Environmental Microbiology (2018) 20(6), 1955–1959
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Editorial
The end of microbiology
Roberto Kolter* and Scott Chimileski
Department of Microbiology, Harvard Medical School,
Boston, MA 02115, USA.
The future will bring the end of microbiology. . . but not
really. With our title we wanted, in part, to be provocative
and also to make our readers stop and think for a bit.
For it appeared to us that perhaps a useful purpose of
these ‘vision’ types of essays should be to provoke
some out-of-the-box thinking among the readers. We
are delighted to be part of the group of authors that Ken
Timmis has invited to contribute short opinion pieces as
a part of the celebration of the 20th anniversary of this
journal.
Can we actually predict the future? By no means. In
fact, one of us (RK) has a proven track record at failing
in prior attempts. One example is recorded on the pages
of Environmental Microbiology Reports, nearly a decade
ago, where he predicted that pediatricians were to be
using topical probiotics to manage recurrent ear and
throat infections (Kolter, 2009). We are not there yet,
though in all fairness, the text stated that to be a couple
of decades away and with all the current interest in pro-
biotics, we might still get there in time. The second
example, however, is a clearer case of failing to predict
the future. This example has, up to now not been written
about. As a newly minted postdoctoral fellow in 1980,
RK was the sole person at Stanford with the expertise
to synthesize short olignucleotides (a technique he had
learned at La Jolla from Richard Ogden of the Agouron
Institute). As such, he was asked to consult for a bud-
ding Bay Area company, Applied Biosynthesis, on mat-
ters related to the use of synthetic oligonucleotides.
Would it be useful to construct a machine that could
synthesize hundreds or even thousands of oligonucleoti-
des overnight? ‘Not at all!’ he advised. ‘There is no way
there could be a market for that many oligos’. Consider
*For correspondence. Email rkolter@hms.harvard.edu
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doi:10.1111/1462-2920.
the facts that PCR was still several years away, that the
cost of synthesis were sky high and that most people
used only a few oligonucleotides for a project that could
last years, for example, site-directed mutagenesis or the
isolation of genes based on the amino acid sequence of
its product. Based on that knowledge, would you have
predicted the vast explosion in the use of oligonucleoti-
des? That is the nature of the business of attempts at
predicting the future in science. Think late 1980s, early
1990s, as Norm Pace and colleagues were developing
culture-independent methods to assess microbial diver-
sity, who would have predicted that, less than thirty
years later and thanks to the truly incredible advances in
DNA sequencing methodology, gigabases of information
would be routinely obtained in a matter of days by any-
one interested in microbial community analyses. These
types of remarkable and, in our view, unpredictable
advances are a large part of what keeps the experimen-
tal sciences so very exciting.
If we are not here to make predictions about the
future of microbiology, what is our aim? Rather than
attempting to tell the future, we aim to be prescriptive. If
we cannot say what will happen, we want to say what
should happen.
So, what should happen to environmental microbiol-
ogy in the future? This query brings us back to where
we began, the provocative statement, now slightly modi-
fied, that the future will bring the end of environmental
microbiology. . . but not really. To explore the statement
in some depth, let us consider what is understood by
environmental microbiology. We can think of no better
way to start this exploration than with an anecdote. The
setting is idyllic, the small Greek island of Spetses, site
of numerous summer life sciences courses since the
1960s (Feldmann, 2013). It is 2006, and we are in the
midst of course organized by Pascale Cossart and one
of us (again RK). The course will cover a broad range of
subjects, from bacterial–-host interactions to microbial
survival strategies in natural environments. Julian Davies
is delivering a lecture, not surprisingly, on antibiotics. A
student asks Julian to describe the different contexts of
antibiotics as they pertain to medical microbiology and
to environmental microbiology. Julian raises his hands
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2 R. Kolter
R. Kolter andand S. Chimileski
S. Chimileski
and, with his patented elvish grin loudly exclaims: ‘It’s
ALL environmental microbiology!’
It is all environmental microbiology! How true it is. To
better understand the significance of that statement, lets
continue our exploring by delving briefly into the history
of the study of microbes, the history of microbiology
itself. The concept that there are life forms so small as
to be invisible to the naked eye dates back to antiquity.
