Why your DNA is not like a blueprint

By Rich Feldenberg:

When future historians may look back on the 20th century they may critical of humanities violent tendencies, and rightly so. We drove ourselves to the point of near self-extinction with global warfare and the creation of nuclear weapons. But maybe they will also see a flowering of our more nobel side, as well, with the 20th century ushering up a new understanding and appreciation of nature and ourselves. Many areas of science saw exponential advancements, with general relativity, special relativity, and quantum mechanics, all being born in the last century. As important as these fields have become, the areas of life science have arguably had an even larger impact on society and our everyday lives. It was in the 20th century that we learned that DNA is the molecule of heredity, and the structure of DNA was described by Watson and Crick in 1953 as the now famous double helix. With improvements in the methods of molecular biology in the 1980s and 90s, genomics has lead us to a more complete understanding of the underlying mechanisms of disease and how the normal processes of life operate, develop, and evolve.

The word DNA is now common in the everyday vernacular, even if not everyone remembers that stands for deoxyribonucleic acid. Also nearly everyone has some idea that DNA is vital to genes and inheritance, and is used in forensics, paternity testing, genetic testing for disease mutations, and for mapping phylogenetic trees to understand the relatedness of all life. Somehow, though, we’ve been repeatedly told that DNA is like our blueprint. That it gives the plans for creating you and me, and anything else that has DNA. That analogy is a little misleading, as DNA doesn’t act as a blueprint at all. Looking at the full genetic code of an organism wouldn’t help you know very much about what that organism looked like. The only way you might really infer this from the genetic information would be by comparing the DNA sequences to other organisms that you already know a lot about. If the DNA you are looking at was very close to the DNA coding for octopus and squid then you could guess that this organism looks cephalopod-like. The DNA would not tell you the body plan by analyzing just the code on its own, however.

So how should we think about DNA? Is there something else we can compare it to that would make a more accurate analogy? Well, instead of being a blueprint, like a technical drawing that lays out the structural relationships of each part to the other parts, it is really more like a running computer program. DNA is a lot more like a large collection of computer programs, some are always running, and others are only running at certain times or in certain cell types. The DNA is giving instructions that are carried out by hardware running the code. In this analogy the DNA is the software and the cell and its molecular machinery is the hardware running the software. Software without hardware is hopelessly ineffectual, and hardware without software is nonfunctional. They both need each other to function. The DNA needs a living cell to carry out its instructions. In the proper setting these instructions are powerful, producing a whole human being from just a single cell, as it did with you during your 9 months of gestation in the womb. So how does it work?

Well, it’s important to recall how the information stored in DNA is interpreted by the cell’s internal machinery. The DNA itself is made of two long strands, forming the famous double helix. Each strand is made of sequences of nucleotide bases, and there are four nucleotide bases to choose from in the DNA alphabet – The DNA letters are A, C, G, and T. These letters are chemically distinct nucleotides, and you can picture a gene as being a string of these letters that make a unique sentence. A typical gene may be hundreds to thousands of these letters in length. For example, the human gene for the AVP-2 receptor, found on the X chromosome, codes for a protein located on the cell surface of certain kidney cells, and is critical to regulating normal water balance. The gene contains 4676 of these DNA letters.

Starting from letter one to ten of the AVP-2 receptor DNA code, the letters read out as CTGCCCAGCC, but all 4676 letters of the DNA code for this gene are known and can be found in genetic databanks. Each strand of DNA has a complementary strand where every base in one strand pairs to another base in the other strand. A:T are pairs, and C:G are pairs. In other words, if you know the sequence of one strand you can easily deduce the sequence in the other strand, so for our first ten bases in the AVP-2 receptor – CTGCCCAGCC we know that the complementary strand would have to be GACGGGTCGG, based on the pairing rule. It is this complementary base pairing that makes it possible for DNA to replicate itself. Each strand serves as the template for making a new DNA strand. The double helix just needs to be unwound at the right time, the complementary bases added to each of the now single stranded DNA strands, and you now end up with two identical double helix DNA molecules, where you initially had just one. This has to happen for cells to divide so both of the new cells created from the original single cell has the same DNA as the original.

