What Should We Think About Genetic Engineering?

What does it mean to give your children the best chance at success? Would it include changing their DNA so they would never get sick? Could it include genetically changing them to make them stronger, smarter, and faster than others? Is that even moral?

These questions used to be relegated to the realm of science fiction, but as genetic technologies advance, they have become more and more real. There are already instances of people using genetic screening during in vitro fertilization.1 While this process is currently used to only identify the correct number of chromosomes in an embryo, the Guardian article states, "If doctors had a readout of an embryo's whole genome, they could judge the chances of the child developing certain diseases, such as cancer, heart disease or Alzheimer's."2

While genetic screening itself opens a host of moral questions, even more provocative is the concept of genetic engineering: changing the gene itself to either rid the embryo of a trait or to enhance natural traits such as strength or intelligence. This morning I read two articles from Christians (J.W. Wartick and ElijiahT) who outlined the issue and offered their views. They've done a good job in laying out most of the arguments, both pro and con, that you find see in the debate, so I won't rehash them here. Both are worthy of your time. But there is an aspect that neither touched on which I think is fundamental to the discussion.

Genetic Therapy and Genetic Enhancement

First, I do wish to distinguish between the two goals of genetic engineering. There is a distinction between genetic therapy, which is basically correcting a genetic defect such as Sickle-cell disease that Wartick offers, and genetic enhancement, which takes a function that would fall within the normal range and improve it. 3 Yet, even here the standard isn't so easily discernable. For example, the deaf community even today has significant disagreement whether deaf children born to deaf parents should receive cochlear implants.4 In fact, one lesbian couple sought out a sperm donor who had five generations of deafness in his family to ensure their IVF child would be deaf.5

I have some problems with the couple's approach, but it does illustrate that defining disability versus difference isn't always so clear. However, with most cases, I think a case can be made that genetic therapies fall within a Christian construct. God has given us the ability to learn about His creation and to try and alleviate some of the suffering brought on by the Fall. Treatments for maladies are currently invasive (they require surgery), artificial (stints, mechanics, etc.) and even happen in utero as with fetal surgeries. Delivering treatments at the genetic level seems to me to be only a difference in degree, not in kind.

We are More than Our Genes

I have a different concern with genetic enhancements however. In his article, ElijiahT quoted Kurt Baier writing, "The best course of action is… the course of action which is supported by the best reasons. And the best reasons may require us to abandon the aim we actually have set our heart on."6 This is a fair standard and one that I think I can use to expand the debate.

The piece missing in both articles above is that every human being is not simply a product of his or her genetics. Human beings are also living souls and God is extremely concerned with the development of the soul as well as the ability of the body. Theologians have understood that while eliminating suffering is important and Christians should help those who they can, God's providential ordering of things is also important. That's why the Psalmist writes "For you formed my inward parts; you knitted me together in my mother's womb. I praise you, for I am fearfully and wonderfully made."7

Part of our fearful and wonderful makeup is our specific limitations in certain areas. These shape us into who we are as much as our ability to excel. While I personally didn't struggle academically, I wasn't a natural athlete growing up. I was very small as a teenager and didn't have much experience with a ball. However, I found sports that stressed endurance such as cross country and wrestling and I was able to do very well in both. Striving there taught me perseverance and discipline that I may not have otherwise experienced. If my strength and height were genetically enhanced in utero, I wouldn't have the soul-shaping experienced I had, which helped form my spiritual makeup and attitude.

In his post, Wartick opines, "It is unclear, though, whether genetic enhancement would undermine the good of accomplishment and human achievement. Indeed, one could argue that genetic enhancement, in fact, bolsters human achievement by widening the scope of possibility for humans."8 Physically, that may be true, but I am not sure that it would be true spiritually. While our culture overburdens the concept of diversity, there are things one can learn from those who have varied obstacles they had to overcome. Sometimes, those experiences inform the rest of us in new way. We can learn from Helen Keller.

