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Manuel Varela: DNA and the 3 Who Found it.

Jun 28, 2017 by

An Interview with Manuel Varela: DNA and the 3 Who Found it.

Michael F. Shaughnessy –

1) Dr. Varela, we hear it all the time- those three initials- DNA, and I learned it back in high school biology. But just for the record, what exactly is DNA (and what differentiates it from RNA?)

The term DNA is actually an abbreviation for deoxyribonucleic acid, but the initialed form, D.N.A., has been largely ignored over the many years since its structure was determined. This central life molecule has been referred to in many ways, such as the molecule that holds the secret to life, the blueprint for life, the hereditary material, the genetic code, genetic information, etc. The maxims are aplenty. The importance, however, of this nucleic acid molecule to all living beings on Earth cannot be overstated.

From a chemical or biochemical perspective, the structure of DNA has three general pieces to it. The first part is actually a sugar, commonly known as deoxyribose, which is composed of the atoms carbon, hydrogen and oxygen. In the sugar there are 5 carbon atoms, and each atom is numbered 1’ through 5’, pronounced “one prime” and “five prime,” respectively. The “deoxy” part of the deoxyribose sugar means that the molecule does not have an oxygen atom attached to it, at carbon number 2’ of the sugar molecule. That is, the oxygen is missing from the second carbon of the sugar, hence, the name deoxyribose.

The sugar is also in a so-called ring form, the technical name being a β-furanose form, in which the molecule circles back upon itself using 4 of the carbons and one of the oxygens to form the ring; so in general the deoxyribose sugar falls into a class of carbohydrates called pentoses, because of the 5 atoms that make up the sugar.

The second part of DNA consists of a series of 4 chemical base compounds, each with nitrogen atoms embedded in them, often called nitrogenous bases, or just simply bases. Two of the four bases, called guanine (G) and adenine (A), originate from a class of molecules called purines. On the other hand, the other two of the four bases, called cytosine (C) and thymine (T) derive from another class of molecules called pyrimidines.

The names have interesting origins. For instance, guanine was extracted from bird manure called guano whereas thymine was extracted from thymus tissue. If the four bases are each attached to sugar, usually at carbon number 1’, then these complexes are called nucleosides, and each of these four sugar-base nucleoside complexes are now specifically called deoxyguanosine, deoxyadenosine, deoxycytidine, and deoxythymidine (or thymidine).

The third and the last part of DNA considered here is called a phosphate, which has a central phosphorous atom linked to four oxygen atoms. The phosphate molecule is attached to carbon number 5’ of the sugar using one of the oxygen atoms to make the connection.

Hence, when all three of these structural parts are attached to each other, they are then called nucleotides, and these four base-sugar-phosphate nucleotide complexes are now each specifically called deoxyguanylate, deoxyadenylate, deoxycytidylate (or cytidylate), and deoxythymidylate (or thymidylate). The nucleotides will make up a sequence of bases along the DNA chain.

The arrangement of these three parts within a DNA molecule are organized with the sugar-phosphates on the outside forming two long chain backbones, like ladder side rails, and the bases on the inside, like ladder rungs or steps. Each of the sugar-phosphate backbone rails are known as strands, and since there are two of these sugar-phosphate strands, the DNA molecules are called double stranded. Inside the double helix, the bases bind to each other using weak hydrogen bonds in which A binds to T, called an A-T base pair, and in which G binds C, forming a G-C base pair. If one knows the base sequence of one strand then you’ll know the sequence of the other strand—this phenomenon is known as complementary base-pairing; it’s also known as Watson-Crick base-pairing.

One strand will go in one direction, called a 5’ to 3’ direction; while the other chain, attached to the first chain by forming hydrogen bonds between the bases, will go in the opposite direction, called the 3’ to 5’ direction. This phenomenon is known has anti-parallel. This anti-parallel nature of the DNA structure was a critical finding when the DNA model was proposed by Crick and Watson in 1953. The sugar-phosphate backbones on the outsides of the molecule and the bases on the inside in their ladder formation, are twisted about to form the famous double helix structure of the DNA molecule.

Structurally speaking, the RNA molecules differ from their DNA counterparts in several general ways.

First, the sugar in the RNA molecule is composed of ribose (instead of deoxyribose like in DNA) with its oxygen atom present on its carbon number 2’.  Second, the bases differ in that RNA has uracil (U), instead of thymine, both of which are pyrimidines. The ribonucleoside, composed of a ribose-uracil complex, is called uridine, and with the phosphate attached to the 5’ carbon of ribose, it is then called uridylate.

Often, RNA molecules are single-stranded, but can fold about themselves to make functional three-dimensional shapes, occasionally even forming double stranded versions of the RNA molecules.

Functionally speaking, the nucleic acids DNA and RNA differ from each other in several other ways. Let’s talk about DNA first. The string of the four bases (G, A, C, T) along the double helical DNA molecule is often called the nucleotide base sequence or simply the DNA sequence. The hereditary material stored in DNA is harbored in its base sequences and contained within certain genetic elements known as genes.