There are two major cell processes involved for turning the DNA code into protein. For the most part it is the protein that does the actual work in the cell, while it is the DNA that is the code-like programming being run. The first process is transcription, where the DNA code is converted or transcribed into an RNA code. The second process is translation, where the RNA code is converted or translated into the protein product. For the sake of simplicity, we are only talking about protein-coding genes, but there are many non-coding RNA genes, as well – we’ll save that topic for another day.

During transcription a molecular machines known as RNA polymerase interprets the DNA code and converts it into an RNA code, in the form of a single strand of messanger-RNA. RNA is quite similar to DNA except for a few key differences. One distinction is that it is single stranded rather than double stranded like it’s DNA cousin. Another is that it contains an extra chemical group called a hydroxyl that is lacking in DNA, and a third distinction is that whereas the letters in DNA are A, C, G, and T, in RNA the T is missing and a U is there in its place. The RNA alphabet, therefore has the letters A, C, G, and U, with A:U forming pairs and C:G forming pairs. The RNA can then be transported to the cell machinery used to make protein, and the DNA (the original code or source code) can remain safe in the chromosome – only the transcribed copy is sent out.

The messenger-RNA (mRNA), finds it’s way to the ribosomes which are complex molecular machines that take the RNA code and make the actual protein. The RNA code is read by the ribosomes with every three bases forming a codon that specifies an amino acid. The protein is a string of amino acids. A few codons also tell the ribosome where the protein ends, and are called stop codons. The protein may still have a few steps to go before it is fully functional. For example it may need to have certain sugars or other chemical groups added at particular locations. It also needs to be folded into a very specific 3-dimentional shape, and it may need to associate with other proteins to form a part of a larger protein complex. Then it may need to be transported to specific sites in the cell, or even exported out of the cell, to do a job located in a different place in the body.

So why is our DNA not like a blueprint? Well, even if you could read the entire DNA code for all the protein producing genes, you would only see the ingredients that the DNA was coding for. That is far from a blueprint that might show you the structure of a building, where it’s doors, windows, elevators, stairwell, and so on, are located in spacial relation to one another. Knowing the protein products only gives you a list of ingredients. How those ingredients interact together, in time and space, is what creates an organism. The genetic code is a set of instructions that is executed on the code reading machinery of a living cell. The beauty of it is that not all the genes are transcribed at the same time and in the same amounts. Only a fraction of genes would be operational at any given time, and in a complex multicellular organism, only certain genes will ever be transcribed in any particular cell type. That is what makes a kidney cell different from a brain cell different from a cell in the heart muscle, and so on. Every cell has all the genetic programs, but only runs a subset of the total programs necessary for its own type.

DNA without the code reading cell machinery can do nothing on its own, which is why the vital flame of life must be passed down from living cell to living cell, uninterrupted since the very beginning of life itself. The genetic program is sophisticated enough that it causes genes to be transcribed that produce proteins that are themselves transcription factors secreted out of the cell to instruct neighboring cells as to which of their genetic programs to begin running. It is this complex coordination, leading to the switching on or off of particular genes in other cells, that starts the process of building a whole multicellular organism. In this way it is not just the genetic program that is necessary for building a animal, or person, or plant, but the local chemical environment that the program of each cell finds itself living in. The chemical neighborhood is just as important as genetic constituency.

In the language of Object Oriented Computer Programming, like Java for example, we might say that the complete genome of an organism is a program with many Classes (genes), and that when these classes are run instantiate Objects (proteins). Each and every cell in a body has the same program, but depending on it’s interaction with neighboring objects will Call only certain classes for use at any given time, and in some cases will never use particular classes that it has access to. These objects then go on to run all the functions necessary for that cell, including affecting other cells to call on certain objects in some cases. A human kidney cell has the entire “Human Program” as part of its software, but will only call on the classes used by a kidney cell, because it was derived from a cell that at one time could use all classes (Pluripotent stem cell), but at a certain point was instructed by its chemical environments to only allow use of the kidney classes. In other words, it differentiated into a kidney cell, thereby losing the ability to be a different cell type.

