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. 鈥淭he claim is so strong, so wild, so game-changing, that you really should send a sample to another lab, get them to check, 鈥榊ep, we see it too鈥�,鈥� says York, who works for a research organisation in the US but was speaking as a private individual. 鈥淚 believe the paper was under review for three years. It鈥檚 plenty of time to send samples to friendly labs.鈥�
The lead researcher, at Dongguk University in Seoul, says his team is working with several biotech companies and other research institutions. 鈥淲e expect these collaborative datasets to be disclosed in subsequent publications.鈥�
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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, and is also being trialled 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鈥檚 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鈥檚 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鈥檚 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 each cell once every 50 seconds or so.
Just how the electromagnetic signal affects cytochrome b5 and triggers the oscillation isn鈥檛 clear. 鈥淭he precise biophysical mechanism is still under investigation,鈥� says Kim.
This oscillation somehow triggers the 鈥渙n switch鈥�, 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 mice.
This would be a huge advance if confirmed, says York. 鈥淚t changes everything about how mammalian systems respond to electromagnetic fields.鈥� But to him, it makes no sense that a 60-Hz signal would drive an oscillation with a period of nearly a minute. 鈥淭he biological response is incredibly implausible,鈥� says York.
Kim says the oscillation period isn鈥檛 being driven by the signal frequency. 鈥淭he subsequent oscillations are governed by independent, internal signalling processes within the cell rather than the frequency of the external stimulus,鈥� he says.
The size of the calcium oscillation is also very large, says York. 鈥淭his is an incredibly physiologically significant response. It鈥檚 like if you said the temperature was changing by 10 degrees.鈥� 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. 鈥淭he magnitude of our observed signal is relatively modest and remains within a physiologically manageable range,鈥� he says.
In one experiment, the researchers linked their electromagnetic switch to a gene for a luminescent protein. 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 鈥渁 computational artefact caused by the curve-smoothing process鈥�.
On a website called PubPeer, a commenter named Yong鈥怌hang Zhou posted that, in figure S5P in the paper, . 鈥淭he mirroring is not something that normally happens when one takes multiple photos of the same sample,鈥� says , who specialises in uncovering scientific misconduct.
鈥淲e 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鈥檚 scientific conclusions,鈥� says Kim.
快猫短视频 asked the publisher of Cell for comment, but has yet to receive a response.
Cell
