Think Bomb

Saturday, September 30, 2006

Sickle Cells

Now that you know about how blood works and the important role of hemoglobin, I’d like to explore the topic of sickle cell anemia as promised.

In the biology course Organisms and Environments we learned that the malaria virus is carried by a protist parasite called Plasmodium, which enters the human body via a mosquito vector. Malaria is the end product of a parasite chain, with mosquitoes carrying Plasmodium, which creates the disease symptoms. In Ecology and Population Biology, we learned that where malaria is present there is a higher prevalence of sickle cell anemia. Sickle cell anemia is almost non-existent in countries where malaria is not found, but something about the sickle cell disease produces resistance to malaria. In Genetics we learned that sickle cell anemia is a genetic disorder in which a change of one single nucleotide led to a novel amino acid substitution in the protein structure of hemoglobin. The disorder is autosomal recessive, so those that have two copies of the allele are fully affected, those that are heterozygous (two different copies) are only partially affected, and those that are homozygous dominant and don’t carry the mutated allele are not affected at all.

Now, after all the build up between three of my biology courses, after years of asking “but how does sickle cell anemia produce resistance to malaria?” my question has finally been answered in Bio-Chemistry this year!

That single nucleotide change that is responsible for sickle cell anemia results in the inappropriate placement of a valine amino acid where a glutamate amino acid is supposed to be in the hemoglobin protein. Due to its polar qualities, the glutamate amino acid has no problem sitting on the outside of the hemoglobin protein facing the aqueous environment of the cell, and is therefore called “hydrophilic.” Valine, on the other hand, is a non-polar, uncharged amino acid and is said to be “hydrophobic.” Water tends to exclude this amino acid, pushing it away. Hemoglobin in its relaxed state favors the binding of oxygen and has no hydrophobic sites revealed. When hemoglobin drops the oxygen and is in the tensed, deoxygenated state though, a hydrophobic niche is revealed, the perfect hiding place for that hydrophobic valine. If, by chance, the valine comes into contact with this site, it will not leave. Water excludes the hydrophobic molecules, forcing them to stick together. If enough hemoglobin valines find their way into this hydrophobic niche, aggregates of hemoglobin form in the erythrocyte (red blood cell), creating long hemoglobin strands. The cell will begin to form a sickle shape as a result of these strands and has potential to clot capillaries and even arteries if enough sickle cells are present. This is why it’s so dangerous for someone who has the sickle cell mutation to be in low oxygen environments; the less oxygen they are getting the higher the chance their hemoglobin will deoxygenate and aggregate to form sickle cells. This risk is so high in individuals who are homozygous for the mutation that they often die in childhood. People who are heterozygous for the mutation are somewhat better off. It’s still a risky disease, but their immune system does a pretty good job cleaning up those sickle shaped erythrocytes before they form clots.

Now, what does this have to do with malaria, you ask? Well, recall from the last article that there are a number of environmental signals that will cause hemoglobin to drop its oxygen. One of those signals is a low pH (acidity), as active tissues are often more acidic. When the parasite Plasmodium enters an erythrocyte the pH drops. The hemoglobin then drop their oxygen all at once, exposing the hydrophobic sites to the hydrophobic valines. They aggregate and cause the cell to sickle up, marking the cell for clean up by the immune system. The immune system is then able to sweep the parasite out, before it has a chance to reproduce!

All info is from my coursework at UI
Sickle cells:

Monday, September 25, 2006

Murder in the Air, Mystery in the Blood

Oxygen, O2, scavenger of electrons, oxidizer of molecules. Given a spark, it will react with molecules in a combustion explosion, given the time it will eat away iron producing rust, if let loose in the body it will wreak havoc, leaching the electrons strait from your tissues. For as good a reputation as it has with us, oxygen is down right murderous. So why do we need? And how do we manage it? If you ask me, it just sounds like a bad idea to begin with. But really, the use of oxygen in metabolism had very clever beginnings…

