Evening star., 1948-05-28
! Stars, Men and Atoms
SuIfone Chemical Doubles
Action Of Streptomycin
Doctors Report on New Findings in
Fight on tuberculosis

Doctors Report on New Findings in
Fight on Tuberculosis
By Thomas r. Henry
The action Of streptomycin against tubercu.
losis is doubled-in some cases nearly trebled--
by combining the use Of this mold secretion
with that of various chemicals.
The combination is believed to have saved
lives of children with tuberculous meningitis,
infection of the lining Of the brain with
tubercle baciili which hitherto invariably has
been fatal
The finding of the so-called "synergistic" ac-
ton of streptomycin and one Of the sulfons
group Of chemicals, related to the sulfa drugs
but with a quite different chemical structure,
Is the work Of DR.. M. I. Smith and his asso-
ciates of the National Institute of Health and
has been carried out with test-tube prepara-
tions Of the highly resistant organism respon-
sible for the dreaded lung infection. and with
experimental animals.
Tests Stin Limited.
When streptomycin was first announced it
was of chief interest because, unlike penicillin
or any of the sulfa drugs. it appeared effective
against the tubercle bacillus. Tests on human
beings with this still limited and expensive drug,
however have been rather disappointing. it
first it is highly effective but the germs soon
acquire an immunity so that doses 50o-fold
greater than the original are required to do
any good. This is above the human tolerance
limit and there is every indication that the re-
quirement will increase.
Shortly after streptomycin the sulfone chem
icals were introduced. In the test tube they
had some effect much less pronounced than
hat NJ ~ k,,kn
germs. On the other hand there was no tend
ency for the organisms to become immune.
The human tolerance for the sulfones was
quite low and they offered little possibility for
treatment per Sc.
Apparently. however, quite small amounts
which are well within the limits of tolerance
may deliver the knockout blow which strepto-
mycin is unable to put across.
Streptomycin. the Public Health Service ex-
periments show, works much better with guinea
pigs experimentally infected with very heavy
doses of tuberculosis germs than with men.
great deal depends on the length of treatment
and it was found early that long period with
moderate doses brought the best effects. Thus
treatment Of two weeks even with doses up
to the limit Of guinea pig tolerance. did no
good at all The animals soon relapsed and
died. -Four weeks was only slightly better. But
with treatments of from ten to eleven weeks
all the infected animals survived and with al
most no relapses The disease could be classified
as definitely arrested" 1t has been impossible
to find any evidence that a tubercle bacillus
from q guinea pig ever developed tolerance
for streptomycn.
BaciIi in Man Differs.
But in some mysterious way man differs from
both guinea pig and glass tube culture OF
the bacilli In treatment of from 40 to 90
days about go per cent of patients develop the
resistant strains. Whereas at the beginning
the germs were nearly all killed by a miuonth
of a microgram-about thirty -billionth of an
ounce-per cubic centimeter of a test-tube cu-
ture, about 40 days later 500 micrograms per
cubic centmeter are required.
With the combined streptomycin- -sulfone
treatment, however, there is no acquired re-
sistance, DR.. Smith and his colleagues have
found. This finding, however, is from culture
studies and not from actual treatment of
human beings.
There are many sulfones, some Of which are
quite poisonous, and DR.. Smith is seeking some
member of this chemical family with the great
est therapeutic effects combined with the least
toxicity. At present he is using drug known
as hydroxyethyl which appears not to be highly
poisonous and tends to concentrate in liver,
kidney and lungs. Some success has been
reported from England with a drug of the
same group called "sufetrone," which also is
not very poisonous but appears to have some
other drawbacks
1t has long been held that the great dificulty
in treating tuberculosis with any drug lay in
the coat of armor" with which the bacillus is
surrounded. The present experiments do not
bear out this view, saws DR. Smith
He believes the time is close at hand when
the combined chemical-streptomycin treat
ment can be tested in clinical practice.