New technology is sometimes created by pushing the boundaries of what science can do.
Sometimes, however, it takes the form of something very ancient.
One group of scientists combined the two approaches in their search for improved ways to peek inside living cells.
They genetically altered something very old—gas-propelled bacteria, one of the earliest mobile life forms on Earth—to respond to sound waves.
When you use ultrasound to ping these modified cells, they respond, like a miniature version of the singing Bluetooth trackers that help you find concealed gadgets.
These locators could one day be used to monitor neurons and detect disorders in their early stages.
“It’s seeking in nature for something that is made, that nature may have evolved for completely other purposes, but you can use it for your purpose as an engineer,” says Mikhail Shapiro, a chemical engineer at Caltech and one of the researchers behind this effort.
Last month, Shapiro and his colleagues published their newest findings in Nature Methods.
The present is influenced by a gassy past.
Tiny aquatic bacteria evolved a technique to move up and down independently billions of years ago in the Earth’s old seas: propelling themselves up with air-filled nanoscale protein tubes.
These tubes are now known as gas vesicles by scientists.
Consider yourself a bacterium. If you spawn some gas vesicles, you’ll become more buoyant, allowing you to float closer to the surface and absorb more sunlight for photosynthesizing into life-giving energy.
Simply pop a few gas vesicles like balloons when you’re ready to return to the depths, and you’ll drop back down.
Gas vesicles are still used by aquatic bacteria today.
For more than a century, a few specialized biologists have been aware of them.
But it wasn’t until the last decade that Shapiro and his colleagues realized they might use this completely normal evolutionary quirk—specifically, the DNA that causes it—for their purposes.
Gas vesicles are particularly fascinating because they respond to sound waves—particularly ultrasound, which is too high-pitched for human ears to hear—by emitting a signal.
The gene that allows microorganisms to produce gas vesicles is referred to be a reporter gene because of its ability.
Scientists can “program” another cell with a feature that allows them to readily locate and peek into it by adding a reporter gene into its DNA.
When a cell becomes active, the reporter gene becomes active as well.
“You can now detect changes in cellular activity very early on,” says Donna Goldhawk, an imaging scientist at Lawson Health Research Institute in London, Ontario, who studies reporter genes but was not involved in Shapiro’s study.
Ultrasound has several advantages.
For example, the technique could detect diseases in humans early on, before they cause tissue damage.
Without the unpleasant side effects of ionizing radiation that X-rays can cause, the detection could also be safer.
The reporter cells might also be followed for months.
“Anytime you give a genetic alteration to a cell, you introduce the potential to monitor that one cell type throughout its natural lifespan,” Goldhawk explains.
There are several different types of reporter genes.
Goldhawk’s team uses a reporter gene to create magnetic iron-containing proteins that glow in an MRI.
Green fluorescent protein (GFP) is a protein that comes from jellyfish and is produced by another common reporter gene.
If you insert its DNA into a cell to make GFP, the cell will do exactly what it says: It will glow green when exposed to the correct kind of light.
However, there are a few advantages to using sound over light, according to Shapiro.
For one thing, whereas GFP can only detect a millimeter below the surface, ultrasonic can look far beyond.
This means that instead of cutting into organisms or organs, ultrasound can be used to examine them.
“Ultrasound is one of the only ways to look at things deep inside tissues,” adds Shapiro.
Ultrasound, on the other hand, is a little more common outside of laboratories, but fluorescent cell technology isn’t.
According to Shapiro, “it is the most commonly utilized biomedical imaging in the world.”
“Ultrasound machines can be found in almost every doctor’s office.”
Depending on your age, your very first picture could have been an ultrasound scan of you in the womb.
The future of reporter genes that pop
Shapiro’s team has been fine-tuning and inserting the DNA for gas vesicles into cells for several years.
They’ve now been able to significantly boost the signal emitted by their reporter genes.
They did this by generating gas vesicles that noisily pop when pinged with ultrasound, just like those in microorganisms about to dive.
That’s what they wrote about in their most recent Nature Methods piece.
According to Goldhawk, Shapiro’s group was the first to create sound-based reporter genes.
“This is unquestionably cutting-edge technology.”
Shapiro envisions a future in which every biology lab has an ultrasound machine, which he uses to examine mice raised with reporter gene-inclusive cells.
But there’s a long way to go before that.
Although ultrasound machines are widely available, Shapiro believes that employing them for this purpose will necessitate improved imaging technology in addition to better proteins.
“At this point, I believe we are at the very beginning of this field’s evolution,” he says.
However, scientists are already considering cell applications that take advantage of reporter genes’ tremendous abilities, such as manipulating cells rather than merely looking at them.
In addition to employing genetically altered cells to diagnose, Goldhawk believes that cells with reporter genes could one day be used to fight illnesses without resorting to antibiotics and risking antibiotic resistance.
“What if we could cure diseases with bugs that recolonize whatever organ they infect and get rid of the infection by reducing the number of cells?” she wonders.