Nucleic Acid Quotes

We wish to discuss a structure for the salt of deoxyribose nucleic acid. (D.N.A.). This structure has novel features which are of considerable biologic interest.

In living organisms, nucleic acid molecules are the only indefinite hereditary replicators, or at least they were until the invention of language and music.

Todd, trust math. As in Matics, Math E. First-order predicate logic. Never fail you. Quantities and their relation. Rates of change. The vital statistics of God or equivalent. When all else fails. When the boulder's slid all the way back to the bottom. When the headless are blaming. When you do not know your way about. You can fall back and regroup around math. Whose truth is deductive truth. Independent of sense or emotionality. The syllogism. The identity. Modus Tollens. Transitivity. Heaven's theme song. The night light on life's dark wall, late at night. Heaven's recipe book. The hydrogen spiral. The methane, ammonia, H2O. Nucleic acids. A and G, T and C. The creeping inevibatility. Caius is mortal. Math is not mortal. What it is is: listen: it's true.

We had to determine structures, because structures, the folds and shapes, are conserved over a longer evolutionary period than the nucleic acid sequences.

Life is information, shaped by natural selection. Carbon’s just fashion, nucleic acids mere optional accessories. Electrons can do all that stuff, if they’re coded the right way. It’s all just pattern.

The tar is an extremely rich collection of complex organic molecules, including the constituent parts of proteins and nucleic acids. The stuff of life, it turns out, can be very easily made.

It’s the pattern that matters, you see. Not the choice of building materials. Life is information, shaped by natural selection. Carbon’s just fashion, nucleic acids mere optional accessories. Electrons can do all that stuff, if they’re coded the right way. It’s all just pattern.

The spirit of a good woman cannot be coded by nucleic acids arranged in a double helix, and only an overeducated fool could think so.

If the results of the present study on the chemical nature of the transforming principle are confirmed, then nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined.

Few scientists acquainted with the chemistry of biological systems at the molecular level can avoid being inspired. Evolution has produced chemical compounds exquisitely organized to accomplish the most complicated and delicate of tasks. Many organic chemists viewing crystal structures of enzyme systems or nucleic acids and knowing the marvels of specificity of the immune systems must dream of designing and synthesizing simpler organic compounds that imitate working features of these naturally occurring compounds.

People of a “scientific” bent have been known to ridicule those, like Harry, who believe unlikely notions such as the idea that the Universe was created in six days and that the first human being was formed by God breathing into a lump of clay. It should be noted that the latest scientific theories entail that (1) all of the matter in the Universe was once compressed into an area smaller than the point of a pin; and (2) life came about when a chance collision of molecules accidentally lined up three million nucleic acids in exactly the right order to form a self-replicating protein.

So while Pauling struggled with his model, Watson and Crick turned theirs inside out, so the negative phosphorus ions wouldn’t touch. This gave them a sort of twisted ladder—the famed double helix.

Even before the exact answer was reached, Crick crystallized its fundamental principles in a statement that he called (and is called to this day) the Central Dogma. It is a hypothesis about the direction of evolution and the origin of life; it is provable in terms of Shannon entropy in the possible chemical alphabets: Once “information” has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence.

My laboratory is interested in the related challenges of understanding the origin of life on the early earth, and constructing synthetic cellular life in the laboratory. Focusing on artificial life frees us to explore novel chemical systems, but what we learn from these systems helps us to understand possible pathways leading to the origin of life. Our basic design for a synthetic cell involves the encapsulation of a spontaneously replicating nucleic acid, which acts as the genetic material, within a spontaneously replicating membrane vesicle, which provides spatial localization. We are using chemical synthesis to make nucleic acids with modified nucleobases and sugar-phosphate backbones.

Human DNA is a ladder a billion nucleotides long. Most possible combinations of nucleotides are nonsense; they would cause the synthesis of proteins that perform no useful function. Only an extremely limited number of nucleic acid molecules are any good for lifeforms as complicated as we. Even so, the number of useful ways of putting nucleic acids together is stupefyingly large- probably far greater than the total number of electrons and protons in the universe. Accordingly, the number of possible individual human beings is vastly greater than the number that have ever lived: the untapped potential of the human species is immense. There must be ways of putting nucleic acids together that will function far better- by any criterion we choose- than any human being who has ever lived. p26

