Adieu, François Jacob

François Jacob. Source: Nobelprize.org

François Jacob passed away on April 20, at the age of 92. He was one of the greatest biologists of the twentieth century and a very fine science writer. (Incidentally, my last post was about one of his latest books.) Excellent obituaries can be found online, including a nice piece written by Carl Zimmer.

Jacob's scientific merits are immense, but it is another aspect of his life that struck me when I discovered more about him in the days following his death. (I read the information below in the post by Zimmer and in an obituary by the French Ministry of Defense.)

In 1940, Jacob joined the French liberation army in England - he was only twenty. Since he was a medical student he served as a medic, participating to campaigns in African countries. Several times he brought back wounded soldiers under enemy fire, and was wounded himself.

In 1944 he participated to the assault at Utah Beach in Normandy, and a week later he was severely wounded (his arm and his leg) while helping the injured. He was then evacuated to Paris, and was demobilized in 1945.

Jacob finished his medical studies after the war; he wanted to become a surgeon. His wounds, however, prevented him to do so and he turned to biology and research. Needless to say, François Jacob made the best (and more!) of this forced career reconversion. 

Jacob was not only a brilliant scientist, he was also a brave man who fought to free his country. May he rest in peace.

The new biology of Carl Woese

Carl Woese. Photo courtesy of Don Hamerman.

Carl Woese, one of the giants of contemporary biology, passed away a day before New Year’s Eve (see the NY Times obituary). Woese, an American microbiologist from the University of Illinois, revolutionized our understanding of life with the discovery of a new domain of living organisms, the Archaea, and the creation of a universal tree of life made of three main branches (Bacteria, Archaea and Eukarya) (Woese, 1990). This discovery is already more than thirty years old, but is not very well known to the general public, to say the least… And now with Woese’s death the possibility of a Nobel nomination vanishes.

Everything we do nowadays in microbiology labs is to some extent influenced by the work done by Woese in the seventies and eighties. This is one reason why I entitled this post “The new biology of Carl Woese”. The other reason is a 2004 article by Woese, “A new biology for anew century”, which offers a great perspective on our job and which contains some juicy controversial elements. But let’s begin with the landmark contribution of Woese to the field of biology.

Before the sixties and the advent of molecular phylogeny, the classification of bacteria seemed an insoluble problem, since morphology and metabolism were not good enough to allow us to order the bacterial life forms. Woese, a physicist by training, decided in 1966 that he could give it a try using the powerful tools of molecular biology. At that time many researchers had turned towards proteins in order to build phylogenetic trees, following the pioneer work of Linus Pauling on hemoglobin. Woese didn’t follow the consensus and decided to use ribosomal RNA as source material. Thanks to a tedious technique called oligonucleotide cataloging, he was able to reconstruct the rRNA sequence and did that for about sixty bacteria. It took ten years.

Francis Crick and Directed Panspermia

Francis Crick. Photo Marc Lieberman

Every biologist knows that Francis Crick is the co-discoverer of the structure of DNA. What is less known, probably, is the fact that Crick was a proponent of a theory that stands at the border of science, the theory of directed panspermia.

In 1973, Crick (together with chemist Leslie Orgel) published an article describing the theory, and in 1981 he dedicated a full book to directed panspermia, entitled Life itself. 

According to Crick, the idea of panspermia – which means “seeds everywhere” – was proposed by the physicist Arrhenius at the end of the 19^th century. Arrhenius suggested that life on Earth originated from space, that our world was seeded by spores of micro-organisms traveling between planets. 

But because the radiations in space were thought to be too intense for the spores to survive, Crick and Orgel postulated a variant of the theory in which spores were transported by an interplanetary spaceship sent by an alien civilization!

The endosymbiotic theory of Lynn Margulis

Published by Basic Books

Lynn Margulis passed away last November, sadly. She was renowned for the endosymbiotic theory of evolution, which is now part of biology textbooks. She had a wonderful insight: the mitochondria and chloroplasts that are found in eukaryotic cells were, in distant past, free-living bacteria. Thanks to at least two distinct endosymbiosis events, they were incorporated—and not digested—in the eukaryotic ancestor. They became responsible of key functions within the new association, namely respiration and photosynthesis. These symbionts persisted until at some point they were indistinguishable from their host, and all merged to become one new organism, a eukaryotic cell. 

Recently I found a copy of her book Symbiotic Planet (1998) in my usual second-hand bookshop in Davis. It is a short book in which Margulis deals with the scientific idea that has occupied her during most of her career: the serial endosymbiosis theory (or SET). The author sums up the book as follows (p.33):

In short, I believe that most evolutionary novelty arose, and still arises, directly from symbiosis.

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. 

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. 

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.