Genome editing gives scientists the power to reorganize life
Tools that would give scientists the ability to limit the spread of diseases, give creatures new traits, and even bring back extinct animals seem possible soon, thanks to ever more powerful and precise genetic editing tools that redesign specific parts of an organism’s DNA.
George Church, a leading genetics professor at Harvard University whose research led to the first genome sequence of a bacterium and who created the Personal Genome Project, spoke about current genetic research at the 2014 New Horizons in Science briefings during the ScienceWriters2014 conference hosted by Ohio State University in Columbus.
Church developed and is using CRISPRs (clustered regularly interspaced short palindromic repeats), special combinations of DNA and enzymes that can be used to isolate genes and edit new instructions into their sequences. CRISPR systems provide a powerful, still-new way to do basic genetic research as well as, in principle, endow creatures with such novel traits as multi-virus resistance. They may even to open the door to de-extinction of vanished creatures by modifying close relatives.
A way to induce resistance to viruses
One way scientists modify organisms is by radically changing genome sequences. The new instructions might even order living cells to employ non-natural amino acids in to construct proteins that no creatures now can make. CRISPR aids in isolating specific genetic and metabolic traits and can give creatures sturdy new mechanisms to resist many viruses.
Church used this technique in looking among 64 codon variations, which are different versions of the same unit of genetic code, for ways to create resistance to multiple viruses.
“We really didn’t expect the first codon out of 64 to be sufficient to cause multi-virus resistance, but sure enough, to our delight — this is unpublished — it has caused resistance to two of the three viruses we’ve tested so far,” Church said during his presentation.
Viral resistance makes genetically modified organisms more valuable in the market, Church said. Resistance can be fostered by changing the genetic code of a host, for example by deleting virus receptor genes.
Modifying a genetic sequence can be particularly useful for combating disease through the use of an RNA-guided gene drive, a genetic packet that greatly accelerates spread of a new trait through a population. Human-designed variations of genes, with the addition of a CRISPR gene drive, can be analogs of the genes provided by a parent. When the enzyme in the CRISPR system cuts a strip of DNA, cell defenses repair the damage by copying the introduced versions of the gene. As a species reproduces, over generations the engineered genes rapidly come to dominate.
Some day gene drives might limit the spread of such diseases as malaria and dengue that are transmitted via mosquitoes by preventing, at the genetic level, the ability of the mosquito to carry a virus or microbial pathogen.
“In many of those cases (the bacteria or viruses) are not sexually reproducing, but the vectors are, and that’s a really good weak point that we can take advantage of,” Church said.
Receptor gene deletion can also be an effective way of combating viruses, such as HIV, that mutate quickly or do not lend themselves well to antiviral drugs, by prohibiting the uptake of that disease into an organism’s genetic code.
Creating new organs, reviving lost species
Genetic sequencing could also encourage improvements in organ transplantation through the development of “universal” organs that, the universal donor blood type O, do not trigger rejection, and by creating transfer-friendly organs out of human and animal cells.
“One option is making human cells into kidneys, lungs, hearts and so forth,” Church said. “Another one is making pigs’ (organs), which are matched in size and physiology with humans.”
Church is hard at work on de-extinction of the mammoth.
His group is using Asian elephants, which are more closely related to the extinct animal than to African elephants, as a template for experiments with the genetic changes that should recreate what would look very much like a mammoth.
“In the case of elephants, we have already made 15 changes with CRISPR,” Church said.
They include modified genetic control of blood hemoglobin, hair length and ear size. Each trait is tested first in tissue cultures. The end result could be cold-weather animals able to occupy the niche of now-extinct mammoths. Church said that at the rate this work are going, the project will be completed in a few years.
“If we can make one, the second one will be much easier than the first one,” Church said. “So it might be possible to do it without breeding, which would be faster.”
The first CRISPR array was first discovered in 1987 in the bacterium E. coli, where it is a part of the immune system. In following years, similar patterns were found in various strands of Archaea and bacteria. The first computational search for CRISPRs was conducted in 2000. Scientists realized that the way microbes edit and repair their genetic codes could be exploited widely to manipulate genes of nonmicrobial species. CRISPRs were first used in animal genetics in 2013.
The economics surrounding genome sequencing has also evolved at an unpredicted rate and is one reason why the practice could impact a wide range of issues.
“Going from a $3 billion genome, which was what the first human genome cost, to something that’s around $1,000 today was predicted to take six decades, hence very few people actually invested in it. Instead it took about six years,” Church said.
Church recognized the hesitation some critics have about bringing species back from extinction and modifying existing organisms, but he also noted the advantages such practices could have on adapting to climate change. While he recognizes such radical genetic engineering is controversial, he says he consults regularly with all factions in debate over genetically modified organisms. So far, his ideas have generated little open hostility.
“Climate change doesn’t mean we shouldn’t bring things back, it means that we should be getting thoughtful about how we make genetic changes that adapt to the environment, and we’re already doing that,” Church said, pointing to the development of heat-, drought-, flood-, salt- and pest-resistant crops.