I am, reluctantly, a self-confessed carbon chauvinist. Carbon is abundant in the Cosmos. It makes marvelously complex molecules, good for life. I am also a water chauvinist. Water makes an ideal solvent system for organic chemistry to work in and stays liquid over a wide range of temperatures. But sometimes I wonder. Could my fondness for materials have something to do with the fact that I am made chiefly of them? Are we carbon- and water-based because those materials were abundant on the Earth at the time of the origin of life? Could life elsewhere—on Mars, say—be built of different stuff? I am a collection of water, calcium and organic molecules called Carl Sagan. You are a collection of almost identical molecules with a different collective label. But is that all? Is there nothing in here but molecules? Some people find this idea somehow demeaning to human dignity. For myself, I find it elevating that our universe permits the evolution of molecular machines as intricate and subtle as we. But the essence of life is not so much the atoms and simple molecules that make us up as the way in which they are put together. Every now and then we read that the chemicals which constitute the human body cost ninety-seven cents or ten dollars or some such figure; it is a little depressing to find our bodies valued so little. However, these estimates are for human beings reduced to our simplest possible components. We are made mostly of water, which costs almost nothing; the carbon is costed in the form of coal; the calcium in our bones as chalk; the nitrogen in our proteins as air (cheap also); the iron in our blood as rusty nails. If we did not know better, we might be tempted to take all the atoms that make us up, mix them together in a big container and stir. We can do this as much as we want. But in the end all we have is a tedious mixture of atoms. How could we have expected anything else? Harold Morowitz has calculated what it would cost to put together the correct molecular constituents that make up a human being by buying the molecules from chemical supply houses. The answer turns out to be about ten million dollars, which should make us all feel a little better. But even then we could not mix those chemicals together and have a human being emerge from the jar. That is far beyond our capability and will probably be so for a very long period of time. Fortunately, there are other less expensive but still highly reliable methods of making human beings. I think the lifeforms on many worlds will consist, by and large, of the same atoms we have here, perhaps even many of the same basic molecules, such as proteins and nucleic acids—but put together in unfamiliar ways. Perhaps organisms that float in dense planetary atmospheres will be very much like us in their atomic composition, except they might not have bones and therefore not need much calcium. Perhaps elsewhere some solvent other than water is used. Hydrofluoric acid might serve rather well, although there is not a great deal of fluorine in the Cosmos; hydrofluoric acid would do a great deal of damage to the kind of molecules that make us up, but other organic molecules, paraffin waxes, for example, are perfectly stable in its presence. Liquid ammonia would make an even better solvent system, because ammonia is very abundant in the Cosmos. But it is liquid only on worlds much colder than the Earth or Mars. Ammonia is ordinarily a gas on Earth, as water is on Venus. Or perhaps there are living things that do not have a solvent system at all—solid-state life, where there are electrical signals propagating rather than molecules floating about. But these ideas do not

If the information coded in DNA were written down, it would make a giant library consisting of an estimated 900 volumes of encyclopedias consisting of 500 pages each. A very interesting dilemma emerges at this point: DNA can replicate itself only with the help of some specialized proteins (enzymes). However, the synthesis of these enzymes can be realized only by the information coded in DNA. As they both depend on each other, they have to exist at the same time for replication. This brings the scenario that life originated by itself to a deadlock. Prof. Leslie Orgel, an evolutionist of repute from the University of San Diego, California, confesses this fact in the September 1994 issue of the Scientific American magazine: It is extremely improbable that proteins and nucleic acids, both of which are structurally complex, arose spontaneously in the same place at the same time. Yet it also seems impossible to have one without the other. And so, at first glance, one might have to conclude that life could never, in fact, have originated by chemical means.6 No doubt, if it is impossible for life to have originated from natural causes, then it has to be accepted that life was "created" in a supernatural way. This fact explicitly invalidates the theory of evolution, whose main purpose is to deny creation.

James Tour is a leading origin-of-life researcher with over 630 research publications and over 120 patents. He was inducted into the National Academy of Inventors in 2015, listed in “The World’s Most Influential Scientific Minds” by Thomson Reuters in 2014, and named “Scientist of the Year” by R&D Magazine. Here is how he recently described the state of the field: We have no idea how the molecules that compose living systems could have been devised such that they would work in concert to fulfill biology’s functions. We have no idea how the basic set of molecules, carbohydrates, nucleic acids, lipids and proteins were made and how they could have coupled in proper sequences, and then transformed into the ordered assemblies until there was the construction of a complex biological system, and eventually to that first cell. Nobody has any idea on how this was done when using our commonly understood mechanisms of chemical science. Those that say that they understand are generally wholly uninformed regarding chemical synthesis. Those that say, “Oh this is well worked out,” they know nothing—nothing—about chemical synthesis—nothing. … From a synthetic chemical perspective, neither I nor any of my colleagues can fathom a prebiotic molecular route to construction of a complex system. We cannot even figure out the prebiotic routes to the basic building blocks of life: carbohydrates, nucleic acids, lipids, and proteins. Chemists are collectively bewildered. Hence I say that no chemist understands prebiotic synthesis of the requisite building blocks, let alone assembly into a complex system. That’s how clueless we are. I have asked all of my colleagues—National Academy members, Nobel Prize winners—I sit with them in offices. Nobody understands this. So if your professors say it’s all worked out, if your teachers say it’s all worked out, they don’t know what they’re talking about.23