This is one reason, that even though we have completely sequenced the human genome, we still have a very incomplete understanding of what most the the genes are doing. Just by looking at their code it is not easy to determine what their affect is in a whole organism. The computer analogy may not be the perfect analogy, but it does illustrate the problem much better than the typical blueprint analogy does.

 

Other interesting things about DNA, and other fun topics:

1. “Intron Retention: a common cause for cancer“.  by Rich Feldenberg. ZME science. 1/25/2016.
2. Alternative Splicing.  Wikipedia.
3. Non-coding RNA.  Wikipedia.
4. “Why the Horta would not have looked like a rock monster“.  Darwin’s Kidneys.  June 18, 2015.

Mutation Monday: OxoG is how radiation turns your own water against you!

by Rich Feldenberg

Welcome back to your mutation station.  Today we’ll examine how ionizing radiation breaks water molecules apart to form oxygen free radicles (or reactive oxygen species), which then go on to wreak havoc with your DNA.

Most of the damage done to us by ionizing radiation, such as X-rays and gamma rays, are not a consequence of direct hits to our DNA,  but are a secondary effect of the radiation splitting water into highly reactive and destructive molecules – the oxygen free radicles.  It is these oxygen free radicles that then go on to damage our cell’s vital components, like DNA.  Water is by far the most common molecule in our bodies, and statistically will be the most likely thing hit by an energetic photon of radiation that strikes us.

The oxygen free radicals are molecular species, such as the extremely reactive hydroxyl radical (*OH),  as well as hydrogen peroxide (H2O2) and the superoxide radical (*O2-).   These are often called oxygen free radicals, but not all of them are technically radicals (having an unpaired electron), so reactive oxygen species is really a more appropriate term.  These reactive molecules can then oxidize susceptible places on the DNA that lead to mutation.  Hydroxyl radical, is by far, the most reactive of the bunch, and basically reacts immediately with whatever is in it’s way as soon as it is formed.

1=singlet oxygen (higher energy state), 2=molecular oxygen, 3=superoxide radical, 4=hydrogen peroxide, 5=hydroxyl radical.

A common site of damage is the oxidation of the nucleotide base guanine (G) to produce 8-hydroxyguanine, also known as oxoG.  Whereas, normal guanine will base pair with cytosine (C), oxoG can base pair with both cytosine and adenine (A).  If oxoG happens to base pair with A, then after the next round of DNA duplication there will be a point mutation from the original G:C to the newly mutated T:A.  It turns out that this particular switch is very common in many tumor cells, and may be due to the damaging effects of radiation.

Oxo-G forming an inappropriate base pair with adenine

In this way, the effects of radiation are mainly by turning your own water against you.   In addition to radiation, oxygen free radicals are produced just by normal metabolism.  As we extract energy from sugar molecules, we pass electrons down the “respiratory chain – a set of enzymes in our mitochondria, that eventually react with Oxygen to form water.  During this process, free radicals are produced that have the same effect as those produced by water’s interaction with radiation.  It has been estimated that in just one year of breathing – something we all have to do if we are alive – is the equivalent of 10,000 chest X-rays worth of radiation.  Just being alive is dangerous!

References:

1. “Oxygen: the molecule that made the world”, by Nick Lane.  See chapter 6 (Treachery in the air) for some of the stats listed.   (a really great book, by the way).

2. “Molecular biology of the gene”, 7th edition, by James Watson;  ISBN-13: 978-0321762436 
Also an awesome text.