The genes on DNA encode the blueprints for proteins that are needed for life to occur. DNA copies itself by making new DNA molecules with largely the same base sequences, in a process called DNA synthesis or DNA replication. The replicated DNA, for example, will then go into a subsequent generation of living organisms.

DNA has essentially two so-called template functions: one for making DNA copies (replication) and the other for making RNA transcripts (transcription).

Let’s consider RNA for a moment. The genetic information that’s stored in DNA is then transferred to RNA, in a process called RNA synthesis or transcription. Essentially, three kinds of RNA molecules have been discovered over the years: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). The mRNA molecule, also called a primary transcript, harbors the information needed to specify the production of protein, a process called protein synthesis, or translation. The code message from DNA that’s now in the mRNA, called codons, is read by the cell’s translational machinery like, for instance, the ribosome plus associated molecules.

The tRNA “transfers” amino acids from the cell’s cytoplasm to the translational apparatus; there are dedicated tRNA molecules for each of the 20 amino acids; the anti-codons on the tRNA molecules are complementary to the codons on mRNA transcript. The rRNA makes up a large part of the gigantic ribosome, along with many proteins. Interestingly, and perhaps shockingly, the ‘enzyme’ which binds the amino acids together is made up of RNA!  It’s the rRNA that’s the enzymatic part of the translational machine. Most people usually think that enzymes are proteins, but in this case, the key enzyme is rRNA.

The translation machinery uses all three RNA types in order to produce proteins, which are chains of amino acids linked together with peptide bonds and are folded into three-dimensional structures to form enzymes and other proteins, which then carry out life’s processes, such as metabolism or cell growth, etc.

The genetic information that’s stored in DNA flows to DNA for the next generation and to RNA and to protein. In the 1950s this was known as the Central Dogma (because it was a central idea about life but with little or no experimental data to back it up, at the time), but in modern times it is firmly established and is now called genetic information flow.

2) Why is it important and what is its major relevance?

Simply put, without DNA there would be no life as we presently know it. DNA is necessary for life to occur. DNA is the center of all life, including bacteria, fungi, plants, trees, animals, and human beings. DNA specifies life.  Every living cell has a copy of all of the DNA that specifies the living being. Even viruses, which investigators are not necessarily sure are alive, have a nucleic acid core; in some viruses, the viral nucleic acid is RNA, while other viruses have DNA.

DNA is important because it manages to copy (replicate) and then convey its hereditary genetic information that’s stored in the DNA to the next generation living beings (progeny) and to all subsequent generations (descendants). Along the way, from generation to generation, DNA changes its base sequences in processes called mutation and recombination and thus results in the evolution of all living beings.

Evolution may thus be defined as the changes in DNA that occur from generation to generation. This is why progeny appear somewhat different from their parents and not identical.

DNA is important for many reasons. It’s important medically because, for instance, in genetic diseases dysfunctional or non-functional proteins may be made instead of the normal functional proteins. These aberrant proteins may then cause other life biomolecules, cells, tissues, organs, or physiological and biochemical processes to malfunction, possibly causing suffering, disease and a loss in the quality of life. It may shorten the lifespan of the individual person who has a genetic disease.

Another major reason why DNA is relevant is because investigators have invented various technologies to manipulate it for good. One such method is called recombinant DNA technology. The method has been used, for instance, to clone genes for both basic and applied studies. Gene cloning allows study of life’s process and production of useful products. Another method has been to determine the base sequences along the DNA double helix. For example, medical tests can be developed to diagnose disease, whether it’s genetic or infectious, etc. DNA can also be manipulated by genetic engineering to produce useful products, like medicines, food crops that resist insects or ripen later to assure freshness, vitamins for making our biochemical reactions work efficiently, immune system development to fight cancer or infections, insulin for diabetes, vaccines for prevention of disease, or to make the normal versions of proteins that are aberrant in genetic diseases for replacement therapy.

There’s even been an advance in the technological DNA engineering development, called gene therapy, which is designed to use non-pathogenic viruses to insert the correctly functioning DNA gene into a person with a genetic disease. A newer technology has emerged recently, called CRISPR (pronounced “crisper”) that’s designed as a gene editing system; it can insert a gap mutation within a targeted gene to inactivate it in order to learn what the gene’s function encodes, or the DNA gap can be substituted with another gene, perhaps the normal gene. Now, if you must know, CRISPR is another acronym, and it stands for clustered, regularly interspaced short palindromic repeats.

The study of DNA base sequences also has led to the development of numerous genome projects in which the entire genetic component, the genome, the collection of an organism’s entire gene make-up, can be determined. The new field, called genomics, allows study of gene function, genetic and species composition of an environment, and allows comparisons of genomes to follow evolutionary processes.

Genomics has led to the development of proteomics, or the entire collection of proteins in a given system, like an organism or group of related organisms. DNA sequence technology has been enhanced to such a great deal that our computer hardware and software cannot keep up with all of the DNA data stored in computer databases. Thus, the new field, called bioinformatics, has emerged in which knowledge of computers is combined with that of biology, in order be able to design new computers that are able to “crunch” the new ever-accumulating DNA genome sequence data.

