Monday, December 9, 2013

Photoshopping DNA: The Art of Molecular Editing


Imagine, a world in which we no longer have to worry about disease. No microbes, bacteria, viruses, or anything can get past our advanced immune system defenses. Steady diets of food filled with antibiotics that the bugs can’t seem to adapt to, drugs that have no long term repercussions to us because we finally understand what it’s going to do on a molecular level to our structure. Now imagine that world not so far away.
When Watson and Crick completed their DNA model of the double helix in 1953 it was groundbreaking. The structure of DNA was so complex and astounding; they never could have fathomed it going much further than that. DNA was the final piece to the puzzle. Of course, that’s what they thought about Vitalism originally and I’ll bet you probably never even heard of that.
So we coasted for a few years, then technology caught up to science and new discoveries were made. Through the merging of biochemistry and genetics a new branch of biology was being formed. Genomics. The study of the isolation and sequencing of genes in order to understand their functions within the human body and the source of their formation. See, before Genomics came along there was a problem. Biochemists weren’t communicating with geneticists and geneticists weren’t communicating with biochemists. It’s not because they were like Marines and Seals, always fighting with each other, it was just because they didn’t see what they were doing as the same. Once they set aside their differences and worked together, there was a huge boom in the medical and scientific communities using techniques developed through gene isolation. We’ll talk about those in a minute, but first, let’s talk a little about the two biology departments that brought us to the fringe of this strange new era.

Biochemistry


The biggest part of science that people often forget is observation. It’s the core of discovery really. You can’t learn how something works without studying it, and the first part of studying whatever it is, starts with observation.
Take for example the seemingly simple process of fermentation. Wine and spirits have been around for thousands of years. The core elements that go into making them remain unchanged. All you need is room temperature, fresh produce of some kind, sugar, water, time, and skill. But wine can brew itself all alone, in fact, the way they discovered the process of this was through observation.
In the early 1800’s they noticed that when a glass of fruit juice was left out at room temperature that over a certain amount of time it began to react strangely. When you looked at it the liquid inside seemed to be churning violently with what appeared to be no outside forces acting upon it. After a while the churning would stop and the juice would become cloudy, when that cloudiness cleared you were left with alcohol. As the brew churned it produced a gaseous byproduct that if not vented properly became explosive. This was discovered to be Carbon Dioxide.
Scientists determined what was happening. The yeast inside the fruit was eating the sugar (so to speak), and this process caused the violent churning. When the sugar was gone, the yeast was consumed. Their waste they expelled during the process was Co2 and the end result was alcohol. But could this process happen without the yeast?
They added chemicals, sulfides, they mashed the hell out of the yeast, boiled it, froze it, but nothing they did would work. They chalked it up to Vitalism; strange forces that at the time were basically unexplainable often became part of this theory. Well the reality of it was that it wasn’t strange forces at work; it was just a funky little enzyme doing his thing.
By adding these caustic chemicals to the mash and boiling the ingredients, in their attempts to understand what caused it they were actually permanently halting this process by killing the main offender. The enzyme that causes yeast to perform its function dies when it comes in contact with the chemicals they were adding and the intense heat they were putting it under. It wasn’t until 1897 they figured it out, and even then some were skeptical.
Enter Eduard Buchner. Before he won the Nobel Prize Buchner made a remarkable discovery, one that would flip the scientific community on its head! Using a modified mortar and pestle he ground the yeast up with a mixture of sand and quartz. He didn’t do this rigorously, just enough to separate the yeast and break it up a bit. The crushed yeast was then squeezed through a press leaving behind yeast juice and guess what? This yeast “juice” could perform the same task that the whole yeast could. It wasn’t the work of cells within the yeast, it was something else.
Enzymes.
That’s right, in 1907, because of his discovery made through observing fermentation; this German chemist discovered the enzyme, one of the fundamental ingredients in modern biology. What’s even funnier, in his acceptance speech he basically says he can’t picture us breaking it down any further than an enzyme! Oh Buchner, if only you could see the field of biochemistry now that you inadvertently fielded.
Vitalism was dead; it was time for a new era of biology.

