Ode to a Dreamer of Dreams

Dear Dr. Sacks,

Like the late Carl Sagan, you have a gentle way of magnifying everything into brilliant resolution and reminding us of our place in the universe. I always look forward to reading your books and opinion pieces, as you put which things matter into perspective. Last month, I was quite delighted to read of your love for the physical sciences, also beautifully described in Frank Wilczek’s A Beautiful Question. Beauty can truly be found in any field or context and Wilczek’s coverage of the concept reminds me of that Gerard Manley Hopkins’ poem, “Pied Beauty,” in which the author pronounces, “Glory be to God for dappled things.” As Adam Frank puts it, “Science — under all its theories, equations, experiments and data — is really trying to teach us to see the sacred in the mundane and the profound in the prosaic.”

Indeed, few experiences prove as humbling as observing the heavens. The night sky brings to mind the opening lines of a personal favorite: “Let us go then, you and I/ When the evening is spread out against the sky/ Like a patient etherized upon a table.” Meanwhile, consciousness continues to prove an elusive idea, as you mentioned. Is it a purely biological phenomenon or does it extend into the philosophical and spiritual realms? I think the most beautiful aspect of our universe is the sense of infinite mystery surrounding it; as Anaïs Nin explains it, “The possession of knowledge does not kill the sense of wonder and mystery. There is always more mystery.”

From your stories of patient case studies to your descriptions on the benefits of musical therapy, your words offered comfort and solace amidst adversity and uncertainty. When I was struggling with my own medical challenges (though nothing as serious as your struggles), I found works such as William Ernest Henley’s “Invictus” and Dylan Thomas’ “Do Not Go Gentle Into That Good Night” to be particularly uplifting and encouraging, and perhaps you will, too. I think the practice of medicine allows one to grow closer to his fellow brethren and fulfill the insightful words of Countee Cullen: “Your grief and mine/Must intertwine/Like sea and river/Be fused and mingle/Diverse yet single/Forever and forever.” I only hope I will fulfill my role with the same patience, compassion, dignity, and grace that you exemplify in your daily life. As one chapter closes and another begins, I wish you laughter and joy in the company of friends and family, exchanges of love among kindred spirits, courage as you confront your final battles, and peace and contentment in the knowledge that you have touched more lives than you know. From the deepest parts of my being, I thank you. Stay gold, dear Captain, our Captain.

Warm regards,

Nita Jain

Top Ten Favorite Scientists

I was recently asked to make a list of my top ten favorite scientists, and after some deliberation, these are the people I chose:

Feynman

  1. Richard Feynman: While Feynman made outstanding contributions to our understanding of quantum physics and to the Manhattan project, he is perhaps most remembered for his teaching as evidenced by the still-beloved Feynman Lectures on Physics. Feynman even rejected a job offer from the Institute for Advanced Study, a research center whose staff boasted luminaries like Albert Einstein and Kurt Gödel, because there were no students there to teach.
  2. Marie Curie: Curie conducted pioneering experiments into the nature of radioactivity and also discovered radium and polonium, receiving Nobel Prizes in both chemistry and physics for her efforts. Upon observing radium’s destructive effects on her own healthy tissue, she reasoned that radium could also be used to destroy infected tissue, giving birth to the idea of radiation therapy.
  3. Isaac Newton: From his work on optics to his laws of motion and universal gravitation, Newton was a central figure in the scientific revolution. He developed the reflecting telescope as well as differential and integral calculus to explain the elliptical orbits of celestial bodies all before his 26th birthday.
  4. Rosalind Franklin: Franklin’s X-ray diffraction data was arguably the most important puzzle piece in the discovery of DNA’s double helical structure. She also contributed to our molecular knowledge of viruses, including tobacco mosaic virus and the poliovirus.
  5. Nikola Tesla: While Tesla is perhaps best known for developing the alternating current motor, the Serbian-American innovator also experimented with X-rays, performed short-range demonstrations of radio communication two years before Marconi, and invented the high-voltage transformer known as the Tesla coil.
  6. Clair Patterson: Not only did geochemist Clair Patterson calculate an extremely accurate estimate for the age of the Earth using lead dating, but he also served as an activist after discovering the toxic effects of lead on human health. His persistent campaigning eventually led to a ban on the use of lead in consumer products.
  7. Linus Pauling: Pauling made incredible insights into the nature of the chemical bond, including the prediction of secondary structures such as the alpha helix and the beta sheet. Pauling also developed the concepts of electronegativity and orbital hybridization and remains the only person to have received two unshared Nobel Prizes – for Chemistry in 1954 and for Peace in 1962.
  8. Michael Faraday: It has often been said that Michael Faraday was the greatest discovery of eminent chemist Humphry Davy. Faraday established the principle of electromagnetic induction, created the first electrical generator, and even initiated the first Christmas Lectures series in 1825 to teach science to children.
  9. Louis Pasteur: Best known for his namesake process to prevent bacterial contamination, Pasteur was instrumental in disproving the idea of spontaneous generation. His work on the germ theory of disease also led him to create vaccines for anthrax and rabies.
  10. Craig Venter: When the Human Genome Project began in 1990, progress initially got off to a very slow start. In 1998, Craig Venter dramatically sped up the process using a technique known as whole genome shotgun sequencing. As we now enter the era of genomic medicine, the variable uses of the sequenced human genome are steadily unfolding.