DNA gene sequences can thus be compared, transcribed into RNA, translated into proteins, and protein sequences can be deduced straight from DNA so that protein structures and functions can be studied. These new fields are important in the biomedical sciences for the benefit of human health, such as immunity or study of new cancer treatments.

3) James Watson, Francis Crick, and Rosalind Franklin- where were they working and how did their discovery of DNA structure come about?

Interestingly, Drs. Franklin, Crick and Watson did not discover DNA.  On the contrary, the discovery of DNA actually happened much earlier in 1869 when Friedrich “Fritz” Miescher had isolated it from the pus of infected bandages as a phosphorous-containing substance he called ‘nuclein.’ The material had been derived from the nuclei of the white blood cells in the pus-laden bandages.

Instead, the work of Franklin, Crick, Watson and others such as Maurice Wilkins and Raymond Gosling, led to the elucidation of the STRUCTURE of DNA—that is, that the bases were on the inside with A binding to T and G binding to C, and that the sugar-phosphates being oriented on the outside, making strands that went in opposite directions and twisted about in a double helix configuration, etc. This was their history changing discovery—the DNA structure.

It was correctly believed at the time that knowledge of its structure would lend insight into its function.

At the time of their great discovery of the DNA structure elucidation in the early 1950s, Crick and Watson were housed in Cambridge, England at the prestigious Cavendish Laboratory, under the direction of the Nobel laureate Sir Lawrence Bragg. Franklin, Wilkins and Gosling were in London, England, at the famous Kings College, in their new biophysics department under the direction of Prof. John Randall.

Crick and Watson came about their discovery by using nucleic acid chemistry knowledge gleaned from the scientific literature and, interestingly, from the precise and carefully collected X-ray crystallographic diffraction data of DNA by collected by Franklin and Gosling—the famous so-called “photo 51,” which had been, up to that time, the best diffraction data ever seen of DNA. It’s considered to be a classic and elegant image that’s often included in textbooks today. The story is often told that this diffraction data in Franklin’s report, was shared with Crick and Watson by Wilkins, and this led them to correctly propose their model of the DNA structure.

Together, Crick and Watson built a molecular model of the DNA structure showing the main atoms and all of the correct bond angles and arrangements of the sugars, bases, and phosphates, complete with its double helical nature of its configuration. All investigators published their papers separately in the same issue of the scientific journal Nature on April 25, 1953.

These seminal Nature papers ultimately led to a revolution in the history of DNA. It led to the development of the field of molecular biology, which is, in one sense, the study of how DNA replicates itself and transcribes to make RNA which is translated to make protein.

In another sense, the discovery of the DNA structure immediately led these investigators to gain tremendous insights into function. For instance, its complementary nature led them to propose a mechanism for DNA replication. Lastly, the DNA structure elucidation led to the field of molecular biology as a methodological approach to the study of living beings at the molecular level in a way that allowed the elucidation of their physiological, biochemical, cell biological, immunological, neurological, pharmacological, microbiological processes, etc. In fact, virtually all fields within the biological and biomedical sciences are using molecular biological approaches for their studies.

4) What do we know about these three individuals?

Rosalind Elsie Franklin was born on the 25th of July in 1920, in Notting Hill, England, to Jewish parents Ellis Franklin, her father, and her mother, Muriel Waley Franklin. The Franklin family was a prosperous one, and the child Rosalind was knowledgeably fortunate in that her family was well-traveled, especially to foreign countries, a practice that expedited the learning process for an intensely curious and gifted child. Interestingly, the family has frequently told the story that, in 1910, a member of the Franklin family, Rosalind’s uncle Hugh on her father’s side, either tried to or indeed had accosted Winston Churchill, who was then England’s Home Secretary and staunchly against the suffrage movement. Apparently, Churchill was unharmed in the incident.

Young Rosalind was enrolled in Norland Place where she was recognized early on as being extremely bright. Franklin later attended The Lindores School for Young Ladies till the month of December in 1931. In early 1932, Franklin then attended St. Paul’s Girl’s School, in west London, and she was known to be an outstanding student and was bestowed numerous academic awards. She studied French, German and Italian languages plus math and science. Unfortunately, however, biology was not taught to females at the school—only to males. Franklin attended college at Newnham, in Cambridge, starting in 1938.

At the time, females at Cambridge University were not accepted as bona fide members of the university. Instead, they were considered students of Newnham College, Cambridge—the females-only component of Cambridge University. Nevertheless, as a college student concentrating in the Natural Sciences Tripos (called Tripos because students taking honors exams sat on stools with three legs), Franklin read Pauling’s famous book The Nature of the Chemical Bond. Franklin learned physics, virology of the tobacco mosaic virus, protein chemistry, and acquired a keen interest in crystallography, especially in the method of X-ray diffraction. Despite having a propensity for self-doubt and being a college student in England during the war years and the blitz, Franklin took her undergraduate degree in the field of physical chemistry in 1941 with very good grades.