Oxygen wasn’t so popular at first, let me tell ya. The first organisms arose about 3.5 billion years ago when free oxygen was a rarity. They were anaerobic cells, and just as their name indicates, they had no use for oxygen. Originally, the process of glycolysis was used to break down organic compounds found in their environment. When the abundance of free organic compounds began to dwindle, photosynthetic organisms that could fix carbon dioxide (CO2) in the air to make their own organic compounds arose. A side effect of the ingenious design of photosynthesis just happened to be molecular oxygen (O2). There was very little O2 in the air at that time, except what they produced, and like us they tended to just let their waste build up (being unicellular, they didn’t exactly have the most creative waste management!). By about 2.5 billion years ago, the levels of oxygen began to poison these anaerobes. Dieing away in their own waste, these organisms seemed doomed…until a new organism hit the scene. One microbe’s trash is another microbe’s treasure, as they say, and an organism arose that took the idea behind photosynthesis, and practically put it in reverse. These organisms would utilize oxygen, and produce CO2 as a byproduct. Many of you have heard this story before, about how our ancestral mitochondrions saved the day and the entire earth from an overly oxidizing atmosphere. But the story goes deeper still.

About 1.2 billion years ago the first multicellular organisms appeared. It was easy at first, getting oxygen to a limited number of cells took nothing more than simple diffusion. As organisms became larger and more complex, around 550 million years ago, a little more effort had to go into getting that oxygen where it was needed. Gastrovascular cavities were a simple way to go about it.

What about a creature like us though? A large creature with a diverse variety of tissues, each with their own special functions, from the tip of the head to the bottom of its toes? Clearly, diffusion is not going to cut it in an organism like us. Oxygen must be carried where it is needed, and CO2 taken away. This requires an efficient system of transport—a cardiovascular superhighway.

Oxygen transport is no small task. As we know, O2 is dangerous stuff; our blood cells might as well be carrying bombs. So how do they do it, these little erythrocytes (the scientific term for red blood cells, I’d like to use it in this article because it’s a very pretty word)? Like super secret agents, they package O2 very carefully in their specialized hemoglobin proteins.

Hemoglobin is a protein with four subunits. It’s not all amino acids; each subunit also contains a prosthetic group, a non amino acid component that is essential to its function. This group, called the heme group, has a little something that oxygen loves very much: iron. Normally oxygen’s relationship with iron is, well, a little abusive. Oxygen takes electrons from iron atoms and leaves iron in an oxidized state, forming rust. The heme group takes precautions against such abuse. The iron is secured all around by a nitrogen ring that holds it steady with a distal histidine guarding its back. Histidine is one of the amino acids comprising hemoglobin and plays two necessary roles. For one, it hydrogen bonds the other end of the O2 molecule, keeping it in place. The other role is dealing with carbon monoxide. Carbon monoxide (CO) also has a love of iron, an affinity that is thousands of times greater than O2s. Luckily, the distal histidine gets in the way of what could be a beautiful relationship between the iron and CO. The distal histidine presses down into the plane where the CO would normally bind, forcing a bent conformation. CO is linear and unhappy in such a state, but O2, when bound to the iron, has no problem being bent and is comfortable at an angle.

So the hemoglobin has packaged its oxygen. Very good, but it still must release this precious load to tissues that need it. How does it know when it’s at just the right place? Several things cue in the hemoglobin molecule. Active tissues are more acidic, with a higher concentration of CO2 and a lower concentration of O2. They also create the molecule 2,3-Bisphosphoglycerate (2,3 BPG) while breaking down glucose. Together, all of these molecules help to produce a conformational change in the hemoglobin protein complex. It releases it's oxygen and is now in the deoxygenated state and ready to pick up CO2. Check here to see the way hemoglobin moves to bind and release oxygen:

I hope you’ve enjoyed this article on oxygen and erythrocytes! It is in part an attempt to get you geared up for my next article though—I’d like to tell you all about sickle cell anemia, why it persists in some countries, and what causes those erythrocytes to sickle. Stay tuned for that this Wednesday.

