Controlling our genes via a magnetic field would be transformative
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It is a major breakthrough if it really works: researchers in South Korea say they have developed a magnetically controlled switch for turning on genes inside cells, which could lead to transformative medical treatments. But others say the results, which were published in a major journal, are implausible and there are issues with the paper, such as an image that is merely a flipped version of another.
The key question now is whether independent groups are able to replicate the result. One of the critics, physicist Andrew York, thinks this should have been tried before the paper was published. “The claim is so strong, so wild, so game-changing, that you really should send a sample to another lab, get them to check, ‘Yep, we see it too’,” says York, who works for a research organisation in the US but was speaking as a private individual. “I believe the paper was under review for three years. It’s plenty of time to send samples to friendly labs.”
The lead researcher, Jongpil Kim at Dongguk University in Seoul, says his team is working with several biotech companies and other research institutions. “We expect these collaborative datasets to be disclosed in subsequent publications.”
There are already ways of controlling various biological processes with light, using a technique called optogenetics, which is based on proteins that respond to light. Once cells are genetically engineered to produce these kinds of protein, light can be used to, say, make nerve cells fire. Optogenetics is widely used in research, for instance, as a treatment for certain types of blindness.
The huge drawback with optogenetics is that light cannot penetrate far into the body. So, various teams around the world are trying to find ways of controlling biological processes with signals that can, such as a magnetic field. This would have many applications in medicine, as well as research. For example, it would make it possible to engineer cells in the body to produce a therapeutic protein and then control when, where and how much of it is produced using magnetic signals.
In a paper that appeared in the prestigious journal Cell, Kim’s team claims to have made so-called magnetogenetics real, by developing a switch that can turn on genes in genetically engineered cells when triggered by a specific magnetic signal that can reach any part of the human body. What’s more, Kim says this signal had no detectable effects of any kind on the mice it was tested on unless the switch was genetically engineered into them, suggesting it should be safe for medical use.
Specifically, Kim’s team applied to cells a 4-kilohertz electromagnetic square wave with a strength of 2 millitesla that was turned on and off 60 times a second, that is, at 60 hertz. By interacting with a protein called cytochrome b5, the paper says, this signal induced an oscillation of calcium ions with a period of just under a minute. In other words, calcium ions were sloshing back and forth across the cell once every 50 seconds or so.
Just how the electromagnetic signal affects cytochrome b5 and triggers the oscillation isn’t clear. “The precise biophysical mechanism is still under investigation,” says Kim.
This oscillation somehow triggers the “on switch”, or promoter sequence, for a gene called LGR4, the team says. Promoter sequences turn on any genes they are inserted in front of, so if this promoter sequence is put in front of other genes, they can be turned on by magnetism, too, meaning it acts as a magnetically-activated gene switch. The paper describes this switch working in mice and human cells of various types, and in entire mice.
This would be a huge advance if confirmed, says York. “It changes everything about how mammalian systems respond to electromagnetic fields.” But to him, it makes no sense that a 60-Hz signal would drive an oscillation with a period of nearly a minute. “The biological response is incredibly implausible,” says York.
Kim says the oscillation period isn’t being driven by the signal frequency. “The subsequent oscillations are governed by independent, internal signalling processes within the cell rather than the frequency of the external stimulus,” he says.
The size of the calcium oscillation is also very large, says York. “This is an incredibly physiologically significant response. It’s like if you said the temperature was changing by 10 degrees.” That should affect a huge range of biological processes in cells, says York, yet the paper claims it turns on just one gene with no other observable effects.
Kim rejects this. “The magnitude of our observed signal is relatively modest and remains within a physiologically manageable range,” he says.
In one experiment, the researchers linked their electromagnetic switch to a gene for a luminescent protein. Adam Cohen at Harvard University noticed that figure S1J in the paper seems to show the modified cells starting to luminesce many hours before the switch was even activated. But Kim says this is “a computational artifact caused by the curve-smoothing process”.
On a website called PubPeer, a commenter named Yong‐Chang Zhou posted that, in figure S5P in the paper, one image appears to be a flipped version of another. “The mirroring is not something that normally happens when one takes multiple photos of the same sample,” says Elisabeth Bik, who specialises in uncovering scientific misconduct.
“We have identified a clerical error in figure S5P where a control image was duplicated during the data [quality control] process. We are currently undergoing a formal correction in Cell to replace it with the correct raw data. This oversight does not affect the study’s scientific conclusions,” says Kim.
New Scientist asked the publisher of Cell for comment, but has yet to receive a response.
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