Revolutionary Gene Editing Technology By William Lama Ph.D.
Revolutionary Gene Editing Technology
By William Lama Ph.D.
CRISPR discovery, mcgovern.mit.edu
Ever since the genetic code carried by the DNA double helix was deciphered, it has been the dream of biologists and medical doctors to be able to modify the code for the betterment of humankind. Nearly seven decades since the publication of the DNA structure by James Watson and Francis Crick, gene editing has become a flourishing technology. This story has been described by two of the gene-editing pioneers, Jennifer Doudna and Samuel Sternberg, in their scientific thriller “A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution.”
Dr. Jennifer Doudna, U.C. Berkeley News
I’d like to condense the story for the readers of Palos Verdes Pulse.
The story begins in a Spanish marsh in 1992 where Professor Francisco Mojica observed a curious structure in the genome of microbes in the salty water. The microbial DNA contained multiple copies of a palindromic sequence of 30 bases separated by spacers of 36 non-repeating bases. He called this odd configuration “Clustered Regularly Interspaced Short Palindromic Repeats,” or CRISPR (pronounced “crisper”). Quite a big name for a tiny part of a microbial cell.
At first, this discovery was puzzling, until scientists realized that the unique sequences between the repeats matched the DNA of viruses—specifically viruses that prey on bacteria. It turns out that CRISPR is a part of the bacteria’s immune system. It works this way.
When a virus infects a microbial cell, the microbe employs a defense mechanism which can precisely snip and slice out the invading virus DNA. The virus is destroyed and the snipped DNA fragment is then stored in the CRISPR (spacer) to retain a genetic memory for disabling future infections. If the virus attacks again, CRISPR recognizes the virus DNA and does a job on it.
The next step was to “reverse engineer” naturally occurring CRISPR to produce a gene-editing machine. This critical step was demonstrated by Jennifer Doudna and Emmanuelle Charpentier. By manipulating the CRISPR DNA their molecular machine could be programmed to target any DNA sequence for cleavage. In their paper, they concluded: “We propose an alternative methodology ….. that could offer considerable potential for gene-targeting and genome-editing applications.” A typical scientific understatement.
Gone are the days when life was shaped solely by the plodding forces of evolution.
Advances in molecular biology and genetic engineering have turned CRISPR into an advanced genome editing technology. CRISPR systems can be programmed to target and edit DNA at precise locations. With CRISPR one can cut-out and paste-in new DNA sequences in the genome. Thus CRISPR could be used to modify “typos” in the three-billion-letter sequence of the human genome in order to treat genetic diseases, the holy grail of medical research as long as genetic diseases have been studied.
CRISPR gene editing, US Government Accountability Office
Potential medical applications of CRISPR abound. CRISPR has already been used in animals to cure muscular dystrophy, Huntington’s disease, hemophilia, and to eliminate HIV. It has not yet been approved by the FDA for use in humans, but there are many exciting possibilities.
One of the most exciting is in the field of organ transplants. In the US there are 112,000 people on the transplant waiting list, but only 40,000 got transplants in 2019 due to lack of donor organs. Pig organs (kidney, liver, heart) would work fine in a human if only the human immune system did not reject the transplant. CRISPR could be used to modify pig organs so that they are accepted by human patients.
Alphabet (Google’s parent company) is bankrolling Verve Therapeutics that plans to use CRISPR to tweak genes with one-time injections that could “confer lifelong protection against heart disease.”
Could CRISPR be our next virus killer? A team at Stanford is investigating a method to attack the coronavirus by directing a CRISPR torpedo at it, attacking the virus genetic makeup that allows it to penetrate human cells.
But with promise there is also peril. (“The Unthinkable Power to Control Evolution”)
Not since the atomic bomb has a technology so alarmed its inventors that they warned the world about its use.
CRISPR Opportunities and Challenges, US Government Accountability Office
In 2018, Chinese researchers announced that they had used CRISPR to genetically modify human embryos, which were then transferred to a woman’s uterus and resulted in the birth of twin girls, the first gene-edited babies. The twins’ genomes were modified to make the girls more resistant to HIV. The work was condemned by most as unethical, while some dream of designer-babies.
The U.S. intelligence community Worldwide Threat Assessment has described genome editing as “one of the six weapons of mass destruction that nation-states might try to develop, at great risk to America.”
Should CRISPR use be confined to somatic cells (heart, brain, blood, skin) whose DNA cannot be transmitted to offspring? Or will we allow its use with germ cells whose genetic material is passed from one generation to the next, potentially changing the course of evolution?
We should have the debate.
Dr. William Lama PhD in physics from the University of Rochester. Taught physics in college and worked at Xerox as a principle scientist and engineering manager. Upon retiring, joined the PVIC docents; served on the board of the RPV Council of Home Owners Associations; served as a PV Library trustee for eight years; served on the PV school district Measure M oversight committee; was president of the Malaga Cove Homeowner's Association. Writes about science, technology and politics, mostly for my friends.
email: wlama@outlook.com