
of LSD," suggesting that the drug mimicked radiation in its damaging effects
on genetic material.  Evidence that was more circumstantial then appeared:
LSD was shown to affect chromosomes of cells growing in test tubes; a few
mothers who had used LSD gave birth to deformed babies.  The scientific and
lay press gave all these findings front-page attention.  The National
Institute of Mental Health eagerly seized upon and disseminated the new
information in a propaganda campaign against LSD.  And, for a few months,
use of the drug appeared to decline.

But throughout this campaign, a number of facts were overlooked.  First was
the total absence of any prospective studies supporting the hypothesis.  No
one had tested the hypothesis in a legitimate way -- by looking at
chromosomes before exposure to the drug, giving the drug in a controlled
fashion, and then keeping watch on chromosomes.  Second was the known fact
that many things affect chromosomal integrity, among them such common drugs
as aspirin and chlorpromazine (Thorazine) and recent viral infections.  No
effort was made to control for these other factors in the clinical cases.
Third was the general problem of tissue-culture studies: cells growing in
test tubes do not behave the way cells do in the body.  In addition, the
doses of LSD that caused visible changes in chromosomes of tissue-culture
cells were far higher than the doses living cells get when a person takes
an acid trip.  Fourth, chromosomal breaks are seen in cells of all people;
the arguments turned on a statistical difference in frequency, not an
all-or-nothing difference, and the frequency of chromosomal breaks in
lymphocytes seems to correlate more directly with laboratory technique than
with other variables.  (The technique of preparing lymphocytes to make
chromosomes visible is complicated and likely to produce factitious
changes.)  Fifth, the lymphocyte is one of the only cells in which human
chromosomes can ever be seen under the microscope.  Even if the changes were
real, they said nothing about the state of chromosomes in other cells (such
as reproductive cells).  In fact, through the whole controversy no one
showed _why_ it was bad to have broken chromosomes in your lymphocytes.  It
sounds bad, certainly, but one cannot say that it is bad without making a
number of shaky assumptions.

All of these logical flaws in the medical arguments against LSD were obvious
in 1967.  They do not mean that the hypothesis should never have been
published, but surely it should not have been promoted by the medical
profession, the press, and the National Institute of Mental Health without
more thought.  And it is significant that these logical flaws were first
pointed out in the _Berkeley Barb_ and other underground newspapers at least
eight months before the _New England Journal of Medicine_ voiced similar
doubts.  The necessary prospective studies were not published until the end
of 1969 (2).  Not surprisingly, they failed to demonstrate any relationship
between LSD use and chromosomal changes.  They generated very little
national publicity.

This episode ought to be profoundly embarassing to journal editors and
government scientists.  At one stroke it created an irreparable gap between
users of drugs and drug experts.  Since 1968 I have not met a single user of
hallucinogens who will believe any reports of medical damage associated with
drugs, and the use of hallucinogens has never been higher.

(1) M. M. Cohen, K. Hirshhorn, W. A. Frosch, "In Vivo and in Vitro
Chromosomal Damage Induced by LSD-25," _New England Journal of Medicine_ 227
(1967), p. 1043.

(2) J. H. Tjio, W. N. Pahnke, A. A. Kurland, "LSD and Chromosomes: A
Controlled Experiment," _Journal of the American Medical Association_ 210
(1969), p. 849.  For a recent review of the whole field, see N. I.
Dishotsky, W. D. Loughman, R. E. Mogar, W. R. Lipscomb, "LSD and Genetic
Damage," _Science_ 172 (30 April 1971), p. 431.