If I were to make a longer list, I would probably include a lot more notable physicists, including Albert Einstein, James Clerk Maxwell, Max Planck, and Alan Guth. Copernicus, Galileo, Cecilia Payne, Annie Jump Cannon, and Henrietta Swan Leavitt all helped advance our understanding of the cosmos. I would also have liked to acknowledge the many scientists who were involved in atomic theory, such as Democritus, James Dalton, Niels Bohr, Ernest Rutherford, and J.J. Thomson. Mendeleev classified the elements periodically, and Carl Woese classified life on Earth. Gregor Mendel founded the field of genetics, and Meselson and Stahl performed an experiment that supported the hypothesis of semiconservative DNA replication. Along with Pasteur, both Robert Koch and Ferdinand Koch helped found bacteriology and establish the credibility of the germ theory of disease. Alexander Fleming accidentally discovered the first antibiotic in the form of penicillin, and Jonas Salk developed the first successful polio vaccine. On the computer science front, Ada Lovelace, Hedy Lamarr, and Tim Berners-Lee made significant contributions, the latter of whom is responsible for having developed the algorithms on which the World Wide Web depends. Polymaths Archimedes, Leonardo da Vinci, and Benjamin Franklin advanced our knowledge of the sciences as well as other diverse fields.

This list is just one person’s opinion, so I invite you to share yours. Who would you include in your top ten favorite scientists? Leave your suggestions in the comments below!

The Sociological Perspective

calvin-verbing

Tristan Bridges argues that “if you can’t find a Calvin and Hobbes cartoon to put on your syllabus for a sociology course, there’s a good chance you’re not teaching sociology.”

This month, I am taking an introductory sociology class in preparation for the “Psychological, Social, and Biological Foundations of Behavior” section of the new MCAT, and it has got me thinking a lot about how genetics and sociology seem to face a lot of the same challenges when it comes to obtaining certain types of data largely due to moral and ethical considerations. After the completion of the Human Genome Project in 2003, the arduous process of genome annotation began. Since it’s not socially acceptable to force people to mate with each other and we can’t always find people who happen to breed in an informative way, we oftentimes use population data over time, genome-wide association studies being a good example of such an approach, to examine individual markers for possible associations between genotypes and phenotypes. Unfortunately, GWAS often fails to employ random sampling, and 96% of subjects included in GWAS have been people of European descent, as of 2013. Generally speaking, scientific disciplines (and others as well, I suspect) often disproportionately sample from WEIRD (western, education, industrialized, rich, democratic) countries, whether studying genetic diseases or human gut microbiota.