U of I's own Dr. Cole
Campbell. Biology, 4th Edition. 1996
Purves, Sadava, Orians, Heller. Life, the Science of Biology, 6th Edition. 2000

Heme and hemoglobin: wikipedia

Wednesday, September 20, 2006

Measuring Genetic Diversity

After my last article, a friend brought up that I had oversimplified the implications of genetic analysis and I think there’s still a lot of confusion on this topic, so I’d like to get right back at it!

You’ve probably read in a pop science magazine at some point that humans are about 98% similar in genetic make-up to Chimpanzees. But what does this mean? To say that two organisms are “98% genetically similar,” is not really saying anything at all. A statement like that begs the question: “how are they similar?” The article you are reading could be talking about chromosomal banding patterns, open reading frames, or expressed DNA, but most people take it to mean the whole shi-bang, a base pair by base pair account of similarity.

The whole shi-bang, what most people are interested in, is a lot to swallow. When we look at DNA in general, there are only four options as far as nucleotides go, and only two different base pairings: A-T and C-G. Like a computer code with only 1s and 0s, the code can look remarkably similar even if they serve different functions. The likelihood of running into some similar sequences between organisms is pretty good, even if they are not closely related. Since there are about 3 billion base pairs in a human being, one could be only 0.1% different from another person and still have 1 million dissimilarities in their sequence!

So what do we count as a dissimilarity? If two organisms have a similar stretch of DNA but they fall on two different chromosomes in one species and only on one chromosome in another species (a common case or chromosomes splitting), do we count it as a difference? How about when a chromosome is duplicated? What about base pair deletions? How about when one part of a chromosome is inserted into another? These are all questions researchers must ask as they compare and contrast the genetic make-up of species.

One of the things we mainly think about when we hear the words “genetically similar” is the genes themselves in the Mendelian sense, the expressed alleles (types of genes). A brother and sister may be 99.9% similar in terms of their total DNA, base pair by base pair, but, cross-over during meiosis aside, they are still likely to share only about 50% of their coding alleles. Often times the differences in genes that make multiple alleles (versions) possible are single nucleotide polymorphisms (SNPs), where just a small change can result in a novel phenotype. A change in one lil’ base pair may not seem like much in a 3 billion base pair human, but it can create a totally different protein and phenotype. Don’t tell a person with color blindness or cystic fibrosis that one little base pair in a billion doesn’t matter! These diseases and others are often a result of small genetic mutations.

The majority of DNA is non-coding, and can harbor both similarities and dissimilarities. In areas like telomeres at the tips of chromosomes or centromeres in the middle, most animals are likely to be similar as these are highly repetitive regions, existing more for the sake of the stability of the chromosome than anything else. Other areas of non-coding DNA, such as microsatellites and other VNTRs, are likely to be highly variable not just between species but sometimes even from person to person. Since the DNA in microsatellites is non-coding and not a structural necessity, conservation is not an issue in these short repeating segments. Their differences add up over time as unchecked mutations build up. These unique segments can be detected through simple gel electrophoresis methods and so are often used in forensic cases or to help determine heredity.

When geneticists do look at DNA to analysis the evolution of species and their relatedness, all of these factors are considered (and much more!) in the holistic field of genomics. From whole chromosomal structures to single nucleotide polymorphisms genomics encompasses all of these features and tries to make sense of speciation.

Sources: Gibson and Muse. A Primer of Genome Science, 2nd Edition. 2004
Images: wikipedia

Monday, September 18, 2006

Answering Some Common Misconceptions About the Evolution of Organisms

After working as an assistant for an introductory level biology class and checking out message boards for some of the religious campus clubs I realize there are a lot of misconceptions circling around about evolution. This is no surprise as evolution is a subject that is often very poorly taught at a secondary school level. It is seen as being antagonistic to religion and so is barely touched upon. Another unfortunate thing is that at the college level, when people are confused about evolution, they are often too shy to ask because they fear they may be dismissed as being stupid or ignorant. Well, I’d like to clear things up without talking down, after all how can one know if one is never taught?