Genetics

So if biochemistry is the study and analysis of how a single process functions within an organism then what’s genetics? Well in a sense, genetics is kind of the opposite of biochemistry. In genetics, instead of studying the process that makes the organism tick, geneticists want to take the gene away, modify it, put it back in, and study the organism then. In a barbaric sense, a biochemist will throw a butterfly in a blender, pull the wings out, and study how they flap. A geneticist will find 30 crippled butterflies and study why it is the wings won’t flap.
1907, Buchner is nationally recognized for his works. Two years later, in 1909, Thomas Hunt Morgan, another brilliant scientific mind is hard at work on something that will once again revolutionize the scientific community. But first we need to talk about someone else. The man who laid the groundwork for his research.
 Decades before Morgan, a Czech scientist by the name of Gregor Mendel while doing work with pea plants made a remarkable discovery.
In plants that exhibited genetic abnormalities, sometimes its offspring would exhibit the same signs. This fascinating observation led to Mendel’s 3-to-1 ratio which basically implies that out of three subjects sharing similar genetic information, one will exhibit the genetic abnormality. Like most fringe scientists, Mendel received his accolades posthumously, for in his study of the pea plants he, like Buchner, had accidentally created a new science, genetics.
Morgan was skeptical of Mendel’s theories of heredity. So he set to work with fruit flies in an attempt to prove him wrong. What he inevitably did however would have made the late Dr. Mendel smile with pride. He proved him right.
By exposing his fruit flies to various harsh conditions, (radiation, ultraviolet light, etc.) eventually an abnormality developed. Some of the flies were born with red eyes. Then the next generation came. Some of these flies were born with white eyes. When the two generations of flies were cross-bred they produced a gene that would sometimes be passed down to their offspring. Remarkably, it was in a 3-to-1 ratio, just as Mendel had described 40 years before.
From wine to flies, the journey to where we are now sure has been a strange one.

Can’t We All Just Get Along?



So now, years later, we finally have all the different biology fields talking to one another. Turns out, we were all playing for the same team the whole time, it didn’t matter what avenue we pursued, the end result always brought us back to the core principles of biology, so why not share with each other? It certainly helps usher progress along.
Turns out it was a good idea, because after three billion dollars and decades of research, scientists isolated tons of human genes. Then they did it again, this time it only cost a couple million dollars. Then again, and again, and again, until thousands of genetic markers had been identified. Markers that identified the onsets of cancers and birth defects. Genes that led to better medicine in treating cardiovascular disease and cystic fibrosis. It doesn’t just stop in the medical world either. Genomics carries over into the agricultural community, creating strains of plants that can stand up to harsher conditions so as to be grown in climates with poor soil or maybe temperamental weather. The applications of it are endless, so it’s a good thing they all decided to play nicely with one another.
Before we go any further into Genomics, genes, splicing, and sequencing however I would like to take a minute to go over some of the terms. As this is a newer science and not a lot is commercially known about genetics (since we all know what Kim Kardashian is wearing is more important than the latest nanotechnology that can kill cancer cells with early detection) due in most part to poor education standards and lack of media coverage. I promise this will be painless.

·         Genomics: the branch of molecular genetics concerned with the study of genomes, specifically the identification and sequencing of their constituent genes and the application of this knowledge in medicine, pharmacy, agriculture, etc
·         Genetics: The science of heredity, dealing with resemblances and differences of related organisms resulting from the interactions of their genes in the environment.
·         Genes: The basic physical unit of heredity.
·         Genetic Sequencing: Determining the number of nucleotides that are present in a polymer chain of DNA or RNA (or amino acids in proteins)
·         Genetic Splicing: Joining of DNA or RNA segments together.
·         DNA: Deoxyribonucleic Acid (or DNA for short) is the carrier for our genetic structure and information. It is a long chain of nucleotides that is composed of chromosomes that carry the heredity information passed down to offspring.
·         RNA: Ribonucleic Acid, plays a vital role in the synthesis of proteins. Like DNA is a carrier, but not for genes.
·         Chromosomes: The gene carriers.
·         rRNA: Ribosomal RNA, the structural part of a ribosome.
·         Ribosomes: An organelle that manufactures proteins, an essential component to the human body.

Holy crap! You mean to understand this I have to understand all that?? Forget this! I have a life…well just hold on a minute. You don’t need to understand how all those elements work together in the body (unless of course you’re a genomics major then it’s strongly advisable that you do know this) but you do need to understand there are a lot of forces at work here that need to be analyzed individually and as a whole, many times over from many different angles. You don’t need to know why they do what they do, you just need to understand they do all this harmoniously.
It took thousands of years of intense study to bring us to where we are, now that you understand a little more about that history, I suppose it’s time we talk about the future. Now that scientists can affordably analyze the human genome, sequence it, and pick out specific genes that cause predetermined effects in the 3-5 thousand dollar range now, let’s talk about why this new science is not only exciting, but extremely important to our future as a species. And what one corporation has done to single-handedly damage the image of Genetics research to a state possibly beyond repair.


