RadioLab: Antibodies Part 1: CRISPR

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History of CRISPR:

  • CRISPR is the sort of thing that gets drunk biologists at parties overly excited
    • CRISPR is a breakthrough approach to gene therapy that can turn Chihuahua into a Great Dane (and much much more).
    • CRISPR was first referenced in 1987 by Japaense scientists.
      • They noticed something strange was noticed in e.coli, which is bacteria, containing DNA.
    • Scientists found a strange stretch of DNA.
      • 5 identical sequences in a row, separated by very short sequences in between that were all different.
    • It was unusual, but they didn’t know what to think of it at the time
  • Scientists began seeing the repeats often in bacteria, and a name was given to the phenomenon: Clustered Regularly Interspaced Short Palindromic Repeats: CRISPR
  • Nature preserved this pattern, sometimes in creatures hundreds of millions of years old
  • In 2005, databases of sequences were available and searches were done to match these repeated patterns with other species’
    • Breakthrough: The bits between the repeats matched virus DNA
      • Bacteria had virus DNA inside them, but why?
    • The origin is unknown. It was first thought that there was virus DNA in particular places of the bacterial genome, like a human finding a segment of mosquito DNA
      • Scientist Eugene Koonin declared it to be a defense system.
        • A virus makes life bad for bacteria.
          • The oceans are full of viruses, and they kill up to 40% of bacteria everyday.
        • It was hypothesized that bacteria were storing pieces of DNA from viruses to recognize them later, like a “most wanted poster” or mug shot.
      • It was thought that the bits of virus was for the bacteria to defend itself by figuring out the virus’
        • A virus comes into a cell, explodes and releases “naked”
        • Usually, multiple “weapons of defense” – enzymes – attack viruses, like ground troops, they fight hard.
        • Usually, they fail and the virus takes over the cell and the bacteria dies.
          • There is some non-zero probability that the cell can survive, though. If so, new enzymes are sent to clean up the stray virus and cut it up into little bits of virus that are then shoved into the bacteria’s own DNA between the patterned repeats.
        • The spaces in the cell’s own DNA act as a storage facility and a memory device, so that next time the virus is there and its DNA spreads, the cell can send out its “big guns” and destroy the virus.
          • The cell manufactures special “molecular assassins” that recognize the virus DNA. A protein “attacker” looks like a clamshell (misshapen Pacman) and has a copy of the virus “mugshot”
          • When it bumps into the virus RNA, it pulls it apart, reads it and if it is not a match to the “mugshot”, it moves on, if it is a match, it locks in, the DNA is trapped and molecular blades chop it up

The Promise of CRISPR: Cheap, Precise, and Possibly Universal

  • What is most exciting, is if we could find a way to use this ability to precisely edit DNA!
    • CRISPR could be used to target genes we know cause awful diseases such as Huntington’s Chorea or hemophilia.
    • It has already been demonstrated in a mice
      • Their cells were given a “mugshot” for a bad gene, and it found the gene and chopped it out.
      • A good gene was then put in its place pretty easily
        • The new, good gene was placed near where the old gene was. It didn’t need to be precisely placed because repair enzymes continually check for breaks and they saw the break in the DNA and saw the good gene and then put it together
      • This is a natural repair pathway
      • From assassination to engineering, from killing to refashioning.
  • Genetic engineering and genome editing technologies have been around for 30 years, but none as potentially powerful as CRISPR
    • Biologist Beth Shupiero from UC Santa Cruize says that two years ago, a gene editor was put into a cell, given instructions to go somewhere, but it might have gone somewhere near where it was supposed to but not actually where it was supposed to.
    • The old technology took a lot of time and money, about $5,000.
      • Now, it is super easy to do
      • The enzyme finds the specific and precise place, and the laboratory method is cheap, about $75.
      • CRISPR can be used in any living thing, from corn to cockroaches.
    • CRISPR hasn’t been found to not work with anything.
      • This is big news for scientists. There are now usable “molecular scissors” programmed to cut DNA wherever they want.
    • CRISPR has the potential to:
      • Treat/prevent disease
      • Resurrect/reconstruct long lost creatures (hello Jurassic Park!!)

Concerns with “Playing God” and Designer babies:

  • Where does the sacred begin and end?
  • Is it tinkering with someone’s body, altering their own cells? – We already do this…
  • We’ve had test tube babies (In Vitro Fertilization) for decades already
    • 60,000 kids a year…some parents could have chosen boy or girl
  • Should we outlaw this? Won’t people just go to other countries that haven’t? – Probably China
    • Should we draw the line at sperm cells egg cells or embryos…
      • How about permanent changes to your DNA that will then be passed on your your children without their consent?
    • Researchers in China have already begun experimenting on non-viable human embryos…
      • They had limited success, but this is just the beginning
        • CRISPR is still considered “dangerous” and not usable on human embryos
      • 4 other Chinese labs doing this work too
    • Could this be a historical moment? What are the risks?

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