No Genetic Lottery

So are we to leave our children to what has been deemed the "genetic lottery"? And, to extend the argument, is seeking a child's excellence through genetic enhancement techniques any different from some of the advantages certain children currently enjoy? Outlining this aspect of the pro-enhancement position, ElijiahT writes:

Parents make choices regarding the life and welfare of their children all the time, yet no one claims the autonomy of the child is being violated. Expectant mothers will regularly take vitamins (to enhance the prenatal environment), read or play music to the developing child and alter her diet, all in an attempt to give the child the best environment possible. After birth, parents deliberately choose the child's nutrition, education, entertainment and health. In fact, to neglect these things is often seen as inappropriate parenting.9

I agree. Yet, the difference is qualitative; it's one of nature versus nurture. One need look no farther than the recent Lance Armstrong scandal. No one would bat an eye if Armstrong was reported taking the best vitamins, using the best trainers, and following the best exercise and diet regimen. It was the artificial input of what should be a natural (e.g. "God-given") function of his body. If we are created fearfully and wonderfully by a holy God, it simply may be that our limitations are there to build our character and our spirit.

Escaping the Playing God Dodge

ElijiahT counters with the argument that "playing God "with another's life may be a fallback excuse: "The actions associated with ‘playing God' are usually new technologies that alter something about the human condition. In this case, genetic engineering is seen as playing God, but couldn't the same argument be used as a ‘catch-all' for anything that makes us uncomfortable?"10

Of course he's right. The objection has been used as a conversation-stopper many times. But that doesn't mean that it is always fallacious. A doctor who indiscriminately euthanizes his patients is playing God; he's taken upon himself the mantle of choosing which people are worthy of life—the province of God alone. Similarly, if God is interested in shaping us into mature souls, he may limit certain physical attributes that we would otherwise wish for ourselves or our children. These differences are not defects caused by the fall, but truly differences that God allows for our good. One shouldn't assume to modify them because we believe they are not as worthy as other characteristics.

There's an interesting scene in the 1999 hit move The Matrix, where Agent Smith tells Morpheus that human beings don't thrive in paradise. The character explains:

Did you know that the first Matrix was designed to be a perfect human world? Where none suffered, where everyone would be happy? It was a disaster. No one would accept the program. Entire crops were lost. Some believed we lacked the programming language to describe your perfect world. But I believe that, as a species, human beings define their reality through suffering and misery. The perfect world was a dream that your primitive cerebrum kept trying to wake up from. Which is why the Matrix was redesigned to this: the peak of your civilization.11

That's an oversimplification, but it does bring up a point. Struggle and hardship may be uncomfortable, but they are not always to be avoided. They can and often do serve to benefit believers. Holding to a "genetic lottery" assumes at the very least a deistic worldview. While we mitigate the defects brought on by sin, including Original sin, we shouldn't be so bold as to assume we can improve physical characteristics that are not defective. The Nazis sought to do that with race, but race isn't a defect. Neither are our lesser or grater physical abilities.

Without a discussion of the soul-shaping nature of bodily limitations, the questions raised regarding genetic modification is incomplete.

References

1. Sample, Ian. "IVF Baby Born Using Revolutionary Genetic-screening Process." The Guardian. Guardian News and Media Limited, 7 July 2013. Web. 15 June 2015. http://www.theguardian.com/science/2013/jul/07/ivf-baby-born-genetic-screening.
2. Sample, 2013.
3. There is also a distinction between treating someone genetically where the modified genes are localized versus recoding the person's entire DNA, as would happen at the first stages of life. Biologists differentiate the two by referring to the first as somatic genetic treatments, where the gene therapy would not be passed on to succeeding generations. Germ-line genetic treatments, however, are passed from parent to child.
4. Ringo, Allegra. "Understanding Deafness: Not Everyone Wants to Be 'Fixed'" The Atlantic. Atlantic Media Company, 09 Aug. 2013. Web. 15 June 2015. http://www.theatlantic.com/health/archive/2013/08/understanding-deafness-not-everyone-wants-to-be-fixed/278527/.
5. Spriggs, M. "Lesbian Couple Create a Child Who Is Deaf like Them." Journal of Medical Ethics 28.5 (2002): 283. Web. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1733642/pdf/v028p00283.pdf.
6. ElijiahT. "Why You Should Genetically Engineer Your Children." ElijiahT. ElijiahT, 07 Dec. 2014. Web. 15 June 2015. https://elijiaht.wordpress.com/2014/12/08/genetic-engineering-and-human-children/.
7. Psalm 139: 13-14, ESV
8. Wartick, J. W. "Genetics and Bioethics: Enhancement or Therapy?" Always Have a Reason. J.W. Wartick, 15 June 2015. Web. 15 June 2015. http://jwwartick.com/2013/02/25/enhance-therapy/.
9. ElijiahT, 2014.
10. ElijiahT, 2014.
11. The Matrix. Prod. Andy Wachowski and Lana Wachowski. Dir. Andy Wachowski and Lana Wachowski. By Andy Wachowski and Lana Wachowski. 1999.