Bad Seeds: Corporate Farming



Perhaps the most damning of all evidence in the fight for people against genetic engineering is the wonderful ecologically friendly (I can barely say that with a straight face) company Monsanto. With wonderful innovations like Agent Orange and DDT what could possibly go wrong with letting them modify our food?
Well, that’s just the problem. You can’t hate the science because of the evil applications some people put to it. Fire may burn down houses, but it was invented to keep you warm originally. Keep that in mind before you condemn the study of GMO foods.
The reality is that it isn’t the scientists, or the farmers. It’s actually the corporations, the politicians, the FDA that are to blame. Scientists tried to argue and say that these were dangerous and needed decades more research in order to be safe for public consumption. Unfortunately companies and investors are only driven by money and not public safety. The dangerous conclusive findings were buried. GMO seeds went to market and effectively infected the organic population.
See what happens is these modified plants go to seed and spread via whatever transport mechanism the species employs. When this genetic material is carried in the water, wind, however, it can mesh with indigenous wildlife say, your neighbors crops for instance.
In a lot of cases that’s actually what happened. Farmers discovered weedkiller was ineffective against some flora on their property. In some cases when they reported this foreign offender, Monsanto sued them and sometimes even won! If that isn’t sickeningly incredulous I don’t know what it is.
What’s worse is all this was made possible by Monsanto getting just the right people, in just the right offices, to sign just the right things, in order to get these GMOs to market against the general consensus of the scientific community they needed decades more research.
But fear not. With daily advances in bioengineering it’s possible to defeat evil corporation’s creations, we just have to keep trying, and scientists are. It’s actually the next point I’d like to bring up, we have biochemistry, and genetics, what about engineering? Turns out, living organism share more in common with a computer program then we thought.

Editing the Code: Cut & Paste, Bioengineering Style



The easiest way to think of Bioengineering is like Synthetic Biology. You’re reading each chromosome and genome like a piece of code in a script. When the whole code line comes together you have a program that can be uploaded into a piece of hardware, like a computer, or in the case of bioengineering, a cell.
That’s exactly what students in the U.K. taking part in the IGEM (International Genetically Engineered Machine) program are doing. By using cells that exhibit certain behaviors and perform specific tasks are being targeted for further applications. By taking a section of the cell’s DNA out and splicing in another strand with totally different properties, with all hopes an intended new bacteria is created that performs a new function, but in most cases retains the original shape and properties of the original cell.
Let me give you an example.
In a documentary, students are trying to splice a strand of DNA into a cell that will make this bacteria, that is produced within the human body, detect harmful parasites in water supplies. In theory, the way this bacteria will function is when it comes in contact with contaminated water, an enzyme in the cells will cause the water to run red, the indicator that the parasite is present.
This is a great concept on paper. Even in our modern day and age poorly filtered water supplies are still bastions of disease and sickness. By using these bacteria one would be able to detect possibly life threatening conditions. There’s just one problem. In places where contaminated water is a concern and a threat clean water sources may not be a solution. At the end of the day the locals could be left with nothing but red water lakes and empty buckets. This doesn’t clean up the parasitic infestation.
Furthermore what happens to the bacteria after it detects or doesn’t detect contaminants in the water? Does it continue living on a reproducing in the wild? If so, what long term repercussions is this going to have on the environment? Don’t worry, these guys aren’t Monsanto, they thought it through. A killswitch so to speak was installed in their bacteria, so after detection the organism consumes itself, effectively stopping it from reproducing in the wild.
Also, the parasite the students are testing for needs certain conditions to survive. According to them if the gathered water is left to sit for 24 hrs the parasites will die and the water will be drinkable. The bacteria indicator is just meant to be a warning that one should wait before consumption.
The end result is that these bacteria didn’t quite take off and died in petri. The concept shouldn’t be thrown away however. Some of our greatest innovations in science were by accidents and experimentation. I think anyone who’s ever had an itch that required Penicillin would agree.

-       Ryan Sanders

From “Mother Goose and Grimm” by the gut bustingly funny “Mike Peters”

For further reading on the wonderful world of genetics, biochemistry, genomics, and Monsanto, follow any of the links below. As always, thanks for reading and happy learning!

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