included burning pain in the feet, cramping pain in
the calves, loss of ankle and knee reflexes, and
tingling in hands (Crawford, 1994). Other reported
toxicity symptoms included severe constipation, diz-
ziness, hangover, loss of memory and hypotension
(D’Arcy, 1994). Chemie Grunenthal A.G. initially
defended thalidomide as a safe product and attribu-
ted the reports to overdosage and prolonged use. A
pharmacologist at the FDA at that time, Dr Frances
Kelsey, noticed this discrepancy and requested more
data from the drug’s manufacturers to show that it
was safe (see D’Arcy, 1994).^3 In what has been
heralded as ‘one of the FDA’s finest hours’ (see
D’Arcy, 1994), Dr Kelsey withheld FDA approval
of thalidomide until it became clear that the reports
on neurotoxicity were valid and that, in addition,
thalidomide was adversely affecting unborn chil-
dren. In 1961, physicians in Germany realized with
alarm that the growing number of otherwise rare
severe congenital malformations, including phoco-
melia (defective development of limbs) and amelia
(absence of limbs), could be attributed to the use by
women of even a single dose of thalidomide during
the critical first few weeks of their pregnancy
(Wiedemann, 1961).^4 Over the next years, it became
clear that thalidomide was one of the most potent
teratogens in the medical pharmacopoiea. Almost
100% of women who took thalidomide during the
sensitive period (days 21–36 of gestation) produced
malformed infants (D’Arcy, 1994). The spectrum of
malformations was also notable for its breadth. In
addition to phocomelia, thalidomide babies suffered
from spinal cord defects, cleft lip or palate, absent or
abnormal external ears, and heart, renal, gastroin-
testinal or urogenital malformations (D’Arcy, 1994;
see also US HHS, 1997^5 ). Before the epidemic was
ran its course, over 12 000 infants were born with
deformities attributable to thalidomide (Sherman,
1986; see also Szeinberg, 1968;^6 see also Flaherty,
19847 ).
In 1971, 62 of the estimated 430 British children
injured by thalidomide sued Distillers Co., the
British marketer of the drug (Dworkin, 1979^8.
The thalidomide plaintiffs’ strongest argument
under strict product liability was that thalidomide
was defective in its design (Cooket al., 1991). To
prevail on this theory, plaintiffs had the burden of
showing that, based on testing procedures and
scientific knowledge available at the time of man-
ufacture, the drug’s danger to unborn fetuses was
known or knowable by the defendant.^9 In the
1950s, though, it was not common practice for
drug companies to test new drugs on pregnant
animals (Ferguson, 1996). Furthermore, even if
tests on pregnant animals had been conducted,
differences between animal and human metabo-
lism of the drug would likely have hidden the
drug’s teratogenic effects.^10
Realizing the difficulties in establishing the ele-
ments of a design defect case against Distillers Co.,
the thalidomide plaintiffs pled in the alternative
that Distillers Co. had negligently breached a
duty of care it owed to all potential consumers of
the drug, including the then unborn plaintiffs. This(^3) Dr Kelsey was also particularly conscious of the potentially
harmful effects of drugs on a fetus having been involved with
a malaria project during World War II in which quinine
(another teratogen) was studied.
(^4) During the 1960s, virtually every pediatric clinic in Germany
had at least one child born with phocomelia or amelia.
(^5) Although it is possible that thalidomide caused this
heterogeneous group of deformities by acting through several
different toxic mechanisms each targeting a different organ
system, it is more likely that thalidomide has a single or few
disruptive effects that can manifest themselves pleiotropically,
depending on what stage the embryo had reached when the
drug was introduced.
(^6) Szeinberg estimates that 10 000 deformed babies were born
in Germany, 1000 in Japan, 400 in England and 280 in
Scandinavian countries.
(^7) Flaherty estimates that approximately 20 thalidomide babies
were born in the United States; most of these to women who
had received thalidomide from their husbands who were
stationed in Europe.
(^8) Distillers advertized thalidomide as a treatment for morning
sickness that could be given ‘with complete safety to pregnant
women...without adverse effect on mother or child’.
(^9) This rule is embodied in the Restatement (Second) of Torts,
Section 402A, comment k, which provides that the supplier of
an ‘unavoidably unsafe product’ is liable only if it was not
accompanied by a warning of dangers that the manufacturer
knew or should have known about.
(^10) This conundrum of adequate drug testing persists even
today; although more complete and rigorous laboratory testing
protocols are now required by pharmaceutical regulatory
agencies, many drug dangers like the action of thalidomide as
a teratogen can be uncovered only post-marketing monitoring
of drug toxicity because of the obvious ethical bar on drug
testing using human subjects.
47.5 LANDMARK CASES 611