While sociology and the sciences have much in common, I’ve also noticed some major differences. The sociological notion of race, for instance, has no scientific basis. I have oftentimes heard the argument that race must exist because people look different and these kinds of differences can be clustered into broad groups, but the genetic signatures that correlate with large land masses are neither exclusive nor unique to any particular group of people. The idea of race serves to reflect patterns of social and economic inequity; race is socially constructed, not biologically based.

An op-ed published in the New York Times yesterday reminded me of some of our assigned reading from Best and Horiuchi on urban legends and Schuman‘s mention of “Newton and his apple in legends about scientific discovery.” In his piece, Mlodinow argues that urban myths surrounding scientific discoveries trivialize the scientific process and its complexities. The author concludes by citing the need for instant gratification among the negative effects of the media today, as such needs are diametrically opposed to the thoroughness of the scientific method. However, some education experts like Lilian Katz argue that the immediacy of social media provides an effective, incentivized social learning tool for teenagers, as the reward of dopamine release is thought to help solidify memories and enhance motivation. As with anything else, the instant gratification aspect of social media appears to be a two headed coin, a double edged sword.

The Creative Power of Destruction

Ceremony

Franklin College of Arts and Sciences ambassadors (left to right: Abiola Fakile, Omar Martinez-Uribe, Blake Edwards, and myself) with Lydia Babcock-Adams (left) and Dean Alan Dorsey at a groundbreaking ceremony for the University of Georgia Science Learning Center on Tuesday, Aug. 26, 2014 in Athens, Ga.

Today, I ran into a beloved biochemistry professor of mine at the groundbreaking ceremony for UGA’s new Science Learning Center. I told him about a book I’m reading called Life Unfolding: How the Human Body Creates Itself by Jamie Davies and about how Chapter 17 began with a quote off a car bumper sticker: “Support bacteria–they’re the only culture some people have.” This professor had himself proposed his own idea for a car bumper sticker in the introductory biochemistry class he teaches: “HONC if you love biochemistry” (HONC referring to the general rules by which hydrogen, oxygen, nitrogen, and carbon form one, two, three, and four covalent bonds, respectively, in stable organic molecules).

A Double-Edged Sword
I asked him if he had heard about the researchers from Johns Hopkins who have been using modified flesh-eating bacteria as anti-cancer agents. The researchers removed the gene responsible for the production of alpha-toxin (responsible for the breakdown of cytoskeletal structures in living cells) from Clostridium novyi, which thrives in hypoxic conditions, and proceeded to test the attenuated strain in various organisms by injecting spores directly into the tumor site. In each case, the modified bacteria consumed tumor cells while leaving healthy tissue intact. Reading about this research got me thinking about the healing power of destruction at large. Similar to the way in which the Johns Hopkins researchers saw the curing potential of flesh-eating bacteria, so did Marie Curie see the potential for panacea with radium. Upon observing radium’s destructive effects on her own healthy tissue, she reasoned that radium could also be used to destroy infected tissue. And thus the idea of radiation therapy was born (today, safer radioactive substances such as cobalt and cesium are used). Oftentimes, destruction seems catastrophic, devastating, and ultimately tragic. But destruction also holds the power to treat disease, create novel forms of life, and ultimately pave the way for new beginnings.

Life will always find a way.
In the natural world, severe disturbances to terrestrial communities, whether the result of natural disasters or human activity, often lead to a process called ecological succession in which a disturbed area is colonized by a variety of species, which are gradually replaced by other species, which are in turn replaced by still other species in a seemingly interminable circle-of-life cycle. Initially, severe environmental disturbances reduce species diversity, but life eventually reemerges. When this process begins in a practically lifeless area where soil has not yet formed, it is called primary succession. The only organisms initially present are usually prokaryotes and protists, and lichens and mosses are commonly the first macroscopic photosynthesizers on the scene. Soil eventually develops as rocks weather and organic matter from the decomposed remains of the first colonizers begins to accumulate. Once soil is present, lichens and mosses are usually overgrown by grasses, shrubs, and trees that sprout from seeds blown in from nearby areas or carried into the area by animals. Secondary succession occurs when an existing community has been cleared by some disturbance that leaves the soil intact, as in Yellowstone following the 1988 fires. Communities subject to these kinds of disturbances recover more quickly than those in which a disturbance has wiped out most of the native, resident life. Nevertheless, life always resurges.

