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  • Molecular Biology's New Paradigm:
    Nano-Engineering Inside the Cell

    by Bill Wilberforce

    Imagine a barcode reader that, instead of decoding black-and-white stripes, would print out the list of parts in any complicated machine. Point it at an alarm clock and its tickertape would start whizzing, "two bells, 18 gears, one spring…" Point it at a laptop and the tickertape would stretch for miles.

    This cool device would be the envy of all your friends, and a handy tool for manufacturers seeking to reverse engineer their competitors' products. But this reader would be even more useful if it could read out parts that would otherwise be undetectable-for example, if a machine had such small parts that even the most powerful microscope couldn't identify them.

    As you might have guessed, this fancy barcode reader is a metaphor for the revolution that the world has experienced in molecular biology over the past 50 years. With commercially available kits, which require less mixing than a cake baked from scratch, a relatively inexperienced graduate student can start to inventory the parts in his or her favorite living organism. And with more powerful automated tools, a complete list of parts from any creature can be obtained.

    What is the nature of these parts that are found in living systems? Primarily, they are chains of amino acids called proteins (a subset of which are called enzymes). There are 20 types of amino acids that can be strung together to make every protein on the planet. The ordering sequence of the amino acids determines which protein. This is analogous to our alphabet of 26 letters being able to form every English sentence on the planet, where the sequence of the letters uniquely determines which sentence is formed.

    How, you might wonder, do commercial kits and automated tools detect these proteins, whose amino acid sequences are invisible to our most advanced microscopes? The answer is by reading the "barcode" of DNA. Deoxyribonucleic acid, or DNA, is the inventory list of parts carried within every cell of every organism in the world. There is a direct correlation between a three-letter "word" of DNA and each of the 20 amino acids. For example, if you find a string of 1000 such words in the DNA (for a total of 3000 DNA letters), that organism will have a protein part that is 1000 amino acids long. More importantly, the exact nature of that protein can be known by the order in the DNA letters.

    The mechanism by which these tools read DNA is beyond the scope of this essay, but the important point is that these tools of molecular biology have revolutionized the way we understand living systems. Before these tools existed, scientists thought cells were rather simple, just a blob of protoplasm (i.e. a chemical soup), surrounded by a thin membrane. But after pointing these new tools at various forms of life, scientist have realized that there are a lot more parts "under the hood" than they had originally expected. (For details, see postscript below.)

    Just to get a taste of what some of these parts do, let us look at one particular protein, namely, kinesin heavy chain. This medium-sized protein, formed from a pair of identical chains (each with about 1,000 amino acids), normally operates with a smaller partner protein called kinesin light chain, which is also made from a pair of identical chains.

    As protein machines go, the pairs of kinesin light and heavy chains, which comprise what is known as conventional kinesin, are a pretty simple system. The heavy chains have two parts. One half of the molecule can use a molecular fuel called adenosine triphosphate, or ATP. This fuel powers a process by which the heavy chain binds and releases from another protein: tubulin. As its name suggests, tubulin can form tubes-microtubules, to be exact-which form part of the skeleton of each cell. Ultimately, the binding and releasing of the heavy chains from these microtubules allows the kinesin system to march from one end of the cell to the other, taking hundreds of steps per second.

    The purpose of this high-speed marching is revealed in the other half of the heavy chain molecule. This half is a long tail, to which the two kinesin light chains, as well as various types of cellular cargo, attach. In essence, by marching through the cell, kinesin carries packages of material that would normally move far too slowly by random mixing.

    Nerve cells present a particularly striking example of how important kinesin transport is for proper cellular functions. Our longest cells, which stretch from our lower back to our toes, are found in the sciatic nerve. Much of what is needed to keep the ends of these nerve cells alive comes directly from the blood in our toes. But some things must come all the way from the beginning of the cells in our lower back. If we had to wait for these things to randomly diffuse their way down to the end of our toes, we would have to wait for years! Instead, we rely on the active transport of kinesin to supply the ends of our nerve cells with the necessary components.

    Kinesin is just one protein among thousands that all work together in each organism. The rich diversity of these protein machines has only been made known recently, as a result of the revolutionary tools of molecular biology. This diversity and the complexity of each individual protein machine underscore a new paradigm in biology: the inner workings of cells are feats of high-tech nano-engineering.

    Biologists most often identify the high-tech nano-engineer as Nature herself, and the implications of intelligent activity are quickly brushed aside. But, as Lehigh University biochemist Michael Behe has said in regard to this situation, "If it looks like a duck, walks like a duck and quacks like a duck, it probably is a duck". Behe's "inducktive" reasoning is quite sound. In any other field, things that look like they have been carefully engineered are presumed to be engineered.

    The fly in this "inducktive" ointment is the fact that the only engineer that could have produced these protein machines appears to be God, or "someone with the same skill-set"-as Jon Stewart of The Daily Show would say. So, instead of embracing the implications of their new paradigm, biologists (for the most part) ignore or denounce them, not wanting their field to destroy the separation between church and state that they feel is so essential for fruitful scientific progress. But at this point, the right question to ask is, Will further applications of molecular biology's revolutionary tools vindicate these denunciations, or continue to highlight the complex engineering of living systems?

    From everything we have learned thus far, the answer seems to be the latter. Though it is possible that the tools of molecular biology will uncover some self-engineering mechanism (akin to self-organization, but which produces complex machines instead of repeating fractal patterns), this scenario seems unlikely. For starters, the trend has been toward the unveiling of more and more complicated systems, not mechanisms that show how they are produced. Furthermore, laws of information production, developed to address questions arising in our computer-driven information age, weigh heavily against such a mechanism.

    What seems, therefore, to be the likely outcome of molecular biology's fantastic revolution is a growing awareness that living things, including us, are best explained as objects of intelligent nano-engineering. This awareness will no doubt follow the normal course that new ideas follow. First, it will be ignored. Then it will be ridiculed. Next it will be grudgingly tolerated. Finally, it will be said, "Well, we knew that all along!"


    POSTSCRIPT: Ballpark figures given for the number of genes in higher organisms represent an interesting exception to this tendency to underestimate the number of parts. For example, before the Human Genome Project, it was thought, based on results from simpler organisms, that we had about 100,000 genes (http://www.ncbi.nlm.nih.gov/SCIENCE96). Now that number is thought to be around 20,000 (http://www.newscientist.com/article.ns?id=dn6561), about the same as for the simplest worm (http://genomebiology.com/2001/2/11/comment/2008)!

    In this case, the overestimation was due to a brute-force extrapolation from simpler organisms, based on the naive assumption that our greater complexity was due to a greater number of genes. Ultimately, this error has shown us that the parts list we obtain from reading genes in DNA is only the tip of the iceberg. The nano-engineering of organisms extends far beyond mere protein parts, and includes intricate networks of feedback signals and three dimensional protein arrays.


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    BIOSKETCH: Bill Wilberforce is the pen name of a young molecular biologist whose future in academics could be thwarted by his involvement on this type of Christian apologetics webpage. He has been trained at one of the world's top institutions and is beginning to publish his own research ideas in leading journals. It is unfortunate that academic freedom is not always generously given to scientists who propose that what looks to be engineered in biology does in fact come from the mind of an engineer. However, this situation will certainly improve as the initial fear of the metaphysical implications of intelligent design subsides. In the meantime, this pen name provides a wonderful opportunity to honor a man who has inspired many to bravely go against the status quo in order to liberate captive human minds.