Franklin’s academic record qualified her for a graduate fellowship at Cambridge, where as a Ph.D. student, she entered the research laboratory of Ronald G.W. Norrish, professor of physical chemistry, who was later to garner a Nobel. Unfortunately, Norrish at the time was possibly an alcoholic and, thus, he had trouble acquiring a security clearance to do war-related research work.

Furthermore, he assigned a trivial and undoable graduate project for Franklin—it was Franklin herself who discovered the fundamental error in the project’s design. Hence, a row ensued between the two, and in 1942 Franklin moved to Kingston, England, taking a government job as an Assistant Research Officer at the British Coal Utilisation Research Association (BCURA).  In her new post, personnel were allowed to use their work towards the Ph.D. degree; the added benefit was Franklin’s work helped the war effort. At BCURA, Franklin studied how bituminous and anthracite coals were permeable to various substances, like helium gas or water.

Successfully completing her Ph.D. thesis in mid-1945, the topic dealt with the physical chemistry of solid organic colloids in coal and related compounds. Franklin’s first publication in a scientific journal in 1946 was based on her Ph.D. work in which she provided experimental data to support her hypothesis about a molecular sieve property attributable to coal materials.

After acquiring her doctorate degree in physical chemistry, Dr. Franklin furthered her career in February of 1947 by accepting a purely research position as postdoctoral fellow in the laboratory of Jacques Mering at the Laboratoire Central des Services Chimiques de L’Etat, a laboratory that was housed in post-war Paris, France. It was a scientifically productive time for Dr. Franklin. In the Mering lab, Franklin honed her skills in the technique of X-ray diffraction in studying clay and coal materials.

The methodology was cumbersome with high maintenance equipment, sophisticated mathematics and exposure to potentially toxic chemicals. Franklin nevertheless published several key papers in the field, including a paper in the prestigious journal Nature, her first in the journal, in 1950. Dr. Franklin’s expertise in X-ray diffraction technology was soon to become a key factor in influencing DNA history.

After finishing her post-doctorate training, in 1951, Dr. Franklin was invited to conduct new research at Kings College, London, England, to become a research associate in the department of physics and biophysics, under the direction of Prof. John T. Randall. In Randall’s historical letter of appointment to Dr. Franklin, he had stated that, as far as X-ray diffraction experiments are concerned, Franklin and Raymond Gosling had their work to themselves.  It later became a problem when Maurice Wilkins had believed that either Franklin was under his direction or that at the very least, they’d be working together on the same project of DNA. Franklin had rightly believed otherwise, of course. In any case, this episode started a long-lasting rift between Franklin and Wilkins.

Nevertheless, it was during this critical time that Franklin and Gosling had obtained their famous X-ray diffraction images, of which Wilkins was to share with Crick and Watson, leading to their deduction of the largely correct structure for DNA. It is unfortunate that in Watson’s personal account of this historical era in his best-selling and famous book The Double Helix, his description of Franklin was a most unfavorable one.  On the contrary, Franklin had been known to many of her friends, family and previous professional colleagues as a warm and amicable person. Watson has been soundly criticized for his portrayal of Franklin. It is clear that without Franklin’s key data, it would have been terribly difficult for Watson and Crick to have accurately elucidated the DNA structure.

Giving up her future putative DNA work in March of 1953, Franklin moved to Birkbeck College, London, in the physics department, directed by John D. Bernal, to study the structure of the tobacco mosaic virus (TMV). Her X-ray diffraction work here was also extremely productive, showing that the RNA genome was located inside of the TMV proteins. This work was to become valuable to the field of virological research. In 1956, Franklin was diagnosed with ovarian cancer and experienced an untimely death on April 16, in 1958, at the age of 37.  It is widely speculated that had she not prematurely passed away Franklin would no doubt have been in the running for the Nobel due to her work on DNA.

It has been further speculated that she might have very well been in the running for another Nobel for her work on the TMV structure. The rules of the Nobel commission state that the prize cannot be bestowed posthumously. After her death, Dr. Franklin has been widely recognized with numerous accolades, one being the building where she did her DNA work having been declared a national historic landmark. St. Paul’s school opening up a Rosalind Franklin Technology Center, and the founding of the Rosalind Franklin Biotechnology Center at Delft, in the Netherlands.

James (Jim) Dewey Watson, Jr. was born on the 6th of April in 1928 in Chicago, Illinois, USA, to parents of modest means, James D. Watson, Sr., his father, and Jean Mitchell Watson, his mother. Watson’s sister, Elizabeth (Betty) was born 2 years later. As a child Watson was intensely curious, a quality he was to have during his lifetime. Growing up during the American depression, he was already recognized as having genius qualities and enjoyed a house filled with lots of books. The young Watson had an acute interest in birds and in books, and a prized possession of his has been a book, given to him in 1935 by his uncle, about the migration of birds. An early influence was his maternal grandmother, Elizabeth Mitchell (“Nana”), who lived with the family for a number of years.