Take, for example, this quote from over 2000 years ago
written by the Roman scholar Marcus Terentius Varro in
the context of the environment: ‘Precautions must also
be taken in the neighborhood of swamps . . . because
there bred certain minute creatures which cannot be
seen by the eyes. . .’ (Hooper and Ash, 1993). When in
the late 1600s, Antoni van Leeuwenhoek peered through
his carefully crafted lenses, he became the first human
to see these minute creatures. It did not matter whether
his samples came from the waters of Delft canals or the
depths of his teeth, the ‘animalcules’ were everywhere
(Gest, 2004). These animalcules became ‘microbes’
when they were so named in 1878 by the French mili-
tary surgeon Charles-Emmanuel Se dillot (Billmann,
2012). By then, the study of microbes was in full force.
Louis Pasteur had made many of his seminal observa-
tions and these would soon be followed by those of Mar-
tinus Beijerinck. Most importantly, both Pasteur and
Beijerinck were equally at home analyzing microbes as
agents of disease and as organisms, which were influ-
enced by, and turn influenced their environments. As far
as they were concerned, it was indeed ALL environmen-
tal microbiology. A wonderful description of Louis Pas-
teur as microbial ecologist can be found in a seldom
read (though it should not be so) 1974 article by Dubos
(1974).
But something else happened in the late 1800s. The
German physician Robert Koch, focused on diagnosing
and treating infectious diseases, was the first to develop
techniques to obtain pure cultures of microbes. Armed
with this powerful tool, he laid down his famous postu-
lates for defining a microbe as a causative agent of dis-
ease. Koch’s findings proved to be of paramount
importance to human health. For many intents on under-
standing infectious diseases, the environment went by
the wayside. It was the beginning of what some have
called the Petri dish versus Winogradsky column culture
war (Grote, 2018), a schism that would last nearly a
century.
The separation between studies of the environment
and infectious disease was maintained in no small part
by the birth and blossoming of molecular biology, where
the quintessential model microbe Escherichia coli and
its phages played such a prominent role. The reduction-
ism implicit in the notion that one species of microbe
causes one disease paired perfectly with the
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reductionism of understanding gene function, immortal-
ized in Jacques Monod’s statement ‘Tout ce qui est vrai
pour E. coli, est vrai pour l’elephant’. (All that is true for
E. coli is true for the elephant.) The two reductionist
approaches eventually linked up in a marriage as
described by Stanley Falkow in his now classic essay of
1988 ‘Molecular Koch’s postulates applied to microbial
pathogenicity’ (Falkow, 1988). As a consequence, there
was an enormous growth of knowledge of molecular
mechanisms of microbes and their ability to cause dis-
ease. The latter half of the twentieth century was indeed
a golden era in the study of microbes. However at the
same time, there came to be separate subdisciplines of
medical microbiology, molecular microbiology and envi-
ronmental microbiology, with the consequent narrowing
of the knowledge base among the practitioners of each.
Communication across these subdisciplines was scant
and, most importantly, it was no longer ALL environmen-
tal microbiology.
Back to our stated aim, what should happen to envi-
ronmental microbiology in the future? In short, the disap-
pearance of the artificial boundaries imposed by the
existence of subdisciplines. We all need to go back to
understanding and practicing the fact that it is ALL envi-
ronmental microbiology. But we will take the argument a
big step further, a big, seemingly impossible step further.
It should ALL be biology. Or perhaps better stated, it
should all be biology in the context of evolution and ecol-
ogy. Because, after all, ‘nothing in biology makes sense
except in the light of evolution’ (Dobzhansky, 1973) and
‘the evolutionary play takes place in the ecological the-
ater’ (Hutchinson, 1965). And we certainly feel that one
victim of the fractionation of the study of microbes into
subdisciplines was the interest in understanding the evo-
lutionary process. For a while, it appeared to have been
placed on the back burner. But certainly not completely
forgotten.
Those who considered evolution of cardinal impor-
tance in biology and also recognized the central role
that the microbial sciences could play in understanding
evolution, felt a great frustration with the fragmentation
of microbiology. This frustration and yet a sense of hope
are reflected in the opening phrases of Woese’s (1994)
review: ‘They cried: “Microbiology is dead! Long live
microbiology!”’. And it was Woese who in the last two
decades of last century initiated the ongoing move to
come back to a fully integrated microbiology. Because
the truth is that what we state should happen in the
future, the integration of the life sciences has already
been happening for a while, with microbiology serving to
nucleate the movement. This was alluded by Woese and
Goldenfeld (2009) in their wonderfully titled review ‘How
The Microbial World Saved Evolution From the Scylla of
and John
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Molecular Biology and the Charybdis of the Modern
Synthesis’.