Fossil evidence indicates that diversity of life has increased after each of the five big mass extinctions, due to adaptive radiations, periods of evolutionary change in which groups of organisms diversify into many new species whose adaptations facilitate the creation and development of new niches in their communities. Several of these radiations gave rise to adaptations that facilitated life on land. The radiation of land plants, for example, is associated with key adaptations, such as vascular systems to support against gravity and waxy cuticles to protect leaves from water loss. Even after events as devastating as mass extinctions, life, resilient as it is, picks up the pieces and begins to rebuild like the phoenix rising from the ashes.

It is a truth universally acknowledged that destruction and creation go hand in hand.
Using a computer simulation, Cardiff University astronomer Scott Balfour and his colleagues have recently reproduced the iconic and aptly named Pillars of Creation, a trio of gas columns located inside the Milky Way’s Eagle Nebula. The pillars themselves are the product of a massive nearby O-type star, but the formation of these star-creating factories has been unclear until now. O-stars are the universe’s largest, hottest stars, which lead very short lives and wreak havoc upon death. Balfour’s simulation shows that O-stars not only initiate the creation of stars in their nearby vicinity but also destroy star-forming clouds by compressing surrounding gas to initiate the birth of stars prematurely.

We are all star dust.
Perhaps the most poignant illustration of the creative power of destruction is the fact that our very existence is predicated upon the occurrence of a very destructive event: the death of a star, which sometimes results in a supernova. In the beginning was hydrogen, the simplest atom that exists. Only a star is capable of synthesizing heavier elements under extreme temperatures and pressures. Near the end of their lives, heavy-mass stars collapse and explode, scattering carbon, nitrogen, oxygen, and other heavy elements across the galaxy. As Carl Sagan famously said, “The nitrogen in our DNA, the calcium in our teeth, the iron in our blood, and the carbon in our apple pies were made in the interiors of collapsing stars.” We are literally star stuff. NASA Astronomer Dr. Michelle Thaller eloquently explains the beautifully violent act by which we come into being:

Through the Looking Glass of Science

IMG_4942 IMG_4935
“The whole secret of the study of nature lies in learning how to use one’s eyes.”
―George Sand

“To see a world in a grain of sand,
And a heaven in a wild flower,
Hold infinity in the palm of your hand,
And eternity in an hour.”
―William Blake, “Auguries of Innocence”

“If you’re scientifically literate, the world looks very different to you, and that understanding empowers you.”
―Neil deGrasse Tyson

1) Science is a tool which indiscriminately allows us to obtain a greater understanding of the laws dictating the phenomena in our world and the universe at large.

The goal of science is to illuminate fundamental truths concerning the workings of the universe. As NPR blogger Adam Frank puts it, “Science — under all its theories, equations, experiments and data — is really trying to teach us to see the sacred in the mundane and the profound in the prosaic.” More than a subject, a discipline, or a field of study, science is a lens through which we can perceive our surroundings. As British biologist Lewis Wolpert expounded, “I would teach the world that science is the best way to understand the world, and that for any set of observations, there is only one correct explanation. Also, science is value-free, as it explains the world as it is.”

2) Closely attached to the practice of science is the cultivation of skepticism and the need for empirical evidence.