We humans look rather different from a tree. Without a doubt we perceive the world differently than a tree does. But down deep, at the molecular heart of life, the trees and we are essentially identical. We both use nucleic acids for heredity; we both use proteins as enzymes to control the chemistry of our cells. Most significantly, we both use precisely the same code book for translating nucleic acid information into protein information, as do virtually all the other creatures on the planet.* The usual explanation of this molecular unity is that we are, all of us—trees and people, angler fish and slime molds and paramecia—descended from a single and common instance of the origin of life in the early history of our planet.

Pharmaceutical companies became very interested in using siRNAs as potential new drugs. Theoretically, siRNA molecules could be used to knock down expression of any protein that was believed to be harmful in a disease. In the same year that Fire and Mello were awarded their Nobel Prize, the giant pharmaceutical company Merck paid over one billion US dollars for a siRNA company in California called Sirna Therapeutics. Other large pharmaceutical companies have also invested heavily. But in 2010 a bit of a chill breeze began to drift through the pharmaceutical industry. Roche, the giant Swiss company, announced that it was stopping its siRNA programmes, despite having spent more than $500 million on them over three years. Its neighbouring Swiss corporation, Novartis, pulled out of a collaboration with a siRNA company called Alnylam in Massachusetts. There are still plenty of other companies who have stayed in this particular game, but it would probably be fair to say there’s a bit more nervousness around this technology than in the past. One of the major problems with using this kind of approach therapeutically may sound rather mundane. Nucleic acids, such as DNA and RNA, are just difficult to turn into good drugs. Most good existing drugs – ibuprofen, Viagra, anti-histamines – have certain characteristics in common. You can swallow them, they get across your gut wall, they get distributed around your body, they don’t get destroyed too quickly by your liver, they get taken up by cells, and they work their effects on the molecules in or on the cells. Those all sound like really simple things, but they’re often the most difficult things to get right when developing a new drug. Companies will spend tens of millions of dollars – at least – getting this bit right, and it is still a surprisingly hit-and-miss process. It’s so much worse when trying to create drugs around nucleic acids. This is partly because of their size. An average siRNA molecule is over 50 times larger than a drug like ibuprofen. When creating drugs (especially ones to be taken orally rather than injected) the general rule is, the smaller the better. The larger a drug is, the greater the problems with getting high enough doses into patients, and keeping them in the body for long enough. This may be why a company like Roche has decided it can spend its money more effectively elsewhere. This doesn’t mean that siRNA won’t ever work in the treatment of illnesses, it’s just quite high risk as a business venture.

They’re working on a third Peptide Nucleic Acid (pna) strand—a synthetic hybrid of protein and dna—to upgrade humanity’s two existing dna strands from double helix to triple. In so doing, these scientists “dream of synthesizing life that is utterly alien to this world—both to better understand the minimum components required for life (as part of the quest to uncover the essence of life and how life originated on earth) and, frankly,

Just as there are four nucleobases (cytosine, guanine, adenine, and thymine) that make up DNA, the nucleic acid that contains the genetic instructions for all living organisms, one might say that suffering, arising, ceasing, and path are the four nucleobases that make up the dharma, the body of instructive ideas, values, and practices that give rise to all forms of Buddhism.

True, viruses are nothing more than a tiny bit of genetic material—a single kind of nucleic acid (segmented or nonsegmented, DNA or RNA) and a coat made of protein molecules. Viruses multiply according to the information contained in this nucleic acid. Everything other than the DNA or RNA is dispensable and serves primarily to ensure that the viral nucleic acid gets to the right place in the right sort of cell in the organism hosting the virus. Viruses

once information has passed into protein it cannot get out again. . . . the transfer of information from nucleic acid to nucleic acid or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible.

The combination of amino acids into proteins and of nucleic acids into strings of RNA established the basic paradigm of biology. Strings of RNA (and later DNA) that self-replicated (Epoch Two) provided a digital method to record the results of evolutionary experiments. Later on, the evolution of a species that combined rational thought (Epoch Three) with an opposable appendage (the thumb) caused a fundamental paradigm shift from biology to technology (Epoch Four). The upcoming primary paradigm shift will be from biological thinking to a hybrid combining biological and nonbiological thinking (Epoch Five), which will include “biologically inspired” processes resulting from the reverse engineering of biological brains.

the transforming principle could not be made of DNA because nucleic acids were all alike. As

Part of the problem was that no one knew exactly how a cell took a nucleic acid sequence and turned it into a blob of protein made up of amino acids.

