Moselio Schaechter


  • The purpose of this blog is to share my appreciation for the width and depth of the microbial activities on this planet. I will emphasize the unusual and the unexpected phenomena for which I have a special fascination... (more)

    For the memoirs of my first 21 years of life, click here.

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March 17, 2014

The Bacterial Chromosome: A Physical Biologist's Apology. A Perspective.

by Suckjoon Jun

I entered the bacterial chromosome field in 2004 as a fresh Ph.D. trained in theoretical physics. Ten years is not long enough for one to gain the depth and breadth of a scientific discipline of long history, certainly not for an early career scientist to write an essay of the status of A Mathematician’s Apology (Hardy 1940). Nevertheless, I agreed to write this Perspective as a physicist who entered biology, because my colleagues are often curious to know what drives physicists to become (physical) biologists, and make them stay in biology despite many challenges. I also wanted to share several lessons I have learned because, while some of them are personal and specific to my field, I have a good reason to believe that they might resonate with many future travelers. This Perspective is for them.

I would like to start with the story of one of the most familiar and yet mysterious forces in nature—gravity. Galileo is said to have dropped two balls of different masses from leaning Tower of Pisa in Italy some five hundred years ago. His experiment was to demonstrate that, on the contrary to Aristotle’s theory, the falling rate of the balls was independent of their mass. A modern version of this experiment was performed on the Moon by the Commander of Apollo 15 with a hammer and a feather. For a movie of this experience, click here. When released from the same height at the same time, the two falling bodies hit the surface of the Moon simultaneously! On the Earth, however, the feather would have fluttered, as if alive, because of the air.

Initially attracted to the beauty of Amsterdam, I started my post-doctoral research at AMOLF, an interdisciplinary research institute known for exciting interactions at the interface between physical and biological sciences. The forces I was interested in were much less tangible than gravity. In particular, I was supposed to explain the driving force underlying segregation of a replicating chromosome in Escherichia coli. It sounded simple to me, except that I barely knew anything about bacteria, certainly without realizing that it was one of the long-standing problems in biology. I knew the DNA biophysics literature fairly well, but when I saw the beautiful 1992 illustration of E. coli in Goodsell, it was obvious that something like the wormlike chain model was not going to be very useful to understand segregation of the whole chromosome. What worried me was the directionality—if I were a small protein sitting on a replicating chromosome, could I tell which DNA segment belongs to which sister DNA? Physicists like questions like that, whether they are rooted in physics or biology.

Continue reading "The Bacterial Chromosome: A Physical Biologist's Apology. A Perspective." »

November 21, 2013

Good Old Days #2

by R.G. E. Murray

There is much that should be remembered about those days of intensive exploratory work and much of it using very simple methods and instruments. There was a remarkable amount of sharing of current work and results without much concern for primacy, which was automatically recognized. Communication was often by hand written notes exchanged with people on a card by mail who were then or later notables (including Lederberg and Luria) with news or questions from the lab bench. There were relatively few workers in the early days and we knew each other and what was going on. Delbruck would send a post card with the penciled statement: "Phage meeting Aug. 14th". So here's a paragraph for you.

My work in the 50’s included cytology of phage infections and for a while it involved collaboration with Joe Bertani on lysogeny. So I visited him at work in Luria’s lab at University of Illinois. This was a lesson in lab activity of those days when experiments often took very long hours of multiple stages. I arrived by train late in the evening and was taken straight to the lab, which was humming with active phage experiments and overflow from the Gunsalus lab. Memory tells me that both Luria and Spiegelman were there with active work in hand. The rush halted intermittently for discussions and I gave a brief talk on my current work about 1:00 am. A short while after that the younger Lederberg arrived to START an experiment. It was exciting enough a time to keep me awake but I retired, tired, to get ready for the more formal but unusually informative and exciting visit to a remarkably distinguished lab.

Bob_murray

Bob Murray is Professor Emeritus at the University of Western Ontario and past president of the ASM. He is known for his many contributions to our knowledge of microbial structure and taxonomy.