So, we’ll start off with some commonly misunderstood topics, along with the quote that pushed me to write about it.

1. Natural Selection
“How can new species just decide to be made? I don’t get how natural selection is supposed to make new animals.”

People have known about selection and evolution and used it to their advantage way before Darwin ever came on the scene. What in the world can I be speaking of? Why animal and plant breeding of course! Breeding is a fine example of evolution at work, but rather than being driven by natural selection it is driven by man’s selection. We breed animals with traits we find favorable until we have faster horses, better hunting hounds, juicier beef, or higher yield corn. Since it is well documented and we can even see the results of breeding within a lifetime, no one argues that this type of selection does not take place. But if we can do it, is it possible that nature can do the same thing if given the time?

In the natural world, organisms that have less favorable traits are less likely to survive and reproduce. Just as breeders may put down a slow horse to eliminate the ill suited genes from their stock, the slower gazelle may be put down naturally by hungry lions on the savannah. Aside from predator/prey type relationships, organisms may be less fit to survive a number of other natural challenges such as weather or other environmental conditions, disease, food shortages, competition, or they simply may not be able to find a mate willing to help them pass on their heritable traits. All of these are considered forms of natural selection.

A funny thing to note about human and natural selection is that they sometimes collide in the most ironic ways. For instance, we’ve bred bananas to be big, high yield, and with minimal seed content. We haven’t given much thought to it’s susceptibility to diseases though and when natural selection hit banana crops with a case of Black Sigatoka, thousands died and the market got hurt pretty badly. Now it is a constant fungicidal battle to keep the banana killer at bay. Although bananas may meet our standards for being tasty and plump, they didn’t stand a chance against natural selection without us!

Cases like this happen all the time. Consider slow, dumb cattle being dragged down by wolves, crops being ravaged by disease, and let’s not forget the genetic abomination that is the chiwawa! It’s all a reminder of what man and nature can do to drive selection and create novel breeds or species.

2. Phylogenetic Trees

"Chickens are 94% similar in genetic makeup compared with humans, so does that mean that chickens evolved apes which evolved into us?"

This is probably the most common misconception people have toward evolution—that it is linear. Rather than seeing evolution as happening in a long line with all species ever existing somehow fitting in, let’s try to imagine it like an aged and expansive family tree, spanning millions of years and generations, with a mind-boggling amount of branches spreading every which way. When the possible relationships between organisms are represented this way, it is called a “phylogenetic tree.” To get away from this idea that evolution is linear, take a look at your own family tree. You would not say that your second cousin came from your niece who came from you in a linear fashion, but you would say that you are related through a common ancestor. In the same way but much farther removed, chickens did not evolve into apes then humans, rather their ancestry all branch back to the trunk of the tree at some point. Think about your own family. You may look nothing like your second cousin, but you both shared a great grandparent. The farther removed a cousin is, the less they tend to look like you. This is similar to a phylogenetic tree, only different species are not just 3rd or 4th cousins, but one thousandth cousins! They’ve had hundreds or thousands of generations between each other, yet they share a common ancestor. In the case of mammals, the first mammal-like reptile is thought to be Therapsids, which were around in the Cretaceous period over 65 million years ago. Earlier still, the first bird-like reptile was thought to be Protoavis, which arose 225 million years ago. As you can see, we are not closely related to birds at all. There are millions of generations between us!

3. Homology

“I don’t understand why DNA is so important if animals are so different but so much of it is the same.”

Most of the DNA in animals is similar because what works tends to stick around. Why change a good plan? The DNA that is similar to all organisms is call homologous or conserved DNA. Just as you are likely to find more of your DNA is similar to your sister than your 2nd cousin, organisms that are more closely related tend to have more DNA in common as they have had less generations to diverge from the common ancestor. Often the DNA that is most retained over time are the portions of DNA which are used to make proteins that have similar functions in all animals. Really, a cat is not much different from a horse on the cellular level!