In 1934, Watson started attending Horace Mann elementary school, where he was bullied—a situation that he grew to resent for many years to come. While in South Shore high school, Watson became interested in science after reading a 1925 Pulitzer-winning novel called “Arrowsmith” by Sinclair Lewis. Both Watson siblings finished high school early, at the age of 15, and attended the University of Chicago, both using academic scholarships and an early-admissions policy, to do so. Initially desiring to become a naturalist, Watson was immensely influenced by another book and a genetics professor. The book was “What is Life” by atomic physicist Erwin Schrödinger; this inspiration was later to have a profound historical effect. One of Watson’s college professors was Sewall Wright, a prominent geneticist who lectured about work from the laboratory of Oswald Avery in which DNA was thought to be the heredity material.

It is at this point in his education that Watson became interested in the nature of the gene; and after he took his undergraduate degree in the field of zoology in 1947, Watson felt he needed to learn genetics.

The four main take-home lessons he learned in college were 1) seek the original primary literature to acquire information 2) solve problems by figuring things out and formulating new theories 3) learn to think instead of memorizing facts and 4) seriously consider thinking about the most important things.

Rejected by Caltech and accepted by Harvard but with no funding, Watson thus entered graduate school in the Ph.D. program at Indiana University, in Bloomington, IN, USA, in 1947. Biographers of Watson relay that it is while in graduate school that Watson, perhaps influenced by others, developed an outspoken and brash manner, of which he was to retain for the remainder of his life—sometimes placing him in rather dire consequences. Watson’s graduate thesis advisor was Dr. Salvador Luria, a physicist by training who became a virologist and studied bacteriophages, which are viruses that infect bacteria.

Watson was assigned the thesis project of studying the effects of X-rays on the bacteriophage infection upon their host bacteria. In graduate school, Watson was fortunate to spend his summers at Cold Spring Harbor, New York, and later Caltech, where he was greatly influenced by biophysicist, molecular geneticist, and one of the great pioneers of molecular biology, Max Delbrück. Watson eagerly become one of Delbrück’s many protégés and consequently another member of the famous ‘Phage Group’ members of which were devoted to the study of the molecular genetics of the phage viruses.

In May of 1950, Watson took his doctoral degree after writing up his thesis project dealing with phage inactivation and reactivation with X-rays. These results did not help Watson learn any more about the molecular nature of the gene, and he felt he needed to learn chemistry in order to do so.

A new postdoctoral student at the age 22 in 1950, Watson arrived in the research laboratory of Dr. Herman Kalckar in the University of Copenhagen, in Demark.  Immediately after his arrival, he realized that he had made a huge mistake as he was bored having to learn biochemistry, instead of DNA.  Watson was becoming convinced that DNA was the hereditary material, based on the work of Frederick Griffith and of Oswald Avery. Watson frequented another Copenhagen laboratory, where the research of which was directed by Dr. Ole Maaloe, and here Watson studied how radioactively-labeled phosphorous atoms were incorporated into progeny DNA, eventually publishing this work in the prestigious Proceedings of the National Academy of Sciences.

It was during this postdoctoral stint that Watson accompanied Kalckar on sabbatical to the Zoological Station, Naples, where Watson had attended a molecular biology conference and learned about the work of Dr. Maurice Wilkins, who presented his preliminary X-ray diffraction data on nucleic acids. It was about this time that Watson became aware of the great Linus Pauling and his then recent discovery of the alpha-helical nature of protein structures.

In 1951, Watson moved to Cambridge, England, to work at the Cavendish Laboratory, where he knew that DNA and other large molecules were being studied. It is here where Watson met Francis Crick, a graduate student working under Dr. Max Perutz.

The story is told that about 30 minutes after meeting, Watson and Crick realized that they shared a common interest in DNA as being important for heredity and immediately became collaborators. Together, collaborators Watson and Crick put their brilliant minds together for the express purpose of solving the structure of DNA, before, they thought, the great Linus Pauling could do so. Watson had visited Kings College to attend a seminar given by Rosalind Franklin. Watson, failing to take notes on the specifics of Franklin’s X-ray diffraction data, incorrectly recalled the necessary parameters, which he and Crick then used to devise an incorrect triple-helical molecular model of DNA. It wasn’t until Wilkins shared the requisite X-ray diffraction data, collected by Franklin, with Watson and Crick that they were able to come up with the proper correct double-helical model for the structure of the DNA molecule.

After publishing their proposed model for the DNA structure in 1953, Watson moved to Caltech and worked with Delbrück.  Watson attempted to solve the RNA structure but failed. In 1955, Watson became an assistant professor in the biology department at Harvard, in Cambridge, MA. Meanwhile, data supporting the Watson – Crick Model for the DNA structure continued to pour into the scientific journals.