***** With our intention to share the flavor of the “Good Old Days,” we reprint a letter from Joshua Lederberg to Bob Murray. Note the many points he makes and his early use of the term ‘microbiota.’ - Elio.*****

Lederberg_letter

October 24, 2013

Recalling the Good in the Good Old Days

by Elio

Figure1
Fig. 1. Salvador Luria, 1912-1991. Source.

In its early days, ca. 1945-1965, molecular biology was a particularly collegial undertaking, characterized by free sharing of research data and a relative lack of egotistical behavior. The reason for this marvel may well have been that there was so much to discover—so many low hanging fruits—that there was room for everybody and enough money for the pursuit. This was a special period in the history of science, not only because stunning discoveries were made with great frequency, but also for the way science was done.

Here is an example of selflessness that I witnessed in person. In 1961 I was a faculty member at the spanking new medical school of the University of Florida. These were not ordinary times. A period of just a few years saw the discovery of the semiconservative replication of DNA by Meselson and Stahl, the postulation of the operon model by Jacob and Monod, and the elucidation of the genetic code by Nirenberg and Matthaei. In a moment of hubris, our faculty invited the future Nobelist Salvador Luria to visit and give a seminar on his research. Luria was one of the founding father of this new science, having made stellar contributions to microbial genetics. His name is associated with the Luria-Delbruck experiment that established with simple clarity that mutations were not induced by the environment but rather occurred at random. Luria’s acceptance of the invitation was a great moment for us.

We went as a delegation to our little airport and waited for the great man to come down the small airplane’s flight of steps and sample the Florida air. Now, we knew that Luria was a person of strong views, not one to hold back his opinions, but we were scarcely prepared for his first pronouncement. On looking around, he blurted out, “I hate palm trees!” So there! Having swallowed that one, we proceeded directly to the auditorium where he was to talk. We had managed to assemble a large crowd for this presentation, including medical and other students. The spacious hall was packed.

Luria ascended to the podium, took out some papers and said something to this effect: “I was going to tell about my work, but I just received a manuscript from Paris that deals with far more important results, so I will talk about that instead.” The work he chose to talk about, done at the Pasteur Institute by Brenner, Jacob, and Meselson, provided definitive evidence for the existence of mRNA. I can't recall ever again witnessing that—a speaker deciding that because of its importance, someone else’s results trumped talking about his own. But unusual as this action was, it seemed entirely in keeping with the spirit of the time. Can you imagine someone carrying out such a gesture nowadays?

June 10, 2013

Finally, Farewell to “Stamp Collecting”...

by Christoph Weigel

The perspective paper by Margaret McFall-Ngai and colleagues was recently featured by Elio in this blog, strongly emphasizing its Chicxulub-like impact on microbiology. Here I offer a postscript, a few loosely connected thoughts from a historical perspective about its impact on biology and life sciences in general.

Until the 50s of the last century, advancement in biology was largely the product of three overlapping generations—students, active scientists, and emeriti—laboring over methods, paradigms, concepts, and theories. With few exceptions, these were European and North American men. Theories put forward by the emeriti during their active time tended to be overthrown by their former students who now become active scientists themselves: a spiral of slow progress. Since experiments were tedious and methodological progress slow, scientists were inclined to heated debates regarding concepts and theories. Few theories held for more than one generation, notable exceptions being Darwin's insight of evolution, Mendel's concept of inheritance, and the cell theory by Schleiden and Schwann. Collecting thousands of different mosses or pinning thousands of insects for a museum collection was considered at least equally important as experiments, the lattermost often designed to prove an existing theory rather than to generate a new testable hypothesis. Nevertheless, Louis Pasteur's experiments disproving the spontaneous generation of life and Robert Koch's postulates for proving disease causation can be considered to have ushered in the dawn of experimental biology.

Continue reading "Finally, Farewell to “Stamp Collecting”..." »

April 15, 2013

Whose Planet Is It Anyway?

by Elio

This is the title my friend Fred Neidhardt recently used for a talk, and a good question it is. I suppose that most microbiologists and the readers of this blog would split the answer down the middle, the biomass of this planet and the chemical transactions therein being about half microbial, half everything else. However, it’s safe to say that most people, many scientists included, are unaware of the colossal importance of the microbial half, not only in biology and medicine but in geology, meteorology, and in our Earth’s habitability. This state of affairs should not be unexpected, given that we have only became aware of much of this during the last few decades. I lived roughly the first half of my life carrying only a vague notion of the global importance of the microbial world. But now we know, and the word needs to go out. A measure of microbial literacy is required for anyone to understand the workings of our living planet.