Many phylogenetic trees these days are constructed with the aid of genetic analysis, especially searching for homology and using rates of genetic change and mutation to develop a time frame. Finding homology in the morphology, or physical layout of organisms, is another common method of creating a phylogenetic tree. Many phylogenetic trees were constructed by examining bone structure combined with isotope dating. Isotope dating is when the rate of radioactive decay of isotopes (carbon, argon, lead, and other types of isotopes) is used to measure the age of the material it was found in. Most frequently, a combination of all methods are used to develop as accurate a phylogenetic tree as possible.
Check here to explore a gene based phylogenetic tree!:

4. Coexistence
“Evolutionists are trying to eliminate religion.”

Can science and religion get along? Of course. Many Christians have moved from the literal interpretation of the bible to a metaphorical view that allows them to accept an older age for the earth while still believing in God. I have heard some say, “a millennia is but a day in the eyes of God.” If you are a religious person and would like to maintain a literary view of the creation of the earth according to the bible, saying it is about 6,000 years old, then at least an appreciation of the modern application of science should be maintained. I have often heard it said that “God helps those who help themselves,” and science is a much needed tool for creating new technology that makes our world more efficient and medical advancements to increase the quality and length of life.

I encourage everyone to learn more about science, if for nothing else than at least to make better, more convincing arguments against what you feel is wrong.

Images: lion and gazelle:

Monday, September 11, 2006

Always on the Move!
From Large to Small, Nothing Stands Still for Long...

One of the things that first fascinated me about biology is the general bustling nature of life. Organisms are constantly working, eating, breathing, and drinking to maintain the essential aspects of their complex internal environments. It’s a wonder that creatures can do it all--from the tiniest aphid to an enormous elephant, every organism must keep a steady temperature, protect against degradation, maintain bodily structure, and supply energy to its cells. The inside of a gnat has more “workers” than any factory and is more intricate and synchronized than any great city of the world.

Even the smallest levels of the orangism are busy at work. As I entered into cellular level biology, I realized the workings of any given cell alone are comparable to a small country. When we first lean the components of a cell in high school, we see it as this mainly empty compartment with a few organelles here and there. It is not until later that they tell us the cell is literally packed. Filled with water, we can envision it more as a sea of enzymes working away on their given tasks, filaments webbing the inside like a great monorail network, RNAs flying about like blueprints on the run, small molecules acting as precursors to great projects or messengers with the latest news, organelles operating like great factories spilling out their products, pores regulating the influx and efflux of this carefully constructed environment. Here is an image of epithelial (skin) cells where the microfilaments have been stained in red.

Although there are more components that are not shown, it is easy to see the cell is far from empty. To see other cytoskeleton structures that can exist in a cell look here.

Just to blow my mind a little further, my bio-chemistry instructor today mentioned “breathing proteins.” A weird phrase to hear at 7:30 in the morning, he had to repeate it once more for the confused and sleepy class. Proteins are usually thought of as strong, inflexible stuff, the scaffolding of bodily structures. At certain low temperatures, we can view proteins and discover their (nearly) immobile structures, but in the high heat liquid environment of the body, these molecules are allowed quite a bit of wiggle room. Each amino acid component of the protein has a degree of freedom to rotate, and all together they can scoot around and create variations in the overall shape of the macromolecule. Dr. Cole calls this “breathing.”

Going deeper, we not only see that molecules like amino acids are active, but the very atoms and the bonds between them are as well. In the study of resonance structures in organic chemistry, we are shown that electrons are quite the flighty bunch. Take a look at this sulfate molecule below (also shown in 3D at left):

As you can see the double bonds (=) appear in different locations on each, as does the charge. Are they all the same molecule? Yes. Any way is an appropriate way to draw sulfate (even more are possible, just not as stable). More correctly than saying they are each correct, is to say that they all together are correct. Each depiction of the molecule is not real, the actual molecule is more like a combination of the 6. The double bonds do not really exist; rather the electrons are shared equally among all the bonds in this molecule, with only a probability of being “found” in any particular place. My o-chem instructor might say that the oxygens all have "1/2 a pie bond and a sigma." To see an organic molecule with even more resonance possibilities, check out benzaldehyde.