Mutation Monday (Your Mutation Station): Thymine dimers

by Rich Feldenberg

Welcome back to your mutation station.  Today we’ll look at a harmful effect on your DNA due to ultraviolet light, which leads to dimerization of the nucleotide bases thymine (T).  If there are two T bases next to each other in the DNA strand and they absorb UV light they can undergo a photochemical reaction that causes them to link-up.   The double bonds in the base break and then form single bonds to their neighbor.

This blocks normal base pairing on to the other DNA strand of the double helix, and results in a mutation.  Fortunately there are cellular repair mechanisms that can find and fix these errors, but some errors escape detection and cause major harm.  Some melanomas are thought to be due to thyimine dimers caused by the effect of UV sunlight.

Thymine dimers are actually a more specific form of what is called pyrimidine dimers.  The bases thymine and cytosine (T and C) are pyrimidines.  Two pyrimidines can dimerize under the same conditions leading to the same sort of DNA mutations.  You could have T-T dimers (thymine dimers), but also T-C, and C-C leading to the same problems.   So, remember to use sunblock and be careful about exposure to the sun!!

Origins Sunday: Evolution of life’s first proteins

Check the link below for some cool research in the origin of life on earth!!
Evidence of key ingredient during the dawn of life

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Is “Bad Luck” really a diagnosis?

By Rich Feldenberg

Earlier this year the mainstream media reported findings from an article published in the prestigious journal Science, which investigated the causes of human cancer.  This would have been all well and good except that it resulted in the appearance of sensational news headlines across many top outlets, featuring the shocking conclusion that approximately two-thirds of cancer in adults is due to sheer bad luck.  Yes, you read that correctly, bad luck is apparently the main cause of cancer!  The title of the original research paper doesn’t actually mention “bad luck”, and the Science article is really about demonstrating a correlation between tissues that undergo high numbers of stem cell divisions with those tissues that have a high incidence of developing cancer.  There is a strong 1:1 correlation, showing that as the number of cell divisions increase in a given tissue type, the development of de novo malignancy also increases, and tissues that undergo low levels of stem cell divisions have a low chance of developing tumors.  That seems to make sense, and is not terribly surprising given that clinical medicine has known for decades that tissues with rapid cell turnover are tissues where cancer is more likely to crop up, such as bone marrow and intestinal epithelium, just to give a couple examples.

The title of the original research article, “Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions”, was published in the Jan. 2nd, 2015 edition of Science.   In the popular media the lead author, cancer researcher Bert Vogelstein at Johns Hopkins University School of Medicine was quoted as saying, “all cancers are caused by a combination of bad luck, the environment, and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development”.  A nice sound bite, to be sure, but attention immediately focused on the bad luck part of the explanation, as most people already assume that environment and heredity have something to do with it.  This became the essence of the mainstream new headlines.  For example, CNN reported that, “bad luck can cause cancer”, and Fox News reported that, “Study concludes that many cancers are caused by bad luck in cell divisions”.

So what does bad luck have to do with all of this?   Are cancer researchers a superstitious lot?  Does invoking bad luck have any real explanatory or predictive power, and does doing so benefit the patient or clinician in any way?  My initial reaction to these headlines was that by describing a phenomenon as lucky or unlucky one seems to be crediting some kind of conspiring supernatural force out in the universe, intent on doing harm to the unlucky, and protecting the favored lucky ones.  It’s probably more likely -I hope- that the author of the study chose to use this sort of language for it’s shock value to gain the media attention.  The language used is almost certainly why the media picked up on this story bringing it to front page status.  If the authors had stuck with wording such as “cancer risk is related to stem cell divisions”, then it is unlikely that it would have drawn nearly the amount of media attention as was obtained by the more provocative “bad luck” statement.

The philosophy of luck can be reasoned about in several ways, and it’s this ambiguity that has the potential to create some problems and unnecessary confusion.  Wikipedia defines luck in one of two major categories, as prescriptive or descriptive.  It is this prescriptive definition that I worry many people will incorrectly assume to be the meaning, when sickness or disease is attributed to bad luck.  In the Wikipedia article, the prescriptive sense is defined as “ a deterministic concept that there are forces (e.g. gods or spirits) that prescribe that certain events occur”.   The same article defines the descriptive sense of luck as when, “people speak of luck after events that they find to be fortunate or unfortunate, and maybe improbable”.

