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York University
Natural Science
NATS 1760
Darrin Durant

Readings:  Barnes & Dupre, Excerpt from Genomes and What to Make of Them (341-344)  Ridley, Genome (pp.7-10) VOCAB  Biotechnology o Coined 1917 o Original associated with brewing, wine (yeast makes alcohol) o But especially good – making more of it o But little discussion about genetics in biotechnology until early 1970s  Genetic engineering o Not quite the same thing as biotechnology – the two stat to fuse in the 70s as ability to do stuff with genes increases o First use of recombinant DNA  Restriction enzymes (scissors)  Recombinant DNA (shuffled around by people)  Plasmid (what has made GE possible) CONCEPTS  Informatics assumption (genome=software) Valid?  Use of metaphors in science and communication o In order to be understood, an expert might use a context that is easily understandable to lay people  Problem of causality o How exactly does a gene „cause‟ a trait to occur? o Later: DNA “codes for” (i.e. tells other cellular organs to make) proteins o Not the computer science language: DNA as „software‟  „Scientific curiosity goes where the money is‟ (shapes direction)  Mosaic view of organism (organism as a collection of traits – hair colour, eye colour, height)  one gene-one trait notion  Risk vs. uncertainty o Known unknowns and unknown unknowns DNA AS INFORMATION  After 1950s, computer science increasingly replaces physics as the model discipline; genetics turns into genomics (sometimes called “bioinformatics” o Genes stop being particles and start being code/codons o Remember that discovery of DNA structure revealed 4 letter „alphabet‟ – ACGT o At the same time, new field of computer science emerges after WW1 o Also, technology and tools; hardware and software makes genetics done “in silico” not just “in vitro”  For instance – 1982 – first „maps‟ and sequences can be searched using program resembling („find‟ on word processing software) o Cultural context  Fits with new notion of “information society” 1970s, emergence of microcomputers (Apple)  Interesting how meanings of words change affect the larger field they‟re attached to o When „program‟ first used in genetics, conceived of as non-computing – like a concert program – different implication o Initial meaning of genetic code – morse code not software was what Watson meant  What does thinking about genes as information only blind us to? METAPHORS IN SCIENCE  Objective science may be thought to banish imagery but uses metaphors/analogies all the time  Geneticist Richard Lewontin: Mendelism (early variant of genetics) later taken up because genes = particles, like molecules (physics, chemistry envy in biology)  Other metaphors? o “selfish” genes (DNA is the „master molecule‟) o Economies „grow‟ o Gene pools can be „polluted‟ (eugenics) o The mind is like a computer o Seen in a moment:  Genes are written in a 4 letter alphabet; the genome is like a book written in the alphabet („book of life‟)  Genes are like computer code (tell body to do something) genome is  Why do we use metaphors so much? What‟s the price of metaphor? Are they unavoidable?  How do these metaphors affect the science (constrain it? Emphasize certain aspects and not others?)  Why is a particular metaphor used in science? Is it the surrounding culture? (ex. The 1980s emphasis on informatics  microcomputers)  Getting to genetic engineering itself: o Notice – genetic engineering – bodies/genomes are machines, they don‟t grow, they have interchangeable “parts” o What if we thought of it as “genetic weeding”? (silly example but shows implications of words) o What does this imply? What does it leave out?  Mosaic view of the organism („beanbag genetics‟)  Implication of monogenic causation HOW GENES CAN BE MANIPULTED/ENGINEERED  What‟s the promise of genetic engineering? o Medical  Particular illnesses are caused by a certain kind of protein, or a lack of it. If an ill person‟s DNA could be changed (particular gene added to DNA, or removed) to remove or produce this protein, then health  Considered as far back as the 1920s o Industrial (medical for ex.)  Some drugs are expensive to produce  Bacteria are really cheap, what id we swapped in a gene to make a bacterium produce this protein o Industrial (climate)  Why not figure out how to GM Super-algae that takes in lots and lots of CO2 and emits oxygen or something else?  