Gene editing wiped out a population of mosquitoes in lab tests | Science News for Students

Gene editing wiped out a population of mosquitoes in lab tests

Success with the genetic engineering tool raises hopes of eliminating this carrier of malaria
Oct 26, 2018 — 9:28 am EST
A photo of an Anopheles gambiae mosquito on human skin

The malaria-carrying mosquito Anopheles gambiae’s days may be numbered. Scientists have devised a gene drive that wiped out the mosquito’s populations in lab tests.

 JAMES D. GATHANY/CDC

Gene editing may push a species of malaria-carrying mosquito to extinction.

These new results come from a small-scale laboratory study. Researchers used a genetic engineering tool to make changes to species called Anopheles gambiae (Ah-NOF-eh-lees GAM-bee-aye). As a result, the mosquitoes stopped producing offspring in eight to 12 generations. The researchers reported this September 24 in Nature Biotechnology. If the finding holds up in larger studies, this tool could be the first capable of wiping out a disease-carrying mosquito species.

“This is a great day,” says James Bull. He’s an evolutionary biologist at the University of Texas at Austin. He was not involved in the study. “Here we are with a technology that could radically change public health for the whole world.” That’s because A. gambiae is the main mosquito spreading malaria in Africa. The disease kills more than 400,000 people each year worldwide, according to the World Health Organization. Many of those who die are children.

The researchers changed the mosquitoes’ genes with a gene drive. Gene drives use the molecular “scissors” known as CRISPR/Cas9 to copy and paste themselves into an organism’s DNA at precise locations. They’re designed to break the rules of inheritance. They can quickly spread a genetic tweak to all offspring.

The new gene drive breaks a mosquito gene called doublesex. Female mosquitoes that inherit two copies of the broken gene develop like males. They are unable to bite or lay eggs. Being unable to bite means they can’t spread the malaria parasite. Males and females that inherit only one copy of the disrupted gene develop normally and are fertile. Males don’t bite, whether they have the gene drive or not.

a composite image showing how female anatomy changed when the doublesex gene was disrupted
Female Anopheles gambiae mosquitoes' development was altered by a gene drive that disrupts the doublesex gene. Females that inherited two copies of the gene drive (bottom right) developed antenna (red arrow) and claspers (blue arrow and enlarged images) similar to males. The females’ mouthparts also changed. That prevented them from biting to get a blood meal. These alterations made the females unable to lay eggs.
K. Kyrou et al/Nature Biotechnology 2018

Changing genes

In each of two cages, researchers placed 300 female and 150 male normal A. gambiae mosquitoes. Then they added 150 males carrying the gene drive. In each generation, 95 percent to more than 99 percent of offspring inherited the gene drive. Normally, only 50 percent of offspring inherit a gene.

Within seven generations, all of the mosquitoes in one cage carried the gene drive. No eggs were produced in the next generation. The population died out. In the other cage, it took 11 generations for the gene drive to spread to all of the mosquitoes and crash the population. The insects in that cage made no offspring in generation 12.

Other gene-drive studies have done computer simulations to predict how long it would take for the drives to spread through a population. This is the first time the approach has succeeded in actual mosquitoes.

two graphs showing how the mosquito population reacted to the inherited gene drive
As more mosquitoes within two caged populations (red and blue lines) inherited a gene drive, the numbers of mosquitoes nosedived. They finally produced no offspring after eight and 12 generations. The trend observed in the lab aligned with computer-simulated predictions (grey and black lines).
K. Kyrou et al/Nature Biotechnology 2018

Other types of gene drives also have been passed to offspring at high rates. But in those experiments, DNA changes, or mutations, that destroy the cutting site for CRISPR/Cas9 popped up. That allowed the mosquitoes that carry the mutation to resist the drive.

A few mosquitoes in the new study also developed mutations. However, “no resistance was observed,” says study coauthor Andrea Crisanti. He’s a medical geneticist in England at Imperial College London. Those mutations broke the doublesex gene. Females with these broken genes were sterile and couldn’t pass the mutations on to the next generation.

All insects have some version of doublesex. “We believe that this gene may represent [a vulnerability] for developing new pest-control measures,” Crisanti says.

A. gambiae likes to bite people. That makes it good at spreading malaria from person to person. The gene drive now raises the prospect of deliberately causing the extinction of this species.

“If you have a technology that could eradicate that [mosquito], it would be unethical not to use it,” says Omar Akbari. He is a geneticist at the University of California, San Diego. He was not involved in the work. But Akbari thinks it is unlikely that the gene drive would work as well in the wild as it did in the lab. That’s because resistance is bound to pop up at some point.

No one knows what will happen to the environment if all the mosquitoes die, either. There could be problems for species that eat mosquitoes, for instance. Also unknown is whether the gene drive could be passed on to other species. What if a “James Bond–style villain” used a similar gene drive to attack honeybees or other beneficial insects, says Philipp Messer. He is a population geneticist at Cornell University in Ithaca, N.Y. “Humans will always come up with ways to abuse [technology]. And in this case, it’s just so easy. That’s what worries me.”

Power Words

(for more about Power Words, click here)

biology     The study of living things. The scientists who study them are known as biologists.

