Tag: DNA

• Visual science journalism’s DNA problem

  Your left hand and right hand are mirror-images of each other. You can’t superimpose them completely even after all manner of rotations and translations. Only mirroring them works. The same thing can happen to some molecules. When two molecules are identical in every way except their geometric structure in space is such that one is a mirror-image of another, they’re said to be enantiomers. These molecules have a chirality, or handedness: like your hands, one is left-handed and the other right-handed.

  On December 3, an international group of scientists published a technical report and commentary in Science warning against work to develop “mirror life”: cells whose chiral molecules are replaced with their complementary enantiomers. To quote from the commentary:

  Our analysis suggests that mirror bacteria could broadly evade many immune defenses of humans, animals, and plants. Chiral interactions, which are central to immune recognition and activation in multicellular organisms, would be impaired with mirror bacteria. This could result in weakened immune recognition, a weakened response by innate immune systems, and (in vertebrates) limited downstream activation of adaptive immune functions. For example, experiments show that mirror proteins resist cleavage into peptides for antigen presentation and do not reliably trigger important adaptive immune responses such as the production of antibodies. We are thus concerned that the function of many vertebrate immune systems against mirror bacteria would be severely impaired. Invertebrate and plant immune systems are less well studied but appear to suffer analogous limitations.

  Given the potential for severe immune evasion, mirror bacteria might not require host-specific factors to invade hosts and cause infection. In animals (including humans), bacteria regularly cross barriers in the skin, mouth, gut, lungs, and other mucosal surfaces because of routine damage and intrinsic leakiness; mirror bacteria would be expected to do the same. In healthy animals, translocated natural-chirality bacteria are typically cleared by immune defenses. However, if the immune response against mirror bacteria is sufficiently impaired, translocated mirror bacteria might replicate within the host and establish an infection. Unchecked replication of mirror bacteria within internal tissues is likely to be deleterious to the host organism and may be lethal.

  While this is very intriguing, the report/commentary reminded me of another problem I’ve been noticing in the science journalism press, especially these days when we’re all writing and publishing more articles about genetics.

  Stock images and illustrations are an important resource both for small newsrooms that can’t hire their own designers and for all newsrooms — including those with designers — lacking the skills to create (even partially accurate) scientific visuals. Articles of science journalism about genetics require such visuals more than others because, while the subjects of these narratives are physical entities, they’re too small to be seen by the naked eye as well as whose visuals as seen through microscopes aren’t particularly visually captivating. Instead, stock images have done the trick.

  Pixabay, Getty Images, and other libraries of such assets are choc-a-bloc with 2D and 3D (or 2.5D?) illustrations of the DNA double helix. But I’ve noticed that a great number of them have a common problem — curiously, in a specific way, echoed in the objection the scientists’ group has expressed against “mirror life”: many of these illustrations show the DNA helix twisting to the left. In all our bodies, DNA virtually always twists to the right. That is, the right-handed enantiomer is what animates our bodies whereas the left-handed enantiomer is absent, but which hasn’t stopped it from dominating stock images of DNA.

  I realise most people don’t care and/or that the image is captioned to be “for representative use only”. DNA of other configurations, including a left-handed one, exist as well to be fair. And most of all, DNA’s chirality has almost never been the narrative subject. But today it is, as the scientists have so clearly articulated, and the visuals of science journalism need to buck up as well.

  2024.12.17

• Similar DNA

  From an article in Times Now News:

  Comparing Prime Minister Narendra Modi with former prime minister Atal Bihari Vajpayee, Union Science and Technology Minister Harsh Vardhan on Wednesday said both have a similar “DNA” and share a passion for scientific research.

  I’m sure I’m interpreting this too literally but when the national science minister makes a statement saying two people share similar DNA, I can’t help but wonder if he knows that the genome of any two humans is 99.9% the same. The remaining 0.1% accounts for all the difference. Ergo, Prime Minister Narendra Modi has DNA similar to Rahul Gandhi, me and you.

  That said, I refuse to believe a man who slashed funding for the CSIR labs by 50% (and asked them to make up for it – a princely sum of Rs 2,000 crore – in three years by marketing their research), who claims ancient Indians surgically transplanted animal heads on humans, whose government passively condones right-wing extremism fuelled by irrational beliefs, whose ministries spend crores of rupees on conducting biased investigations of cow urine, and whose bonehead officials have interfered in the conduct of autonomous educational institutions even knows how scientific research works, let alone respects it.