What Vogelstein is referring to as bad luck is actually the unpredictable random gene mutations that occur more frequently in the tissue where stem cells divide more rapidly.  This appears synonymous with bad luck because it seems to defy a satisfying explanation, but it’s not bad luck in the magical prescriptive sense.  The universe is not conspiring against the person who get cancer anymore than it is protecting the person living a long cancer free life.  The prescriptive definition of luck also hints at the idea that your luck can’t be changed until something happens to change it.   You have bad luck, after all, so why should you expect the future to hold any different sort of fortune.  If you got cancer because of bad luck, well then you’re probably not going to be very lucky in the treatment for your cancer, or the way you handle chemotherapy, or if your wife is going to support you through this challenging time, and so on.

Well, let’s look at what the original article is really telling us.  Why are more frequently dividing stem cells more likely to turn into cancer cells?  When a cell divides through the process of mitosis, the complete set of nuclear DNA is copied so that each new daughter cell can begin it’s life with the same DNA as the parent cell.  The cellular machinery to copy DNA is sophisticated and there are both proofreading and repair methods to ensure high fidelity of the DNA copy.  However, if a mistake is made in the copy process that escapes the proofreading and repair mechanisms then it remains as a new mutation.   Keep in mind that at this point, we are not even talking about the mutations that can arise from radiation or cancer causing mutagens, such as stray cosmic rays from space, an X-ray from that chest X-ray taken at the hospital, or even the carcinogenic chemicals inhaled from second-hand smoke.  We’re simply talking about mistakes made during the normal process of cell division.  In this case you couldn’t have ducked behind a steel beam as the cosmic ray zipped through the atmosphere from deep space or held your breath as you passed those smokers on the sidewalk.  These mutations are going to happen because you’re a working machine that acquires wear and tear as you go about the business of living.  Despite billions of years of evolution to minimize such mistakes, they have to happen at a certain rate because the proofreading and repair processes simply aren’t perfect, and cells have to divide a lot to get you from a fertilized egg to a full grown human being.  Some cells continue to divide even after maturity to maintain the cell line.  This is true for red blood cells derived from the bone marrow, for example, since the circulating RBC has only a limited life span in the bloodstream of around 120 days and needs to be replaced by stem cells in the bone marrow to prevent anemia.  Even though the error rate in DNA copying is incredibly low, only about 1 in 10¹¹ (that is one in a 100 billion), when you consider that there are about 3 billion (10⁹) base pairs in the genome of each and every human cell, and that there are trillions of cells in the human body, the number of base pairs being copied is rather astronomical!  It’s actually amazing that the process is as efficient as it is.

There are several factors that make it impossible for perfect fidelity to ever be achievable in the replication of DNA.  One such factor is a chemical reaction known to affect the nucleotide bases in DNA known as tautomerization.  The nucleotide bases are what accounts for the genetic information encoded in the DNA molecule.  The DNA also contains a sugar called deoxyribose, and a phosphate backbone.  The four DNA bases are adenine, thymidine, cytosine, and guanine, usually referred to as A, T, C, and G respectively.  These bases contain complex functional groups (in the language of organic chemistry) such as keto-groups and conjugated dienes.  There is a rapid interchange in chemical structure that naturally takes place so that the keto-group transforms into an enol and back again.  These two forms of the molecule interchange so quickly that they are really considered the same molecule, and are a special type of isomer.  The keto-form, is the “right” form for base pairing to the proper nucleotide on the other DNA strand, and if it happened to have flipped to the enol form during he critical period of base pairing, then it will have paired with the wrong base.  Most of the time the base will be in the keto-form, but in about 1 in 10⁵ bases the other tautomer will be found.

