Diseases with an upside!

Diseases with an upside.

By Rich Feldenberg

Since life’s earliest emergence on planet earth, disease has been our constant and unwelcome companion.  Even the first single celled organisms were susceptible to break down, nutritional deficiencies, and harmful genetic mutation.  When single celled life upgraded to the multicellular stage, finally becoming large, it was then susceptible to a host of new disorders, such as cancer that interfered with the organization and growth of cells that now had to survive as part of a collective.  Humankind is no different than the rest of the animal kingdom in this regard, and throughout human existence disease has lead to untold suffering, death, and at times the threat of total extinction.  It may therefore be surprising to learn that some diseases confer protection against other types of illness, and this seems to account for the high prevalence of some of these disorders in the human population.  If the protective benefit of the disease mutation on a large portion of the population outweighs the suffering and death of a small portion of the population, natural selection will swing the balance in favor of keeping those mutations in the gene pool.  Not only may the disease mutation simply persist in the gene pool, but it may become very prevalent because it is selected for in the right environment, where the other illness it protects against is a major threat.   To illustrate how this works I’ll give some detail on two well known examples of diseases and their upside – in other words, how they protect against other threats to our species.

The first example is that Sickle Cell Anemia (SCA), which has the best documented evidence as to its evolutionary risk versus benefit ratio in its effected population.  Sickle Cell Anemia is a genetic disease that causes anemia (low red blood cell counts), and can lead to painful, and potentially deadly pain crises.  It is inherited as an autosomal recessive trait – meaning that if you receive one copy of the mutated gene from each of your parents, then you have two abnormal copies of the gene (are homozygous, in the language of genetics) and will have the disease.  Each of your parents, however, has only one mutant copy and also one normal copy (is heterozygous), and so is only a carrier (has sickle cell trait) and will not show symptoms of the disease under normal circumstances.

SCA is due to a single base switch in the DNA that codes for the beta-chain of the hemoglobin molecule.  Adult hemoglobin is made of two alpha chains and two beta chains.  This is the major oxygen carrying protein in the blood, although, there are other versions of hemoglobin that are produced (one example is fetal hemoglobin with two alpha chains and two gamma chains).    In SCA, there is a substitution of the amino acid glutamic acid for valine at the 6th amino acid in the beta chain.  Since valine is more hydrophobic than glutamic acid this has the unfortunate consequence of causing the hemoglobin molecules to polymerized and compact together, deforming the shape of the red blood cells (RBCs) that carry them, into a sickle shape – hence the name Sickle Cell Anemia.  The polymerization event is more likely to happen if the affected individual is dehydrated, in a low oxygen state (hypoxic), or otherwise ill with another illness.  The deformed red blood cells can not get through the tiny capillaries very well, causing blockages that deprive tissues of blood and oxygen.   The result is pain and organ damage.

Over time, people with SCA damage their spleen so badly that they lose the its important immune function, which normally you against encapsulated bacterial infections.  These are certain bacteria that are surrounded by a polysaccaride capsule, that helps them to escape detection by the immune system.  Someone without a functioning spleen can then die of these types of infections, whereas those with normal spleens would be able to fight off the infection easily.  The blockages to blood flow due the abnormal sickle shaped RBCs can lead to strokes and to Acute Chest Syndrome.  If people with SCA become infected with the common virus Parvovirus B19, they can develop severe life threatening anemia, with hemoglobin levels that get so low they can develop heart failure.

Sickle cell anemia is common in sub-Saharan Africa, and about 300,000 are born with disease each year.  All the complications of SCA listed above can be fatal so why would this disorder have such a high prevalence?  The answer seems to be that although people with full blown Sickle Cell Anemia are at a most definite disadvantage from a survival aspect, those who are carriers of SCA are protected against another common killer – Malaria.  Malaria is an infectious disease caused by the protozoan Plasmodium.  It has a complex life cycle, part of which is spent inside the mosquito Anopheles, and part is spent inside a vertebrate host – such as a human.  When an infected female mosquito bites a human, the organism is transmitted into the persons blood stream where it travels to the liver, infects liver cells, reproduces, and then is released back to the bloodstream where it infects RBCs.  The symptoms of Malaria include fever, vomiting, joint and muscle pain, headache, and in some cases seizures.  As the Plasmodium organism goes through its life-cycle within the host, from liver to RBC and back again (these are known as the liver phase and the erythrocytic phase respectively), the symptoms return in a cyclical fashion.  In some cases the organism passes through the blood-brain barrier leading to Cerebral Malaria, which is a very serious complication.  Malaria has a high mortality rate if untreated – as would have been the case before the age of modern medicine.

It was observed, early on, that in regions endemic to malaria, people who were carriers of the sickle cell mutation showed resistance to the malaria infection, and that full blown SCA has a high prevalence in those same regions where malaria is endemic.  Further studies confirmed that those individuals who are carries for the sickle cell mutation, do in fact, enjoy a protection due to their gene mutation.  Unfortunately, those with actual sickle cell anemia (homozygous for the gene mutation) are not protected against malaria.  Not only do they have to suffer the fate of SCA, but if they get malaria they have a worse prognosis because the malaria damages their already vulnerable RBCs.

For a long time it was thought that sickle cell trait most likely confers its malarial protection by making it difficult for Plasmodium organisms to infect the abnormally shaped RBCs, and that the abnormal RBCs are removed more readily by circulating macrophages, helping to rid Plasmodium infected cells more readily.  More recent research seems to suggest that the protective mechanism is more complex that that, and involves the up regulation of an enzyme called heme oxygenase-1(HO-1).    HO-1 causes the breakdown of heme, and the release of carbon monoxide (CO), iron, and biliverdin, resulting in an anti-inflammatory effect.  HO-1 is upregulated or produced to a greater extent in RBCs that have the abnormal hemoglobin associated with SCA, and it is the production of CO that seems to have a detrimental effect for the Plasmodium organisms.  It confers protection against cerebral malaria, and decreased mortality for those with sickle cell trait who become infected with malaria.  This might also be the answer to why several other diseases or disease traits have also been observed to offer protection against malaria, such as thalassemia trait and Glucose-6-Phosphate Deficiency.  These disorders might also increase the activity of HO-1.

We’ll move now to another deadly disease that seems to have remained in the population because it offered a survival advantage.  This is the kidney disease called Focal Segmental Glomulosclerosis (a real mouthful) or just plain old FSGS for short.  FSGS can be caused by chronic infections, such as hepatitis or HIV, but many cases are due to a genetic mutation.  It is a subset of the genetic form that may have been selected for to protect against Sleeping Sickness.  In FSGS the tiny filters in the kidneys, called glomeruli, become scarred until they can no longer filter.  This can eventually progress to kidney failure and the need for dialysis or kidney transplant.  Kidney failure is fatal without modern medical care and FSGS is one of the more common causes for young people to be on dialysis.  Its also, often more common and resistant to therapy in African Americans and other people of African descent.

