WORLD OF MICROBIOLOGY AND IMMUNOLOGY History of Microbiology273•
adjuvants.
1949 Macfarlane Burnet & Frank Fenner formulate
immunological tolerance hypothesis.
1959 Niels Jerne, David Talmage, Macfarlane Burnet
develop clonal selectiontheory.
1957 Alick Isaacs & Jean Lindemann discover interferon
(cytokine).
1962 Rodney Porter and team discovery the structure of
antibodies.
1962 Jaques Miller and team discover thymus involve-
ment in cellular immunity.
1962 Noel Warner and team distinguish between cellular
and humoral immune responses.
1968 Anthony Davis and team discover T cell and B cell
cooperation in immune response.
1974 Rolf Zinkernagel and Peter Doherty explore major
histocompatibility complexrestriction.
1985 Susumu Tonegawa, Leroy Hood, and team identify
immunoglobulin genes.
1987 Leroy Hood and team identify genes for the T cell
receptor.
1985 Scientists begin the rapid identification of genes for
immune cells that continues to the present.See alsoAntibody and antigen; B cells or B lymphocytes;
Germ theory of disease; History of the development of antibi-
otics; History of public health; Immunity, active, passive and
delayed; Immunity, cell mediated; Immunity, humoral regula-
tion; Infection and resistance; T cells or T-lymphocytesHHistory of MicrobiologyISTORY OFMICROBIOLOGY
Microbiology was born in 1674 when Antoni van Leeuwenhoek
(1632–1723), a Dutch drapery merchant, peered at a drop of
lake water through a carefully ground glass lens. Through this
he beheld the first glimpse of the microbial world. Perhaps more
than any other science, the development of microbiology
depended on the invention and improvement of a tool, the
microscope. Since bacteriacannot be seen individually with the
unaided eye, their existence as individuals can only be known
through microscopic observations. Indeed, it is interesting to
speculate on how microbiology might have developed if the
limits of resolution of the microscope were poorer.
The practical and scientific aspects of microbiology
have been closely woven from the very beginning. Perhaps it
is for this reason that microbiology as a field of study did not
really develop until the twentieth century. Nineteenth century
“microbiologists” were chemists and physicians and a few
were botanists. At that stage, the science of microbes was
developing to solve very practical problems in two clear sci-
entific fields, the science of fermentationand in medicine.
Although medicine and fermentation presented the
practical problems that stimulated the development of micro-
biology, the first studies that put the subject on a scientific
basis arose from a problem of pure science. This was the con-troversy over spontaneous generation. Although the crude
ideas of spontaneous generation (e.g., maggots from meat)
were dispelled by Francesco Redi (1626?–1698?) in the sev-
enteenth century, more subtle ideas such as that protozoaand
bacteria can arise from vegetable and animal infusions, were
still accepted in the nineteenth century. The controversy also
involved fermentations, since it was considered that the yeast
fermentation was of spontaneous origin.
Many workers became involved in the study of fermen-
tation and spontaneous generation, but Louis Pasteur
(1822–1895) stands out as a giant. He came into biology from
the field of chemistry and was apparently able to remove all
the philosophical hurdles that blocked the thinking of others.
Within a period of four years after he began his studies, he had
clarified the problems of spontaneous generation so well that
the controversy died a natural death.
Pasteur was also able to go easily from fermentation
into the field of medical microbiology, which occupied the
later part of his life. His contributions in that field were
numerous, and his work in fields such as microbial attenuation
and vaccinationhas been the basis of many modern medical
practices. It should be emphasized that the development of
sterilizationmethods by researchers such as Pasteur and John
Tyndall (1820–1893), so necessary to the solution of the spon-
taneous generation controversy, were essential to put the sci-
ence of microbiology on a firm foundation. The workers did
not set out to develop these methods, but they evolved as a
bonus that was received for solving the spontaneous genera-
tion question.
Other important developments were in medicine. The
microbiological aspects of medicine arose out of considera-
tions of the nature of contagious disease. Although the phe-
nomenon of contagion, especially with respect to diseases
such as smallpox, was recognized far back in antiquity, its
nature and relationship to microorganismswas not under-
stood. It was probably the introduction of syphilisinto Europe,
which served to crystallize thinking as here was a disease that
could only be transmitted by contact and helped to formulate
the question, what is being transmitted? Gerolamo Fracastoro
(1478–1553) gave syphilis its name in the sixteenth century
and came close to devising a germ theory of disease, an idea
that later attracted a number of workers all the way down to
the nineteenth century. By the late 1830s, Schwann and
Cagniard-Latour had shown that alcoholic fermentation and
putrefaction were due to living, organized beings. If one
accepted the fact that the decomposition of organic materials
was due to living organisms, it was only a step further to rea-
son that disease, which in many ways appears as the decom-
position of body tissues, was due to living agents. Jacob
Henle, in 1840, further commented on this similarity and with
the newfound knowledge on the nature of fermentation, he
proceeded to draw rather clear conclusions also saying that
experimental proof would be required to clinch this hypothe-
sis. That evidence came later from Robert Kochprovided, in
1867, the final evidence proving the germ theory. He estab-
lished the etiologic role of bacteria in anthraxand as a result
proposed a set of rules to be followed in the establishment of
etiology. The key to Koch’s observation was the isolation ofwomi_H 5/6/03 3:20 PM Page 273