Figure1
(Top) Upper atmospheric oxygen concentration, as a percent of current levels, plotted against geological time. (bottom) Phylogenetic history of life on Earth, scaled to match the oxygen timeline. Note that the origin of the eukaryotes and the subsequent diversification of animals both correspond to periods of increasing atmospheric oxygen. Source.

Through the years, many influential writers have endeavored to convey the global influence of microbes to scientists and non-scientists alike. We can now add to these efforts a new contribution that speaks to scientists of all spheres, but especially to other biologists. It was recently published as a Perspective in PNAS, a most appropriate venue. Entitled Animals in a bacterial world, a new imperative for the life sciences, it is authored by 26 scientists whose names are bracketed by those of Margaret McFall-Ngai and Jennifer Wernergreen. It deals specifically with the role of microbes in the lives of animals. While interactions with plants and the inanimate environment are not included, this seems a fitting focus given the anthropocentric interest of most readers. The other stories are for another day, to include the viruses, the most numerous of all players and which interact with all other living things.

Continue reading "Whose Planet Is It Anyway?" »

March 11, 2013

Feynman Said “Just Look At The Thing!”

by Jan Spitzer

On October 28, 2010, Elio posted this Talmudic Question: “Richard Feynman, the famous physicist, said: It is very easy to answer many of these fundamental biological questions; you just look at the thing! To take him up on it, imagine a microscope that lets you observe single molecules in a living cell at one Angström resolution. What's the first thing you would do with it?” Thank you, Elio for allowing me to provide some thoughts on the matter from the perspective of a physical chemist/chemical engineer.

Such a microscope could indeed help address some of the fundamental issues in biology today. I must say upfront that I am surprised that microbiologists would want to look at (small) molecules (‘pure’ chemistry), or at the chemical details of ‘bigger things’, as suggested by the very notion of using a ‘Schaechter-Feynman supermicroscope’. This hypothetical instrument would have a resolution of 0.1nm with exposure times in the picosecond range (making it a bit akin to an infrared spectrophotometer) and would operate in Feynman’s quantum mechanical world. It would look at the chemistry of biology, dissecting cells into their molecular components that are then chemically characterized individually. But let me explain this more…

What Should We Look At?

Feynman suggested that ‘seeing better’ is ‘better.’ However, what we see often depends on what we are looking for. At such very high resolutions, we risk focusing on details so small that we lose context and perspective, like looking at the leaves of individual trees and losing sight of the surrounding forest. We will also miss the lakes, the meadows, and even the blazing sunset—the reddish light scattering forward from the nucleating particles of the nano-fog, the beauty of which, Feynman insists, a mere poet may miss (1). Similarly, a narrowly-focused molecular researcher overlooks the relationship of the detail to the living whole (2,3). I would suggest observing at a slightly larger scale, say dimensions of 10 to 100 nm and durations of a millisecond, to see the ‘metabolons’, ‘modules’, ‘hyperstructures’, and the many functional protein complexes (signalsomes, stressosomes, transcriptomes, dividisomes, etc.) to find out if and how they exist as discrete physical objects. We might then see these large, transient biomacromolecular clusters appear and disappear, and see them interact at the subcellular level. We could take full advantage of the atomic resolution of this supermicroscope to visualize ionic currents of ATP, GTP, phosphates, K and Mg ions, bicarbonate, glutamate etc., tracking them from their origins to where they sink and disappear. Even the vectorial ionic currents generated in the cell envelope with their movements through and around the large ‘omic’ biomacromolecular clusters could be visualized as the cell grows. What would we see when a bacterial cell begins to die? Will the ionic currents ‘die’? (4-6). So many events to explore with our supermicroscope!

Continue reading "Feynman Said “Just Look At The Thing!” " »

December 03, 2012

Why Medical Microbiology Is Not Like Stamp Collecting

by Elio

Figure3
Wonder, at the 2010 Edinburgh International Science Festival. Image credit: Edinburgh Festival Guide. Source.

