Manuel Varela: Who was Carl Woese? And what three things do we say about him?

Jul 16, 2017 by

An Interview with Manuel Varela: Who was Carl Woese? And what three things do we say about him?

Michael F. Shaughnessy –

1) Dr. Varela, I have always believed that scientists often think differently than other normal folk. And apparently, Carl Woese also believed that the minds of scientists were somewhat more organized. So, today, let’s look at the factors that make up the mind of a scientist. First of all, what do we know about where he was born, and when and his parent’s environment.

Prof. Carl Richard Woese, an American biophysicist and bacteriological microbiologist, was born on the 15th of July in the year 1928 in the city of Syracuse, New York. Woese’s middle-class parents were Carl Frank, an engineer, and Gertrude Nadler Woese.

2) His early education- is there any significant record or things that stand out?

As a high school student in the 1940s, Woese was enrolled in the prestigious Deerfield Academy, a boarding school founded by Samuel Adams in 1797 and housed in the town of Deerfield, MA, in the U.S. The school was a largely college preparatory institution. Many of its graduates went onto Ivy League colleges and universities. In a popular book, Woese mentions that in K-12 schools in the U.S., students are taught about Petri dishes and culturing bacteria, or how to grow plants, or about the importance of environment. Presumably, Woese may have experienced these and other concepts as a student.

3) Where did he go to college? I know that some colleges teach higher order thinking and critical thinking more extensively than others.

After high school graduation, Woese attended Amherst College, a small and privately-owned liberal arts institution, situated in the city of Amherst, MA. Majoring in physics and mathematics, Woese took his Bachelor of Science degree from Amherst in 1950. While an undergraduate, his academic advisor encouraged Woese to pursue the study of biophysics. Entering the research laboratory of Dr. Ernest Pollard at Yale University, Woese became a virologist and studied the physical effects of heat and ionizing radiation on hemagglutinin from animal viruses, such as the rubella virus, avula virus, and influenza virus. Woese earned his Ph.D. in the field of microbiology from Yale in 1953, and published these works starting in 1954 at the age of 26 in the journal called Archives of Biochemistry and Biophysics.

As a postdoctoral fellow at Yale, Dr. Woese studied the induction of certain viruses, called bacteriophages or phages, which infect the endospore-producing bacterium called Bacillus megatarium during the process of germination when a bacterium is converting from an endospore to an actively growing and metabolizing state. The phage induction involves converting the phage from an integrated state, in which the phage genome is inserted into the bacterial genome, to a lytic state, in which the virus multiplies inside the germinated bacterium, producing many viral progeny and lysing the bacterial cell in turn. Dr. Woese published this work in 1960.

After briefly working at General Electric Research Laboratory as a biophysicist, Dr. Woese became a faculty member at the University of Illinois located in Urbana-Champaign, Ill, later called the University of Illinois Institute for Genomic Biology, where he remained for the rest of his academic career.

4) What is this “three domain theory of taxonomy”? And how does it apply to science?

Essentially, in 1977 Carl Woese proposed the presence of a brand new domain called the Archaea and that all living organisms on Earth could be grouped into three fundamental domains:  the Archaea, the Bacteria and the Eukaryotes. The Archaea consist of so-called ancient bacteria, most of which can be found in extreme environments, like extreme heat or cold, or in acids, salts, etc. The Bacteria domain consists of the rest of the prokaryotes. The Eukaryotes domain consists of every eukaryotic life form: all of the animals (including humans), plants, fungi, and protists.

The Three Domain system of classification (or taxonomy—the science of classification for living organisms) came about starting with Darwin’s evolutionary biology, the notion of a universal common ancestor, and subsequent groupings of related organisms into taxa (groups).  These groupings into taxa allowed a naming system for organisms so that investigators anywhere will know and understand what one means when, e.g., Escherichia coli is stated in the literature or at a scientific conference; everyone is brought to the same page when an organism’s taxonomic name is mentioned. Secondly, the Domain system facilitates learning new pieces of biological information about newly discovered organisms. The term phylogeny refers to evolutionary history. Invoking the knowledge gained from genetics, the term phylogenetics has emerged to describe the inherent evolutionary relationships.

In the 1950s and 1960s, the fields of molecular-based evolution and bioinformatics were developed. These branches started with Frederick Sanger, who developed techniques for determining the sequences of amino acids along a protein chain and later for determining the sequences of nucleotide sequences along a DNA chain. Prof. Sanger earned two Nobel Prizes for Chemistry, one in 1958 for his studies of insulin structure using its amino acid sequence, and the other in 1980 for developing his technique for determining DNA nucleotide sequences.

Then, during the 1960s, Linus Pauling and his collaborator Emile Zuckerkandl theorized that these protein and DNA sequences could be used to study evolution. The idea was that closely related groups of organisms would have related protein and DNA sequences. This is where Carl Woese enters the picture.  Woese began to study the DNA sequences of genes that he felt all living organisms should harbor, namely, DNA genes encoding ribosomal RNA, found in ribosomes.  All living organisms have ribosomes, for making proteins.

Dr. Woese collected DNA samples from all of the living beings that he could get his hands on and sequenced their rRNA gene sequences. The work was painstaking, slow, and labor-intensive. What he found after all of his hard work, however, greatly surprised him!

First, he found that the Archaea and the Bacteria, both of which are prokaryotes, were, nevertheless, distantly related to each other! Then, even more shockingly, he found that the Archaea were more closely related to the Eukaryotes than to the Bacteria! On a molecular level all life could be grouped into the famous Three Domains.

