A locus is a specific location or section of genetic material. The r_II locus is one of three loci composing the genetic material of bacteriophage T4 (described below).

Scientists often make models to describe something cumbersome and complicated. In the experiments above, the scientists used synthetic RNA as a model for natural genetic material.

In this paragraph, Crick is assuring us that the results are not an "artifact" of the model: Synthetic RNA is fundamentally the same as natural RNA.

DNA with only one additional base generates a completely different protein than that of the original code. The same is true of DNA with two additional bases.

However, when bases are added in triplets, the generated protein is identical to the native protein with one minor difference: an extra amino acid.

Scientific knowledge is open to revision in light of new evidence.

Science addresses questions about the natural and material world.

Great scientists tend to think in terms of questions which guide their discoveries. Good questions keep us curious, objective, and goal-oriented.

The process of making proteins.

In other words, how many bases in a row translate into one amino acid?

Let's do a thought experiment (which is considerably cheaper than a laboratory experiment):

Assume that each amino acid is coded for by two bases in a row. The code would have one of four different bases in the first position of the code (A, G, C, T) and one of four different bases for the second. How many combinations of pairs would be possible?

For example: (1) A A (2) A G (3) A C (4) A T (5) G A (6) G G (7) G C (8) G T …

If you continued to write out every combination, you would come up with 16 possible pairs of bases. However, that's four short of the 20 natural amino acids. This is a good sign that two bases is not enough to code for all possible amino acids (and, in fact, we now know that it takes three bases in a row).

How many combinations would be possible if the code were a grouping of three bases?

Ribonucleic acid, or RNA for short, is one class of genetic material. It is an example of a nucleic acid molecule.

RNA is composed of three chemical building blocks: a sugar (called ribose), a phosphate group, and a nitrogenous base.

RNA has many functions in a cell, and scientists are still studying RNA today. Some hope that RNA might be the key to disease prevention.

https://cen.acs.org/pharmaceuticals/decade-RNA/97/web/2019/01

A special class of proteins which catalyze (i.e., cause or speed up) a chemical reaction in biological systems.

Remember, that a protein is a chain of amino acids.

The chemical building blocks of proteins. All amino acids contain an amine group (-NH₂) and a carboxylic acid group (-COOH).

https://www.neb.com/tools-and-resources/usage-guidelines/amino-acid-structures

In this seminal Nature paper, Crick and co-workers demonstrate that a group of three bases codes for one amino acid; the code does not overlap; the sequence of bases is read from a fixed starting point; and the code is degenerate.

This review paper is an extended version of the paper you've read here with sections dedicated to similar questions such as: "Is the code universal?" and "Is the code overlapping?"

Since mammals and E. coli (a bacterium) are extremely different biological species, it is remarkable that their genes are comprised of identical genetic codes. Their similarity suggests the genetic code is not different per species, but universal across all living organisms.

Now scientists believe that the genetic code is universal, unambiguous, and redundant. In other words, that all living things use the same code, with few exceptions: "universal." That a codon encodes only one amino acid is "unambiguous," but that there are multiple ways to code for the same amino acid is "redundant."

But what if we could expand the genetic code or reprogram it? Professor Chin of the University of Cambridge explores this possibility here (see also in the Related Resources tab).

Nirenberg and co-workers saw that poly A was not decoded, specifically at low pH (acidic environments). At low pH, poly A is double stranded. These results suggest that the residues may need to be exposed—that RNA must lack secondary structure—to be decoded.

Hydroxyls are -OH groups and are found on the sugar ribose on the second and third carbon. In RNA, only one chemical unit in the entire strand has a hydroxyl on both the second and third (2' and 3') carbon.

Check out this image to identify the hydroxyls found on second and third carbon.

Just as your left and right hands are distinct mirror images, certain molecules have distinct mirror images, too. When a molecule has a distinct mirror image, we say the molecule is chiral.

All sugars in the body are "right handed." On a strand of genetic material, the sugars are linked together such that only one end of the chain is "handed."