“The skeptic does not mean he who doubts, but he who investigates or researches, as opposed to he who asserts and thinks that he has found.”
―Miguel de Unamuno

“A central lesson of science is that to understand complex issues (or even simple ones), we must try to free our minds of dogma and to guarantee the freedom to publish, to contradict, and to experiment. Arguments from authority are unacceptable.”
―Carl Sagan

“If it disagrees with experiment, it’s wrong. In that simple statement is the key to science. It doesn’t make any difference how beautiful your guess is, it doesn’t matter how smart you are who made the guess, or what his name is… If it disagrees with experiment, it’s wrong. That’s all there is to it.”
Richard Feynman

Being a scientist requires having faith in uncertainty, finding pleasure in mystery, and learning to cultivate doubt. There is no surer way to screw up an experiment than to be certain of its outcome.”
Stuart Firestein

Much of the beauty of science lies in its objectivity. Science advances on a foundation rooted in empirical observation, painstaking data collection, accuracy, and reproducibility. Commitment to the scientific method is not a matter of faith. That being said…

3) Science is nourished not only by reason and observation but also by imagination. Science makes use of that wonderful blend of curiosity, skepticism, and imagination to create and innovate.

I believe in intuition and inspiration…Imagination is more important than knowledge. For knowledge is limited, whereas imagination embraces the entire world, stimulating progress, giving birth to evolution. It is, strictly speaking, a real factor in scientific research.”
Albert Einstein, Cosmic Religion: With Other Opinions and Aphorismsp. 97 (1931)

“It is, I admit, mere imagination; but how often is imagination the mother of truth?”
Sherlock HolmesThe Valley of Fear

“In general we look for a new law by the following process. First we guess it…No! Don’t laugh―it’s really true!”
Richard Feynman

“It is important, at the present time, to bear in mind that the human soul has still greater need of the ideal than of the real. It is by the real that we exist; it is by the ideal that we live.”
―Victor Hugo, “William Shakespeare”

Kathleen Taylor, a research scientist in the department of physiology at Oxford University, writes about the complementarity between knowledge and imagination: “At both group and individual levels, knowledge facilitates community and continuity, while imagination facilitates change. Knowledge binds us to a sometimes-oppressive existence; imagination helps us escape it. However, imagination evolved as a tool for facilitating survival. Imagining, we take a step beyond what we know into the future or into another world. We see alternatives and possibilities; we work out what we need to reach our goals.”

Imagination and creativity often fuel the fires of scientific innovation. In the process, ideas previously considered impossible often become reality.

4) Science only adds to the mystery, wonder, and excitement; it cannot subtract. Sometimes, not having all the answers is part of the fun.

“I have a friend who’s an artist and has sometimes taken a view which I don’t agree with very well. He’ll hold up a flower and say ‘look how beautiful it is,’ and I’ll agree. Then he says ‘I as an artist can see how beautiful this is but you as a scientist take this all apart and it becomes a dull thing,’ and I think that he’s kind of nutty. First of all, the beauty that he sees is available to other people and to me too, I believe. Although I may not be quite as refined aesthetically as he is … I can appreciate the beauty of a flower. At the same time, I see much more about the flower than he sees. I could imagine the cells in there, the complicated actions inside, which also have a beauty. I mean it’s not just beauty at this dimension, at one centimeter; there’s also beauty at smaller dimensions, the inner structure, also the processes. The fact that the colors in the flower evolved in order to attract insects to pollinate it is interesting; it means that insects can see the color. It adds a question: does this aesthetic sense also exist in the lower forms? Why is it aesthetic? All kinds of interesting questions which the science knowledge only adds to the excitement, the mystery and the awe of a flower. It only adds. I don’t understand how it subtracts.”
―Richard Feynman

“The possession of knowledge does not kill
the sense of wonder and mystery.
There is always more mystery.”
―Anaïs Nin

“Music and physics are nourished by the same sort of longing.”
―Einstein’s character, Einstein and Eddington

 When I heard the Learn’d Astronomer

 When I heard the learn'd astronomer;
 When the proofs, the figures, were ranged in columns before me;
 When I was shown the charts and the diagrams, to add, divide, and
       measure them;
 When I, sitting, heard the astronomer, where he lectured with much
       applause in the lecture-room,
 How soon, unaccountable, I became tired and sick;
 Till rising and gliding out, I wander'd off by myself,
 In the mystical moist night-air, and from time to time,
 Look'd up in perfect silence at the stars.