Sharing the Nobel Prize in 1962 in the area of Physiology or Medicine, Watson, Crick and Wilkins (for providing supporting evidence of the DNA structure) became widely celebrated for their historic and monumental achievement. It is considered by many scientists that the solving of the DNA structure is one of the greatest discoveries in scientific history.

During the Harvard years, between 1956 and 1976, Watson became a member of the National Academy of Sciences, wrote a definitive textbook “Molecular Biology of the Gene” in 1965, got married to Elizabeth Lewis in 1968, published his widely popular and famous “The Double Helix” in 1968, became director of the Cold Spring Harbor Laboratory (CSHL), also in 1968, and worked to devise policy on the safe use of recombinant DNA, in 1975. In 1976, Watson left Harvard and became full-time director of the CSHL, in New York.

Incidentally, Watson was to experience much trouble with his “The Double Helix” memoir. First, Crick (and others) became adamantly opposed to its publication because of the personal portrayal of himself and others. In fact, Harvard University Press had cancelled the project; although the manuscript was later accepted by Atheneum Press and by Weidenfeld & Nicolson.

This was to create a rift between Crick and Watson, lasting many years. Second, Watson, and by extension, Crick, Wilkins and Perutz, were to be widely and enduringly criticized for their handling of the affair involving the incognito use of Franklin’s X-ray diffraction data. Watson’s personal portrayal of Franklin, in particular, was summarily and extensively criticized, as many of her close friends knew her to be an extremely intelligent, warm and friendly person.

In 1979, Watson published another popular textbook, Molecular Biology of the Cell, with Beatles album covers used as themes for the artwork in later editions. The current edition of the textbook is used by many institutions of higher learning in courses devoted to the study of fields that cover DNA.

In 1986, Watson became involved in establishing the Human Genome Project, a massive effort aimed at mapping all of the genes in the human genome and then determining the sequence of every nucleotide base pair in the human genome. Among the many donors of their DNA for the project, Watson’s genome sequence was one of them; his full genome was published in Nature in 2007, using newly developed technology to complete it fairly quickly.

Starting in 2000, Watson began writing a series of essays, plus new memoirs and reminiscences, among them the sequel to “The Double Helix,” called “Genes, Girls and Gamow” in 2002, plus “DNA: the Secret of Life” in 2003 and “Avoid Boring People” in 2007. In an unfortunate interview for a book tour promotion, Watson was quoted as making racist remarks. Even though he released a public apology, the damage was done. He was fired from some positions and resigned from others. His financial situation being dire, in an unprecedented move in 2014, he actually sold his Nobel medal at auction in order to conduct research—a first in history.

Francis H. C. Crick was born on the 8th of June in 1916 to middle-class parents Harry Crick and Anne Elizabeth Wilkins Crick, nearby to the town of Northampton, England. Harry Crick was in charge of a footwear production factory, namely of shoes and boots. The child Crick was described by his mother and Aunt Ethel (on his mother’s side) as resembling an archbishop but with piercing eyes that implied a critical inquiry of the human subjects at hand. Like the young Franklin and Watson, Crick had also been recognized early on by others as being both extremely curious and gifted with exceptional intellectual abilities.

As a child, Crick was also an enthusiastic reader of various topics, including art, history and literature, but was primarily attracted to the subjects of science and math. At home, Crick set up a make-shift laboratory, attempting but failing to make silk, but succeeding in collecting flowers (earning first-place in the local science fair) and in producing small explosions—the latter of which was of a concern to his parents, of course. Interestingly, the story has been told that the young Crick lamented to his mother that by the time he grew up everything will have already been discovered, and there wouldn’t be anything left for him later. His mother reassured him that there was indeed plenty left for him to discover.

Crick’s first years of his formal education began at Northampton Grammar School, England. In 1930, Crick earned a scholarship to attend private school in London, at Mill Hill School. It is here that the young Crick eagerly read the entire freshmen chemistry textbook of Linus Pauling, “General Chemistry.” He also studied medical biology, physics and, on his own, genetics.

In 1934, Crick entered enrolled at University College, in London, majoring in physics and minoring in mathematics. Crick took his Bachelors of Science undergraduate degree, with honors, in 1937. Crick had lamented that he was taught classical (historical) physics because the new modern physics topics, e.g., quantum electrodynamics, hadn’t yet been discovered.

In 1937, Crick then entered graduate school in the Ph.D. program at University College studying water viscosity at boiling temperatures in sealed copper containers under the supervision of his graduate advisor Prof. Edward da Neville da Costa Andrade. Finding the project unfulfilling, Crick turned to the study of biophysics, but in 1939, World War II started, and Crick worked during the war as a civilian with the Admiralty, in the department of Mine Design; he also married Doreen Dodd and had a son, Michael, during this time. Returning to his Ph.D. laboratory at the end of the war, he found that his experimental apparatus had been destroyed during the war, freeing him from continuing with the water viscosity project.

With the war now over and at a loss about what to do with his career, Crick, in his autobiography, relates the advice given to him by his good friend, Georg Kreisel, a noted mathematician, who was reported to have encouragingly said to Crick, “I’ve known a lot of people more stupid than you who’ve made a success of it.”