Crick defines poly(Y, Z) as a DNA strand with equal amounts of two bases "Y" and "Z" in random order. Here, poly(U, C) is then a strand of genetic material with equal amounts of uracil and cytosine in random order.

An RNA molecule in which every base is uracil.

RNA that is made in the lab as opposed to natural RNA found in a cell.

Nirenberg and Matthai discovered that "special RNA"—now called tRNA—was critical to protein synthesis. A protein could only grow with enough tRNA available, demonstrating that tRNA was a critical material to generate proteins.

To hear a contemporary scientist give an in-depth account of protein synthesis, watch Johns Hopkins University's Rachel Green detail the process on this iBiology video.

Lippman and Von Ehrenstein showed that genetic material (mRNA) from a mammal could be decoded with genetic material (tRNA) from a bacteria to form the protein hemoglobin. Because hemoglobin is not found naturally in bacteria but is found naturally in mammals, this was a remarkable result: The biological material of a bacterium decoded mammalian genetic material!

The result suggests that vastly different biological species share a genetic language. This is strong evidence that the code is universal.

See a visualization here.

Von Ehrenstein and Lipmann demonstrate the genetic materials of a rabbit (a mammal) and E. coli (a bacterium) are compatible, suggesting the genetic code is universal!

This "frame shift" experiment tests whether the bases are read in singlets, pairs, or triplets.

https://ghr.nlm.nih.gov/primer/illustrations/frameshift.jpg

An organic molecule that is not naturally found in cells, as they are substituted derivatives of the parent ring.

Acridines were previously used in some dyes and many have antiseptic properties, but usage largely stopped since acridines are also a skin irritant.

By incorporating acridine into genetic material, Crick and coworkers produced mutations in DNA. These mutations led to either the addition or subtraction of one base pair in the genetic code.

A bacteriophage is a type of virus that infects bacteria. The T4 bacteriophage is a specific bacteriophage that infects E coli. Bacteriophages—like all living organisms—have genetic material.

A section of DNA or RNA that codes for a specific chain of amino acids, or "polypeptide chain." Cistron is synonymous with gene, meaning A and B cistrons are two different genes. The term cistron has largely fallen out of favor.

A section of DNA or RNA that codes for a specific chain of amino acids, or "polypeptide chain." Cistron is another word for gene. As such, it's not normally used much nowadays.

Imagine kids lined up holding hands: The line leader will have no one to hold her left hand and the caboose will have no one to hold her right hand.

Amino acids on a protein have a similar feature. The first amino acid will have an amine group exposed and the last amino acid will have an acid group exposed. The "amino end" refers to the end of the strand where the amine group is exposed.

Tsugita used an acid (nitrous acid) to chemically mutate RNA. The acid most often changed cytosine bases into uracil bases. The mutant genetic material encoded a different amino acid sequence than the unmutated, or native, form.

George Gamow (1904–1968) was a theoretical physicist. Curious about the natural world, he was often in contact with scientific giants outside of physics, such as Crick. Despite his inexperience in chemistry and biology, Gamow learned about these fields and ultimately influenced their progress. Gamow is just one of many historical examples of an outside, non-expert perspective having a profound influence on a difficult problem.

James Watson (1928–) co-discovered the structure of DNA with Francis Crick (the author of this paper).

https://www.nobelprize.org/prizes/medicine/1962/watson/biographical/

George Beadle (1903-1989) was a Nobel Prize-winning scientist credited with discovering the inherent connection between genes (DNA) and enzymes (proteins).

https://www.nobelprize.org/prizes/medicine/1958/beadle/biographical/

The exchange of genetic material between two different organisms. In the case of T4 bacteriophage, this is done by infecting a single E. coli cell with multiple phages. The phage genomes then recombine and produce new variants.

Chemically induced mutations occur when a scientist uses chemicals to alter a DNA sequence.

A class of RNA that acts as a messenger of genetic information, delivering the code from DNA to a ribosome where it is translated into amino acids, eventually resulting in a polypeptide or protein.