  Vardhan himself goes on to extol Vajpayee as the man who suffixed ‘jay vigyan‘ (‘Hail science’) to the common slogan ‘Jay jawan, jay kisan‘ (‘Hail the soldier, hail the farmer’) and, as an example of his contribution to the scientific community, says that the former PM made India a nuclear state within two months of coming to power. Temporarily setting aside the fact that it takes way more than two months to build and test nuclear weapons, it’s also disturbing that Vardhan thinks atom bombs are good science.

  Additionally, Modi is like Vajpayee according to him because the former keeps asking scientists to “alleviate the sufferings of the common man” – which, speaking from experience, is nicespeak for “just do what I tell you and deliver it before my term is over”.

  2017.11.30

• Lab test to check for beef works best if meat is uncooked

  Featured image credit: snre/Flickr, CC BY 2.0.

  Ahead of Eid al Adha celebrations on September 13, the police in Haryana’s Mewat district were tasked with sniffing through morsels of meat biryani sold by vendors to check for the presence of cow beef. Haryana has some of India’s strictest laws on the production and consumption of cow-meat. The state also receives the largest number of complaints against these acts after Uttar Pradesh, according to the National Crime Records Bureau. However, the human senses are easily waylaid, especially when the political climate is charged, allowing room for the sort of arbitrariness that had goons baying for the blood of Mohammad Akhlaq in Dadri in September 2015.

  The way to check if a piece of meat is from a cow is to ascertain if it contains cow DNA. The chemical test used for this is called a polymerase chain reaction (PCR), which rapidly creates multiples copies of whatever sample DNA is available and then analyses them according to preprogrammed rules. However, the PCR method isn’t very effective when the DNA might be damaged – such as when the meat is cooked at high temperatures for a long time.

  The DNA molecule in most living creatures on Earth consists of a sequence of smaller molecules called nucleotides. The sequence of nucleotides in their entirety is unique to each individual creature as long as its cells contain DNA. A segment of these nucleotides also indicate what species the creature belongs to. It is this segment that a molecular biologist, usually someone at the postgraduate level or higher, will mount a hunt for using the physical and chemical tools at her disposal. The segment’s nucleotides and their ordering will give away the DNA’s identity.

  The Veterinary and Animal Sciences University in Hisar, Haryana, is one centre where these tests are conducted. NDTV reported on September 10 that the university had been authorised to do so only two days before it received its first test sample. The vice-chancellor subsequently clarified that two other centres in the state were being set up to conduct these tests – but until they were ready, the university lab would be it.

  What would need to be set up? Essentially: an instrument called a thermal cycler to perform the PCR and someone qualified to conduct the PCR, usually at the postgraduate level or higher. The following is how PCR works.

  Once some double-strands have been extracted from cells in the meat, they are heated to about 96 ºC for around 25 seconds to denature them. This breaks the bonds holding the two strands together, yielding single strands. Then, two molecules, a primer and a probe, are made to latch onto each DNA single-strand. Primers are small strands of DNA, typically a dozen nucleotides long, that bind complementarily to the single-strand – i.e., the nucleotides adenine on one strand with thymine on the other, and cytosine on one with guanine on the other. Probes are also complementary strands of nucleotides, but its nucleotides are chosen such that the probe binds to sequences that identify the DNA as being from cows. They also contain some fluorescent material.

  To enable this latching, the reaction temperature is held at 50-65 ºC for about 30 seconds.

  Next, an enzyme called a DNA polymerase is introduced into the reaction solution. The polymerase elongates the primer – by weaving additionally supplied nucleotides along the single-strand to make a double-strand all over again. When the polymerase reaches the probe, it physically disintegrates the probe and releases the fluorescent material. The resulting glow in the solution signals to the researcher that a nucleotide sequence indicative of cow is present in the DNA.

  If the Taq polymerase, extracted from microbes living around hot hydrothermal vents on the ocean floor, is used, the reaction temperature is maintained at 72 ºC. In this scenario, the polymerase weaves in about 1,000 nucleotides per minute.

  A molecular biologist repeats these three tasks – denaturing the strands, latching the primer and probe on and elongating the primer using polymerase – in repeated cycles to make multiple copies of DNA. At the end of the first cycle, there is one double-strand DNA. At the end of the second, there are two. At the end of the third, there will be eight. So each cycle produces 2ⁿ DNA double-strands. When 20 cycles are performed, the biologist will possess over a million DNA double-strands. After 40 cycles, there will be almost 1.1 trillion. Depending on the number of cycles, PCR could take between two and six hours.

  These many DNA molecules are needed to amplify their presence, and expose their nucleotides for the finding. The heating cycles are performed in the thermal cycler. This instrument can be modified to track the rate of increase of fluorescence in the solutions, and check if that’s in line with the rate at which new DNA double-strands are made. If the two readings line up, the molecular biologist will have her answer: that the DNA identifies meat from a cow.