The Rosetta Stone, SETI, and the Existence of God

For centuries, the hieroglyphics that adorned Egyptian ruins were a mystery to all. Those that saw them recognized them as some type of communication system, but no one knew if the pictures stood for words, letters, or something else. When archaeologists finally discovered the Rosetta Stone, they were very excited because they felt this would finally give them a chance to decode the mystery.1 How did they know this? They saw the same inscription was carved into the stone three ways: in Greek, in Demotic script, and in the hieroglyphs. Since scholars had a strong knowledge of ancient Greek and a little understanding of the Demotic, which was an outgrowth of the ancient Egyptian language, they had the basic pieces in place to begin unraveling the hieroglyphics. But you should ask yourself at this point how did they know that the hieroglyphics were decipherable at all? The answer is simple on this point: language represents ideas and ideas can be transferred between mediums. Information exists separately from the systems that carry it.

Because this is a hard point, let me unpack this a bit further. The Rosetta Stone inscription basically declares the newly-crowned King Ptolomy V a god and provides details on feast days, temples, and such.2 Even though the people who engraved the stone lived 2300 years ago and the language they spoke bore no resemblance to English, we can still understand their intent because the underlying ideas contained in the Stone do not exist only in Egyptian hieroglyphics. The ideas, that is, the information that is contained within the Stone, existed in the mind of the writer prior to the Stone's engraving. We are able to understand it not because we understand the language, but because we understand the ideas that the language represents. I can be fluent in many languages, but I must first have an idea before I can use any of those languages effectively. With no idea behind them, words become like those letters on my refrigerator door. They may accidentally fall into place at times, but they really don't mean anything. Information must precede the message system that carries it.

Searching for SETI

The concept that information comes from minds is one that scientists have accepted, a belief that can be readily demonstrated by their formulation of the SETI project.3 SETI is the Search for Extraterrestrial Intelligence. It is a scientific venture "to explore, understand, and explain the origin, nature, and prevalence of life in the universe."4 One of the ways they do so is by trying to observe transmissions from outer space. The SETI scientists use very powerful radio dishes pointed towards space searching for transmissions from intelligent life on another planet.5 But space can be a very "noisy" place. Pulsars and other phenomena emit electromagnetic waves that can either be seen or heard. Therefore, the scientists who are working on the SETI project have a way of determining if the signals they receive are from intelligent life or just signals occurring naturally in space.

In order to determine if a signal shows signs of intelligence, SETI researchers use the same basic principles that we have outlined in our discussion above. They look for orderly signals, not random static. They look for complex signals, not a blip at regular intervals. They look for a specific pattern that would have the earmarks of coming from a mind. In the movie Contact, which used SETI as its basis, researchers found a signal broadcasting the first twenty prime numbers. If these three traits were confirmed in a signal, the scientists at SETI could reasonably conclude that what they are receiving was some type of message system that came from a mind.