That is, a specific sequence of bases encodes a specific sequence of amino acids. Within this code, which is used by all living organisms, there are only four kinds of bases and 20 kinds of amino acids.

Here, bases refer to the chemical pendants—side groups of molecules—that are found on the backbone of nucleotides. Nucleotides consist of a sugar called deoxyribose, a phosphate group, and one of five bases.

An example of a base is guanine.

Francis Crick, James Watson, and Maurice Wilkins published the seminal papers about the structure of DNA, winning them the Nobel Prize in 1962. Rosalind Franklin was a major contributor to the discovery; her experimental evidence was critical for understanding DNA's structure.

Rosalind Franklin has often been uncredited and overshadowed in this historical discovery. Read more here and here.

Scientists have since tried to extend the genetic code to encode for more than the 20 natural amino acids. Read more in Science.

Poly means many and phenylalanine is a specific amino acid. Therefore, polyphenylalanine is a chain of many phenylalanine residues.

The carboxyl end refers to the carboxylic acid group exposed on the protein chain. (Remember the analogy of kids lined up holding hands? This is in the Glossary annotation of "amino end.")

A set of nucleotide bases which codes for one amino acid.

An agent that changes one base into another either by chemical methods or radiation. Acridine is not a mutagen since it does not modify existing bases in DNA, but rather adds or deletes bases.

The iron-rich proteins in our red blood cells that transport oxygen from our lungs to the rest of our body.

See the supplemental figure below.

Dintzis and Naughton demonstrated that a protein is synthesized from one end of the amino acid chain to the other, like stringing beads on a necklace one by one.

Crick has evidence from his frameshift experiments that some triplets do not code for any amino acids, but these triplets are rare.

By adding and subtracting bases from the genetic code, certain patterns arose. These patterns were consistent with three bases coding for one amino acid.

For example, if a DNA sequence contains ...CCGGAUC...

Then an individual codon might be (1) CCG (2) CGG or (3) GGA. One of these would be correct and the other two incorrect.

A chain of amino acids.

Bretscher and Grunberg-Manago debunk the hypothesis that all codons must contain uracil by analyzing the coded proteins from poly(C, A).

The 1980 Nobel Prize in chemistry went to Paul Berg, Walter Gilbert, and Frederick Sanger for successfully sequencing DNA! This scientific feat is now commonplace, generating a mixed response of enthusiasm and concern.

Read more at NPR.org:

https://www.npr.org/sections/health-shots/2017/06/26/534338576/routine-dna-sequencing-may-be-helpful-and-not-as-scary-as-feared

If codons do not overlap, then a single base change would alter the code for only a single amino acid. If codons do overlap, then a single base change may alter the code for multiple amino acids.

Since the complement base to A is U, the complementary code hypothesis would suspect AAA to code the same amino acid as UUU. Instead, AAA codes for a different amino acid (lysine) than UUU (phenylalanine), ruling out the complementary code hypothesis.

Since a strand of RNA lacking uracil encoded for various amino acids, uracil is not necessary to encode for an amino acid.

Since the only base found on the synthetic RNA was uracil (U), Crick concludes that triplets of uracil must encode phenylalanine residues.

An unproven principle assumed to be true for the basis of further discussion or logical reasoning.

This experiment is an extension of the frameshift experiment. If the bases are read in triplets, then you'd expect that four or five extra bases would ruin the code. However, six extra bases would still encode the amino acids for the native protein (with two extra amino acid residues).

Scientists now call these STOP codons.

A change in the DNA base sequence. There are many types of mutations, but here Crick refers to changing a single base of DNA (a point mutation).

A mutation that occurs naturally in biochemical systems.

A section of DNA or RNA that codes for a specific chain of amino acids.

A chemical chain made up of nucleotides. "Bases" (see previous) are one component of a nucleotide.

A chemical chain of amino acids.

Deoxyribonucleic acid, or DNA for short, is one class of genetic material. It is an example of a nucleic acid molecule.