Confirmation of the Three Domain idea was established with the sequencing of the entire genome of an Archaea microbe in the 1990s. The sequence comparison results that Woese had found with rRNA genes from many different organisms all held up to scrutiny when entire genome sequences were determined in organisms from all three domains and compared to each other.

The ramifications and consequent importance of Woese’s Three Domain concept were profound. First, the molecular sequence and phylogenetic evolutionary data were used to construct a so-called tree of life, encompassing all known genomic sequence data. The tree of life pointed to a common ancestor for all life on Earth, described as the Last Universal Common Ancestor (LUCA). The LUCA concept holds up whether the phylogenetic trees are built using genes or genomes.

The tree of life also shows how modern eukaryotes have mitochondria that are derived from bacteria!  All eukaryotes have mitochondria, which are sub-cellular organelles that make ATP energy for life’s processes to occur. For instance, the human mitochondrial DNA is unlike any other eukaryotic organism’s DNA; it’s more bacterial than human!

It is widely thought that 3.8 billion years ago, during the primordial conditions of Earth, the Archaea emerged and invented new biological mechanisms that later life forms absconded with, such as enzymes that neutralize the dangerously oxidative oxygen and its equally harsh derivatives, or invented photosynthesis, or developed cellular mechanisms for the synthesis of molecular building blocks of life, such as nucleotides or amino acids. Because of these and other inventions made billions of years ago by the microbes within the Archaea domain, life on Earth became possible for eukaryotes, too, such as humans.

Further, if DNA is collected from an individual, e.g., a bacterium or a person, or if DNA is taken from an environment, e.g., soil or sea water, etc., that harvested DNA, with all of the individual genomes from the organisms present in the samples, can now be easily sequenced, then compared to the known sequences already stored in computer databases and all of the organisms identified to the species level. This new field is called meta-genomics. Because of Woese’s work, to this day whenever an investigator wishes to identify a newly discovered organism, he or she must look at the rRNA gene sequences in order to do so.

This is especially important in microbial ecology, where only an extremely small fraction of the known microbes have been discovered, thus far. Recently, it was proposed that there are at least a trillion microbial species!  Clearly, therefore, there is much more work to be accomplished if we want to know and understand who all of the microbes on Earth are. Some of these yet undiscovered microbial species may prove to be extremely beneficial.

Another ramification of Woese’s work was that using the protein sequences of amino acids, the three-dimensional structures of the proteins could be predicted and studied. This will permit investigators to learn the biochemistry of these molecules and to use them for improvement of biomedical and biotechnological products, such as in diagnostics, advances in new medicines, or in understanding how normal physiology and biochemistry happens versus how disease states manifest themselves.

Furthermore, using computers to analyze DNA or protein sequences, a field known as bioinformatics was formed. The computer analysis of protein and RNA sequences could be used to identify key evolutionarily conserved structures within these molecules that are important for determining their important functions. If evolution has kept a gene, protein, RNA, or their structures throughout time, then bioinformatics can be used to identify these so we may learn new and important cellular and molecular mechanisms.

Thus, if a new gene is discovered, and its function is unknown, a bioinformatics work-up could help identify its function. Additionally, in molecules that are homologous, i.e., they share a common evolutionary origin, their physiology could be studied closely and used to develop new therapies for disease treatments, etc.

5) What else was Carl Woese known for?

Another important field in the biological sciences that Woese had a hand in involves the study of the origin of life on Earth. The interest is in learning how life on Earth began. Towards this, Woese, along with biologists Leslie Orgel and Francis Crick, proposed a so-called RNA World theory, in which RNA arose first in the ancient primordial Earth, and that the ancient RNA could form three-dimensional structures and act like enzyme catalysts to make new molecules, like other RNA molecules and ribosomes, etc. From the RNA world, the DNA then took over as it is more stable.

Woese is also known for the concept of the so-called “progenotes” which are pre-cells with poor protein making machinery and lots of mutations in their DNA, and which may facilitate movement of new DNA between them and other cells, a process referred to as horizontal gene transfer.

6) What accolades did he receive when he was alive, and where was most of his work done?

Prof. Woese received many accolades during his life, such as entry into the National Academy of Sciences in 1998, receipt of the National Medal of Science in 2000, and the prestigious Crafoord Prize, in 2003. It is unclear, however, why Woese did not become a Nobel Laureate, as well.

The bulk of Woese’s work was conducted while he was a faculty member at the University of Illinois and the Institute for Genomic Biology. After Woese passed away on the 30th of December, in the year 2012, the institute was named after him, the Carl R. Woese Institute for Genomic Biology.

7) His later years- what did he spend his time doing?

Woese worked all of his life and in later years he became philosophical, writing books and review articles. He speculated about the evolution of non-living entities and in identifying new and future areas that he felt needed further study, such as the ecology of the planet, the usefulness of microbial ecology, finding solutions needed to solve environmental problems, and the role of the biological sciences in society.

8) What have I neglected to ask about this fascinating scientist and the way his mind seemed to work?

It may be surprising for some to know that Carl Woese, a molecular evolutionary biologist whose work has permanently altered the way authors write the textbooks, was not an atheist. He was a firm believer in God, but was leery of organized religion and of people claiming to be religious. Furthermore, he was greatly suspicious of anyone using evolution in order to argue for or against the existence of God. Woese felt that the faithful understood God as a mystery, and the truly faithful required no proof of God’s existence; and Woese understood that science was based on evidence—thus, the two areas are essentially unmixable, and should thus be kept separate. It is fascinating that many organized religions have no problem with evolution, especially if one knows that evolution involves simply the changing of DNA from generation to generation.

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