What shape have the initial steps in integrating the life
sciences taken thus far? Two trends come immediately
to mind. First is the gradual decline of strictly reduction-
ist approaches using molecular mechanisms in model
microbes. These are being steadily replaced by more
whole-system level approaches where the application of
rigorous mathematics and computer modeling is key. As
a result, we estimate that more mathematicians, physi-
cists and computer scientists study microbes today than
ever before.
The widespread exploration of microbiomes was the
second and perhaps most striking step towards the inte-
gration of the life sciences. What started with the explo-
ration of microbial diversity in the peculiar environments
of Yellowstone hot springs in the early 1990s quickly
evolved into what we like to consider the 21st century
equivalent to the Voyage of the Beagle. Except this time,
the intrepid naturalists numbered in the thousands and
the environments under investigation encompassed
every conceivable corner of the biosphere, from the
depths of frozen lakes in Antarctica to the showerheads
under which so many of us carry out our daily cleansing.
And everywhere they have searched, modern-day
explorers have found astonishing diversity and clear evi-
dence that we have barely begun to understand the intri-
cate webs that keep this planet alive. It took a good 10–
15 years for a similar explosion in investigation to begin
within the realm of the human body, but since it began
in earnest a dozen years ago, the studies of the human
microbiome have taken off with a passion. The ensuing
beauty is the increased recognition of the human body
as an ecosystem. The consequence is that the
approaches used to analyze metagenomic data, be it
from the human skin or the Atacama sands, are the
same. Thus, the language is the same and it is the lan-
guage of ecology and evolution. Once again it has
become clear that it is indeed ALL environmental
microbiology.
We envision newfound opportunity to integrate all of
biology through explorations of the diversity of microbial
life. We know that microbial life is foundational to the
one universal ‘Tree of Life’ (or Web of Life) and that
microbial activities continue to play a major role in sus-
taining the biosphere. Plants and animals have evolved
and go through their life cycles steeped in countless
microbes. Bacteria and other microbial organisms inter-
face with larger organisms through an entire spectrum
of interactions, be it within ecosystems or in some cases
through extremely close symbioses (McFall-Ngai et al.,
2013; Segev et al., 2016). Environmental microbiologists
ourselves have also over the last centuries and decades
revealed that there are no strict divisions between
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of microbiology 3
organisms based on size. There are individual bacteria
that are visible to the naked eye (Kalanetra et al., 2005;
Bailey et al., 2011). There are macroscopic stages of
natural bacterial lifecycles, like the fruiting bodies formed
by Myxobacteria (first discovered by Roland Thaxter in
the late 1800s) (Thaxter, 1892; Dawid, 2000). Consider
the diversity of slime molds and fungi with lifecycles that
truly border the realms of visible and invisible, not to
mention natural macroscopic manifestations or lifestyles
of bacteria, archaea and microalgae such as biofilms, fil-
aments, microbial mats, biological crusts and blooms
(Moissl et al., 2002; Muller et al., 2010; Claessen et al.,
2014; Chimileski and Kolter, 2017; Lyons & Kolter, 2015;
Raitsos et al., 2006). There are microscopic multicellular
animals and giant viruses larger than the smallest free-
living eukaryotes (Courties et al., 1994; Abergel et al.,
2015). Upon close inspection, the categories of microbe
and macrobe are fuzzy, paraphyletic groups that do not
reflect the full diversity in natural forms among the
domains Bacteria, Archaea and Eukarya. We believe
that the concept of a ‘microorganism’ is more than any-
thing a legacy of the (relatively recent) invention of the
microscope – conveniently yet arbitrarily based on
human visual acuity, rather than on any other value of
general biological significance. Life is truly seen as a
beautiful continuum of sizes (Chimileski and Kolter,
2017).
Combining these arguments that call into question the
usefulness of dividing between microbes and macrobes,
we see a unique opportunity to explore a unified biology
starting from basic principles of molecular mechanisms,
evolution and ecology. One of the best examples of this
new biology that we have heard of is the teaching of an
undergraduate-level biology course based on these
basic principles at Caltech through a joint effort by Dia-
nne Newman and Margaret McFall-Ngai. This type of
integrated biology curriculum may someday help bring
down barriers that isolate subdisciplines in the life
sciences.