Some people with the genetic form of FSGS have a mutation in a gene called APOL1, and if you are an individual with two mutated copies of the APOL1 gene, your risk of developing FSGS and kidney failure is 17 times higher than if you have two normal copies of the gene.  That adds up to around a 4% chance of developing FSGS over your lifetime if you are homozygous for mutant APOL1.  This mutation is also thought to explain 18% of all cases of FSGS that currently exist.  There are two types of mutations in the APOL1 gene that can increase risk for FSGS kidney disease.  These is the G1 variant, which contains two amino acid substitutions – one is a replacement of glycine for serine at amino acid 342 in the protein (S342G), and the other switch is a replacement of methionine for isoleucine at amino acid 384 in the protein (I384M).  You have to have both of these switches you have the G1 variant.  The other variant is the G2 variant where 6 base pairs are deleted in the DNA coding for APOL1 starting at base 388.  People can have either a G1 variant or a G2 variant, but never have both types.

APOL1 is a protein that circulates in the blood and is part of the high-density lipoprotein (HDL – otherwise known as the “good” cholesterol).  Exactly how the mutated form of APOL1 causes kidney disease is still not known.  What is known, however, is that those individuals with either a G1 or G2 specific gene mutation in APOL1 have protection against African Sleeping Sickness, caused by the protozoan Trypanosoma brucei.  This tiny single celled eukaryotic organism is transmitted to its human host by the bite of the tsetse fly.  It is a common and dangerous disease in sub-Saharan Africa.  In 1990 it caused 34,000 deaths, but the death rate dropped to 9000 in 2010, thanks to efforts of the World Health Organization to prevent and treat the infection.

Those affected by the parasite experience two distinct stages of infection.  In the first stage the victim develops headaches, fever, and severe itching.  This resolves only to eventually progress to the second stage of the disease which effects the central nervous system causing confusion, paralysis, neuromuscular weakness, and sometimes psychiatric illness.  There is a reversal of the sleep-wake cycle, giving the disorder its common name.  Infected persons often sleep in the day and remain awake at night.  Without treatment the disease always ends in the death of its victim.   It can be treated with the drug pentamidine, when in the first stage, or drugs such as eflornithine or melarsoprol for second stage disease.

Like the association of Sickle Cell Anemia and malaria, those geographic regions with a high incidence of sleeping sickness also have a high incidence in the population of APOL1 G1 or G2 variants.  This is because those gene variants protect against the ravages of the Trypanosomes.  The APOL1 variants cause the lysis (breaking apart of the cell membrane) of Trypanosomes that cause sleeping sickness.  The normal gene for APOL1 gives us resistance to other species of Trypanosomes that do infect other mammals, but are unable to harm us.  The sleeping sickness Trypanosome (Trypanosome brucei rhodesiense) is immune to the normal APOL1 since it has evolved a serum resistance-associated protein (SRA) that blocks a portion of the APOL1 protein, neutralizing its anti-trypanosomal action.  Not so for the APOL1 variants G1 or G2, however.  They are able to get around this SRA and destroy the parasite.  From an evolutionary point of view, the advantage of being more resistant to sleeping sickness in an area of high risk, outweighs the cost of having a higher than average chance of kidney disease.  There is no advantage, however, to having these variants if your ancestors originated where sleeping sickness is not a problem, so other populations aren’t found to have these gene mutations.

The two examples of Sickle Cell anemia and Focal Segmental Glomerulosclerosis (APOL1 mutation) are not the only situations where a disease mutation protect us against another illness.   I’ll just briefly mention two more.  Tay-Sachs disease, which is a lethal neurodegenerative disorder in the homozygous state, seems to protect against Tuberculosis in carriers (heterozygotes).   Also Cystic Fibrosis (CF) which usually leads to severe and chronic lung disease in the homozygous state, may have protected against the effects of cholera in the heterozygous carriers.  The CF mutation inactivates a chloride channel called CFTR, in the cell membrane.  Being a carrier for this mutation may have prevented the lethal dysentery that would have accompanied infectious cholera, by preventing water loss in the intestines due to poorly working chloride channels.  It is a very common gene mutation, with 1 in 25 people of European descent being a carrier for the CF gene mutation.

When we think disease we think of the suffering of its victims and the cost to society.  We are often unaware of the balance of the many forces involved, which influence why a particular disease may be so common in a given population.  The factors involved are typically much more complex than we appreciate, and most of them are still unknown to us.  Natural selection is working behind the scenes in ways that are difficult to detect on just a casual examination.  It may be of no consolation to the sufferers of a serious disease, or the family members devastated by a loved ones sickness and loss, but natural selection, with its cold blind eye to pain or suffering, seems to have fixed some of this in place to allow more genes to be passed onto future generations.  Evolution is not directed toward any particular goal and has no empathy or sense of compassion.  It only selects those traits that happen to give the organism the best chance to pass on its genes in its evolved environment.  This is where the human mind comes into play.  Now that we are finally learning to understand the root causes of disease at the genetic and molecular level, we can work to treat, cure, and eradicate disease.  Although we are not there yet, in theory it should be possible to cure a condition like sickle cell anemia with gene therapy.  At the same time, we shouldn’t have to worry about worsening the burden of malaria if SCA were eliminated, since we can also work on better therapies to treat the malaria, and more effective strategies to prevent infection with Plasmodium.

References and other reading:

 

1. “Mystery solved: How sickle hemoglobin protects against malaria”, ScienceDaily; April 29, 2011

http://www.sciencedaily.com/releases/2011/04/110428123931.htm

2. “Sickle Cell Anaemia and Malaria”, Lucio Luzzatoo, Mediterranean Journal of Hematology and Infectious Disease; Oct. 3, 2012.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499995/

3. Sickle Cell disease;  Wikipedia.

https://en.wikipedia.org/wiki/Sickle-cell_disease

4. Malaria;  Wikipedia.

https://en.wikipedia.org/wiki/Malaria

5. Heme Oxygenase-1;  Wikipedia.

https://en.wikipedia.org/wiki/HMOX1

6. “APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy”,  Jeffrey B. Kopp, et al., Journal of the American Society of Nephrology;  Nov. 2011.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231787/

7. “Association of Trypanolytic ApoL1 Variants with Kidney Disease in African-Americans”,  Giulio Genovese, et al., Science, August 13, 2010.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980843/

8. “A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome”, Paul Capewell, et al., Parasitology, June 26, 2014.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413828/

9. “A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9”, Giulio Genovese, et al., Kidney International, Oct. 2010.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001190/

10. African Trypanosomiasis;  Wikipedia.

https://en.wikipedia.org/wiki/African_trypanosomiasis

Can we genetically engineer Rubisco to feed the world?

Today’s atmosphere is brought to you by Rubisco.

Fine makers of oxygen since 3.5 billion B.C.

By Rich Feldenberg

If you happen to peak outside on a nice sunny summers day to admire the green grass, shady trees, and pleasant bushes, your field of view is, in actuality, filled with Rubisco, busily helping the plants do their special thing of making sugar and churning out oxygen.  Rubisco is by far the most abundant enzyme on the earth and accounts for 30%, or more of the protein found in the green leaves of plants.  Without it there would be no oxygen producing photosynthesis, so if you’re a fan of breathing then you’re probably going to be happy to learn about Rubisco.  And, If you’re thinking to yourself, “if there is that much of it in the world it must be doing something important”, congratulations, you’d be right!

