he became a Nobel laureate in 1938. The nostrum
artists could hardly believe their luck: now they
could peddle a drug that actually worked! The
favored formulation at the time was an elixir, prob-
ably a holdover from evasion of alcohol restrictions
duetoreligion,or the earlier flirtwithprohibition. In
any case, one Company, supposedly laudibly,
searched for a nonalcoholic solution for their sulfo-
namide. They chose diethylene glycol. In four
weeks of marketing, the product was not a success:
only 353 patients drank it; of these, 107 died. They
were mostly children, and there was no renal
dialysis in 1936. Thousands could have been
killed had the Company’s market analysis been
accurate.
But finally, therewas sufficient groundswell, and
FDA obtained passage of the Food, Drug and
Cosmetic Act (FD&C Act) in 1938. Thus, the
FD&C Act added safety as the second pivotal leg
of drug approval.
There was still no requirement to prove product
efficacy. But in 1941, with most of theworld at war,
an often overlooked piece of US legislation was
passed. The FD&C Act was amended, to reflect an
FDA proposal. Henceforth, FDA was empowered
to certify the potency of insulin. This required a
bioassay, and for the first time FDA was able to
regulate pharmacodynamics. It was a short step to
therapeutic efficacy.
In 1943, the Supreme Court again got involved.
In an otherwise obscure case, it held that FDAwas
empowered to establish standards for products
labeling. The four principal arms of drug approval
were finally concentrated in the hands of a single
agency: purity, safety, efficacy and labeling. To this
day, much of the power of FDA is exercised by its
control of what a label says, and not by the phar-
macological characteristics of the particular drug
in question. To Europeans this is sometimes a
surprising concept, but in fact the principal extends
to other areas of American commerce: for exam-
ple, cars may be imported into California depend-
ing not upon whether the vehicle meets the
emissions standards, but rather upon whether it is
labeled as meeting those standards.
In the 1950s, the Delancy Amendment to the
FD&C Act authorized an investigation into the new
dyes, flavorings and preservatives that were
becoming available in an era of unprecedented
chemical innovation. There was already a clear
need to update the FD&C Act, and the Food Addi-
tive Amendment of 1958 was one result, which,
among other things, prohibited carcinogenic mate-
rials from foods and drugs. This required a method
to establish carcinogenicity, which is now an impor-
tant element in the toxicology package for an over-
whelming majority of approved drugs. There are
now exceptions. Antineoplastic drugs are often
themselves carcinogenic, and the absolute restric-
tion on such materials is somewhat tempered.
Furthermore, we now understand the dose relation-
ships for chemical carcinogenesis, and how to mea-
sure it, very well; high-school exercises now
routinely exceed limits of detection available in
the 1950s. But the principle had been established
inlaw.November1958sawFDArecalling theentire
cranberry crop, just before the Thanksgiving holi-
day, because there was a fear that weedkiller con-
tamination which they had established was a
carcinogen in animals!
The other major piece of legislation in the 1950s
was the Durham-Humphrey Amendment to the
FD&C Act. Humphrey (unsuccessful Presidential
candidate and later Vice-President) had been a
pharmacist; he wanted to clarify what should and
should not be an OTC drug. Hitherto, the only
reason to get a prescription from a physician and
have it filled by a pharmacist was because the
patient did not know of an OTC drug to meet his
or her need, and the prescription was one which
needed to be compounded by a professional. The
amendment provided, perhaps artificially, that
when a disease or a drug side effect needed a
physician’s attention, then any treatment required
a prescription, and that only a licensed pharmacist
could fill a prescription. Some view this as the
genesis of general diagnostic education by the
pharmaceutical industry, and, in turn, the origins
of direct-to-consumer advertising designed to
drive patients into their doctors’ offices.
In the late 1950s, there were also many other
reasons to seek reform. FDA’s ability to regulate
efficacy assessments was still restricted to a small
number of highly specialized products, and mod-
ern advertising techniques were getting under way.
As usual, there was public resistance, and it398 CH31 UNITED STATES REGULATIONS