Journal of The Association of Physicians of India ■ Vol. 63 ■ July 2015
89
Pioneers in Infectious Diseases
Pioneers in Conventional and Molecular Diagnosis
Kinjal Patel1, Mehul Panchal2, Camilla Rodrigues3, Rajeev Soman4
T
he milestones of progress
in microbiology from
conventional to molecular diagnosis
involved contributions of many
scientists who devoted their lives
to revolutionize microbiology.
he learned to grind lenses, making
simple microscopes, which he used
to make simple observations.
Leeuwenhoek made more than
500 optical lenses. He also created
Antonie Philips Van
Leeunwenhoek
(1632 – 1723)1
Leeuwenhoek was the son of a
Dutch basket maker and worked
as a draper in his youth. He was
an unlikely scientist, since he came
from a family of tradesmen, had
no fortune and received no higher
education or university degrees.
While running his draper’s shop,
at least 25 microscopes, of differing
types. It is said that Leeuwenhoek
possessed some microscopes that
could magnify up to 500 times. He
maintained throughout his life that
there are aspects of microscope
construction “which I only keep
for myself”, in particular his most
critical secret of how he created
lenses. For many years no-one was
able to reconstruct Leeuwenhoek’s
design techniques.
He used to observe almost
anything that could be placed
under his lenses, and described
Clinical Assistant in Microbiology, 3Consultant Microbiologist and Chairperson Infection Control, 4Consultant
Physician and Infectious Diseases Specialist, PD Hinduja National Hospital and MRC, 2Associate Consultant
Microbiologist, Sir HN Reliance Foundation Hospital, Mumbai, Maharashtra
1
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Journal of The Association of Physicians of India ■ Vol. 63 ■ July 2015
what he saw. Although he himself
could not draw well, he hired an
illustrator to prepare drawings of
the things he saw, to accompany
his written descriptions. Using his
handcrafted microscopes, he was
the first to observe and describe
single-celled organisms, which he
originally referred to as animalcules,
and which are now referred to
as microorganisms. He was also
the first to record microscopic
o b s e r va t i o n s o f m u s c l e f i b e r s ,
bacteria, spermatozoa, and blood
flow in capillaries.
from a Dutch neighbour emigrated
from the island of Java, Indonesia.
Agar turned out to be an ideal
gelling agent that stayed firm even
in the incubator and could not be
digested by any bacterial enzymes.
Walter Hesse notified Koch of this
new technique, who immediately
added agar to his nutrient broths.
Hans Christian Joachim
Gram (1853 – 1938)3
Walther Hesse
(1846 – 1911)2
Hesse studied medicine at the
University of Leipzig from 1866
till 1870, when he received his
doctorate in pathology and began
his career as a country doctor.
Hesse joined Robert Koch’s
laboratory in 1881 to study air
quality. He was convinced that
m i c r o o r g a n i s m s we r e p r e s e n t
everywhere, even in water and in the
air. He used a series of filters, made
mainly from wadding, to capture
and observe microorganisms. He
used a gelatin-containing medium
for culturing the organisms trapped
with his filter. Frustratingly, the
medium always melted during
the summer months, thus ruining
the experiments. Additionally,
many of the organisms he cultured
degraded the gelatin medium, also
ruining his experiments.
One day, Hesse went on a picnic
with his wife Angelina Fannie
and noticed that the jellies and
puddings that she had brought
along did not melt in the hot
summer weather. When asked, his
wife replied that they contained
agar and that she had borrowed it
Gram was a Danish bacteriologist
studied botany at the University of
Copenhagen. His study of plants
introduced him to the fundamentals
of pharmacology and the use of the
microscope.
Gram entered medical school
in 1878 and graduated in 1883. In
Berlin, in 1884, while examining
lung tissue from patients who
had died of pneumonia, he
d i s c o ve r e d t h a t c e r t a i n s t a i n s
were preferentially taken up and
retained by bacterial cells. Within
a few years, Gram developed a
staining procedure which divided
almost all bacteria into two large
groups - the Positive and Negative
- Purple and Pink. This technique,
the Gram stain, continues to be
a standard procedure in medical
microbiology. In his initial
publication he remarked, “I have
therefore published the method,
although I am aware that as yet
it is very defective and imperfect,
but it is hoped that in the hands of
other investigators it will turn out
to be useful.”
James Watson (1928-)
and Francis Crick
(1916-2004)4
J a m e s Wa t s o n wa s b o r n o n
April 6, 1928 in Chicago, Illinois.
He was a very intelligent child.
James loved birds and initially
studied ornithology. He later
changed his specialty to genetics.
Francis Crick was born in Weston
Favell, England. His father was a
shoemaker, but Francis soon found
a love for learning and science.
In 1951, When Crick and Watson
met at Cambridge they quickly
learned that they had the same
passion for solving the DNA
structure. They both had similar
ideas as well on how the problem
could be solved. Using stick-andball models, Watson and Crick
tested their ideas of how the DNA
molecule might fit together. Their
first attempt in 1951 failed, but they
kept at it. They generated flawed
models with the chains inside and
the bases pointing outwards. Later,
Rosaline Franklin who was an X ray
crystallographer presented some
of her experimental findings for
DNA at a public seminar to which
Watson and crick were invited. By
studying X-ray diffraction images
taken by Franklin and her colleague
Williams, the solution became
apparent to Watson and Crick and
they prepared DNA model. In 1953,
they immediately published there
results in the journal Nature.
References
1.
Ford B J. From Dilettante to Diligent
E x p e r i m e n t e r, a R e a p p r a i s a l o f
Leeuwenhoek as microscopist and
investigator, Biology History 1992;5.
2.
Hesse W. Walther and Angelina Hesse-Early
contributors to bacteriology. ASM News
1992; 58:425-428.
3.
Casanova JM. Bacteria and their dyes:
Hans Christian Joachim Gram. Historia de
la inmunologia 1992; 11.
4.
Pollock MR. The discovery of DNA: An ironic
tale of chance, prejudice and insight. J Gen
Microbiol 1970; 62:1-20.