There are three things I’d like to point out about Rubisco. One is that Rubisco is freaking amazing.  It is an awesome protein with interesting molecular properties, catalyzing fascinating chemistry, and dating back to some of the earliest life on earth.  The second thing is that as amazing as Rubisco is, it is incredibly poorly mesigned (mesigned is my word meaning designed by natural selection).  Rubisco is horribly inefficient and slow, and it’s amazing it hasn’t been fired from it’s post and replaced with a new, younger, more hip version.  And finally, Rubisco could, in principle, be engineered to be much better, possibly increasing crop yields to feed an increasing global population, and removing CO₂ from the air to combat global warming.  Let’s tackle each of these points.

Point One:, Rubisco is amazing.  Without it life on earth would likely still be living as simple single celled mats of slime on the ocean floor in a oxygen free world.  Rubisco is the abbreviated form for the formal name of the enzyme Rubulose-1,5-bisphosphate carboxylase/oxygenase.  Yeah, that’s why Rubisco (rhymes with San Francisco) rolls off the tongue so much nicer, and is way easier to say three times fast.  This enzyme goes way back to the good old days when singled cell organisms ruled the world, and appears to have a common origin in all three of the major kingdoms of living things -bacteria, archaea, and eukaryotes- indicating a very early origin sometime around the time of the Last Universal Common Ancestor (LUCA).  It appears to have arisen even before the evolution of oxygen producing photosynthesis.  There are, by the way, other types of photosynthesis that do not produce oxygen as a byproduct – so called anaerobic photosynthesis- which are less efficient than the oxygen producing types.  Based on the study of related proteins, known as Rubisco-like proteins (RLPs), Rubisco may have evolved from RLPs that performed other enzymatic functions before it was eventually modified to it’s modern role in photosynthesis.

Rubisco is a big protein, that is itself composed of two main types of subunits – the large subunit (L) and the small subunit (S).  There are three major forms of Rubisco, but in most plants and algae, the Rubisco is composed of a combination of eight L-subunits and eight S-subunits.  Rubisco catalyzes the first step in the photosynthetic process taking CO₂ and making it react with the compound ribulose 1,5-bisphosphate (RuBP).  That is way the Rubisco enzyme is named Rubulose-1,5-bisphosphate carboxylase/oxygenase.  In one of it’s reactions, it is carboxylating the substrate RuBP.  This leads to the formation of two molecules of phosphoglyceric acid (PGA), that then go through a metabolic pathway called the Calvin cycle.  The PGA products eventually go on to other metabolic pathways, and the result is sweet sweet sugar!

Space filling model of the Rubisco protein structure 

The L subunit has the active site with a critical lysine residue for binding CO₂.  It actually takes two CO₂ molecules to get things going.  The first CO₂ molecule is used just as an activator for the enzyme’s active site, but isn’t used in the carboxylation reaction.  The second CO₂ molecule is what is used to react with RuBP, and it is this carbon that is added onto the molecule.  The O₂ that is eventually released at the end of photosynthesis does not come from the CO₂ but is taken from water, which is also necessary in the reaction.   The genes for the L subunit of Rubisco are found in the chloroplasts, tiny organelles within the cells, where Rubisco is conducting its important job.  The S subunit is more of a stabilizing part of the protein and its gene is located in the nucleus, and once the protein is made, needs to be shuttled into the chloroplasts.

 

 

Also necessary for the enzyme to function is the presence of an ion of Mg⁺² ,which acts to stabilize the activation site.  This process allows one CO₂ molecule, along with a molecule of H₂O to become incorporated in RuBP.   There is a whole lot of Rubisco in the green leaves of plant to carry out this important chemical reaction.   As we said above, about 30% or more of the protein in the leaves of plants is in the form of Rubisco, so it therefore accounts for a huge amount of nitrogen stored in the biosphere, since proteins contain nitrogen as part of their structure.  

Point Two: Rubisco is so mind numbingly inefficient I am almost embarrassed for our plant cousins.  It turns out that the carboxylase function of Rubisco (you know the really important thing it does by taking CO₂ from the air and attaching it to RuBP to begin the process of making carbohydrate) is not the only reaction it performs.  In fact, it’s very name -the unabbreviated one that is- tells you right off that it it also is an oxygenase.  That is the carboxylase/oxygenase last portion of the name.  This means that Rubisco is not terribly selective for CO₂, but can also react at the activation site with a molecule of molecular oxygen (O₂), which has some chemically similar properties.  This leads to a horribly counterproductive metabolic pathway called photorespiration.  In other word, it is not very selective, and is so nearsighted that it may grab onto an O₂ as easily as a CO₂.  Normally about 25% of the reactions that Rubisco is catalyzing are with oxygen going down the photorespiration pathway.  Also, keep in mind that in the atmosphere today, and for at least the last billion years, the concentration of O₂ has been way in excess of that of CO₂.  The atmosphere these days is 21% O₂ and only 0.04% CO₂, so that makes it even more difficult for poor little Rubisco to discriminate effectively.

Ribulose 1,5-bisphosphate (RuBP)

Photorespiration leads to RuBP being converted into one molecule of PGA and one molecule of 2-phosphoglycolate.  This doesn’t lead to carbohydrate production.  Even worse this uses energy in the form of ATP and released CO₂ into the air.  Totally wrong if you want to store energy from the sun in the form of yummy sugar molecules.  So we can clearly say that Rubisco has a poor affinity for CO₂.  An enzyme’s affinity for its substrate is measured by a characteristic called K_m, and Rubisco’s K_m is kind of wimpy.   This relative non-selectivity may be a reflection of the world in which Rubisco first evolved.  At that time the concentration of CO₂ in the atmosphere would have been much higher and the concentration of O₂ would have been extremely low since photosynthesis was just getting started.  Rubisco probably didn’t need to be too selective since O₂ was just a trace gas back then.

The selectivity of Rubisco for CO₂ over O₂ is affected by temperature.  Warmer temperatures decrease the selectivity making Rubisco even more inefficient.  That can be a problem for plants in a hot dry climate.  Also a change in the amounts of CO₂ to O₂ with respect to each other will influence the enzyme efficiency.  These two factors may become a significant concern in a world of global climate change where the both the temperature and concentration of CO₂ are on the increase.  How this could affect the world’s already insufficient food supplies will have to be seen.

Besides it’s affinity for reacting with a substrate, another characteristic of an enzyme is it’s rate of reaction called the Vmax.  Guess what, Rubisco’s Vmax also really sucks.  Probably not what you would expect for an enzyme that is the most abundant in the world.  Where as most enzymes catalyze thousands of reactions per second, Rubisco is only able to catalyze about 10 reactions per second.  Now, I hate to sound so judgmental, but that is really pathetic!  It is certainly possible that Rubisco was never able to evolve to be more efficient due to constraints on its structure once it became vital to the plant way of life.  Any alteration in the critical active site may have affected too many other protein-protein interactions necessary for normal function, and so never took place.  Alternatively, there may be some advantages to photorespiration, after all, so that completely shutting down that pathway would, likewise, be detrimental to growth.  There seems to be a trade off between having organisms who’s Rubisco has good affinity for CO₂ (K_m) and those who’s Rubisco has a fast reaction rate (Vmax).  It’s a case of, you can’t have your cake and eat it too.  If you favor one quality then you suffer in the other.