DNA is composed of three chemical building blocks: a sugar (called deoxyribose), a phosphate group, and a nitrogenous base.

Einstein's letter was originally published in the 28 November 1919 issue of The Times, a British daily national newspaper.

During the war, Einstein lived and worked in Berlin, Germany. Communication between England and Germany seems to have been limited during the war, even among scientists in those countries. Because science is a collaborative endeavor that spans countries and cultures, Einstein understandably appreciates the renewed communication between these two important countries.

Einstein published his equations that describe gravity with respect to space and time in 1915 —right in the middle of World War I (1914-1918).

Despite poor political relations during this period, two Englishmen published experimental evidence that supported Einstein's theory. Einstein commended the English scientists and institutions for prioritizing scientific pursuits over politics.

In 1959, the Pound–Rebka experiment confirmed that light moving out of a gravitational well is in fact red-shifted.

Read more in The New York Times:

https://www.nytimes.com/1959/12/13/archives/way-to-test-an-einstein-premise-found-by-2-harvard-scientists.html

In A New Determination of the Orbit of Mercury and its Perturbations (1843), Urbain Jean Joseph Le Verrier reported a peculiar precession of Mercury's orbit that was not accounted for by Newtonian mechanics.

Relativity theory, however, provides a robust account of Mercury's motion.

General relativity theory expands special relativity theory to include any reference frame (not just inertial ones).

With no constant frame of reference, general relativity theory cannot consider space and time as separable entities.

Instead, general relativity theory describes something called "space-time" which is warped by massive bodies. Objects traveling through space-time that has been warped by these bodies will follow a warped path (even though it may appear "straight" to the object). We call this effect "gravity."

Solids are 3D objects, such as cubes, spheres, or pyramid structures.

Euclid was a mathematician in Ancient Greece. His book Elements is arguably the first mathematics textbook. In the text, Euclid describes the geometry we seem to experience in our everyday lives in which parallel lines do not intersect.

This is also the same geometry we still learn in high schools across the country (2000 years after Euclid wrote it).

Inert mass (m) is conceptually different from heavy mass (M). Heavy mass is a value that determines the strength of gravitational attraction, whereas inert mass (or inertial mass) is a value that indicates how resistant a thing is to a change of motion.

Modern physicists use the term "gravitational mass" instead of "heavy mass."

The Eötvös experiment measured the correlation between inert and heavy mass (or inertia of a body and its weight) and showed that these two masses have the same value although are conceptually distinct.

General relativity theory allows us to describe space and time regardless of a choice of coordinate systems or reference frames.

Unlike special relativity, general relativity does not assume an inertial (i.e., static) frame of reference..

Physical laws are mathematical expressions that generalize physical phenomena. Physical laws explain and predict experimental results. Conservation of energy (ΔE=0) is one example of a physical law.

Special relativity theory concludes a relationship between mass and energy (E=mc²).

Therefore, the theory marries the conservation of mass and conservation of energy as one and the same law.

Einstein states a major consequence of special relativity: We can only say two events occur simultaneously when those events share a system of coordinates.

We can always put two events into the same coordinate system, but whether they are simultaneous depends on which coordinates we use.

Einstein uses a famous thought experiment to describe this. Imagine a train traveling on railway tracks and equidistant between two trees (one ahead, one behind). If lightning strikes both trees at the same time, an observer on the train will see the lightning strike ahead before the lightning strike behind. However, an observer standing still next to the tracks (also equidistant between the trees) will see both at the same time. Thus, whether the lightning strikes are simultaneous depends on the observer's frame of reference.

Kinematics is a branch of mechanics concerned with the geometry of motion.

(Einstein clarifies what he means by "kinematics" throughout the paper. When Einstein says kinematics, he specifically refers to the physics that treats space and time as separable entities.)

This is the second principle of special relativity:

Light can be thought of as many particles (called photons) that move through space. These particles always travel at the same constant speed regardless of the inertial system in which light is observed. This has been well established by the work of many physicists.