Crick had had interests in many topics but he soon realized that he was most interested in those topics in which he “gossiped” about the most to his colleagues, narrowing the topics to molecular biology and neuroscience. In 1947, Crick was accepted to once again continue his graduate career at Strangeways Laboratory, under the direction of Prof. Honor Bridget Fell, in Cambridge, England. During this period, Crick and Doreen divorced in 1947, and in 1949 he married Odile Speed. In his new laboratory setting, Crick cultured macrophages and studied the behavior of the insides of their cytoplasmic contents. His experimental efforts led to the publication of his first paper in a scientific journal, in 1950.

In 1949, Crick was accepted into the new research laboratory of Dr. Max Perutz at the Cavendish Laboratory, under the directorship of Sir Lawrence Bragg. The institution was established by the Medical Research Council, forming a unit for the purpose of studying the molecular structures of proteins. Thus, Crick set about studying the mathematics of X-ray diffraction upon protein structure, namely oxygenated hemoglobin, until, of course, the arrival of Jim Watson to the Cavendish, in the fall of the year 1951.

Together, Crick and Watson set about to invoke the Pauling method of model building to eventually propose a largely correct molecular model for DNA that they had built using atoms built for molecular modelling. Again, Franklin’s X-ray diffraction data being a key element in pushing Crick and Watson onto the correct DNA structure elucidation, they published their famous Nature paper in 1953. Interestingly, after they closely examined their structure, Crick and Watson immediately noticed that it pointed to a key element in its function to undergo replication—that the complementary base-paring produced a template function of one strand for the synthesis of a new strand of DNA, but Watson was plagued by the fear that perhaps they had gotten the structure wrong—so they left out this and other speculations about replications and other mechanisms in the Nature paper of 1953.

However, when new data were increasingly supporting their notion of the DNA structure, they felt emboldened to follow-up on their speculations by publishing these new ideas a little later. In the meantime, however, Crick got on with his protein structure work and completed his Ph.D. in 1954, in his late 30s.

Having just astutely participated in what is considered by many scientists and historians alike to be one of the greatest scientific discoveries of all time, the DNA structure, Crick then focused his attentions onto solving the genetic code.

That is, it was not known at the time how the code embedded within the base sequences in DNA actually specified the amino acid sequences embedded in folded up and functional proteins.

Moving to the Polytechnic Institute in Brooklyn, NY, and collaborating with many other molecular biological converts, some of whom started the so-called RNA Tie Club, each of the 20 members receiving a tie with one of the amino acids on it, these investigators began the enormous effort required to solve the genetic code. In 1956, Crick formulated the so-called “adaptor” hypothesis, a molecule that is now what modern molecular biologists consider to be the tRNA molecule. These investigators also formulated their so-called Central Dogma about the flow of genetic information.

With much of the subsequent and compelling experimental data supporting the proposed Crick- Watson DNA structure, Wilkin’s work amongst these data, Crick, Wilkins, and Watson became Novel Laureates in 1962 in Physiology or Medicine, for their work. Working with Dr. Sydney Brenner, he and Crick formulated the term “codon” to describe the three-base code on mRNA that is read by the ribosome machinery to make protein. The codon principle of specifying amino acids is still used in all major textbooks that deal with DNA and the genetic code.

In 1977, Crick moved to La Jolla, CA, USA, to work at the Salk Institute for Biological Studies, where he switched fields completely to focus on neuroscience, namely, the study of consciousness. Another hobby, so to speak, was the notion of life on Earth being seeded by microbes from outer space, a phenomenon known as panspermia. Crick stayed on at Salk till his death on the 28th of July in 2004 at the age of 88.

5) On the television shows, we often hear about DNA matches. How important is our understanding of DNA to the average individual? Now how important is it for the average scientist?

I think that for the average individual, it is important to know about DNA for the following reasons. First, with the advent of rapid genome sequencing technology continually advancing for individual people and at increasingly inexpensive rates, individual people may now determine their entire personal genome sequences and consequently find out, for instance, that they may acquire a disease later in life, thus, having to make the necessary arrangements. Diagnosis of a disease may depend on the status of one’s genetic composition. New medical treatments or novel useful products from biotechnology may be heavily dependent upon DNA. Therefore, one’s general health status and quality of life may be significantly improved, if one understands one’s DNA.

Additionally, people may disturbingly find out their parents are not necessarily whom they might have previously thought. Frequently, paternity disagreements require that the biological parents are definitively identified, and this in turn calls for knowledge of the DNA status for all parties involved. Forensic biological approaches that are conducted properly will often use DNA to help solve serious crimes, and to identify victims or their perpetrators. These DNA data are routinely presented in the form of a statistical value or chance that any DNA matches did not occur by a random chance.

Importantly, it will be in a person’s best interest that one’s genome composition and sequence data be kept private, so that, for example, those in the insurance sector don’t obtain it, find out you may have (or might have at a later time) a condition perhaps requiring treatment, but that which might also be exploited by inordinately raising certain treatment costs and insurance rates. On the other hand, one’s personal physician may find their patient’s genome information handy in keeping them healthy.