Plants have come up with a few smart ways of helping to boost the efficiency of Rubisco.  One way is to attempt to concentrate the amount of CO₂ around the enzyme.  C4 plants do this by adding the carbon from a CO₂ molecule to phosphenolpyruvate (PEP), then through a series of chemical reactions, the organic compound malate is produced.  The malate is shuttled to the plant cells that contain Rubisco and the CO₂ is removed.  This concentrates the CO₂ in the vicinity of Rubisco so it can act more efficiently.  The waste in energy to produce the malate is more than made up for by the better efficiency of the Rubisco in C4 plants due to this CO₂ concentrating ability.  C4 plants are a more recent evolutionary development, but only represents about 3% of land plants.  They are well suited for living in desert conditions where C3 plants would not be able to photosynthesize effectively and would rapidly lose too much water.  C3 plants to well in moderate climates with only moderate sun light.  The lower temperatures helps to improve Rubisco efficiency at utilizing CO₂ over O₂.  

 

C4 plants are therefore more efficient, especially in warm dry climates.  CAM (Crassulacean acid metabolism) plants close their stomata in the day to prevent fluid loss and open them at night to allow diffusion of CO2 into the leaves, where it is stored in malate.  During the day the CO₂ is again removed from the malate so it can be used by Rubisco to make carbohydrate.  CAM plants can be either land or aquatic.  

 

The C4 plant, Maize, busily concentrating CO2 to boost Rubisco efficiency

Point Three: Perhaps we can make a better Rubisco, one that can select CO₂  over O₂ more effectively, and react more quickly.   Nature has had billions of years to figure this out, so maybe its our turn now to design a Rubisco that can be improved in a variety of different ways.  This might be accomplished by artificial selection or genetic engineering – to produce a Genetically modified organism (GMO) with the desirable traits we choose.  In fact, there is a great deal of research looking into possible ways to improve Rubisco, but so far progress seems to have been rather modest.  A super Rubisco could in theory produce more carbohydrate under warmer, drier, and lower light conditions, decrease the amount of nutrient nitrogen necessary for plant growth, and remove more CO₂ from the atmosphere, and release more O₂.  This could be vital to consider for a growing global population that is outstripping its food resources and heading towards potential disaster due to global warming.  How could it be done?

It is known that red algae has a Rubisco with the highest value yet found for CO₂   affinity.  It is nearly 3 times better at discriminating CO₂ from O₂ than is the Rubisco from crops, like corn.  It may be theoretically possible to engineer crop plants to express the red algae Rubisco.   Other studies have looked to genetically engineering Rubisco by substituting key amino acid residues in critical areas of the enzymes protein structure and observing the effect.  This has resulted in some mild success.  In one study, by switching a particular alanine residue in the L subunit with a asparagine, the affinity was increased by 9%.  Not a huge increase, but potentially a good starting point.  

Other research has focused on speeding up Rubisco’s slow rate of reaction.  One way to accomplish this could be to create a CO₂ concentrating mechanism in C3 plants like corn and rice, that is similar to the natural CO₂ concentrating mechanisms found in C4 plants.  The ways to make this happen are less clear, but could involve manipulations that would put certain types of CO₂ transporter in the membranes of chloroplasts to help concentrate the gas where it needs to be.  

It should also be noted, that while the intended effects for changes to Rubisco protein would be for the common good of the planet, if we get to the point where such genetically modified plants are possible, it would need to be studied, not only to determine that there are no unintended consequences on the environment, but also that these changes actually result in greater plant growth and yield.  There may be some reasons why photorespiration is allowed to occur at the high rates it does.  One theory is that this is a protective mechanism for the plant so that in intense light conditions energy overload does not occur that could result in oxidative damage to the plant.  There may be a certain limiting factor where carboxylation can be maximized to a certain degree, but once you cross some threshold it actually becomes detrimental to the organism.  

There is no doubt that Rubisco is a curious and fascinating protein, and one on which our lives, and continued survival, are completely dependent.  It is certainly worthy of our admiration for its important and ancient role in maintaining earths biosphere.  There seems to be much more we need to understand about its biochemistry before we can tell if it will be a tool we can utilize to improve and protect our planet.  It could also potentially be altered in algae or cyanobacteria to terraform other planets like Mars, which although it has an extremely thin atmosphere, does have an abundance of CO₂ over O₂.  If we eventually discover life on other world that have evolved some form of photosynthesis, it will be interesting to learn what proteins or other methods they came up with to catalyze the carboxylation reaction that Rubisco serves for us here on earth.

References:

1. M. A. J. Parry, et al., “Manipulation of Rubisco: the amount, activity, function, and regulation”. Journal of Experimental Botany, Vol 54, No. 386,  pp. 1321-1333, May 2003.

2. Spencer M. Whitney, et. al., “Advancing our understanding and capacity to engineer natures CO2-sequestering enzyme, Rubisco”, Plant  Physiology, Vol. 155, pp. 27-35, Jan. 2011.

3. Wikipedia article on Rubisco:  https://en.wikipedia.org/wiki/RuBisCO

4. Wikipedia article on Photorespiration:  https://en.wikipedia.org/wiki/Photorespiration

5. Article on Mesign:     http://darwinskidneys.blogspot.com/2015/07/another-clever-mesign-brought-to-you-by.html

Why New Horizon’s journey to Pluto is so important for us here on earth.

Why New Horizon’s journey to pluto is so important for us here on earth.

by Rich Feldenberg

  

Almost like a time traveler sent 10 years too far back in time before an important event, I’ve been waiting for July 14th, 2015 for a long time.  Ever since the New Horizons space probe was launched from Cape Canaveral, way back on January 19, 2006, I knew this day would get here eventually.  It just seemed like our little space probe was taking its sweet time.  Nine and a half years is a long time to wait to see a new world – a world never before seen up close and personal.  In actuality, New Horizons was doing anything but taking its time.  It has been speeding towards its destination at over 36,000 miles/hour!  It passed earths moon in a mere 9 hours.  It happens to be the fastest man made object ever.  It’s just that it had a very long way to go to reach its destination.  Today New Horizons will make its closest encounter with Pluto, and almost certainly will increase our knowledge and understanding, not just of Pluto and its entourage of little moons, but of the origins and history of our solar system.  

Pluto was only discovered as recently as 1930 by Clyde Tombaugh at the Lowell Observatory.  Even from the beginning it seemed a little odd in comparisons to the other planets.  It takes about 247 years to orbit the sun and has a very eccentric orbit with its closest point in orbit at 2.7 billion miles from the sun (and inside the orbit of Neptune), and its farthest point in orbit being around 4.5 billion miles away from the sun.  It has five known moons, but the largest is Charon, which has a diameter that is more than half as big as the diameter of Pluto itself.  No other planet has a moon so close to its own size.  For that reason, many planetary scientists consider the Pluto/Charon system a binary system.  

Today’s post will go live on Tuesday instead of the usual Darwin’s Kidneys Original Wednesday (sorry Atomic Tuesday) to coincide with this historic occasion.  In this post I’m not going to write about the New Horizons discoveries, or much about the mission itself.   I’m not even going to write about whether Pluto should be classified as a planet or not.  I don’t really care that Pluto got “demoted” to dwarf planet because no matter what we label it, Pluto is a fascinating object with a history as old as our solar system.  Instead this article will focus mostly on why we should be interested in a tiny, human made hunk of electronics, computer chips, and metal, speeding to the edge of the solar system to photograph and measure a dark, frozen, ancient celestial body whose chance of harboring life is somewhere between zero and not bloody likely.  Why should we, as a society, spend money and resources to design, build, and launch this thing that may not even make it all the way there intact.  