Which brings me to the next eerie point: the existence of electrons is only a probability, never an actuality. The orbitals we recall from high school chemistry are like the orbitals of the earth around the sun. This is not an accurate representation. Rather, orbitals are the most probable place to "find" an electron.
Below is a graph of the electron density probability of a simple s orbital:

The Y axis is the nucleus of the atom, the only place where the probability of finding the electron is zero. The density is most probable where we would normally draw the shell, all around the nucleus. This can also be represented by a “cloud” graph:

One thing to recognize about the electron density graph is that it progresses asymptotically; it never reaches a probability of zero as the electron travels away from the nucleus. Could it be that an electron from a hydrogen atom at the tip of my nose is somewhere flying out by the sun? Yes, just far less probable than the more likely ~5X10^-11 meters away from the nucleus of that atom.

Even stranger still, is that you’ll never run into an electron, whether it’s by the sun or on my nose. Electrons exist as waves (standing waves), not particles. So not only are they constantly moving, but they are defined as a movement. Even the deadest creature or mundane rock is very “lively” when we look at the atomic level. Electrons are restless and even neutrons within the core move about (that is how we get isotopes like C14 to date organic material). It turns out if you look close enough, every inch of our world is a very dynamic, ever changing place.

Check out my o-chem professor's page:
And my bio-chem professor's:

Electron density probability graph and electron density cloud:
Sulfate resonance structures:

Saturday, September 09, 2006

Dear Readers:

Since classes are underway, I've been having a hard time getting people interested in having an interview because they are pressed for time. My article scheme may be less consistent than during the summer with my interviews appearing less than weekly. I will still include interviews, field trips, science of yum, and feature articles as they happen.

Thursday, September 07, 2006

Exploring the Genome

In light of last week’s article I thought it would be fun to share some
great genomics databases.
Here is a good place to start, with basic information on the human genome project: The Human Genome Project

Here is a page with general links to all sorts of gene related databases: NCBI gene databases

One of my favorite sites is
Online Mendelian Inheritance in Man (OMIM). This site will allow you to search any trait for possibly related genes. For example, if you type in “breast cancer” you will find all of the genes thought to have a link to the disease.

~A brief history of the study of genes~

Remember Gregor Mendel from high school biology? He was the monk with a certain love of peas who used probability to predict the expected ratio of traits in offspring. Mendel identified whether the physical traits of his pea plants were dominant (always expressed), partially dominant, or recessive (masked in the presence of dominant traits). If you were like me, you remember the "punnet square" method and getting stuck with any guy other than the one you liked, forced to make predictions about what eye color, brow line, etc., your offspring might have. Other uses of Mendel's findings are not always so traumatic. These methods can still sometimes be used to help predict the characteristics of offspring in breeding, research, and agriculture or anticipating a genetic disorder in humans. Although we now know that many traits are a result of multiple gene expression and most genes have more than just a dominant and a recessive allele (version), it was an amazing start and novel idea.

Archibald Garrod later used Mendel’s methods in humans to anticipate carriers of the rare genetic disease alkaptonuria (black urine) in 1902. This sparked a new interest in genetics and a revival of the monk’s work.

The famous Thomas Morgan (left) began his research career shortly after discovery of Garrod and others. Because humans don’t reproduce frequently and you certainly can't tell them who to breed with (unless they are high schoolers engaged in hypothetical crosses), Morgan thought his work would be better suited to a model organism: Drosophila melanogaster, the fruit fly. Working with the relatively simple genome of D. melanogaster, Thomas Morgan was able to demonstrate that genes are the carrier of traits and theorized that they resided in a linear fashion on “chromosomes.” The existence of actual genes was previously unknown, as Mendel had simply called them “heritable traits.” He and his student Alfred Sturtevant realized that these chromosomes underwent recombination—swapping of alleles on like chromosomes—before gametes (eggs or sperm) were produced. Sturtevant discovered he could utilize this meiotic property to reveal the relative location of individual genes on the chromosome. Genes that are closer to one another are less likely to be recombine, while genes lying far from one another are more frequently recombined. Recombinant frequencies were used to create the first genetic map of the Drosophila melanogaster X chromosome in 1913.