–Walt Whitman

The poem that Joan Feynman references is actually written by Walt Whitman. Nevertheless, I couldn’t disagree more with its fundamental claim: that science somehow robs nature of all its wonder and beauty. On the contrary, I feel that the science and math behind the laws of nature have a certain elegance of their own. The scientific beautifully complements the aesthetic, and for this reason, I will never be a proponent for the perpetuation of the “two worlds” ideology; science and the arts are two sides of the same coin. Rather than reduce the universe to a bunch of facts and figures, science frees the mind to experience the universe in all its glorious fullness, as it really is.

The Twice-Forbidden Fruit: A Quest to Create a Living Tree of Knowledge

apple tree, NPR

Image Credit: Catalin Petolea/iStockphoto.com

Last semester in my biology lab class, my peers and I read some research on DNA sequencing as a form of information storage, including a paper from the lab of George Church. We compiled information from several sources into a research paper, and I have shared mine below:


DNA’s Potential for Digital Information Storage Solutions

The onset of the Information Age has given rise to a need for more efficient methods for data storage and retrieval, as archiving data has become an increasingly complex task. In light of this problem, solutions such as cloud computing have been proposed as the savior of storage and now constitute a burgeoning market. However, to quote Einstein, “We can’t solve problems by using the same kind of thinking we used when we created them.” The key to our data storage problems may not lie in thinking bigger but in thinking smaller. DNA offers the possibility for storage of large amounts of data in a small amount of space. Additionally, data storage in the form of DNA can withstand the test of time, unlike many currently used data storage methodologies. DNA-based storage has potential as a practical, cost-effective solution to the digital archiving problem.

Although successful on a small scale, a significant limitation to the large-scale practical application of DNA-based information storage lies in the difficulty of synthesizing long strands of DNA de novo. George M. Church and his colleagues at Harvard Medical School were the first to attempt to tackle this problem using next-generation DNA synthesis and sequencing technologies. Rather than work with a single long stretch of DNA, the team opted to use shorter, overlapping fragments which together contain all the necessary information, yet individually are easier to manipulate. To move beyond the limited encoding of uppercase text which served as the basis of previous approaches, the team chose to encode an entire book, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves, which included 53, 426 words, 11 JPEG images, and one JavaScript program. The text was converted into a 5.27-megabit stream, and the resulting bit sequence was converted to DNA code using a 1-bit per base encoding. Following PCR to amplify the library, the sequence was read using an Illumina HiSeq next generation sequencer. All data blocks were recovered with a total of 10 bit errors out of 5.27 million, most of the errors being located within homopolymer runs (Church et al., 2012).

Researchers at the European Bioinformatics Institute used a similar strategy to create a way to store data in the form of DNA. In their study, Nick Goldman and his colleagues managed to create a code that is resistant to error and can last for at least 10,000 years (Goldman, et al., 2013). As was the case in the Harvard study, this code was created using short strings of DNA, which were broken up into overlapping fragments that ran in both directions (Church et al., 2012; Goldman, et al., 2013). In an effort to improve upon Church’s work, Goldman’s coding scheme did not allow for repeats in order to reduce error in DNA reading and writing. Goldman’s method ensures that no homopolymers are generated, significantly reducing high throughput sequencing errors. Given that a majority of errors associated with the Church method can be ascribed to homopolymers, the Goldman strategy is much less error prone than its predecessor (Church et al., 2012; Goldman, et al., 2013).

To test the efficacy of Goldman’s method, five files were encoded: all 154 of Shakespeare’s sonnets (ASCII), Watson and Crick’s seminal paper, “Molecular Structure of Nucleic Acids” (PDF), a medium resolution color photo (JPEG), an excerpt from Martin Luther King’s 1963 “I Have a Dream” Speech (MP3), and the Huffman code used to convert bytes to base-3 digits (ASCII). From these files, corresponding pieces of DNA were synthesized into base pair sequences. Four out of the five resulting DNA sequences were fully decoded without intervention. The fifth file contained 2 gaps, 25 bases each, but inspection of neighboring regions allowed researchers to hypothesize the missing fragments and manually insert the 50 missing bases, resulting in original files that had been reconstructed with 100% accuracy (Goldman, et al., 2013).