We are a species of explorers.  Our ancestors traveled the globe and colonized nearly every part of it.  We are no strangers to taking risk, and thinking big when it comes to wondering what’s over the next hill or beyond the distant horizon.  Human consciousness first awakened on this planet on the continent of Africa, and from there spread to all corners of the world, from stone age Europe and Asia, and over the frozen Bering Straits of the last Ice Age, into North and South America.  Early humans even sailed across the forbidding oceans to Australia and the Pacific islands.  We have adventure in our blood.  

Pluto the most distant target that we have tried, so far, to reach out and touch.  Not a journey that humans, with laughably fragile bodies susceptible to harm from radiation and microgravity, and entirely too needy for food, oxygen, warmth, and even companionship, can make anytime soon.  Instead we send our stoic little robot ambassador out on a entirely peaceful mission of scientific discovery.  It represents the best part of humanity with no thought whatsoever to invasion, conquest, or exploitation of new territory for gain or profit.  It represents what’s best in us – our childlike curiosity, enthusiasm for discovery, and sense of awe at living in a universe that is so much bigger than our everyday concerns.  

Going to Pluto inspires us to be great by doing great things.  It is no trivial task to design, build, and implement a machine to do what New Horizons is doing right now.  That’s, of course, why it has never been done before.  The accuracy necessary for the mission to reach its target, and the durability of its components to remain functional after 9 years in the cold vacuum of space, are a triumph of human engineering and understanding of Newtonian mechanics.  The challenge of the mission elevates us up onto a more noble plane.  Teams of individuals made the mission possible, but also the millions of taxpayers that contributed to a successful human achievement, are all part of the process that show we as a society care about things beyond the mundane and everyday.  We are all apart of the mission, and we all have a right to see what New Horizons can tell us about the edge of our cosmic neighborhood block.  

Going to Pluto also inspires curiosity in the unknown.  From earth, even from the Hubble Space Telescope, Pluto is not much more than a dim dot in the night sky.  We want to know, what is it like on Pluto?  Why is it so different than the planets like the Earth, Mars, Jupiter, and so on?  What is it made of and why is its orbit around the sun so unusual?  Does it hold clues to the formation of the solar system and the planets?  Could it hold clues to the origins of life’s chemical building blocks that lead to our own origins on earth?  We humans really want to know the answers to things.  When we have a real mystery it inspires a lot of careful thinking, formulation of hypotheses, and ideas about how to test those hypotheses.  Being curious is one of our most outstanding traits as a species.  Far from the old adage “curiosity killed the cat” in reality, curiosity is how we learn who we are, where we come from, and what our place in the universe really is.  “Curiosity killed the cat” is meant to keep us afraid and in the dark.  Curiosity keeps us moving forward, but the spirit of curiosity is easily doused by others who are perfectly satisfied by not knowing and who have long ago lost their curiosity.  We need to keep that spark of curiosity alive.  Not only is a mission like New Horizons the scratch to satisfy the itch of our innate curiosity, but it inspires new levels of curiosity in those sharing in the discoveries, and in the imaginations of young people who then begin thinking about what is next out there to explore.

There are also the unforeseen consequences from a mission like New Horizons.  It is not why these missions are undertaken, but we have reaped the benefits of the collateral developments (the opposite of collateral damage) of basic science research before.  From the World Wide Web developed by theoretical physicists at CERN, to advances in computer and laser technology, basic science research has provided benefits to society at large that were never predicted or expected.  When Nobel prize winning physicist, Edward Purcell was asked what practical applications his discovery of nuclear magnetic resonance in bulk matter could ever be used for, which he developed to better understand the quantum transition of hydrogen atoms from one energy state to another, his answer was, “I can see no practical applications”.  It turned out that this discovery changed modern life giving us Magnetic Resonance Imaging (MRI) in medicine to peer into the living body in exquisite detail, as well as transforming the field of chemistry with Nuclear Magnetic Resonance (NMR) which has revolutionized our understanding of molecular structure and material science.  The truth is that we don’t always know what the final impact of fundamental research may be for our everyday lives.  The knowledge we gain from studying Pluto might help us better understand the threat of comets and asteroids to life on planet earth, and perhaps aid in our survival as a species.  The most likely benefit will be ones we don’t see coming at all.   There are also economic gains that programs, such as the space program provide to our country, as far as more jobs, and it signals to the world our national strengths and that intellectual endeavors are an important priority.  Being a leader in science and space exploration is no small thing in the eyes of the rest of the world.  

Missions like New Horizons remind us that we live in a much bigger universe than we are used to thinking about.  On a day to day basis, it’s easy to focus on the minor details, to think your little neighborhood is all there is.  We don’t look up at the night sky and observe the stars very often- not nearly enough.  Going to Pluto forces us to think about our place in the cosmos.  The solar system is big and the planets are far away.  How much bigger is our galaxy than the solar system, and what about the billions of distant galaxies?  We are not just in the universe, the universe is in us.  We are a part of the universe and it’s good to be reminded of that from time to time.

I’ve waited a long time for today.  I don’t know what pictures and information will be sent back to earth by our little robotic probe as it speeds past Pluto, but I know it will be amazing.  Just to know that something of earth is out there, so far from home and continuing its flight outward into the galaxy, is pretty cool in itself.  And once New Horizons leaves Pluto behind, there will continue to be new and exciting discoveries to anticipate, some from future robotic space missions, others from telescopic observatories examining the universes largest structures, and still others from basic science research facilities like CERN examining the universes smallest components and fundamental forces.  We will continue to have a lot to learn and look forward to so long as we as a society continue to decide that the nobel pursuit of new knowledge is a goal worth achieving.  For today, I just want to say, “Hello Pluto, it’s great to finally meet you”.

References:

1. NASA New Horizons website.

https://www.nasa.gov/mission_pages/newhorizons/main/index.html

2. Pluto:  Wikipedia

https://en.wikipedia.org/wiki/Pluto

3. Cylde Tombaugh:  Wikipedia

https://en.wikipedia.org/wiki/Clyde_Tombaugh

4.  Pluto Safari is a cool app you can down load on your tablet from iTunes.

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.

Origins Sunday: Early life liked it salty!

Cool link below describing research that shows how a certain set of 10 amino acids will fold when exposed to high salt concentrations, like those found naturally in certain regions of the early earth.  This may have allowed proteins to be functional before the cellular machinery to fold proteins had yet evolved.  Our earliest ancestors may have been halophiles (salt lovers).  Unfortunately, many of us retain that salt loving trait, and perhaps that’s why I love pizza so much?!? – craving the salt that my Archean ancestors loved so!

http://www.sciencedaily.com/releases/2013/04/130405064027.htm

Fossil Friday: Tiktaalik, and the transition from water to land.