This means that it does not matter how fast you travel towards or away from a source of light—it will always travel at a constant velocity, the speed of light.

An inertia system of coordinates is a coordinate system that we can approximate to be stationary.

For instance, we can describe the displacement of a baseball (the object of interest) relative to the baseball field (an inertia system of the baseball). Since both the baseball and the field are subject to the same rotational motion of Earth, the movement of the baseball can be described relative to the seemingly stationary field.*

Einstein gives us a way to determine if a system of coordinates is an inertia system:

A system of coordinates moving in the same direction and at the same rate as a system of inertia is itself a system of inertia.

*For the purposes of this example, we have ignored the (negligible) effect of Earth's rotation. An observer on the surface of Earth must be accelerating to follow a circular path, and the entire system is subject to the non-inertial effects of gravity.

Systems of coordinates indicate the location of a point in space in reference to some other point. In doing so, systems of coordinates form a mathematical map of physical space.

In Einstein's example, the system of coordinates for the railway train is the ground.

Einstein says the analytic method is used to form theories of principle, whereas the synthetic method is used to form constructive theories. We can understand the methods as contrasts.

The synthetic method supposes premises that help explain natural phenomena, while the analytic method reduces all natural phenomena to their common denominator. The synthetic method is a bottom-up approach, whereas the analytic method is a top-down approach.

Another way to think about the difference is that the analytical approach starts with observations, whereas the synthetic method starts with hypotheses.

(For those who are philosophy-inclined, Immanuel Kant discusses this distinction between the analytic and the synthetic.)

The kinetic theory of gases describes the motion of atoms in the gas phase and makes a number of assumptions such as:

1. The gas molecules have negligible volume compared to their container.
2. The molecules are constantly moving.
3. All collisions are perfectly elastic.

Aristotle contemplates absolute and relative motion in his book On the Heavens. He describes how heavy bodies move down and lighter bodies (like air or fire) move up relative to the center of the universe.

Read more: https://plato.stanford.edu/entries/spacetime-theories/#2

Einstein's theory of relativity is a two-part theory. Together, the two parts explain the motion of subatomic particles and gargantuan masses and address some of the shortcomings of earlier theories of motion.

The theory is well known for combining the concepts of space and time, revealing that they are inseparable.

Again, this was found by Arthur Eddington and Frank Watson Dyson in their paper.

Maxwell's equations describe how electric and magnetic fields manifest from charged particles. Together, Maxwell's equations suggest the speed of electromagnetic waves (i.e. light) is constant.

The Lorentz Force Law says that the force felt by some charged particle is related to the surrounding electric and magnetic fields.

Together their work describes special relativity, but only for electromagnetism.

Empirical methods involve observation and experience, rather than logical deduction alone.

Einstein's "English colleagues" are Arthur Eddington and Frank Watson Dyson, astronomers who obtained experimental evidence of Einstein's theory of relativity.

Modern physicists have debated whether the error bars in the Eddington experiment were larger than the effect they measured. Nevertheless, the results have been confirmed.

Read Eddington and Dyson's work here.

In the image below, the solar gravitational field influences the sun's rays framing the moon. Notice that the light bends around the moon due to the gravitational field, rather than forming a spherical halo.

A value that indicates how resistant a thing is to a change of motion.

Modern physicists use the term "inertial mass" instead of "inert mass."

James Clerk Maxwell and Hendrik Antoon Lorentz were physicists of the late 1800s and early 1900s. Their work is the foundation of the branch of physics called electromagnetism.

This is the first principle of Special Relativity:

The laws of physics are the same for all observers in uniform motion relative to one another.

This is the second kind of theory that Einstein delineates. He tells us that a theory of principle is one that is formed from the most consistent and basic observations seen across all natural phenomena.

A constructive theory is one that is built up (i.e., constructed) from assumptions to explain a natural phenomenon.

A proposition states a claim that can be either true or false.

The science that studies the relationship between heat (thermo) and work or movement (dynamic).

The region of space around the sun that is attractive to other massive bodies (i.e., the planets).