Church and Goldman were not the first to hypothesize about DNA’s powerful potential for information storage. Researchers at the University of Phoenix conducted a study comparing and contrasting the structure and function of computer hard drives and DNA. The study proposed that the same properties necessary for information processing in the hard drives of digital computers also reside in the DNA of eukaryotic cells. David D’Onofrio and Gary An identified four essential properties of information in a centralized storage and processing system: (1) orthogonal uniqueness, (2) low level formatting, (3) high level formatting, and (4) translation from stored to usable form. D’Onofrio and An asserted that both the DNA complex and the computer hard drives contain these components characteristic of centralized information storage and processing systems. While computer hard drives and the DNA of living organisms seem to exhibit functional equivalence, D’Onofrio and An acknowledged that there are places where the analogy breaks down. For example, biological systems do not have an external source for a map of their stored information or for a set of instructions; instead, they must possess an organizational template within their intermolecular structure. For this reason and several others, the authors of this study are weary to think of hard drives and DNA interchangeably. The implication is that attempts to disrupt DNA sequences by manipulating its components will invariably lead to unintended consequences, suggesting that the use of DNA for storage solutions is ill advised (D’Onofrio and An, 2010). While some, such as D’Onofrio and An, may approach the idea of DNA storage solutions with hesitancy, others, like Church and Goldman, champion DNA storage solutions as the beginning of a new digital frontier.

References:

Church, G.M., Gao, Y., Kosuri, S. 2012. Next-Generation Digital Information Storage in DNA. Science. 337(6102): 1628.

D’Onofrio, D.J. and An, Gary. 2010. A Comparative Approach for the Investigation of Biological Information Processing: An Examination of the Structure and Function of Computer Hard Drives and DNA. Theor Biol Med Model. 7(3).

Goldman, N., Bertone, P., Chen, S., Dessimoz, C., LeProust, E.M., Sipos, B., Birney, E. 2013. Toward Practical High-Capacity Low-Maintenance Storage of Digital Information in Synthesized DNA. Nature. 494 (7435): 77-80.


Now, an artist from George Church’s lab, Joe Davis, plans to use synthetic biology to insert a DNA-encoded version of Wikipedia into a 4,000-year-old strain of apple to create a a living, literal tree of knowledge. He calls his endeavor Project “Malus ecclesia.” (Malus, the genus name for all apples, means both “evil” and “apple tree” in Latin. Ecclesia translates to “church,” an homage to George Church.) The process of inserting this extra information into an apple’s genome is akin to writing in the margins of a book; he will not alter any of the apple’s existing genome–responsible for the apple’s appearance, texture, and taste–but add to it. Furthermore, since the English version of Wikipedia contains two and a half billion words and the space in the bacterial genome is limited to a few thousand words, Davis plans to spread Wikipedia’s information out across many apples and many trees, which will likely compose a large grove. Because the Animal and Plant Health Inspection Service of the U.S. Department of Agriculture has strict regulations concerning the consumption of genetically altered plants, the engineered apple, when complete, will be twice forbidden.

What do you think of this project to create a living tree of knowledge? Are there potential advantages to storing information in this manner as opposed to using a digital platform? [Added December 20, 2014: Perhaps the only pertinent question left is, “Are you, are you coming to the tree?”] Leave your thoughts in the comments section below!

RNAi Therapies as Possible Cure for TTR Amyloidosis and Other Diseases

TTR amyloidosis is a rare hereditary disease characterized by abnormal production of a protein called transthyretin, or TTR, which is responsible for shuttling the thyroid hormone thyroxine (T4) and retinol (an animal form of vitamin A) around the body. Hence, the name transthyretin: transports thyroxine and retinol. The defective version of the protein is unable to perform its task and ends up getting lodged in the nerves and heart, forming insoluble clumps known as amyloid deposits.