For the average scientist, I’m convinced that it is imperative to know all about the biology and chemistry of DNA. The topic of DNA is central in basic courses in biology, genetics, cell biology, biochemistry, molecular biology, bioinformatics, immunology, physiology, microbiology, etc. As I mentioned earlier, just about every major discipline within the life sciences are going molecular. Without knowledge of DNA, it will become increasingly difficult to make novel and important discoveries in their chosen fields of interest.

Knowledge of the genomic statuses of entire populations of living organisms in all ecological and environmental niches may be tremendously useful in keeping our planet healthy for its inhabitants in the long run. Investigators have been interested in determining the biomes of various locations, such as the human gut, fresh waters, the Earth’s vast oceans, and soil environments—these all involve collecting DNA samples, determining their genomic nucleotide sequences, comparing the retrieved sequences with all of the other sequences within gigantic sequence databases and learning the biology, the chemistry, the ecological relationships, etc. In particular, I think that our knowledge of the genome sequences of the microbes, many of which we already know, but many orders of magnitude more microbial genomes for which we don’t, will become extraordinarily important for us all, and in many ways for which we have not yet anticipated.

6) What have I neglected to ask?

I feel extremely fortunate that someday I will be able to tell my grandchildren that I actually had the opportunity to listen to both Crick and Watson give scientific seminars. Being a biochemist by training I was converted to become a molecular biologist after reading Watson’s “The Double Helix.” After reading the book, I greatly wanted to know more about DNA. As a Ph.D. graduate student in a biochemistry and molecular biology program in the late 1980s and early 1990s, I had read the flyer on a bulletin board advertising Crick’s presentation.

The seminar was, however, to be held at the Los Alamos National Laboratories (LANL), in Los Alamos, NM, about an hour-and-a-half drive through rugged mountains in my beat up old car. The trip made safely without car trouble and arriving on the night before Crick’s seminar, I slept on the couch of my good friend and fellow graduate student, Kevin Laubscher.

The next morning, the normally highly secure gates to the auditorium were now open to the public, for Crick’s publicly held seminar. I followed Kevin as he moved past the gate entrance. I was, thus, greatly surprised as I approached the auditorium gate when the guard pointed to me still in line and asked what my nationality was—I replied that I was American (my family arrived in what is now New Mexico in 1598 with Oñate, some 20 years before the pilgrims arrived in Provincetown, but I felt this was simply just too much to explain that day).

Obviously ignoring that I said I was American, the gate guard then requested that he needed to see an ID, such as a passport, a visa, or a green card. I showed him my driver’s license. After looking at the front and back he returned it and said nothing. Not knowing what to do, I brazenly walked through the gate. I never realized it would be so much trouble just to attend a seminar!

Anyway, it was all worth it because Crick’s talk was fascinating!  He took us through the story of the DNA structure determination, in technical detail—being a graduate student and having kept up with the literature, I was able to understand it, and it was all thoroughly enjoyable! I was captivated and mesmerized. I shall never forget that day.

You can perhaps imagine my good fortune, then, when during the following year, there was yet another flyer—this time advertising a seminar to be given by Jim Watson, in LANL, of course. This time, I made double sure that my beat up old car was tuned-up as I made my drive to the hill that is Los Alamos, NM. I slept on Kevin’s couch again; the next morning, driver’s license at the ready, I boldly flashed the license, said the obligatory “American” as I again brazenly flew past the gate entrance.

In the LANL auditorium, I was not to be disappointed. Watson took us through his technical version of the DNA talk, even going so far as to predict the good that shall come as a result of the human genome project. I didn’t want the talk to end. It was so wonderful! And just when I thought the event was over, there was the announcement that students were invited to meet with Dr. Watson after the seminar, where there would be refreshments, as well.

Kevin and I made our way to the meeting room where we had hoped to meet with Watson and were supremely disappointed to find Watson there completely surround by non-students! We didn’t know who these people were but they were most certainly not any students we knew. Anyhow, Kevin and I literally elbowed our way into the front of the group, and there was Watson himself speaking, with everyone listening.

We were only about a meter away from Watson—in the same room, and he was in the middle of irascibly criticizing Crick’s notion of panspermia!

In the midst of Watson’s dressing down of Crick, I interrupted to ask the great Dr. Watson in front of everyone in the room what he had thought of “What Mad Pursuit?”

This is Crick’s book in which he had given his account of DNA and of his involvement of the genetic code work, etc.  I had read it just a few months prior to Watson’s seminar. Watson looked directly at me for what seemed to be an uncomfortable long time and finally said “Oh that’s a good book!” Then he went right back to the dressing down of Crick, precisely where he had left off, before I had interrupted him. Therein lies my personal account of Watson’s account of Crick’s personal account.

It was all too much! It was magnificent! It was great to know that these amazing scientists were also real human beings, just like ourselves. I shall never forget that day, either.

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