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Chemical Eye on Synthetic Biology
 He represented a literary breakthrough for Mary Shelley, and commercially, Frankenstein’s monster has been a worldwide success for almost two centuries. Source: morguefile.com |
On May 20th, the journal Science posted online the historic account of how the research team led by thrill-seeking biochemist J. Craig Venter, whose life and science are boldly told in his autobiography A Life Decoded , had succeeded in designing and synthesizing the genome of an entirely new species of bacterium. There is nothing microscopic, however, about the storm of legal, ethical, and even moral controversies that this scientific breakthrough has created.
I imagine the atmosphere at the J. Craig Venter Institute in Maryland must have been absolutely electric when they realized “It’s alive!” and was reproducing as bacteria normally do.
The cell created by Venter’s group was made by putting the new, purely synthetic DNA molecule containing 1,077,947 base pairs (which required a complex multi-stage assembly, not unlike that used to collaboratively compete very large jigsaw puzzles), into an unrelated bacterium that had all of its DNA removed. And after months of normal bacterial life - digesting and dividing--there remains virtually no trace of the original host cell in the colony of the new organism. That is simply amazing to me.
I am sure that it is equally frightening to others. For two centuries now, Frankenstein’s lab creation has been the poster child for science run amok, and there has been no shortage of Internet villagers angrily condemning Venter for playing god and creating an artificial organism that could have unimaginably devastating consequences if it escaped - just like Frankenstein’s monster did, not to mention the dinosaurs in Jurassic Park.
In actuality, there are no dangers posed by Venter’s creation that we have not been living with since 1972. That was when other American researchers--mostly biochemists and in the San Francisco Bay area--invented recombinant DNA as a chemical means of genetic engineering. The fruits of this earlier scientific breakthrough--as well as the vegetables, medicines, oil-eating microbes and all sorts of other products and processes--have become economically extremely important since then.
The World Wide Web didn’t exist in 1972, but the ethical and environmental concerns raised by genetically modified organisms were raised then almost as quickly as they have been since Venter’s announcement a few weeks ago. By 1975, researchers in the field, all very eager to explore and expand the scientific possibilities of genetic engineering, had voluntarily agreed to establish safety measures and means of regulating the new biotechnologies. This became known as the Asilomar Conference, after the seaside state park in California where the conference was held.
As far as I know, the biochemists and biologists who met at Asilomar did not feel like they were playing god when they manipulated the DNA of microbes. Do Poodle breeders have qualms when they do essentially the same thing with dogs? The conferees knew they had to be very careful; so do bomb squads. The idea that there is a vital force that distinguishes living matter from inanimate matter is as old as medicine. But the electro-chemical discoveries of Alessandro Volta were of recent renown in Europe when Mary Shelley imagined her monster, and I suspect that this may have been her inspiration for the “spark of life” that Dr. Frankenstein tried to recreate.
Judging by how things turned out for Dr. Frankenstein, I don’t think Mary Shelley and Craig Venter would have good chemistry between them. We can’t test that theory, even with the most advanced cloning technology, but I would be interested to know if she ever met or read about her contemporary Friedrich Wöhler, and what she thought of the Wöhler synthesis in 1828.
Wöhler was the German chemist who first synthesized a type of living matter from inanimate materials--organic from inorganic. Most famously, he synthesized indistinguishable samples of urea, which is a main component of our urine, from ammonium cyanate crystals, which were themselves obtained by reactions of rock stable minerals. If I had been around at the time, that would have been simply amazing to me.
Within a few decades, the newfound power of synthetic organic chemistry revolutionized industry and later medicine in Europe and America. I don’t think it will take anywhere near that long for synthetic biology to bring our economy back to life.
Preston MacDougall is a chemistry professor at Middle Tennessee State University. His "Chemical Eye" commentaries are featured in the Arts and Public Affairs portion of the Murfreesboro/Nashville NPR station WMOT (www.wmot.org).
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Chemical Eye on Oil and Water
 Source: Facebook.com The Grand Ole and water don’t mix either, but they are easily parted when artists are determined and alternative venues are generously offered. |
Here’s something you don’t see on live TV every day – a portable classroom was submerging into eastbound traffic that was bobbing up and down on I-24 between Nashville and Murfreesboro.
As surreal as that image was, it was just the beginning of a historic two-day monsoon that literally swamped large portions of Middle Tennessee, drowning ten people just in Nashville and dissolving untold amounts of uninsured home equity.