A Computer Code Inside Your Cells

Whether it's archaeology, SETI, computer data, or another medium, the principles for identifying an information-bearing system are the same. But what about biology? The DNA inside your cells meets all the criteria of the SETI researchers' qualifications: it is a complex, non-repetitive, specific four-letter code that very much resembles computer code. DNA carries quantifiable information, and like the Rosetta Stone, that information exists independently of its alphabet. The human genome project has cataloged the sequences of the 3 billion chemical base pairs that comprise the human DNA.6 We can express them in other forms of writing (such as "begin to assemble this protein"). And even though DNA only uses four letters, it is still capable of carrying out the most complex instructions. Computers today use a binary language comprised of only ones and zeros. Four letter languages actually have an advantage. And like the letters on my refrigerator in the example above, if you rearrange them, you no longer get a cogent message; instead you will get corruption and the message will be lost. They must be organized in a specific sequence to provide a proper blueprint for a human being.

DNA —Evidence of a Mind

So what do we make of this? The conclusion should be readily apparent. If the identification of a message system proves there is a mind at work, and DNA is an information-rich message system, then it follows that DNA must have come from a mind. That's the inescapable conclusion from the premises that precede it. Message systems come from minds, DNA is a message system, so DNA must have come from a mind. Good science has revealed this to us.

Scientists routinely object to this argument within the Intelligent Design community by dismissing ID as not being "science," saying things like ID cannot be tested by experiment and that it isn't falsifiable.7 However, the criteria I've proposed is exactly the same as all those scientists use on the SETI project. The SETI Institute lists over fifty people involved with the project classified as "Scientists and Senior Staff."8 Although I know many who are skeptical about the SETI project successfully finding intelligent extraterrestrial life, I've never met an honest person — believer, skeptic, or atheist — who didn't believe that the SETI project is real science. Even the popular scientist Carl Sagan, who very vocally dismissed a personal God,9 felt that this was good science, vigorously promoting the SETI project.

So if the scientific community are going to be honest, they must either discount the SETI project as non-science or admit that the criteria is good science and is fair game to determine the origin of life. If the criteria are good enough for the astronomers at JPL viewing Mars, the archaeologists investigating the Whiteshell rocks, and the SETI researchers, then they're good enough to prove that there's an intelligent mind responsible for our DNA. DNA points to the existence of God.

References

1. See the foot note on page 9 of Clarke, Edward Daniel. Travels in Various Countries of Europe, Asia and Africa: Greece, Egypt, and the Holy Land. London: T. Cadwell and W. Davies, 1817. You can access this book online at http://books.google.fr/books?id=l14GAAAAQAAJ&printsec=frontcover&source=gbs_ge_summary_r&cad=0#v=onepage&q&f=false

2. A fully translated text of the Rosetta Stone may be read at the British Museum's web site. http://www.britishmuseum.org/explore/highlights/article_index/r/the_rosetta_stone_translation.aspx
3. I've found several examples in writings of Intelligent Design advocates using both the SETI project and the motion picture Contact starring Jodie Foster as examples. William Dembski used Contact as his illustration in his "Science and Design" (First Things: Oct 1, 1998), Walter L. Bradley and Charles B. Thaxton used SETI in their article "Information and the Origin of Life" (The Creation Hypothesis. J.P.Moreland, Ed. Downers Grove, Il.: Intervarsity Press. 199.)
4. Taken from the mission statement of the SETI Institute at . Accessed August 31, 2010.
5. The SETI website explains, "Currently the Center for SETI Research develops signal-processing technology and uses it to search for signals from advanced technological civilizations in our galaxy." SETI Institute. The Center for SETI Research. Accessed September 2, 2010.
6. Human Genome Project Information. "About the Human Genome Project". . August 19, 2008. Accesses September 2, 2010.
7. See footnote #2 on "Why Intelligent Design is Not Science." Union of Concerned Scientists. Web. http://www.ucsusa.org/scientific_integrity/what_you_can_do/evolution-and-id-footnotes.html#4-2 Accessed September 6, 2010.
8. SETI Institute. "Leadership Team, Scientists and Senior Staff". . Accesses September 2, 2010.
9. Sagan, Carl "A Sunday Sermon" Broca's Brain: Reflections on the Romance of Science. (New York:Ballantine Books). p. 330.