I started teaching microbiology to medical students in 1958, at a time when biomedical science was in its full ascendancy. Grant money was there practically for the asking, jobs were plentiful, universities and their medical schools were frenetically building up their science base. Not entirely surprising, the general feeling of young Ph.D.’s such as myself in basic sciences departments was that we were doing the medical students a favor by stooping to teach them. Maybe I exaggerate, but not by much. We had a long ways to go.

Continue reading "Why Medical Microbiology Is Not Like Stamp Collecting" »

September 29, 2008



The View
From Here

by John
Coffin

10banner

Searching For Achilles’ Heel

Why is it so hard to make an HIV vaccine? The answer lies in the unusual relationship of this particular virus with its host.

By and large, viruses of humans and other animals interact with their hosts in one of two ways. After an initial period of rapid (often symptomatic) infection, some viruses (e.g., influenza) are cleared completely by the immune system. Others (e.g., many herpes viruses) establish a lifelong latent infection, only to reappear much later when conditions allow. In either case, the immune system effectively clears the virus from the host. Once established, the adaptive humoral response can prevent future infection with antigenically similar viruses. This is what makes vaccines work.

Achilles

Achilles Wounded in the Heel
by Paris. Sculpture by Charles
Alphonse Gumery, 1850. Gumery
shows Achilles as nonchalantly
inspecting his wound, even
though it will eventually kill him.
Source.

Relatively recently, we learned that some retroviruses, including HIV and its dozens of primate lentivirus relatives, have evolved to infect hosts other than their original ones. In the original hosts, the primary infection is usually fairly mild, but the virus is only partially cleared by the immune system. Later, virus replication and cell killing continue at the same pace for the life of the host, although at a lower level. Usually, this process has little or no effect on the host’s lifespan, allowing the opportunity for transmission to naïve animals. When the virus jumps to a new host (such as the recent transfer of HIV-1 from chimpanzees to humans and of SIVmac from monkeys called sooty mangabeys to rhesus macaques), the process of infection is essentially the same, but eventually something goes awry. Infection leads to the slow, progressive loss of the target CD4+ (helper) T cells, and thence the nearly inevitable immune collapse and death of the host.

Clearly, the benign relationship of primate retroviruses with their primary hosts is the product of a very long period of coevolution. In the process, the virus has evolved two features to avoid the immune response and therefore to make an effective vaccine highly elusive to produce. Both arms of the immune response, humoral (antibodies) and cellular are so affected.

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The View
From Here

by John
Coffin
" »

September 15, 2008



The View
From Here

by Richard
Losick

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Back to the Wild!

My dear friend Linc Sonenshein introduced me to Bacillus subtilis forty years ago when he was a graduate student with Salvador Luria. The remarkable capacity of B. subtilis to transform itself into a spore has been the focus of my research ever since. Before too long, Sonenshein and I focused on 168 and related strains, the E. coli K12 of the B. subtilis world. We did so for the reason that, thanks to the pioneering work of John Spizizen (with some magic from Charley Yanofsky and Norm Giles sprinkled in), strain 168 exhibited the remarkable capacity to take up DNA from its environment and recombine the DNA into its chromosome. This discovery of genetic competence opened the way to traditional and, eventually molecular, genetics in B. subtilis and made the bacterium a premier model organism. At the same time, and what I did not realize until many years later, we also paid a price for using a strain that had been passaged many times in the laboratory.

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The View
From Here

by Richard
Losick
" »

September 01, 2008



The View
From Here

by Julian
Davies

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The "Parvome"

This is in response to Mark Martin’s prompt*; he is an interesting and eclectic character. Well, I was not inclined to write anything, but since this week has been spent on grant writing (for not very much money, this being the style in Canada) and today, being a sunny day, I decided to cut the grass but the handle kept on coming detached from the push mower which put me in a good mood for a rant (not a blog); I am also upset about the fact that Roger Federer lost again and I don't like to see bad things happen to my heroes. But to come back to Mark’s prompt, why do microbes make so many small molecules?

Continue reading "

The View
From Here

by Julian
Davies
" »

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