Water is an incredible solvent, for instance it can dissolve more than its weight in sodium hydroxide, also known as lye or caustic soda. But it can’t dissolve mineral oil, hence the saying that oil and water do not mix. They don’t mix in a test-tube, and apparently they don’t mix very well on the boob-tube either. I say that because while Nashvillians were swimming for their lives across interstates, the nationally televised news coverage was focused on the tens of thousands of barrels of oil – per day - that were gushing out of a ruptured well on the floor of the Gulf of Mexico, with no end in sight but the delicate estuaries of Louisiana ominously down-current.
While the water was rising in Nashville, there was another big story breaking in New York City. The unexploded car-bomb found in Times Square, and the Connecticut jihadist who put it together, were headline news in print and on TV for days. This story, unlike the water-based one, seemed to easily blend with headlines about the oil-gusher in the gulf. Perhaps the chemical metaphor explains this better than the regional bias that was widely blamed by Tennessee bloggers: The Times Square would-be bomber had ties to Pakistani Taliban, who are in league with al-Qaeda, which has the Saudi Osama bin Laden at its head. In other words, the bomb story was oil-based.
To get back to chemistry, oil and water don’t mix, but they do form an emulsion. And that’s where Anderson Cooper comes in. He brought the attention of mainstream news to the floodwaters of Nashville, even while the gushing in the gulf seemed to worsen.
Anderson Cooper has also done wonders for the hair gel industry, but gels are structurally different than emulsions. Gels have “body” because they contain very long polymer molecules that are cross-linked with each other, forming a kind of scaffold at the nano-scale. The many pores can be filled with compounds that have either cosmetic or medicinal purposes. They can also be left empty, as in aerogels that can be made into curious solids that are lighter than air and described as solid smoke.
Emulsions on the other hand, are homogenized liquid mixtures made from two or more immiscible liquids, such as oil and water. For instance, olive oil and vinegar, which is mostly water, form an emulsion when shaken vigorously. You might call it salad dressing, but I call it chemistry, which is my bread and butter. If you let this mixture sit for a while, it will separate into two liquids, with the oil layer floating on top.
To prevent this from happening, or to stabilize the emulsion, surfactants are added to the mixture, and this is the only purpose of many of the odd-sounding ingredients that you see on bottles of salad dressing or shampoo, such as sodium laurel sulphate. Without going into much chemical engineering, these surfactant molecules like being at the interface of the two immiscible liquids, but try to keep their distance from each other.
Until the gushing of oil could somehow be stopped in the gulf, one of the methods initially used to mitigate the environmental catastrophe that would occur if large amounts of oil were to reach the wetlands was emulsification. At the milligram level, surfactants are quite a useful trick, but at the tonnage level needed to disperse the oil that was not mixing with the gulf waters, even the oil industry’s environmental engineers had their doubts.
Nobody is sure what’s in store for the gulf coast, but we will certainly learn a lot about the chemistry of mixing oil and salt water.
The floodwaters are still receding in Nashville, but the clean-up is well underway. The stage of the Grand Ole Opry was underwater on Tuesday, May 4, but “the show must go on” is another saying, and it did, on higher ground.
Preston MacDougall is a chemistry professor at Middle Tennessee State University. His "Chemical Eye" commentaries are featured in the Arts and Public Affairs portion of the Murfreesboro/Nashville NPR station WMOT (www.wmot.org).
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Chemical Eye in Nostradamus Mode
After the Iron Lady catalyzes the oxidation of the Iron Curtain,
An angel will arise after a murky election in the land of Bayer.
The identity and material power of the central science is certain,
Therein will crystallize the first President from the sex more fair.
Call it providence, or perhaps the promise of “better living through chemistry”, but the first female President of the United States of America will be a chemist. My apologies to Hillary and Sarah.
And, in case you couldn’t decipher the Nostradamus-style quatrain, our future Madame President will follow in the high-heeled footsteps of the first democratically elected, female leaders of the United Kingdom and Germany--Dame Margaret Thatcher and Dr. Angela Merkel.
Dr. Merkel’s ability to solve complex problems, such as those that she specialized in as a quantum chemist at the Academy of Sciences in East Berlin, no doubt helped her piece together a “grand coalition” government after Germany’s “hung election” in 2005. Given the rarely-seen (at least in Europe) political squabbling following the election, that was a feat few thought possible.