(Image Credit: J.Kelly, The Scripps Research Institute)

(Image Credit: J.Kelly, The Scripps Research Institute)

In the beginning, this kind of damage may lead to loss of physical sensation, and some patients even become bedridden. As the disease progresses, the amyloid deposits may damage the nerves that are responsible for processes such as digestion, giving rise to a multitude of symptoms, including diarrhea, vomiting, constipation, and low blood pressure.

Transthyretin is produced in the liver, so in 1990, physicians began offering patients with the disease liver transplants. However, this strategy wasn’t terribly effective. Liver transplants are difficult to come by, and for many patients this approach fails to produce the intended results. In recent years, researchers have developed two stabilizing drugs–diflunisal and tafimidis, which are intended to keep the abnormal TTR from misfolding. Both drugs do seem to slow the progression of the disease, but neither constitute a cure.

According to an article published by NOVA Next, researchers are now working to develop a class of medicines aimed at accomplishing what no other therapies have before: silencing the TTR gene. Rather than merely treating the symptoms of TTR amyloidosis, this therapy will tackle the root of the problem by blocking production of the problematic protein. In 1998, Andrew Fire and Craig C. Mello took a major step towards this approach while working with the nematode worm C. elegans. They discovered the double-stranded RNA could trigger gene silencing. They called this process RNA interference, or RNAi. The pair won the 2006 Nobel Prize in Physiology or Medicine for their innovative work.

In the following years, researchers began to uncover the mechanisms behind this promising process. In order to produce a protein, cells require messenger RNA, which carries instructions for the production of proteins to the ribosomes in a cell’s cytoplasm. Double-stranded RNA, however, disrupts this process. Upon encountering dsRNA, enzymes called dicers slice the dsRNA into small chunks around 20 nucleotides long. Next, these double-stranded bits, known as small interfering RNAs (siRNAs), bind to a class of proteins called Argonautes. The Argonautes can then seek out mRNA with a complementary base sequence and slice these mRNA strands, rendering them useless. Without mRNA, a cell cannot produce proteins. The siRNAs have the ability to bind to Argonautes multiple times, so a single siRNA molecule can effectively destroy hundreds of mRNA molecules within a cell.

Mechanism of RNA Interference in Mammalian Cells (Photo Credit: Dan Cojocari, University of Toronto)

Mechanism of RNA Interference in Mammalian Cells (Image Credit: Dan Cojocari, University of Toronto)

Conventional drugs attack a protein by binding to them, but many proteins lack a good active site. Out of more than 100,000 proteins that the body is capable of producing, researchers have only been able to target a few hundred. RNAi offers a single method to block all of them. In 2002, Philip Sharp, a Nobel laureate and molecular biologist at the Massachusetts Institute of Technology in Cambridge, teamed up with scientists involved in the early development stages of RNAi to launch Alnylam, the first company aimed at developing RNAi therapies. John Maraganore, CEO of Alnylam, says, “With RNAi we can stop a flood by turning off a faucet. Small molecules can only mop up the floor.”

In July 2010, Alnylam launched the first human study to test the efficacy of its therapy for TTR amyloidosis, an siRNA wrapped in a lipid nanoparticle. Participants received a single dose, and the initial results were promising. In 2012, the company launched another study to test the safety of the drug and its impact on TTR production. One dose of the medicine ended up inhibiting TTR production by as much as 94%. Last winter, Alnylam launched a phase III clinical trial. The 18-month study is aimed at examining whether the medication has any impact on the participants’ nerve function. One group will receive a saline solution and the other group will be administered the drug, called partisiran. Because partisiran and other RNAi therapies depend on lipid nanoparticles, they must be administered via an IV.

Partisiran is the first RNAi therapy to enter a phase III clinical trial and may become the first RNAi therapy on the market. But RNAi offers hope for developing therapies that extend far beyond amyloidosis. Alnylam is currently working on developing therapies for seven other diseases, including hemophilia and high cholesterol. And other companies are developing siRNAs to treat everything from ebola to liver cancer. However, even if partisiran succeeds, the drug will not be widely available for the next several years. Alnylam won’t have the results of the phase III trial until 2017.