Later, in 1931, Harriet Creighton and Barbara McClintock (left) used corn to prove the physical existence of chromosomes and recombination. Using a chromosomal mutation in corn that made the ends of the chromosome distinguishable from one another under the microscope (one end with a “knob” and the other with extra length); they were able to show that recombination actually occurs. Genes more closely associated with the knobby end would recombine less frequently with one another and more frequently with those on the elongated end. McClintock’s research continued to contribute to genetics well into the 60’s, including her 1948 discovery of transposons (“mobile genes”) which she received a Nobel Prize for in 1983. Recombinant frequencies as well as other techniques are still used today to create relative genetic maps that aid in the sequencing process.

It would take longer before technology would advance in such a way to prove the physical characteristics of genes and pave the road for sequencing of whole genomes. 1947 papers by Chargaff revealed that nucleotides adenine and thymine, guanine and cytosine always appeared in equal proportions suggesting possible pair bonding. In 1948 Linus Pauling (my bio-chem instructor’s favorite chemist) discovered the alpha helical shape of proteins which could potentially be applied to nucleotides. Later x-ray diffraction data produced by Maurice Wilkins and Rosalind Franklin showed the possibility of DNA’s helical form. Putting all of this insight together, Francis Crick and James Watson (left) were able to publish the first structural model of DNA in 1953.

Advancements in molecular cloning via E. coli in the 1970s led to a desire to sequence genomes and discover the molecular components of genes. An eager effort to sequence the human genome was sparked in the 1980’s. Technology was such that it was slow going at first. In 1993, the invention of PCR (which can amplify DNA without the use of a living organism) by Kary Mullis greatly expedited the process. By the time the first draft of the human genome was published in 2000 (remember that year!); we had already sequenced the genomes of several other species with the now incredibly fast technology. Genomics is constantly growing with more genomes sequenced and better, more statistically accurate versions continue to come out. I may have teased a bit the “worship” of DNA, but genes are far from insignificant.

Sources: Benjamin Pierce. Genetics, A Conceptual Approach. 2005
Watson and Crick:

Saturday, September 02, 2006

A Metronidazole and Vodka Cocktail

Recently I was placed on the antibiotic drug metronidazole (top) to treat an infection. In anaerobic (oxygen free) conditions, metronidazole acts on DNA repair enzymes and is an excellent tool against anaerobic bacteria such as Bacteroides, Clostridium, and Eubacterium while it does not harm the aerobic tissues of the human body.

Unfortunately, no alcoholic beverages can be consumed while taking this drug. Being a party-going college student, I became curious as to why I had to avoid this traditional Friday night favorite.

In the liver, alcohol (right) is broken down by alcohol dehydrogenases into acetaldehyde with the help of NAD by the following reaction: CH3CH2OH + NAD+ → CH3CHO + NADH + H+. Next, the acetaldehyde interacts with the acetaldehyde dehydrogenase (also in the liver) to form acetic acid (CH3-COOH, a very weak acid with many biological functions). Metronidazole is believed to obstruct the acetaldehyde dehydrogenase enzyme in much the same way disfulfiram, an anti-alcoholism drug, does. This allows excess acetaldehyde to build up in the body, 5-10 times as much acetaldehyde as one would normally experience after consuming an equal amount of alcohol with out the metronidazole. Since acetaldehyde is the primary cause of hangover, one can experience severe hangover-like symptoms including hot flash, shakes, nausea, and stomach cramps with even the slightest alcohol intake when combined with metronidazole.

Sources: Tillonen et al. Alcohol Clin Exp Res. “Metronidazole increases intracolonic but not peripheral blood acetaldehyde in chronic ethanol-treated rats.” 2000