Tiktaalik is one of the coolest fossils.  This little guy was alive about 375 million years ago in the Devonian period.  At that time the land was colonized with plants and arthropods, but vertebrates had yet to make the transition to life out of water.  Tiktaalik was a predecessor of later vertebrates that did make that important transition to the land.  Tiktaalik was a water animal and very fish-like but had limbs similar to land animals today.  It probably used its limbs to move along the bottom of shallow lakes and streams and move over debris on the bottom.  It may have been able to move out of the water for short periods of time, supported on its legs and primitive lungs.  It still had fully developed gills, and was not quite an amphibian and still classified as a lobe-fined fish.

http://www.sci-news.com/paleontology/science-new-fossils-tiktaalik-roseae-01686.html

Atomic Tuesday: The Magic Numbers of Nuclear Physics

Atomic Tuesday:  The Magic Numbers of Nuclear Physics.

by Rich Feldenberg

Similar to the way electrons reside in atomic orbitals around the atom, the protons and neutrons that make the atomic nucleus are also organized into orbitals or shells.  The Nuclear Shell Model addresses the structure and energy levels associated with these nuclear shells.  No two protons or neutrons (nucleons) can be found in the same shell if they contain the same quantum state (again very similar to the quantum rules followed by electrons going into atom orbitals- Pauli exclusion principle). 

Each energy shell can hold up to a certain “magic number” of protons or neutrons, but all nucleons within the shell must be of different quantum states.  If all the quantum states for that shell are already taken, then they will go to the next available shell.  The magic numbers are 2, 8, 20, 28, 50, 82, and 126 – indicating the number of nucleons possible in each of the shells.  If an atom happens to contain a magic number or protons or neutrons it is found to be very stable, and these also correspond to atoms that are the most prevalent in the environment.   An example would be element 10 (2 for the first shell plus 8 for the second shell).  Element 10 is neon which is a stable nucleus.

If an element has both a magic number of protons and a magic number of neutrons it is “doubly magic”, and has a tightly bound nucleus.  An example would be Lead-208, which has 82 protons and 126 neutrons.  Heavy elements like lead (Pb) usually have more neutrons than protons since the electrostatic repulsion of the protons needs to be balanced out by more neutrons which provide the strong nuclear force to keep the nucleons bound together.

References:
1. The Nuclear Shell Model; University of Nebraska

2. The Nuclear Shell Model: University of California

3. The Nuclear Shell Model – Wikipedia



Mutation Monday: Lactase Persistence

Welcome back to your Mutation Station.
by Rich Feldenberg

Today we will examine the importance of the LP-mutation (Lactase Persistence-mutation), and its impact on human survival and global colonization.  Creationist like to ask the tiresome question, “name a mutation that increases the information content of a gene”.  I don’t think they really understand the question that they are asking, but today we will give one example of a simple mutation in human DNA that offered an advantage through natural selection to our species.  There are other examples, and we’ll address some of them in later blog entries.

Lactose is a carbohydrate found in mammalian milk.  It is composed of two simple sugars bonded together.  Humans and other mammals evolved to be dependent on mother’s milk during infancy, but then to be weaned off milk once the animal was mature enough to begin finding food on its own.  In order to digest lactose the enzyme lactase is required.  Lactase is produced in the digestive tracts of the infants and young mammals, but after weaning is generally no longer produced.  This is to conserve resources in the sense that it makes no sense to keep making an enzyme or other protein that is not being used.

This was true of early humans, as well, but a mutation occurred about 7500 years ago that allowed the lactase enzyme to remain expressed much longer throughout human life.  This mutation would then make drinking milk possible by adult humans, whereas prior to this, adult humans would not have tolerated drinking milk.  It is probably no coincidence that this mutation took place around the same time as the domestication of cattle and goats – sources of milk.

The mutation, itself is due to a simple switch of one DNA base in the gene coding for lactase, for another base – a single nucleotide polymorphism (SNP).   This lead to a change in the regulation of expression of the gene so that it wasn’t shut off when it normally would have been.  To our stone age ancestors, this would have been a wasteful and useless mutation, but with the development of an agricultural society it became indispensable as a way to increase ever rare nutritional sources.  It may have been responsible for allowing humans to migrate into and successfully inhabit Europe.

References:

1. “The Milk Revolution”, Andrew Curry; Scientific American special collector’s edition.  July 2015.

Origins Saturday: Origin of America!

by Rich Feldenberg

Today, in honor of Independence Day weekend, we will do something slightly different with Origins Sunday.  For one thing we are temporarily converting it into Origins Saturday so it can coincide with Independence Day.  As a critical thinker it is important not to be rigid in your thinking, but to remain flexible so as to adjust to ever changing conditions – but that’s a topic for another time.

In this episode of Origins, we also diverge from the usual topic of life’s origins, and instead will show the origins of the North American continent, and the place we now call The United States of America.  Today is the 239th birthday of the USA (happy birthday America), but the land mass that we live on is much older than that, and has been apart of other supercontinents in the distant past.  Below, you can see the distribution of the present day continents placed over the supercontinent Pangea.

Pangea was a fully formed supercontinent about 299 million years ago, and began to break apart due to continental drift, around 200 million years ago.  That was during the Permian Period when the dry land was ruled by primitive reptiles and the mammal-like reptiles (of which, included our ancestors at that time).   The mammal-like reptiles could be considered as Proto-mammals, with features of both reptiles and mammals.  Check out below:  aren’t they cute, but be careful they bite!

On Pangea, the inhabitants of the time could move across the continent, at least in principle.  The interior may have been very dry and inhospitable to many forms of terrestrial life at the time.   One line of evidence for the formation and breakup of the supercontinent is the distribution of fossils found in various locations.  Their pattern shows that before the breakup there were the same creatures living on both sides of fault lines, in a non-random distribution.

Before America came to its present location it drifted across the globe and had been in physical contact with what would become Africa, Europe, and South America.  Due to plate tectonics it is continuing to drift today, and in another 200 million years the map of the world will look vastly different from the one we are used to seeing.  This should remind us that we are all truly global creatures.  Our ancestors have lived all over this planet, from the ancient seas, to many of places among the land masses.  Have a fun and safe July 4th weekend!!

References and further reading:
1.  “Pangea | Supercontinent”, The Encyclopedia Britannica; http://www.britannica.com/place/Pangea

2. “Nine of Your Relatives That Ruled Before Dinosaurs”,  Tor.comhttp://www.tor.com/2014/02/05/nine-of-your-relatives-that-ruled-before-dinosaurs/

Does carbon production in stars reveal design in nature?

Does carbon production in stars reveal design in nature?

Why the triple alpha process appears so unlikely, but is absolutely vital to our existence.

By Rich Feldenberg

In Douglas Adam’s remarkably clever and entertaining sci-fi-philosophical comedy, The Hitchhiker’s guide to the Galaxy, the solution to the most profound and vexing of problems, the ultimate question of Life, the Universe, and Everything turns out to be “42”.  Unfortunately, that answer didn’t seem to really satisfy any of the characters in the story, and simply brought increased puzzlement and confusion.  Does that mean that there is no answer, or that we aren’t intelligent enough to understand the answer, or as Deep Thought, the super computer in the Hitchhiker’s guide points out, that we haven’t really figured out how to ask the question in the right way, so the answer churned out will be obviously incoherent?

