Alan Stahler: The alphabet that makes us us
August 11, 2017
The three Rs, reading, 'riting and 'rithmetic, were invented long ago. Close to four billion years ago, for reading and writing, back to when life evolved.
Early living things needed to read and write, to remember how to build and repair their primitive, single-celled bodies, and to pass that information on to the next generation.
The early alphabet had only four letters, but it worked pretty well — well enough that you and I still use it to remind ourselves how to build and repair our bodies. The letters are made of DNA.
Early life had no way to see, so reading was (still is) done by feel. Each of the four letters has a different shape. As the letters evolved, so did machines to recognize them, to recognize their shapes and read out what they'd spelled. Other machines evolved to carry out the instructions the words spelled out.
The nuclear arms race of the 20th century saw the U.S. and USSR inventing better ways to attack each other, better ways to defend against attacks, better ways to get around those defenses, better ways to defend against those better ways of getting around.
As living cells evolved, so did parasites: viruses. Thus began a biological arms race — attack, defense, counterattack — an arms race that continues to this day.
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To defend themselves, bacteria and their single-celled neighbors evolved machines that could kill the parasites by slicing and dicing viral DNA.
Scientists in the second half of the 20th century borrowed these slicing and dicing machines to modify organisms' genes, not by selective breeding, but by directly modifying DNA.
To adapt these tiny machines for genetic modification — not just for killing viruses — was slow, painstaking work, and it was never super-precise. Experiments had to be done over and over to get the desired results.
The past decade has seen the development of a new gene-modification tool, based on a different bacterial defense system: CRISPR. CRISPR is a game-changer.
I spoke recently with Megan Hochstrasser of UC Berkeley's Innovative Genomics Institute. (Hochstrasser got her Ph.D. working with Jennifer Doudna, one of the co-developers of CRISPR.) She stressed was how much faster, easier and more precise CRISPR is to use. No longer must you painstakingly sculpt tiny machines to recognize the DNA you want to cut. Rather, you spell out letters — rather like writing an address — and the tiny machines go to work.
More precise, faster, easier, and therefore cheaper. Labs around the world are taking the new technology and running with it.
CRISPR evolved in primitive, single-celled organisms. Experiments would demonstrate that it would also work in plants, in animals — in the last two years, that it would work in the human animal. Workers are already using CRISPR to attack HIV and other diseases.
The word "germ" comes from a Latin word for "sprout" — seeds germinate. The germ of an idea may grow into something larger (germ as "disease-causing microbe" came much later).
The "germ line" is composed of cells that lead to the next generation — sperm and egg, embryo in mom's belly.
Many genetic diseases could potentially be cured by manipulating genes in sperm, egg or embryo. But unlike genetic modification in an adult, changes in the human germ line would be heritable, affecting not just today's patient, but future generations.
Last February, an international committee assembled by the National Academy of Sciences issued a report, giving a green light — a cautious green light — to using CRISPR to manipulate the human germ line to cure disease — after the safety and ethics are explored and discussed, and only if there were no other way to effect a cure.
The Academy's report emphasized the need for caution.
Al Stahler enjoys sharing nature with students of all ages. His science stories can be heard on radio station KVMR (89.5 FM), and he may be reached at email@example.com