Another event that few thought possible was the tearing-down of the Berlin Wall. Prior to November 9, 1989, this impermeable barrier separated Dr. Merkel from the Christian Democrats, the political party that she was destined to lead. The wall, and The Iron Curtain that it was part of, did not collapse under its own weight - not literally anyway. Margaret Thatcher had been Prime Minister of the United Kingdom for over ten years prior to this precipitous event, and she had earned the nickname of The Iron Lady. So, in this case, when the unstoppable force met the immoveable object, the object moved. (Sir Isaac Newton would have been gratified to see his First Law of Motion obeyed by world politics.)
Prior to her political career, and marriage to Mr. Thatcher, Margaret Roberts was a chemistry major at a second tier college. Her intellectual gifts earned her a transfer to Oxford University, where she was tutored in advanced chemistry and crystallography by Dorothy Crowfoot Hodgkin. While Professor Hodgkin would go on to win the 1964 Nobel Prize in Chemistry (for X-ray crystallographic analysis of the structures of molecules with biological importance, such as penicillin and vitamin B12), Ms. Roberts took a Masters degree in 1947 and entered politics. It would take over thirty years, but she eventually became leader of the Conservative Party, and then her country. And, some said, "the free world."
This predicted migration pattern of chemically-talented, first female leaders of major economies - United Kingdom, Germany, United States - oddly follows the migration of world dominance of the modern chemical industry. In 1856, with rudimentary facilities in his family’s East London home, young William Perkins transformed primitive organic chemistry into the new, and immensely profitable, synthetic dye industry.
Industrial chemistry is the ultimate labor-saving social development. Its custom designed reagents and catalysts, both organic and inorganic, do the work of yeomen, without wages, and never go on strike. As such, the United Kingdom, land of the Luddites, wasn't the most hospitable environment. The center of mass action shifted to Germany just as the chemical industry was starting to branch out into pharmaceuticals.
Bayer launched the new blockbuster drug Aspirin in 1899. Synthetic dyes and drugs both begin their new molecular lives as the result of clashes between chemically forceful catalysts, and rock-stable, over geological periods, petrochemicals. Sir Isaac's First Law rules again.
The first World War, which cut off the supply of German chemicals to U.S. manufacturers, spurred the development of American chemical companies, such as Dow Chemical which initially supplied the drug industry with the bromine that it needed to make the bromides everybody needed to cope with a world that was at war.
The second World War had a similarly boosting effect, particularly in supply of the automobile industry that was getting into high-gear in the U.S. Cars need a steady supply of evermore refined fuel, and the chemists who had demonstrated that they were masters of the petrochemical domain, soon started a new, and hefty branch of the chemical industry.
As the Nazis embroiled Europe in World War II, in addition to supercharging American industries, American universities welcomed many of the world’s most chemically talented refugees. Some have gone on to win a Nobel Prize, others started their own market-leading chemical company. All in all, the center of mass action shifted again, this time to the United States, where it rests uneasily.
There is nothing that can shield the U.S. chemical industry from Sir Isaac's First Law. What forces might emasculate it, as the labor movement did, to some extent, in the United Kingdom, or the Nazis did in Germany? The one that worries me is the diminishing scientific literacy of the American public.
So, Madame President, if in the future you have searched the internet archives, and are reading this commentary that called you into existence, please make scientific literacy of all Americans a priority for your administration, and a core responsibility for those who follow you.
Preston MacDougall is a chemistry professor at Middle Tennessee State University. His "Chemical Eye" commentaries are featured in the Arts and Public Affairs portion of the Murfreesboro/Nashville NPR station WMOT (www.wmot.org).
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Chemical Eye on Homeopathic Education
In homeopathic medicine, the more diluted a treatment is, the more powerful its effect is believed to be. This branch of medicine dates back to Germany in the late 1700s, before germ theory and DNA added a few twists to our understanding of disease. Nevertheless, this form of alternative medicine has a loyal following despite the skepticism of critics such as James Randi. With the increasing cost of drugs, it certainly has economic advantages.Recent news from Middle Tennessee is suggestive of a new counter-intuitive movement that would bring incredible tax-relief if we all believed in it--homeopathic education.
As far as I know, nobody is openly promoting homeopathic education in the way that followers of Samuel Hahnemann have promoted homeopathic medicine for over 200 years. But when I read about some school board decisions, I often ask myself “What were they thinking?”
Pisa is a city in Italy that is famous as a center of Renaissance thinking. It is where Galileo was born, educated, and began shaping modern science with his sharp tools of critical thinking. PISA is also the acronym for the large-scale Program for International Student Assessment, which is given every three years to almost a half-million 15-year-olds from 30 industrialized countries.