This lead to mutation due to the incorrect base being copied from the DNA strand opposite the enol-form of the base.  The cell’s proofreading machinery will not be able to tell that a mistake was made in this case.  And so, some low level of gene mutation is inevitable.  For this type of mutation forming process, everyone has essentially the same risk.  Cells that replicate more often would be expected to accumulate these types of replication errors more often.  Even without processes like tautomerization, the replication machinery will simply put the wrong base in the wrong place at some low level rate, and occasionally this will escape detection by the proof reading part of the process.  Mistakes just happens!  Poor DNA polymerase is held up to an unrealistically high standard.

Besides replications errors, other cancer causing mutations may vary depending on your exposure to high risk situations, but still occur to some degree even under low risk, normal conditions.  Examples are exposure to radiation, carcinogens, or inherited genes that raise the risk of cellular malfunction.   There is a constant low level background exposure to radiation from uranium, and other radioactive elements, in the rocks and ground, or from cosmic radiation from space.  Carcinogens are all around us, and include exposure to tobacco smoke, but also many other naturally occurring carcinogens such as aflatoxin B produced by fungus growing in peanut butter and nuts and even certain viral infections such as Hepatitis B and Human Papilloma virus.  Well known types of inherited gene mutations that increase cancer risk considerably include BRCA1 and BRCA2 in relation to breast and ovarian cancer, but there are most likely many other more subtle gene variants that alter your odds of other cancers, as well.  This is the environment and heredity part of the equation.

It should also be kept in mind that mutations that do arise supply the variation necessary for evolution by natural selection.  Now, most mutations will be silent, meaning they don’t produce any noticeable effects at all.  This is due to the fact that most of the DNA in our cells are not part of genes, and do not code for any particular proteins.  Only about 2% of DNA is codes for protein.  Another small percentage of the non-coding regions (it’s unclear and how much and different sources report different amounts) of DNA have the job of regulating which genes are expressed and when to express them, and a small bit more code for RNA that serve in protein synthesis.  Most of the DNA has no known function and appears to be remnants of ancient viral infections and gene duplication events.  The term junk DNA has been used to describe this wasteland of the genome, and while the term is not without controversy, since there is almost certainly more functional parts of the genome in there yet to be found, it is probably true that the majority of it is dead weight, being replicated from generation to generation without any true utility.  Mutations here will not cause disease, but are very useful for making phylogenetic trees to identify which organisms are more closely related to each others by comparing the similarities and differences that accumulate over time showing common decent.

Some mutations, however, may chance to happen in an actual protein coding gene, but in such a way that the protein expressed is unchanged due to the redundant nature of the genetic code.  More than one of the triple DNA base codons (the code that DNA uses to specify an amino acid) can code for the same amino acid.  Other mutations, however, will alter the gene in some important way, such as placing the wrong amino acid in the protein altering the protein’s function is some critical way.  Sickle Cell anemia is a classic example of this where a mutation has turned the codon GAG into an alternate codon GTG, so instead of glutamic acid being placed in the hemoglobin protein, horrible valine is placed there instead.  This alters the chemistry of hemoglobin considerably.  Even worse, a mutation might turn a codon for a particular amino acid into a stop codon instead, which tells the cell to end production of the protein, resulting in a shortened protein missing vital parts needed to function.  If such mutations happen in a gene necessary for regulation of the cell cycle then a cancer cell might just have been born.