I think that almost all of us have a deep desire to understand something a bit more about Life, the Universe, and Everything, than we know right now, but just like Douglas Adam’s hyper-intelligent pan-dimensional beings, we don’t really know where to even start asking the question in a formally logical and structurally coherent way.  If a hyper-intelligent species can’t even figure out how to do it what chance do we have to get it right?  One thing that seems clear is that humans have been trying to figure out their place in the cosmos for a very long time.  Even in prehistoric times there is evidence for a developing concept of the supernatural, suggested in artifacts and signs of ritual.  It is easy to to imagine early humans during the last ice age feeling tiny and afraid in a big world of danger and death, wanting desperately to gain an edge by understanding the world just a little better.  And thanks to human intellect, our early ancestors did learn important facts about the world that helped them to survive, such as learning about the seasons, migration patterns of large herd animals, how to identify stones that can be crafted into technology, and so on.  Some things remained a mystery, such as where all the humans originally came from, how the world was created, and why everyone eventually dies, so myths were invented to answer these important questions.

Jump forward 50,000 years, and we humans managed to survive against odds, not due to strength, but due to intellect and the fierce instinct to reproduce.  Today we know a lot more about the universe, thanks to the development of science over the last 400 years, but as the frontiers of science are pushed ever outward, we still stumble against the age old questions of Life, the Universe, and Everything.  How did we get here and what is it all for?  To illustrate why it may look like the universe was specially made for us, I want to describe the triple alpha process, which is really a cool thing to know about in its own right, but also because it is a feature of our universe that theists commonly use to justify the concept that the universe has to have been fine tuned in order for us to be here.

The triple alpha process (also known as the Hoyle resonance) is the mechanism by which carbon is produced in the universe.  Carbon is pretty important for us earthlings since all earth life is carbon based.  From the carbon in our DNA, to the that in our proteins, carbohydrates, and lipids, carbon is our most important building block for making a living thing.  Based on the chemical properties of carbon, it seems to be the most likely element to play the staring role featured in the movie of life across the universe.  Any other potential candidate atoms (such as silicon – see my blog post from June 18th, 2015 on the implausibility of silicon based life forms) don’t appear to have the versatility necessary for the complexity of chemical reactions we call life.

The carbon in our bodies, in all living things, and in the environment in the form of carbon dioxide in the atmosphere or carbonates dissolved in the oceans, was not produced in the big bang.  The big bang occurred about 13.7 billion years ago, and in the intense temperature and density all the primordial hydrogen and helium was created, with a trace amount of lithium and a few other elements.  Carbon is the fourth most abundant element in the cosmos today, so it had to be produced through another route.  That route involves its synthesis inside of hot dense stars.

Main sequence stars like the sun are busy fusing hydrogen into helium.  This process ultimately takes four hydrogen nuclei (protons) and with the temperatures and densities achieved in the core of stars fuses them into a helium nucleus (two protons and two neutrons represented as He-4).  During that process energy was released in the form of gamma rays as two of the protons were transformed into neutrons, with the small mass difference (protons have slightly more mass than neutrons) being converted to energy.  The gamma rays continue to be absorbed and reemitted at slightly lower energy by other atomic nuclei until they have lost so much energy they are eventually released at the stars surface as visible light.  This is why the sun and other stars shine.  As you might have noticed, this process did not generate any carbon.  That’s because the sun will not produce carbon until it runs out of its hydrogen fuel and falls off the main sequence.

When a star like the sun runs out of hydrogen fuel, the radiation pressure that was holding it up against the intense gravitational force weakens, so that gravity collapses the core.  This collapse has the effect of heating up the core further, and causing helium nuclei to fuse.  The outer layer of the star get pushed outward, and the star will become a Red Giant, swelling many times its original size.  This where the triple alpha process comes in.  Each helium nucleus – composed of two protons and two neutrons – is called an alpha particle.  The carbon-12 (C12) has 6 protons and 6 neutrons, and its production is a two step process in the heart of Red Giant stars.  In the first step two alpha particles fuse to produce beryllium-8 (an atomic nuclei with 8 protons and 8 neutrons represented as Be-8).   Beryllium-8 will have a tendency to almost immediately break apart into two alpha particles, but in the collapsed core of the Red Giant star, the production of beryllium-8 is even faster than it has a chance to fall to pieces.  This allows another alpha particle to fuse with a beryllium-8 nucleus and thus creates our beloved carbon-12 atomic nuclei.

This seems all well and good except that the energy of the beryllium-8 nuclei plus the alpha particle is higher in energy than the carbon-12 nuclei produced.  In order for the nuclear reaction to proceed the reactants and the products need to have fairly close energy levels.  This means that the odds of this ever actually happening is so small as to be insignificant, and so “no carbon for you”, to paraphrase the Soup Nazi from Sienfield!

Around 1953, the British Astronomer Fred Hoyle realized that for carbon to be produced by the triple alpha process, the carbon nucleus had to have an excited state that was somewhere in energy near the combination Be-8 + He-2 + plus a little extra energy to account of the kinetic energy of the two reactants.  Hoyle then went on and calculated the energy that this theoretical excited carbon state should have in order to explain the carbon that is obviously very abundant in the universe, and necessary for us to exist at all.  His calculation was that the excited carbon state was at 7.69 MeV (MeV = mega electron volts), and he went to his nuclear physics colleagues to try to get them to look for this carbon state.  He didn’t have much luck initially convincing the physics community to look for this state, but several years later an excited state of carbon with an energy of 7.656 MeV was found that verified Hoyle’s prediction.  The remarkable thing is that Hoyle predicted this state of matter based only on the anthropic principle – that it had to exist in order for us to be here to wonder about it.

This excited carbon-12 state, now known as the Hoyle state or Hoyle resonance, makes carbon production in our universe possible.  Because the energy of the excited carbon state is close to the energy of the Be-8 + He-2, the reaction can proceed, then lose energy settling down into the lower and more stable C-12 state.  Recent studies have shown that the carbon nuclei can be thought of as clusters of three alpha particles in the way they are arranged and interact.  In the stable ground state of carbon-12 (remember we are talking about the energy states of the nuclei themselves and not the energy levels of the electrons around the nuclei, as we would be if talking about chemistry) the three alpha particles can be thought of as forming an equilateral triangle with an alpha particle at each vertex.  In the Hoyle state carbon nucleus the three alpha particles form an obtuse triangle, or what has been called a “bent-arm” configuration.  Almost no carbon formed this way in the Big Bang because the temperature and density of the universe dropped too quickly for anything but a trace amount, at best, of carbon to be made.  It had to be in the hearts of these dying stars that the process would have millions of years to accumulate the universal carbon content.

The triple alpha process is one of several arguments theists have used for the, so called, fine tuning problem.  By fine tuning they mean that the physical constants and other parameters of the universe are so exquisitely tuned that any adjustment in their values would have produced a universe devoid of life.  In our example above, if there was no excited carbon state at the Hoyle resonance then there would be a universe with stars and galaxies, hydrogen and helium, but no carbon or higher elements, and therefore no planets, living creatures, or people.  Seems like a pretty lucky coincidence – right?

First, I would have to say that in my opinion, in a reasoned scientific debate, the fine tuning problem is the most sophisticated argument for the existence of a cosmic intelligence or creator being.   There is already so much overwhelming evidence for evolution that the illusion of design in the living world is no longer a valid argument, and hasn’t been so for at least a hundred years.  Almost all scientifically educated people will accept evolution as fact if they have not already been intellectually blinded by dogma.  That still leaves apparent design in the physical world to be  adequately explained.