Having prescribed that the subdisciplines of the life
sciences should make every effort to bring down the
barriers that separate them, we would like to explore
more specifically directions that we consider would be
useful to take to gain a better understanding of the func-
tioning of microbial communities. Currently, much of the
work that is aimed at describing these matters has been
focused on massive sequencing efforts after sampling
natural communities from diverse settings. This has
proven to be an extremely fruitful approach. Yet, in our
opinion, these sorts of approaches will always be limited
in their ability to get down to the detail of molecular
mechanisms. In general the diversity present in almost
all natural microbial communities is too complex to
address in a systematic way the roles played by, for
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4 R. Kolter andand S. Chimileski
S. Chimileski
example, individual species. Or better yet, individual
genes or molecules.
We learned from molecular biology the power of
genetics in deciphering the roles played by individual
components in complex systems, but applying genetics
to natural communities is nearly impossible. Is there any
way in which microbial ecology studies can be aug-
mented by applying more reductionist approaches that
involve molecular and chemical genetics? We believe
there is and that this can be achieved by a ‘middle
ground’ of complexity through the analyses of synthetic
‘model communities’. Initial forays into generating simple
yet representative communities already have proven
quite promising. There are examples of such recon-
structed communities from diverse microbiomes and
very interesting new information regarding community
assembly, robustness and resilience has been gained
from them (Niu et al., 2017). Therefore, our recommen-
dation is not all that novel. We have an idea, in itself
also not new but not currently being practiced at scale
that should be considered more widely. This idea goes
at the heart of how science is being practiced and
funded in many nations today.
While the growth in our knowledge of microbial commu-
nities has been remarkable, accelerating at an amazing
rate, there is a sense that most investigators are aiming to
differentiate themselves by investigating yet another natu-
ral system, one that has unique properties that no one
else has investigated. Innovation in environmental micro-
biology today is largely defined by looking where others
have not seen before. The time is thus quite ripe for a few
intrepid investigators to join forces and intensively look –
together – at the same system. There is a wonderful
example where this type of approach yielded some of the
most exciting years in the history of the life sciences: the
birth of molecular biology.
If one looks back at the 1940s, 1950s and 1960s, it is
absolutely evident that tremendous progress was made
in our understanding of genes and their functions. At the
start of those years, there were key ‘big’ questions in
the life sciences to be answered: What is the nature of
the gene? How do genes function? Those questions
were largely answered by a few investigators focusing
on a few and related model systems. When Max
Delbru €ck proposed that phages represented an ideal
system to understand how life begets life he attracted
an outstanding collection of investigators trained in
diverse disciplines, physics, chemistry, biology, etc. The
so-called ‘phage school’ was born (Cairns et al., 2007).
Most importantly, it was not a case of every investigator
going out and finding him/her a new phage. Quite the
contrary, there was the clear decision to focus the efforts
of many investigators on a very small number of phages,
initially mostly the ‘T’ phages (then lambda) and work
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jointly. There was a wonderful sense of cooperation in
the early years of molecular biology of investigators
spending their summers at the Cold Spring Harbor Lab-
oratory and this sense was then echoed in diverse loca-
tions such as Cambridge University and the Pasteur
Institute.
There are aspects of microbial ecology that make this
area of the life sciences ideally suited to learn from the
example of the early years of molecular biology. As we
said, some of the key questions of microbial community
assembly, maintenance and function could be answered
by intensively studying one (or a few) synthetic model
community, it does not matter so much which one. Using
approaches that involve chemistry, physics and genetics,
along with computational modeling and focusing the
efforts from many investigators working jointly we feel
will provide major gains in basic knowledge. Rather than
continuing along the lines we are following today, where
there are about as many microbial communities under
study as there are investigators studying them, we advo-
cate the formation of eclectic groups of multiple investi-
gators working together at locations where these
collaborative efforts can blossom. The ideal locations
could be the sites where experimental summer courses
are currently being held. Would it not be wonderful if the
Marine Biological Laboratory at Woods Hole – where
the Microbial Diversity course has been held for decades
– were to host investigators to carry out this type of col-
laborative research? But there are numerous such loca-
tions that have sprouted in recent years all over the
world. The key will be to gather investigators who are
fully committed to collaborating in such a scheme. It is
what should happen. Will it ever happen? Only if a few
brave investigators decide to set their hearts to it.
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