Cas9     An enzyme that geneticists are now using to help edit genes. It can cut through DNA, allowing it to fix broken genes, splice in new ones or disable certain genes. Cas9 is shepherded to the place it is supposed to make cuts by CRISPRs, a type of genetic guides. The Cas9 enzyme came from bacteria. When viruses invade a bacterium, this enzyme can chop up the germs DNA, making it harmless.

coauthor     One of a group (two or more people) who together had prepared a written work, such as a book, report or research paper. Not all coauthors may have contributed equally.

CRISPR     An abbreviation — pronounced crisper — for the term “clustered regularly interspaced short palindromic repeats.” These are pieces of RNA, an information-carrying molecule. They are copied from the genetic material of viruses that infect bacteria. When a bacterium encounters a virus that it was previously exposed to, it produces an RNA copy of the CRISPR that contains that virus’ genetic information. The RNA then guides an enzyme, called Cas9, to cut up the virus and make it harmless. Scientists are now building their own versions of CRISPR RNAs. These lab-made RNAs guide the enzyme to cut specific genes in other organisms. Scientists use them, like a genetic scissors, to edit — or alter — specific genes so that they can then study how the gene works, repair damage to broken genes, insert new genes or disable harmful ones.

develop     To emerge or come into being, either naturally or through human intervention, such as by manufacturing. (in biology) To grow as an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape.

disrupt     (n. disruption) To break apart something; interrupt the normal operation of something; or to throw the normal organization (or order) of something into disorder.

DNA     (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

ecology      A branch of biology that deals with the relations of organisms to one another and to their physical surroundings. A scientist who works in this field is called an ecologist.

egg     The unfertilized reproductive cell made by females.

engineering     The field of research that uses math and science to solve practical problems.

eradicate     To deliberately eliminate or wipe out, such as a population of vermin (rats or cockroaches, for instance) inhabiting a particular site.

evolutionary     An adjective that refers to changes that occur within a species over time as it adapts to its environment. Such evolutionary changes usually reflect genetic variation and natural selection, which leave a new type of organism better suited for its environment than its ancestors. The newer type is not necessarily more “advanced,” just better adapted to the conditions in which it developed.

evolutionary biologist     Someone who studies the adaptive processes that have led to the diversity of life on Earth. These scientists can study many different subjects, including the microbiology and genetics of living organisms, how species change to adapt, and the fossil record (to assess how various ancient species are related to each other and to modern-day relatives).

extinction     The permanent loss of a species, family or larger group of organisms.

fertile     Old enough and able to reproduce.

gene     (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

gene drive     A technique for introducing new bits of DNA into genes to change their function. Unlike other such genetic engineering techniques, gene drives are self-propagating. That means they make more of themselves, becoming part of every unaltered target gene they encounter. As a result, they get passed on to more than 50 percent of an altered animal’s offspring, “driving” themselves quickly into populations.

gene editing     The deliberate introduction of changes to genes by researchers.

generation     A group of individuals (in any species) born at about the same time or that are regarded as a single group. Your parents belong to one generation of your family, for example, and your grandparents to another. Similarly, you and everyone within a few years of your age across the planet are referred to as belonging to a particular generation of humans. The term also is sometimes extended to year classes of other animals or to types of inanimate objects (such as electronics or automobiles).

genetic engineering     The direct manipulation of an organism’s genome. In this process, genes can be removed, disabled so that they no longer function, or added after being taken from other organisms. Genetic engineering can be used to create organisms that produce medicines, or crops that grow better under challenging conditions such as dry weather, hot temperatures or salty soils.

insect     A type of arthropod that as an adult will have six segmented legs and three body parts: a head, thorax and abdomen. There are hundreds of thousands of insects, which include bees, beetles, flies and moths.

malaria     A disease caused by a parasite that invades the red blood cells. The parasite is transmitted by mosquitoes, largely in tropical and subtropical regions.

mutation     (v. mutate) Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.

organism     Any living thing, from elephants and plants to bacteria and other types of single-celled life.

parasite     An organism that gets benefits from another species, called a host, but doesn’t provide that host any benefits. Classic examples of parasites include ticks, fleas and tapeworms.

population     (in biology) A group of individuals from the same species that lives in the same area.

resistance     (as in drug resistance) The reduction in the effectiveness of a drug to cure a disease, usually a microbial infection. (as in disease resistance) The ability of an organism to fight off disease.

simulation     (v. simulate) An analysis, often made using a computer, of some conditions, functions or appearance of a physical system. A computer program would do this by using mathematical operations that can describe the system and how it might change over time or in response to different anticipated situations.

species     A group of similar organisms capable of producing offspring that can survive and reproduce.

sterile     An adjective that means devoid of life — or at least of germs. (in biology) An organism that is physically unable to reproduce.

technology     The application of scientific knowledge for practical purposes, especially in industry — or the devices, processes and systems that result from those efforts.

World Health Organization     An agency of the United Nations, established in 1948, to promote health and to control communicable diseases. It is based in Geneva, Switzerland. The United Nations relies on the WHO for providing international leadership on global health matters. This organization also helps shape the research agenda for health issues and sets standards for pollutants and other things that could pose a risk to health. WHO also regularly reviews data to set policies for maintaining health and a healthy environment.

Citation

Journal:​ ​​K. Kyrou et al. A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nature Biotechnology. Published online September 24, 2018. doi: 10.1038/nbt.4245.