Synthetic life and vitalism

Illustration courtesy of Harry Campbell

In 1966, Francis Crick—the co-discoverer of the structure of DNA—gave a series of lectures at the University of Washington in which he discussed vitalism and the nature of life (Crick, 1966). Vitalism is this old idea according to which some sort of special force is present in living organisms, and that this force cannot be explained in terms of physics and chemistry. Crick notes that a way to refute vitalism would be to create a living organism synthetically—in other words, make a cell from scratch. Crick's remark finds a striking echo in today's research in synthetic biology, particularly in the efforts of Craig Venter.

In 2010, Venter and his team from the J. Craig Venter Institute achieved a scientific tour de force: the synthesis of a whole bacterial genome (one circular chromosome) and its transplantation into a recipient cell (a mycoplasma). The resulting bacterium was able to grow and multiply thanks to its artificial chromosome. The results were announced during a press conference in May 2010 and published in Science two months later. The long-term goal of the JCVI is not to disprove vitalism, but to design and implant synthetic genomes that can perform specific tasks, such as to produce biofuels. The mycoplasma synthetic genome, which is only slightly different from the original, serves as a proof of concept, paving the way to more important genome (re-)engineering. 

Reporter bacteria to monitor arsenic concentration in groundwater

Vials containing bioreporter bacteria. Photo courtesy of UFZ.

It is not widely known, but analytical measurements with bacterial bioreporters can 
compete with commercially available detection kits, inasmuch as the bioreporters' efficiency (sensitivity, detection limit, etc.) is often comparable - if not better - than the chemical-based systems. So why are bioreporters not more widespread? Well, the leap from the laboratory to the field is a difficult one, which demands a tight collaboration between fundamental research and engineering. In addition, economical and policy challenges need to be overcome. Today, most developed bioreporters have never left the lab.

But this may change, and a recent study by Konrad Siegfried et al. published in Environmental Science & Technology is a remarkable demonstration of the usefulness of reporter bacteria in the field. [Among the authors of this paper are three scientists with whom I had the privilege to work: Antonis Chatzinotas and Hauke Harms from the UFZ in Leipzig and Jan Roelof van der Meer from the University of Lausanne (HH directed my master thesis and JRvdM directed my PhD thesis).]

In this study, the authors used a strain of E. coli that produces bioluminescence when it is exposed to arsenite and arsenate (oxidized forms of arsenic). Bacteria detect the poison thanks to a specific activator protein which binds arsenic and triggers the expression of specific genes. The result is the production of a set of proteins, including the bacterial luciferase, which makes the bacteria glow. 

Jacques Monod and the origins of molecular biology

A beautiful model or theory may not be right; but an ugly one must be wrong. 
Jacques Monod 

 Published by ASM Press

After his work on bacterial growth, I'm now reading about Monod's later career and the discoveries that contributed to the creation of molecular biology. And for that purpose, I warmly recommend the revised edition of "Origins of molecular biology – A tribute to Jacques Monod", published at ASM Press. In this book, Agnes Ullmann and André Lwoff (two former collaborators of Monod) have compiled a collection of essays by colleagues and peers who recall their memories of the great scientist (among whom François Jacob, Francis Crick, Salvador Luria and many others). The book should be praised for providing a mosaic view that tells both the story of the science and the story of the man. And what a man! Bacterial growth kinetics, messenger RNA, enzymatic repression, lac operon, allosteric proteins… A Nobel prize received in 1965 (together with André Lwoff and François Jacob) rewarded their «discoveries concerning the genetic regulation of enzyme and virus synthesis». But, although the book portrays Jacques Monod as an extraordinary man and a great scientist, this is no hagiography, and the darker sides of his personality are evoked as well. 

The mechanics of bacterial cluster formation on plant leaf surfaces as revealed by bioreporter technology

Green and red fluorescent bacteria on the surface of a leaf

Our new publication is out there as an early view in Environmental Microbiology, and I shamelessly take this opportunity to write about it here!

Here's the story. The plant foliage is colonized by a crowd of microbes (with bacteria on the front line—up to 10⁸ bacteria per gram of leaf has been reported!). Some of them can be pathogenic, hence a threat, but most of them are harmless or even favorable inhabitants of the plant ecosystem.

Bacteria form large clusters (aggregates) of cells on the surface of leaves, but the mechanism of formation of such structures is not very well understood. What we want to know is how these bacteria grow and colonize this specific environment at the microscale, that is, at their own scale.