The results of the most recent international assessment were echoed by this year’s National Assessment of Educational Progress, often called the National Report Card. The results are even more disappointing than previous ones when you consider that the No Child Left Behind legislation signed into law in 2002 was meant to directly address the core competencies that are the focus of PISA.
As before, we learned that high school students in the U.S. score far below average in their mathematical competency, and slightly below average in their ability to apply scientific reasoning in problem-solving. For U.S. students, officials said that all the results of the reading portion of the test were discarded because of a printing error.
In a global economy, it is surely not a good prognosis when American teens were out-performed by their peers in 23 out of the 30 industrialized countries on the mathematics portion of the test. Math is often said to be the language of science and engineering, so perhaps not all of our “reading” results are invalid.
In response to the PISA results, then-U.S. Secretary of Education Margaret Spellings echoed the disappointment and cited ongoing initiatives to strengthen math and science education in American schools. In particular, a National Math Advisory Panel was appointed by President Bush in order to “recommend ways to improve public school math instruction, with a focus on algebra.” President Obama has continued this initiative, and has repeatedly mentioned mathematics explicitly during his speeches on education.
So far, so good. But here’s where my fears of homeopathic education started creeping in. Last fall, the Metropolitan Nashville school district decided to stop teaching algebra to 7th grade students who were ready for advanced mathematical education. As a point of reference, on my bookshelf there is a middle school textbook from Japan where the quantum theory of atomic structure is introduced--quantitatively.
If you are like me, you might be wondering what the school board planned to replace the advanced mathematics instruction with. In homeopathic medicine, the drugs are diluted with pure water. Perhaps a hint of the tenets of homeopathic education is contained in news from another Middle Tennessee school district that announced the formation of an elementary school competitive basketball league.
So even though international student assessments don’t give us much to feel good about, at least half of the hometown crowd can cheer for the winners when Central Elementary plays Main Street Grammar.
Basketball or basket-weaving, I am inclined to root-out any and all efforts to dilute math and science education since this is the training that will give our students the sharpest competitive edge in the technology-driven global arena.
For tax-weary sports fans, former president of Harvard University, Derek Bok, looked at things from an economic perspective when he said “If you think education is expensive, try ignorance.”
Getting back to the medical analogy, since all credible clinical studies have concluded that homeopathic medicine offers nothing but a placebo effect, it is only economical if you place a low value on your health.
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Chemical Eye on Raveling DNA
The normal fate of a pair of jeans is to be worn out. Never mind the different definitions of “worn out” on either side of the generation gap. In between wearings, however, they must be stored, and again the generation gap inserts itself. Like I did at his age, my son prefers the crumpled pile method. Nowadays I opt for folded. I’ll admit it; I did try hanging, but later discovered that Mommie Dearest was right--no metal hangers, ever! Vertical creases go in and out of style, but horizontal creases? Definitely a fashion faux pas.
There is undoubtedly some interesting chemistry behind why cotton is more susceptible to being creased than other fabrics, which may involve the specific protein molecules that are fabricated in the cells of cotton plants, but a bigger mystery is the long-sought secret code to packing long DNA molecules into compact chromosomes. Since our DNA also contains the codes for our numerous inherited genes, you could say that this new, embedded code may reveal nature’s preferred method for folding genes.
During cell division, and when the gene codes are being read, or “transcribed”, in order to synthesize proteins following natural just-in-time procedures, our chromosomes must quickly unfold and unravel into the stringy double-helix form that has become iconic.
After taking care of business, the 23 pairs of double-stranded DNA molecules, which would range a few meters in length if completely straightened out, and contain thousands of genes each, must just as quickly ravel and fold back into the familiar butterfly shapes that can be seen under the microscope. Properly folded, they all fit in a drawer (our cell nucleus) that only measures a few millionths of a meter in diameter.
Ever helpful, my mother sent me a link to the “How to fold a shirt ” movie clip. I couldn’t understand a word of the folder’s explanation, but I was impressed by the simplicity of the method. Just one fold, a couple of shakes, and voilà - a perfectly folded shirt! We do a far more impressive folding job with our genes, but scientists aren’t completely sure how we manage to do it.
We have known for decades now that metals are needed to begin the process. In particular, positively-charged metal ions both balance the electric charge on a DNA molecule in cell conditions, and act as a sort of template for coiling the double-helix in the first phase of gene folding.
Metal ions are much too small to assist in the next folding phase, which involves wrapping the thickened coil around tiny spools to form evenly-spaced beads called nucleosomes. You can think of a very long pearl necklace (unfastened) where the valuable part is not the pearl, but the string. And the string doesn’t go through holes in the pearls, but is wrapped around neat stacks of eight pearls each - precisely 1.65 times, or 147 units of genetic code.