Dream of this – occurring late 1990s o Fisheries  Faster growing salmon o Agricultural  Golden rice  Insertion of 3 genes for producing beta carotene (i.e. pre-Vitamin A)  Insect resistance – bt corn  Expression of insecticidal protein, GE done through Basillus (soil bacterium lives in caterpillars stomachs, gets ingested, dies)  Pesticide tolerance  Introducing a chemical that is resistant to glyphosphate, GE done through Agrobacterium  May lead to less GHG pollution because makes no till agriculture possible (release less carbon)  Nitrogen  Canola in Canada, 40% less fertilizer (less nitrogen spill-off which leads to algae blooms and dead spots in lakes)  Want to reduce fertilizer that is used GE REALLY INSPIRED BY THE MOSAIC VIEW OF ORGANISMS  Mosaic view – organism is a bundle of traits caused by genes, not unified organism  Imaginative project of engineering: can one „swap in‟ good genes and remove bad ones? HOW DO I START TO DO STUFF TO THE GENOME?  First point – DNA doesn‟t split itself up or join itself up – has lots of sophisticated helpers to do this  „trick‟ DNA into doing things o these things occur naturally – ironically, genetic engineering uses same tools as nature does  think of it largely as issue of cutting and pasting o Cutting  Cutting: if codons code for amino acids/ genes code for proteins, then cut out or paste sequences what you want and don‟t want  Scissors: restriction enzymes, originally used bacteria to defeat viruses by cutting up the virus‟s (400 types of restriction enzymes that only work in a particular sequence) o Pasting  Ligase – used to pull the fragments back together  Use particular restriction enzyme to cut where you want; then attach sequence where you want  What results is a „recombinant DNA  where do you do it? to what do you do it? o bacteria, specifically plasmids o It's easier to insert / move a gene in a bacterium (look at plasmid pic on iphone); o basically you take the DNA sequence you want, splice it into a bacterium's plasmid, and then let the bacteria replicate (clone) naturally (bacteria split very quickly - every 20-30 minutes) - thus produce huge amounts of the DNA sequence and the protein you need. If all you want is GE'd bacteria, this may be all you need (ex. use of e.coli to produce insulin by Genentech) o If you want to then transmit DNA into other organisms, more tricky)... o much, much easier to do in bacteria (b/c of plasmids) than in humans (multicellular)! o If you want to genetically manipulate a multicellular organism (like human) have to either insert a gene into all the cells you need to, or start with a single-celled embryo which then develops  way easier to do in a single-celled embryo- the problem is that this single-celled embryo is the germ line, which means the changes will recur in future generations (way more controversial) o exactly how does one mess around with genes?  directly - pipettes - inject DNA into a nucleus of a cell  take the DNA sequence you want, put in pipette; inject pipette into new embryo (one of the cell's nuclei). It may get integrated into the nucleus's chromosomes. Only 5% success rate. o deliberately infect with a virus -  viruses are parasites, inserting selves in larger cells and using them to reproduce (can't reproduce themselves). Viruses infecting bacteria are called bacteriophages - phages. They insert their DNA into the host o deliberately infect with a retrovirus  undermining the notion of the central dogma - a retrovirus, discovered in early 70s, has RNA that can actually insert itself 'upstream' into DNA, and tell it to make a copy of itself forever.  interesting possibility that much of human DNA thought to be 'junk' is the remnants of millions of years of retrovirus infections (i.e. our DNA is filled with traces of ancient diseases)  idea is to deliberately 'infect' a patient with a retrovirus carrying the message you want to have in their DNA  but still not much help - immune system pretty good at preventing infection; it has to infect particular portion of chromosome etc  retroviruses - may make human gene therapy possible (more later, next week) o in plants:  Use of Agrobacterium  a bacterium called Agrobacterium discovered, that has effect of infecting some plants with its plasmids if you just rub it on a leaf.  so you GE the Agrobacterium with the plasmid you want, then rub it on a leaf  get the infection to occur, then take cuttings from the plant (i.e. cl
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