First, bacteria have to land on the leaf. Wind, rain, insects can all contribute to bring microbial visitors onto the leaf surface (what we call the phyllosphere), usually few cells at a time. Once on the leaf, these immigrants will grow at the expense of the plant sugars available on the leaf and, if the conditions are favorable, rapidly multiply to form clusters of up to thousands of cells. Do these clusters result from the random aggregation of cells or do they result from the reproduction of a single bacterium? The two mechanisms—that we call aggregative and replicative—are fundamentally different but not necessarily mutually exclusive. 

Thanks to fluorescence microscopy it is possible to visualize glowing bacteria on the surface of a leaf. One difficulty, however, is that we cannot follow the same microarea of leaf overtime… We are limited to a snapshot view, and so it's impossible to decide whether a given cluster was formed through aggregative or replicative behavior. For this reason we developed techniques that would enable us to deduce a posteriori what was the mechanism of formation. 

The role of textbooks in biology

"Hey, this is textbook knowledge, you should know that!"

This is what I would be told, if I were to ask a stupid question about microbiology in the laboratory. (And for the record, I believe that such things as "stupid questions" do in fact exist.) 

"Textbook knowledge" is often used to define the core knowledge that a biologist (or any scientist, as far as I can tell) should possess as a result of her education. When I was an undergraduate biology student, we used to talk about "the Campbell" and "the Alberts" to refer to our textbooks of general biology and molecular biology, respectively, and today I talk of "the Brock" to mention a reference textbook in microbiology. Textbooks are not only useful to students; personally, I often find relevant information in them, although most of my readings are scientific papers. 

A textbook should provide you with the background knowledge sufficient to operate in the current state of your discipline. (Although, of course, some will be more general or conversely will be more specific than others, depending on their goals.) 

The University of Chicago Press (Image source)

The reason I want to write about textbooks here is a consequence of my reading of "The structure of scientific revolutions" (1962), the landmark book by science philosopher Thomas Kuhn. Together with Popper, Kuhn is among the most famous philosophers of science: he coined the term "paradigm shift", which is not only a fascinating concept, but also a very catchy idea. Scientists like to use it often and in many different contexts. (Probably too often in my opinion, since paradigm shifts do not take place that frequently—if they take place at all.) 

Kuhn's book is an excellent read because it is rather concise (my edition is about 200 pages, with a 30 pages postscript) and almost devoid of jargon, which makes it very engaging. My only regret was maybe that I felt I already knew too much of it, since Kuhn's ideas have been widely explained and discussed. For instance, I remember reading a very good recapitulation of Kuhn's theses in a French translation of Alan Chalmers' book "What is that thing called science?". Nonetheless, a lot of fascinating details were still to be found.

Jacques Monod and the study of bacterial growth

Source: nobelprize.org

Among the great scientists of the 20^th century, Jacques Monod holds a prominent place. Together with François Jacob and André Lwoff he contributed to the creation of molecular biology through his study of genetic regulation, in particular the lac operon in E. coli. Before this achievement, which was awarded a Nobel prize in 1965, Monod helped define the nature of bacterial growth in a variety of experiments that took place during his doctorate. He published it in 1942, exactly seventy years ago, under the title "Recherches sur la croissance des cultures bactériennes" (a second edition, the one I read, was published in 1958).

In his experiments, Monod followed the growth of liquid bacterial cultures in flasks at controlled conditions of temperature and oxygenation. The turbidity of the culture, which was used as a surrogate value for bacterial biomass, was measured with a nephelometer (in laboratories, today, a spectrophotometer is usually employed, but the principle is the same). Bacteria were grown in complex (brain broth) or defined media with variable sources of carbohydrates. Monod used Bacillus subtilis and Escherichia coli (that he calls B. coli—Bacterium coli I suppose, which is the ancient taxonomy). 

Most notably, Monod showed that bacterial growth is limited by the amount of nutrients, but that the yield is independent of the concentration of these nutrients. The growth rate, however, is dependent of the nutrients' concentration and rapidly reaches a limit. What is more, this maximal growth rate can vary a lot with different carbon sources and temperatures. Today, we still talk about 'Monod kinetics' when we describe the growth of bacterial cultures.

What news from the ‘arsenic life’ front?

Mono Lake, CA, photo by NASA

This story has already become sort of a case study. In December 2010, NASA held a press conference about its astrobiology research program and the discovery of a bacterium from Mono Lake (CA) allegedly capable of substituting phosphorus by arsenic in its DNA. The research was published in ScienceExpress and attracted a lot of attention from the media - mostly as a consequence of the ‘hype’ factor brought by NASA, which went as far as saying that “The definition of life has just expanded”. All life on Earth shares the same DNA, whose backbone is made of sugar and phosphate. If any organism could replace phosphate by arsenate, that indeed would be very surprising and exciting.