Each of our cells contains millions of such spool assemblies, which are themselves called histones. Despite their rocky name, and the analogy to pearls, histones are not mineral, but made of protein, and have been studied in atomic detail.
DNA doesn’t just wrap around histones in a repetitive manner--the looseness of the fit also responds in a highly predictable way to changes in the chemical environment. Harvard chemist Stuart Schreiber is among those at the forefront of what has been called epigenetics . Such research is unraveling the changes in molecular structure, to either DNA or the histone surface, which cause DNA to unravel completely, or just enough to enable some essential biochemical process to occur.
One of the key chemical changes is acetylation. This is the same minor chemical modification that Bayer chemist Felix Hoffman made to willow bark extract over 100 years ago. Students routinely redo this experiment in freshman chemistry labs when they make Aspirin on their own. Various diseases, and embryo development failures, are thought to be caused by erroneous folding or unfolding of DNA. So this research is not just an elaborate Sudoku puzzle - done just for fun.
The atomic understanding of histone structures in various organisms, as well as accumulated knowledge of the effect of site-directed chemical modifications, has led to clues about what causes DNA to fold and unfold at the proper place and time. In particular, research by large teams of molecular biologists and biochemists, undoubtedly wearing out numerous hard-working grad students, has led to the supposition that our DNA has a so-called “histone code” embedded along with its genetic code.
Scientists figured that there was no other way to explain the regular, and chemically regulated, attachment of genetic material to histones. I suspect that a few Nobel Prizes will be won for key discoveries and technical prowess during the ongoing race to decipher the nuances of the histone code. One thing is sure though, unlike Dan Brown blockbusters, this unfolding story is non-fiction.
Preston MacDougall is a chemistry professor at Middle Tennessee State University. His "Chemical Eye" commentaries are featured in the Arts and Public Affairs portion of the Murfreesboro/Nashville NPR station WMOT (www.wmot.org).
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Chemical Eye on Superheroes vs. Superbugs
The purveyors of death and destruction freely continue their mountainous transit from Afghanistan into Pakistan, and there is nothing that more boots on the ground or drones in the air can do about it.
In fact many local leaders welcome these parasites, and protect them from multinational defenses. You would think that replacing fear of death, with life and liberty, would garner a hero’s welcome. But no, some imams are preaching falsehoods, vilifying true heroes, and endangering the lives of countless innocents.
I am not referring to the ruinous spread of the Taliban, although their barbaric ways seem to get a free pass in this border region. It is news of harboring microbial pathogens that disturbs me. The U.N. has reported that the polio virus, a distant nightmare of the elderly in Western countries, is hacking its way into unprotected Pakistani children via infected Afghan refugees.Thanks to heroic efforts of people like Jonas Salk, polio vaccination had all but eradicated this microscopic terror, from nearly all corners of the globe. Unfortunately, beginning in northern Nigeria in 2003, a new strain of the virus has now spread to at least 16 countries. It is predominantly Muslim-ruled countries or regions that are being hit the hardest.
It is not the religion that poses a health danger, but rather the mutating doctrine of some practitioners. For instance, Indonesia has long been a producer of polio vaccine for the region, and thought it had treated its last case of childhood polio in 1985. But that was before some Muslim leaders, for reasons that I cannot fathom, began spreading the big lie that the vaccine was created to spread AIDS among Moslems and sterilize Muslim girls. I haven’t yet seen Dr. Salk burned in effigy, but it wouldn’t surprise me. On a map, the virus seems to be following in the wake of the lies, and Indonesia was hit by a wave of new polio cases in 2005.
Fortunately, current vaccines are still an effective defense against the virus, and rapid coordinated action by the World Health Organization and the Indonesian government put an end to the resurgence. Now if only there were a vaccination for ignorance that was as easy to administer.
Another dangerous example of fool’s logic is “the enemy of my enemy is my friend.” For much, much longer than humans have been contracting syphilis or spreading tuberculosis (both bacterial infections), viral particles and bacterial cells have been engaging each other in mortal combat on microscopic battlefields.
But, since the polio virus attacks our cells that control muscle movement, and in advanced stages of AIDS, the HIV virus can attack many types of cells in our bodies, it would be a stretch to call these little nasties our friends.
In fact, a growing concern in the medical community are so-called superbugs--infectious bacteria that are resistant to the most potent antibiotics that medicinal chemists can