OPINION
DOCTORS Lounge
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CRISPY Not Classic
Mary G . Barry , MD Louisville Medicine Editor editor @ glms . org
Were you born with sickle cell anemia ? Maybe there is help at hand .
During the Civil War , the Austrian monk Gregor Mendel did experiments proving that plants inherited certain traits , and posited the existence of genes . In 1869 , the Swiss physician Friedrich Miescher was first to notice and identify DNA as a separate entity by isolating what he called “ nuclein ” ( he studied pus ). In 1879 , Dr . Walther Flemming , a German military doctor , observed his own chromosomes and described their activity as “ mitosis .” Over the next two decades Theodor Boveri , a German biologist , worked with cell division ( he studied worms ), and said that chromosomes carry the genetic material , and that individual chromosomes carry different parts of it .
In 1928 , the British biologist Frederick Griffith proved that Strep bacteria could be transformed from non-virulent strains into lethal ones while inside a mouse . In 1944 , Oswald Avery , one of the first molecular biologists , along with Rockefeller Institute
colleagues McLeod and McCarty , showed that DNA was not a typical protein , but the actual hereditary molecule . The year I was born , Watson , Crick , Rosalind Franklin , and Maurice Wilkins discovered the double helix structure of DNA ( Franklin was left out of the Nobel Prize , because she was female ). In 1961 , the US biochemist Marshall Nirenberg discovered how RNA works . In 1977 , the British biochemist Frederick Sanger , with his partners , identified the amino acid sequences of DNA information , and DNA sequencing began in earnest . In 1983 , US biochemist Kary Mullis ’ refinements in DNA sequencing produced the polymerase chain reaction , which opened the door to rapid copying of DNA , to the tune of 100 billion in a few hours .
The Human Genome Project , thus enabled , began with planning in 1984 and launched in 1990 . Millions of computer-hours and hundreds of scientists , with the help of $ 13 billion in worldwide and NIH funds , began mapping the entire human genome , finishing in April 2003 . The genome map refers to complete sequencing of each chromosome , not a whole map of
any one person .
Meanwhile , after many years of work based on Francisco Mojica of Spain ’ s discovery of short repeated DNA sequences , in 2002 Ruud Jansen et al . in Holland first coined the term CRISPR ( Clustered Regularly Interspersed Palindromic Repeats ). This refers to an adaptive immune mechanism whereby microbes defend themselves against invading viruses . The microbes record and then target the viral DNA so they can mount a precise counterattack . In 2005 , Alexander Bolotin , a Russian immigrant working in France , found the large endonuclease enzyme CAS9 and the protein PAM , required for target acquisition and recognition . CAS stands for CRISPR Associated Protein . CAS9 is RNA-guided . It memorizes and then interrogates and precisely cleaves foreign DNA . After much work by many scientists , biochemists Jennifer Doudna and Emmanuelle Charpentier at Berkeley , and Gasiunas et al . in Lithuania showed that they could change the sequence of the inserter RNA to reprogram the CAS9 to target a site of their choosing .
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