Tailor-made genes at bargain prices: A CRISPR tomorrow

Bacteria use CRISPR for defence; what will we do with it?

From the potato to the human, a new tool can manipulate genes to change organisms with a combination of accuracy, speed, flexibility and low cost that we've never seen before. It is so easy to use there's even a do-it-yourself kit. That's right - everyone can now tinker with genes. Imagine what the experts can do.

Should we be scared or excited? The new technique could lead to organ transplants from pigs, population-wide sterilization of malaria-carrying mosquitoes, the eradication of genetic disorders from an entire family line, a cure for HIV, and the great auk brought back from extinction after nearly 200 years.

Great auk, currently extinct

Image:John Gerrard Keulemans

That is the potential of CRISPR (“crisper”), a tool that is used in nature by bacteria to defend themselves against viruses. If a bacterium survives a viral attack, it can sometimes take a part of the viral DNA and store it with other captured sequences in a specially designated area of their own DNA. Once there, it will be inherited by offspring. Next time the virus attacks any of this line of bacteria, genes that flank the stored viral sequences will produce a “Cas” protein to swoop in and destroy. While some of these Cas proteins tear the invading DNA to shreds, Cas9 is far neater, making just one cut in a predictable place of the DNA. That makes CRISPR-Cas9 a great package for manipulating genes.

Genes are long sequences of DNA letters that instruct the cell to make certain proteins. A change of just a few letters, a mutation, can be enough to alter the protein production and change a characteristic. Mutations occur naturally all the time; they drive evolution. CRISPR-Cas9 is a way to introduce beneficial mutations artificially, because by choosing the stretch of DNA you include in the CRISPR, the system can be adapted to locate and cut an exact DNA sequence. The cell's own repair process will stitch the gene back together again with a DNA segment conveniently included with the CRISPR-Cas9 package.

Teosinte, maize-teosinte hybrid, maize,
by John Doebley, CC BY 3.0

This form of gene editing has myriad potential uses, and the benefits over other forms of genetic engineering go beyond costs and flexibility. One cause of public concern over genetically modified food comes from putting genes from one organism into a different species - genes from a soil bacteria to make corn that is toxic to pests, for example. That's not an issue with CRISPR. Because it tweaks existing genes, CRISPR is much closer to traditional breeding methods. Take corn as an example. Corn started out as a grass called teosinte. A few mutations led to maize, which has been selectively bred over thousands of years to give the many-kernelled juicy ears we know today. With CRISPR, the changes that are made deliberately could in theory eventually come about through a mutation. CRISPR takes out the close-to-zero chance factor and the long waiting game.

Animals, too, have traditionally been bred to be bigger or to grow faster, and indeed humans have pushed this beyond anything natural evolution might have created. Evolution tends to favour healthy animals, while today's chickens have been bred to grow so big so quickly they often develop leg deformities and heart failure. Many people are happy to eat these animals, so how about eating beef from a cow that, thanks to CRISPR, could be born without horns and hence spared the pain of dehorning? CRISPR could also create pigs with more human-like organs, bringing pig-human organ transplants a step closer. If it was your only option, would you say no?

Which leads to us. CRISPR could change our genes, too, but to cure a condition there's the problem of getting CRISPR into every affected cell. One entrepreneur recently injected himself with muscle-building CRISPR-Cas9 on video, but he admits one shot was unlikely to have been effective in changing his overall muscle mass.

8-cell human embryo, by ekem

CRISPR’s real power to the human genome lies in a much more controversial method: changing the genes of a future person and their even-more-future descendants by carrying out CRISPR on embryos. Such changes would be included in every cell of the future baby, and eventually handed down to their children. Clearly for a carrier of a life-limiting genetic condition, the chance to put an end to the family suffering not just in their own children but in their grandchildren too could be enthusiastically welcomed. However, the power to do good doesn’t come alone. The same technique could be used to create people with superior genetics: people who need less sleep or who have more muscles. And then there’s the middle ground, people with lower “bad” cholesterol or a family line with no risk of sickle cell disease but a lost protection against malaria.

In an ethical quagmire, where should the line be drawn, who is qualified to draw it, and, once drawn, how long before it shifts? It is only a few years since people first used CRISPR-Cas9 to change genes. The advances to health, agriculture and raw science will undoubtedly continue to build over the next few years, and so will the questions.

(CRISPR = Clustered Regularly Interspaced Short Palindromic Repeats

Cas = CRISPR-associated genes/proteins)


Further reading:

A Crack in Creation: Gene editing and the unthinkable power to control evolution, by Jennifer A. Doudna and Samuel H. Sternberg, 2017

The Moral Imperative for Bioethics, Steven Pinker in The Boston Globe

CRISPR, the Disruptor, Nature