DMSO has been used with excellent results in transporting antibiotics to areas of the body that are hard to reach like the bone marrow and brain. DMSO can leave a virus unprotected by dissolving the virus protein coating with its nucleic acid exposed to the immune system.

Although we have yet to unlock the secrets of epigenetics, there is a growing appreciation of its impact. As Kara Rogers wrote, “[T]hey [the epigenes] do lurk, and silently, they exert their power, modifying DNA and controlling genes, influencing the chaos of nucleic and amino acids. And it is for this reason that many scientists consider the discovery of these entities in the late 20th century as a turning point in our understanding of heredity, as possibly one of the greatest revolutions in modern biology—the rise of epigenetics.

In college, whenever I struggled to remember all of the proteins and nucleic acids I needed to know intimately for my major, I would think about the surfeit of Bible verse knowledge taking up space in my brain and wish that I could empty it all out to make room for other things.

Life, as we know it on earth, appears as a synthesis of two macromolecular systems. The proteins, because of their versatility and chemical reactivity, do all the work but are unable to replicate themselves in any simple way. The nucleic acids seem tailor-made for replication but can achieve rather little else compared with the more elaborate and better equipped proteins. RNA and DNA are the dumb blondes of the biomolecular world, fit mainly for reproduction (with a little help from proteins) but of little use for much of the really demanding work. The problem of the origin of life would be a great deal easier to approach if there were only one family of macromolecules, capable of doing both jobs, replication and catalysis, but life as we know it employs two families. This may well be due to the fact that no macromolecule exists which could conveniently carry out both functions, because of the limitations of organic chemistry; because, that is, of the nature of things.

Although molecular biology was not born in 1953 with the discovery of the structure of DNA by Watson and Crick, its elucidation has provided the molecular biologist with tools and techniques that have propelled the science forward. All the information required to make a human being is contained in a single cell. The molecules comprising this fertilized egg will organize the development, sustain the life, allow for the reproduction of, and ultimately execute the demise of an individual. Molecular biology is the study of the way in which molecules function to organize life. Remarkably, the same molecules and principles lie at the heart of all the life sciences, as they control the fundamental machinery of cells. The field of molecular biology concerns macromolecules such as nucleic acids, proteins, carbohydrates, and fats, and their interrelationships, that are essential for life itself.

Yet this unlearning is precisely what needs to be done if we are to make the shift from a belief-based Buddhism (version 1.0) to a praxis-based Buddhism (version 2.0). We have to train ourselves to the point where on hearing or reading a text from the canon our initial response is no longer “Is that true?” but “Does this work?” At the same time, we also need to undertake a critical analysis of the texts themselves in order to uncover, as best we can at this distance in time, the core terms and narrative strategies that inform a particular passage or discourse. If we subtract the words “noble truth” from the phrase “four noble truths,” we are simply left with “four.” And the most economic formulation of the Four, to be found throughout Buddhist traditions, is this: Suffering (dukkha) Arising (samudaya) Ceasing (nirodha) Path (magga) Once deprived of the epithet “noble truth” and no longer phrased in propositional language, we arrive at the four keystones on which both Buddhism 1.0 and Buddhism 2.0 are erected. Just as there are four nucleobases (cytosine, guanine, adenine, and thymine) that make up DNA, the nucleic acid that contains the genetic instructions for all living organisms, one might say that suffering, arising, ceasing, and path are the four nucleobases that make up the dharma, the body of instructive ideas, values, and practices that give rise to all forms of Buddhism. ( 9 ) Craving is repetitive, it wallows in attachment and greed, obsessively indulging in this and that: the craving of sensory desire, craving for being, craving for non-being. —THE FIRST DISCOURSE Following Carol S. Anderson (1999), I translate samudaya as “arising” rather than the more familiar “origiṇ” I also

The other theory argues that replication based on nucleic acids (RNA and/or DNA) came after biological entities could support metabolism. Günter Wächtershäuser proposed a version of this metabolism-first theory in which hot water from volcanoes flowed over mineral-rich rocks to ignite (catalyze) chemical reactions that fused simple carbon-based compounds into larger ones. While catalytic enzymes, which are proteins, did not yet exist, minerals, such as those in rocks, can and do function as prebiotic catalysts for chemical reactions. According to this theory, a key step occurred when, through a series of these prebiotic reactions, the circle was closed by the regeneration of the original compound. Through such a process, complex biological molecules (proteins, nucleotides, lipids, and carbohydrates) could be made, forming the basis of simple protocells that made energy and replicated.