Message Systems Come from Minds

Egypt holds fascination for many people. The practice of mummification, the pyramids, and all those hieroglyphics shrouded the ancient Egyptians in mystery and wonder for hundreds of years. It was widely known that Egyptian hieroglyphics were used as the primary way of written communication in their day, but no one could read them until the French discovered the Rosetta Stone, unlocking the secrets of the pictorial message system and allowing scholars to read and understand the thoughts of those who lived 3500 years ago. Before the decoding of Egyptian hieroglyphics, studying ancient Egypt was a lot of guesswork. After finding the Rosetta Stone and deciphering hieroglyphics, archaeologists could suddenly understand so much more about who the Egyptians were, what they believed, how they lived, and why they built the pyramids and created mummies.

In recent years, modern scientists have discovered another Rosetta Stone of sorts. The DNA molecule that exists in every cell of our bodies was first successfully modeled by James Watson and Francis Crick in 1953. Crick, after further investigation, also provided a model for how the genetic code in DNA is transferred within the cell.1 Soon it was understood that our DNA functions like a set of blueprints; it holds all the instructions to build your body so you look like you. But such a find is more than amazing when you think about it. You see, message systems are very special things that have certain attributes — attributes which can come only from minds.

What Makes a Message?

In 1976, NASAs Viking I spacecraft had reached Mars and was taking close-up photographs of the planet for the first time ever. One photo immediately caught the attention of everyone in the project. It seemed that there was a face carved into the Martian surface that measured over two miles across! NASA released the picture with the caption "huge rock formation ... which resembles a human head ... formed by shadows giving the illusion of eyes, nose and mouth."2

 Now, scientists have discovered rocks that look like humans or animals before. Whiteshell Provincial Park in Manitoba, Canada has many different tone shapes like the one you see in photograph #2. These stones are in an arrangement where they look to resemble a man. So, why did the NASA scientists immediately assume that the face on Mars is a natural formation while archaeologists looking at the stones in Whiteshell Provincial Park assume that these were placed by prehistoric people? What's the difference?

In a nutshell, the difference is the rocks in Canada have three traits of an information-bearing system, all of which are necessary for us to assume that something is trying to be communicated:

1. They are orderly. The rocks at Whiteshell park are placed in a very specific arrangement. Most rocks one sees on the ground are randomly located. This squares with the idea that all things will tend towards randomness unless otherwise constrained. The "face" on Mars doesn't rely only on order, but also on shadow. If you look again at the picture, you can see that over a third of what would make up the face is obscured. The shadows themselves become part of the feature-making surface, so we cannot tell if the surface below holds the same order as the well-lit area. The Whiteshell rocks are unmistakable ordered and one can see where there is a start and a stop for each glyph.
2. They are complex. While order is more rare than randomness in nature, it does happen do to certain chemical or physical constraints within a system. Ice crystals, for example, are very orderly in their form. Water can push on rocks and line them up in a sequence. However, the Whiteshell rocks are not merely orderly, they are complex in their order. The rocks are found at 90 degree angles and places on a sequence that would be nearly impossible to explain through natural processes. For example, the rocks are all close to the same size, they are all equally spaces, yet those in photograph #2 are set a different angles and then they stop until another formation is found with the same ordered complex arrangement.
3. They are specific. The final piece in identifying an information-bearing system is that the rocks are placed very specifically in patterns that are recognizable to another mind. The angles of the Whiteshell rocks in the photo are in perfect proportion of a human being. If one were to invert the angle at the bottom of the image, the image of a stick figure is marred and the concept is lost on the viewer. The rocks must be specifically placed so the idea that the creator has will be properly received. This is true for any message system. Replace one letter in "I Love Mary" and you get wither confusion ("I live Mary") or a radically different message ("I love Hary")!

And no matter if were looking at ancient stones or looking for messages from outer space, these are the traits we look for to determine whether what we find is an accident of nature or generating from a mind: order, complexity, and specificity. Since DNA shows those same three traits, it should be reasonable to conclude that there was a mind behind the creation of DNA.