Secondly, I would conclude that the fine tuning arguments do not apply to those who hold to a literal interpretation of scripture, whether that individual adheres to the Christian bible, Jewish torah, or Islamic koran.  To hold a literal interpretation would mean that fine tuning argument is completely irrelevant, as the universe, in this view, was created in a short period of time – just 6 days!, and has existed for only a short time period – less than 10,000 years.  Therefore, there is no need to worry about the unlikely Hoyle resonance associated with the triple alpha process, as it didn’t take hundreds of millions of years for stars to form the carbon for us to have available for life, since everything necessary was just created when animals and humans were suddenly brought into existence.  The same logic would apply to many of the other examples of fine tuning arguments, such as the strength of the gravitational constant, for instance.  Again, it doesn’t matter too much if the constant is just right to account for the longevity of stars or the expansion rate of the universe, or so on.  Stars were just created in the beginning, and there was never any concern that they would all collapse into black holes too soon, or not have enough gravitational force to collapse from interstellar clouds of gas and dust to begin fusion in their core.

So where does this leave us then?  Well, the fine tuning argument might be of use to the theist that believes the creator of the universe works through physical laws, and sets things into motion at the earliest stages of the universe.  This would be most consistent with the deist, who might interpret god as the initiation force of the universe or the laws of nature itself.  Once the universe is wound up it is released to progress based on the laws put in place, like a computer program being executed after the user presses “start”.  Does that fit at all with an interpretation of a personal god?  Again, it doesn’t seem to fit well with a young earth creationists world view.  For those who can accept an old universe that operates by physical law it may be compatible, but there is nothing about the fine tuning argument that requires a personal god.  

If we look more closely at the fine tuning arguments we find that even there, the assumptions may be over emphasized.  Again, it is claimed that if even one physical parameter, such as the gravitational constant, or the strength of the electromagnetic force, are varied even slightly the universe could not have evolved in a way that life as we know it would ever be produced.  Several theoretical physicists, including the late Victor Stenger had shown that if you alter a particular physical parameter, but also allow other physical parameter to vary at the same time, then there can be many balances that essentially cancel themselves out.  In other words, there are many more “sweet spots” that are possible for a habitable universe than the one we find ourselves living in.  That means the universe is not as fine tuned as sometimes claimed.  As far as the wild coincidence of the Hoyle resonance state, Stenger too showed that the excited state of carbon could vary by a lot more and still produce as much, and in some cases even more carbon than our universe is able to produce.  He calculated that the excited state of carbon could have a wide range of values – from 7.596 MeV up to 7.716 MeV- to produce the same amount of carbon that we see in our universe.  It didn’t have to be precisely the 7.656 MeV that we observe for our universe.  In addition, enough carbon could still be formed if the energy value were up 7.933 MeV, and even more carbon may form at a range below the 7.596 almost down to the ground state of the carbon-12 nucleus.

This suggests the Hoyle resonance was not terribly finely tuned after all, and therefore life’s dependance on this unusual state is not as unlikely as initially thought – a rather poorly tuned cosmic dial could still have resulted in the same conditions.  Not only that, but some values of the excited carbon state may actually have made life potentially more common throughout the cosmos.  If it had only happened to have a slightly lower value it would have resulted in more carbon production in stars.  In that sense, our current universe is not very well suited for life.  Life just barely makes it out here!   It might have been better for evolving life if made by design.

Can science do any better at providing an explanation for a universe containing physical constants consistent with life?  In recent years serious consideration has been given in scientific circles to the possibility that we live in a multiverse of universes.  In the multiverse model our universe is just one of many, possibly an infinite number, of universes.  Each universe could, in turn, have their physical constants randomly set to a particular value.  This would mean that there are many universes that exist in the multiverse where the physical laws do not allow life to develop.  These universes may be interesting in certain ways, but would be completely devoid of any life forms.  Other universes in the multiverse, would be like ours, and happen to have their physical parameters randomly set in a way that makes the development and evolution of life possible or even inevitable.  Because every variation of combinations of physical parameters are manifest in some universe somewhere it shouldn’t be surprising that we wake up in a universe that is suitable for us.  Even if a universe exactly like our own had only a 1 in 10500 change of occurring, it would be inevitable to occur an infinite number of times in an infinite multiverse.

The truth is that no one knows for sure if we live in a multiverse.  It is very important to point out the multiverse idea wasn’t invented to solve the fine-tuning problem, it was a natural consequence of existing scientific theory.  Certain serious scientific theories, such as inflation theory, which describes the very early stages of our universe following the Big Bang seem to demand a multiverse as part of their mathematical structure.  Inflation hasn’t been satisfactorily verified as of yet, and no other evidence has provided strong enough proof of a multiverse at this stage in our cosmic understanding.  Still, continuing down the path of naturalistic explanation still seems the most prudent path to take since this approach has taken us so far in such a short amount of time.  To the deist, there is nothing disproving that a supernatural force set the laws of physics in motion some 13.7 billion years ago, but as has been pointed out by others, this does not seem to be the most parsimonious explanation, since this merely pushes back the question by one step, and we are still left with the question where did such a complex and intelligent being come from.  For those who demand that the creator being was always there, then the same argument can be used for the universe itself.  Even if science can never answer this question – a distinct possibility – this does not mean that therefore god did it.  If one theory is proven wrong that does not mean the rival theory is therefore the correct explanation.  It simply means one theory was proved wrong.  The rival theory may be right or wrong, but still needs evidence to stand on its own.  Unfortunately, if science can never satisfy our curiosity by getting to the bottom of our ultimate origins there is no reason to think that religion can do any better.  There is also every reason to feel hopeful that the discoveries of science will continue to shed some light on the origins of the universe – that we are not at the end of scientific discovery.

The triple alpha process is a fascinating mechanism by which the carbon so vital for life as we know it is produced in our universe.  Perhaps it doesn’t answer the ultimate question of, Life, the Universe, and Everything, but appreciating its complexity certainly adds to the beauty of trying to understand our place in the cosmos.  If we did learn someday that the multiverse exists, and we are here because it is inevitable that some universes in the multiverse would be just like our own for no good reason but by a statistical roll of the dice, I’m sure that many would still feel that the ultimate question was still not satisfactorily answered.  Is that because we don’t know what the question really is?  Is it that we don’t know how to formulate the question so that it brings in the whole cosmic perspective plus our own personal one?    In the mean time, for those of us who value evidence, logic, and reason, while we continue to look for the answers to the deep questions, all I can offer is the advice of the HitchHiker’s Guide to the Galaxy – Don’t Panic!

References:

1. “Is Carbon Production in Stars Fine-Tuned for Life”?, Victor Stenger, Center for Inquiry,  Volume  20.1, March 2010.

http://www.csicop.org/sb/show/is_carbon_production_in_stars_fine-tuned_for_life

2. “The Hoyle State: A Primordial Nucleus behind the Elements  of Life”, Natalie Wolchover and Quanta Magazine.  Scientific  American,  December 6, 2012.

http://www.scientificamerican.com/article/hoyle-state-primordial-nucleus-behind-elements-life/

3. Wikipedia:  “The triple-alpha process”.

https://en.m.wikipedia.org/wiki/Triple-alpha_process

4. “Carbon’s Hoyle state calculated at last”,  Edwin Cartlidge, Physics World,  January 3, 2013.

http://physicsworld.com/cws/article/news/2013/jan/03/carbons-hoyle-state-calculated-at-long-last