As a pediatric nephrologist I care for children that often have very serious kidney disease, that may sometimes lead to kidney failure making chronic dialysis or kidney transplant necessary in order to survive.  As you might imagine, this can be a devastating blow to a family.  It is quite common and natural for the parents of my patients to ask why their child got their particular disease.  Although we’re continually learning more about the genetic and molecular basis for diseases like cancer or kidney disease, the fact is most of the time we have no good explanation for why one particular individual out of thousands got the disease.  It is usually not very satisfying for either the parent or the physician to simply say, “I don’t know”, although that is often the honest answer.   I recall one of my professors while I was in my nephrology fellowship training at Yale, who responded to a parent asking why their child had a very serious type of kidney disease, known as Focal Segmental Glomerulosclerosis (FSGS), that has a high likelihood of leading to kidney failure despite any available treatment options.  My professor’s response was, “Damn bad luck”.  While that particular family seems to accept that assessment, I’ve witnessed other physicians use that same line with less pleasant results, even to the point of a parent becoming extremely offended by talk of bad luck.  It was almost like the diagnosis of bad luck was the same as being told that someone had placed a Voodoo spell on them.  Personally, I most often simply state that we just don’t really understand why some people get a particular disorder and most people don’t, and move on from there to what we do know about the condition.  I’ve found this to usually be effective in moving the conversation forward.

I’ve also seen many patients that do seem to have one unfortunate event after another happen in their lives.  For example, a patient with a congenital birth defect of the heart may have to go through many heart surgeries and life threatening events only to later down the road develop a cancer, and the treatment of the cancer may inadvertently lead to kidney failure, and so on.  It seems natural to think of bad luck when you consider their situation.  The “law of large numbers” would be a more logical explanation, even if it is not always a satisfying one to the family.  This concept reminds us that if you have a large enough sample size (our sample is the entire human population) then essentially anything that is possible will eventually happen, no matter how unlikely it appears to be.  Even if that particular sequence of events has only a one in a million chance, if your sample size is a million, it should happen at least once.  My guess is that for the example given above the chance is actually a lot more likely than a million to one.

The results of random chance can appear like bad luck due to the way our human minds process information.  Human minds evolved to detect other minds that contain thoughts and intentions like our own, evolved to react in an emotional manner to events so that decision making would be quick and helpful in many commonly occurring situations, and evolved to find patterns even in random background noise.   Unfortunately, this leads to many false positive results, so that the human mind may therefore perceive an intelligent agent where none exists, give an emotional response unfair weight over a rational interpretation of events, and find significant patterns in random noise.

So, is bad luck really a diagnosis?  It is! But only if it is clear that this is being used as short hand for random, unpredictable events, and not evil forces with intent on harm.  Many people are superstitious and naturally assume that there are universal powers out there, with an interest in us, benign or otherwise, and playing with our fates.  The prescriptive sense of the term implies some sort of universal apathy in the case of bad luck, or empathy in the case of good luck.  There is no objective evidence that this is the case.  Our minds didn’t evolve to see statistical patterns.  It takes work to find statistical patterns (usually by conducting well designed scientific studies – something our distant ancestors didn’t do), and even then a statistical explanation may not feel satisfying or even to agree with “common sense”.  Our brains try to find patterns where none might exist.  If an unusual event happens to us or a loved one, we have the need to try to explain that unlikely occurrence through some narrative, not realizing that many rare events are happening all the time.

Bad luck, the kind of bad luck that has any real meaning, is the product of random chance.  Just a statistical roll of the dice, and that’s what this paper in Science is really showing.  The universe is not trying to help us succeed, but neither is it trying to wipe us out.  It is absolutely indifferent to us being here.  Even our DNA polymerase that replicates and proofreads our DNA is not trying to help us.  DNA polymerase has simply evolved to be only as effective as necessary to propagate the genes for making more DNA polymerase.  It has no reason to be more efficient than that, but can’t be less efficient either or else it won’t survive into the coming generations.  We are the ones that care what happens to each other.  We have the brain power to decipher the world and have an interest in what happens to ourselves and our fellow humans. By taking luck out of the equation we can search for the real explanations for how things work and the events that transpire in our lives.  Science is the tool to do so and has so far been an invaluable tool for finding true patterns in events that once seemed random.  We still have a lot more to learn, but bad luck should never be the full diagnosis, just the short hand notation for when don’t have enough information to give a satisfactory explanation.  Even then it should only be used carefully so not to misguide the patient.  It is ok to admit when we don’t know why, but reassure the patient that we will keep looking for the answer, and in the meantime will provide the best care using the available science-based evidence.