References

1. For an extensive history of how Watson and Crick uncovered the shape of the DNA molecule and its further understanding, see Stephen C. Meyers comprehensive treatment in Signature in the Cell. (New York:Harper Collins, 2009).

2. NASA Science. "Unmasking the Face on Mars." 24 May 2001. 24 August 2010 . Web. http://science.nasa.gov/science-news/science-at-nasa/2001/ast24may_1/

An Untangled Problem for Evolution: DNA Topoisomerase.

Background

DNA replicates itself. That is Biology 101. The process is quite complex and any biology student required to rattle off the procedure on an exam can confirm. Although there are separate kinds of topoisomerase,1 they perform the same essential function within the process of replication.

What is topoisomerase?

In each human cell, there are approximately 2 meters of DNA compacted within a nucleus of the diameter of about 10 micrometers.2 For perspective, imagine that the nucleus is represented by a standard basketball. The length of all the DNA compacted into the ball would go round-trip between the earth and the moon just shy of twice. Topoisomerase has the job of ensuring that the shape of DNA is manageable. Add in the fact that DNA is not just a helix, but a double-helix. As one might imagine, the task of trying to do anything productive with this material presents very serious concerns that need to be dealt with. During replication, the topology (i.e. the shape and structure) of DNA and the movement in unzipping result in issues like tangling and kinking, so the process faces a formidable and complex challenge of bioengineering.3 It’s topoisomerase’s job to alleviate those issues so they don’t halt the replication process.4 If DNA cannot replicate, then an organism cannot grow. Additionally, DNA doesn’t just unzip for replication. It unzips in a process called transcription, which, with the help of RNA, is the first half of producing vital proteins in the cell.

Two examples might help illustrate some of the mechanical concerns that arise. Without even trying, the ordinary use of a wired phone produces coiling in the helical cord. No extraordinary spinning or energy is required to produce the effect, but it doesn’t take long for the cable to go from fresh and neat to knotted spaghetti, which seem to never come out. Even if the tangle is gone, there always seems to be a small bend or a missing turn were the tangle was. The second illustration may serve to demonstrate the problem of kinking just prior to cutting the DNA strand in two. To demonstrate the concept, you can take a piece of twine and try to unwind it by pulling away both its twisted strands away from each other. A "Y"-shape forms: the two strands being pulled apart are each the top segments of the "Y" and the rest of the twine is the bottom. Now at some point, enough tension will build up at the center of the "Y" to where you can no longer pull the strands apart. Fortunately, topoisomerase is there to work out these sorts of problems. Its process is so vital and complex that some have referred to topoisomerase as the "magicians of the DNA world"5 because of their uncanny ability to manipulate the DNA strand and master its topology. 

The Problems for evolution

1: Does not fit early evolutionary models for an ancestral topoisomerase

It is still unclear how exactly topoisomerase originated on an evolutionary model, particularly because all the different types of topoisomerase appear to have originated independently of one another.6 A core tenet of evolutionary biology is that all life can be traced to a common ancestor (more technically, LUCA: last universal common ancestor). It is natural to assume that LUCA would have some master topoisomerase that would have developed into the varying domains7 of natural life: Achaea, Bacteria, and Eukaryota. But, this seems to be an incorrect inference that does not align with the actual data.8  It is speculated that topoisomerase might have emerged with either an ancient viral lineage or a LUCA that began with RNA genetic information or a combination of the two.9

These RNA-infused models would be controversial, because such scenarios involve the already contested10 (among researchers in that field) RNA-world hypothesis for the origin of life. And, the progressive introduction of topoisomerase and other necessary replication proteins into the evolutionary lineup seems an inventive proposition, but requires massive amounts of biological informational leaps that are unfounded, especially within the limited time window for the emergence of life on earth that evolution demands. 