  The test gets trickier when the meat is cooked. The heat during preparation could damage the DNA in the meat’s cells, denaturing it to a point beyond which PCR can work with. One biologist The Wire spoke to said that if the “meat is nicely overcooked at high temperature, you cannot PCR anything”. A study published in the journal Meat Science in 2006 attests to this: “… with the exception of pan frying for 80 min, beef was determined in all meat samples including the broth and sauce of the roasted meat” using PCR.

  At the same time, in March 2016, a study published in Veterinary World claimed that PCR could check for the origins of cooked and raw meat both, and also ascertain the presence of a small amount of beef (up to 1%) present in a larger amount of a different meat. The broader consensus among biologists seems to be that the more raw the meat, the easier it would be to test. The meat starts to become untestable when cooked at high temperatures.

  A PCR test costs anywhere between Rs 2,000 and Rs 7,000.

  The Wire
  September 15, 2016

  2016.09.18

• The DNA-based computer that can calculate π

  I’m not fond of biology. Of late, however, it’s been harder to avoid encountering it because the frontiers of many fields of research are becoming increasingly multidisciplinary. Biological processes are meshing with physics and statistics, and undergoing the kind of epistemic reimagination that geometry experienced in the 19th and 20th centuries. Now, scientists are able to manipulate biology to do wondrous things.

  Consider the work of a team from the Dhirubhai Ambani Institute of Information and Communication Technology, Gujarat, India, which has figured out a way to compute the value of π using self-assembling strands of DNA. Their work derives from previous successful attempts to perform simple mathematical calculations by nudging these molecules to bind to each other in specific ways, a technique called tile assembly.

  It was first formulated as a tiling problem by Chinese philosopher Hao Wang in 1961. Wang wanted to know if a set of square tiles could cover a plane in a periodic pattern if each tile had four different colored edges and only edges of the same color could abut each other. The answer was that they could cover a plane but only with an aperiodic pattern.

  In a DNA tile assembly model (TAM), each tile represents a section of the DNA molecule, called a monomer. When adjacent tiles’ abutting sides line up with the same color, then the two monomers attach themselves across the abutting sides according to a strength corresponding to that color. This way, given a tile to start with – called the seed tile – and a sequence of tiles coming up next, the DNA monomers can link up to form diverse patterns.

  By controlling the sequence of colors and their strengths, scientists can thus use TAM to control the values of variables moving through the resultant grid. Connections of monomers between tiles can be made become stronger or weaker, and to different extents, in ways mimicking how the voltage between different electronic components in a computer’s circuit allow it to perform mathematical calculations.

  So, Shalin Shah, Parth Dave and Manish Gupta from the Institute used four new variations of TAM that they’d developed to calculate the value of π. Each of these variations performs a specific function, much like the logic gates inside an information processor.

  1. The compare tile system decides which number is greater between two numbers, or if they’re equal
  2. The shift tile system shifts the bits of a number by one bit to the right, and adds a 0 to the leftmost bit. For example, 11001 becomes 01100.
  3. The subtract and shift tile system subtracts one binary number from the other, then right-shifts its bits by one bit to the right, and finally adds a padding 0 to the leftmost bit
  4. The insert bit tile system inserts a bit in a number

  Using a combination of these systems – all with the TAM at their hearts – the trio has been able to compute the value of π like below:

  

  You can see that the calculation is an ongoing infinite series – specifically, the Leibniz series, which estimates π as an infinitely alternating sequence of additions and subtractions between smaller and smaller fractions. Because it is infinite, the trio’s calculator’s ability to find a more precise value of π depends only on how many tiles are available. Second, because the calculator can compute infinite series, any number or problem that can be reduced to the solution of an infinite series is now solvable using this calculator.

  This would merely be a curious yet tedious way to calculate if not for its potential to exploit the biological properties of DNA to enhance the calculator’s abilities. Although this hasn’t been elaborately outlined in the trio’s pre-print paper on arXiv, it is plausible that such calculators could be used to guide the development of complex and evermore intricate DNA structures with minimal human intervention, or to fashion molecular logic circuits commoving microscopic robots delivering drugs within our bloodstreams. Studies in the past have already shown that DNA self-assembly is Turing-universal, which means it can perform any calculation that is known to be calculable.

  The DNA molecule is itself a wondrous device, existing in nature to store genetic data over tens of thousands of years only for a future inheritor to slowly retrieve information essential for its survival. Scientists have found the molecule can hold 5.5 petabits of data per cubic millimeter, without letting any of it become corrupted for 1 million years if stored at -18 degrees Celsius.

  2015.02.28