Phoebus Levene was characteristically blunt: ‘Nucleic acids carry no individuality, no specificity . . . It may be just to accept the conclusion of the biologist that they do not determine species specificity, nor are they carriers of the Mendelian characters.

In the management of cancer, a big problem with traditional methods has been that the patient can perceive the treatment as almost worse than the disease, since the chemicals given to attack the cancer cells also attack many other types of cell. In the frontline of cancer drug development today is a sophisticated range of drugs with names ending in ‘mab’, standing for monoclonal antibody. One half of the therapeutic molecule is an antibody against specific proteins on the surface of the target cancer cells and the other half is an enzyme. (This strategy relies on the surprising fact that, often, if the genes for two proteins are joined end to end, they successfully encode an enlarged protein combining both functions—i.e. both halves still fold successfully.) When this delivery vehicle reaches its destination, the whole molecule is taken up into the cells. The other half, chemically attached to the antibody, is the enzyme ‘warhead’ that inflicts the damage. The enzyme itself could be one that, for example, attacks the cells’ nucleic acids.

First in importance are the nucleic acids, DNA and RNA, which contain the genetic information, the software of life.

Collectively, these three cellular elements—nucleic acids, proteins, and the lipid bilayer membrane—exist for the purpose of maintaining the cell as a living system, but for this it needs a fourth class of materials, sugars (saccharides, typically glucose or sucrose).

It could simply have taken a procedure that didn’t consist of words. As a fixed memory trace it’s a protein structure. Like the head of a spermatozoon, or an ovum. After all, in the brain there aren’t any words, feelings, the recollection of a person is an image written in the language of nucleic acids on megamolecular asynchronous crystals.

Liquid water has importance as a solvent, a solute, a reactant and a biomolecule, structuring proteins, nucleic acids, cells and controlling our consciousness. In the meanwhile, water makes up over about half of us and the most abundant solid material and fundamental to start formation. There is a hundred times as many water molecules in our bodies as the sum of all the other molecules. Life cannot evolve or continue, or in other words, everything is nothing without water. Thus, we say that water plays a central role in many of the human activities. However, we nearly always overlook deep researches in the structure and properties of water and the special relationship it has with our lives.

the sample volume the protein concentration and viscosity of the sample the degree of purity of the protein product the presence of nucleic acids, pyrogens, and proteolytic enzymes in the sample the ease with which different types of adsorbents can be washed free from adsorbed contaminants and denatured protein.

Consider how the principles of the law of accelerating returns apply to the epochs we discussed in the first chapter. The combination of amino acids into proteins and of nucleic acids into strings of RNA established the basic paradigm of biology. Strings of RNA (and later DNA) that self-replicated (Epoch Two) provided a digital method to record the results of evolutionary experiments. Later on, the evolution of a species that combined rational thought (Epoch Three) with an opposable appendage (the thumb) caused a fundamental paradigm shift from biology to technology (Epoch Four). The upcoming primary paradigm shift will be from biological thinking to a hybrid combining biological and nonbiological thinking (Epoch Five), which will include “biologically inspired” processes resulting from the reverse engineering of biological brains.

Why are we so confident about carbon’s essential role in creating living things? The answer has to do with the core properties of the carbon atom itself. Carbon has four valence electrons residing in the outermost shell of the atom, which, for complicated reasons, makes it uniquely talented at forming connections with other atoms, particularly with hydrogen, nitrogen, oxygen, phosphorus, sulfur—and, crucially, with other carbon atoms. These six atoms make up 99 percent of the dry weight of all living organisms on earth. Those four valence bonds give carbon a strong propensity for forming elaborate chains and rings of polymers: everything from the genetic information stored in nucleic acids, to the building blocks of proteins, to the energy storage of carbohydrates and fats.

On the other hand, intact fiber—found in Real Food—has many benefits, and not just short-chain fatty acids (SCFAs). In the processed food industry, the germ of the grain (the nucleic acids, flavonoids, polyphenols) is removed along with the fiber because they can go rancid (see Chapter 19). Protecting the liver means maintaining the fiber and keeping the germ intact as well. Two simple precepts—protect the liver, feed the gut. Real Food (low-sugar, high-fiber) does both. Processed food (high-sugar, low-fiber) does neither. Processed food is the primary suspect in our current health and healthcare debacle, because it doesn’t improve our eight subcellular pathologies, our three nutrient-sensing enzymes, and our two physiologic precepts.