2: Conceptual Paradox11

Most of all, the origin of topoisomerase presents a chick-and-egg paradox. To replicate itself the DNA molecule needs topoisomerase to unwind it. And, DNA would need to code for a protein to do the unwinding (in order to pass on the genes to code for topoisomerase). It’s like having a car with no gas. You need to drive to the gas station to get gas, but you need gas to get to the gas station. DNA might have obtained topoisomerase from somewhere else, but the instant it makes a copy of itself, the other strand needs topoisomerase also. The scenario requires the leap to the reality, where DNA actually codes for this protein itself. That is not to mention that the actual mechanics of unwinding get even more complicated, because topoisomerase is able to cut and re-join small sections of DNA, which require precise biochemistry to ensure the right pieces get linked back up with each other and at the proper speed. Too slow, and the DNA doesn’t unwind fast enough for cell division (mitosis) and the cell dies before replication can occur.12 Too quickly, and the cell can set off its own self-destruct sequence (apoptosis) or cause irreversible damage to the genes that results in cancer.13

Conclusion

Lastly, it is also important to keep in mind that this is only a piece of a wider issue for evolutionary biology to explain DNA replication in general: proteins that function as stabilizing clamps, ones that actually unzip the DNA strand, others that error-check the new copies, or the fact that one side of the DNA is duplicated backwards and in sections…

References

1. For the sake of simplicity, all types of topoisomerases will just be noted as 'topoisomerase'.

2. Joseph E. Deweese and Neil Osheroff, "The DNA cleavage reaction of topoisomerase II: wolf in sheep’s clothing," Nucleic Acids Research 37, No. 3 (2009): 738-748.
3. Ibid.
4. James J. Champoux, "DNA topoisomerases: structure, function, and mechanism," Annu Rev Biochem 70 (2001): 369–413.
5. James C. Wang, "Cellular roles of DNA topoisomerases: a molecular perspective," Nature Reviews Molecular Cell Biology 3 (June 2002): 430-440. Wang also makes use of this phrasing in his conclusion of his ‘Minireview’ in "Topoisomerases: Why So Many?" in The Journal of Biological Chemistry vol. 286, 11 (April 1991): 6659-6662.
6. Patrick Forterre and Daniele Gadelle, "Phylogenomics of DNA topoisomerases: their originand putative roles in the emergence of modern organisms," Nucleic Acids Research (2009), 1. The two coauthored a similar article with Simoneta Gribaldo and Marie-Claude Serre, called "Origin and evolution of DNA topoisomerases," in Biochimie (April 2007): 426-446. 
7. A domain is the largest formal classification of living organisms on earth. By contrast, a species is the smallest formal classification.
8. Forterre and Gadelle, 1, 12 (and throughout the article in fact).
9. Ibid.
10. Patrick Forterre, one of the authors mentioned in this article, notes the RNA-world hypothesis, but references its implausibility on page 146 in the chapter entitled Origin and Evolution of DNA and DNA Replication Machineries of "The Genetic Code and the Origin of Life," published by Kluwer Academic and Plenum Publishers. Jonathan Filée and Hanny Myllykallio.
11. This paradox seems lost on some. The article by Allyn J. Schoeffler and James M. Berger entitled, "DNA topoisomerases: harnessing and constraining energy to govern chromosome topology," Quarterly Reviews of Biophysics 41, 1 (2008): 41–101, puts forth: "Understanding topoisomerase specialization is necessary to illuminate the evolutionary interplay between supercoiling homeostasis and the requirement for multiple topoisomerase activities to shepherd DNA through transcriptional, replication, and recombinational processes." The authors acknowledge that topoisomerase is subject to the mechanisms of evolution. How exactly does a mechanism necessary for evolution to work – even at the basic level – get thrown into the mix if it’s not functional with the first strand of DNA? That is not to say that it cannot improve or adapt with time, but it must work from the onset to begin with. And not just it, but DNA and its other requisite enzymes and processes.
12. Deweese and Osheroff, 741-742.
13. On the other hand, however, the essential nature of topoisomerase to cell replication (which requires DNA replication) has been exploited in anti-cancer drugs, which target the topoisomerases within the unwanted cells.

Image entitled "Replication complex" by Boumphreyfr - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons.