Cells Act Like Tape Recorders To Monitor Health

One of the newest discoveries of molecular biology is the existence of retrons, sequences of "junk" DNA that serve to record the experiences of a cell. Researcher Timothy Lu at the Massachusetts Institute of Technology believes that these DNA fragments, known to exist in E. coli bacteria, may also exist in humans and hold the potential to explain health and disease in an exciting new way.

Retrons Record Cellular History

Dr. Lu and his MIT colleague Dr. Fahim Farzadfard discovered that retrons encode the instructions for making still more DNA when the cell is exposed to certain events, such as ultraviolet light or a toxic chemical. If the cell survives the event, these new strands of DNA are incorporated into the genome. Lu and Farzadfard still haven't explained precisely how the cell acts differently after its DNA is changed, but they recognize that these strands of DNA create a kind of diary inside the cell. By locating the new DNA sequences, scientists can tell what the cell has been through.

How can this provide useful information? In terms of looking at a single cell, there isn't a lot to be learned. But in terms of looking at groups of cells, retrons begin to tell a story. Not every cell is exposed to the same stimulus. If an ultraviolet light shines into the Petri dish where millions of E. coli cells live, for example, some will get a stronger dose than others. Their retrons will change first. If the light continues to shine, more and more E. coli will have changes in their retrons that record the event. Analyzing the number of changes in groups of cells will tell the scientist how long the light has shone or how bright it is.

Of course, we don't really care a lot about the health of E. coli cells growing in a Petri dish. But we do care, say, about the health of tissues composed of cells that make up our own skin.

The next time the beach goer spends the day in the sun without sunscreen, more skin cells will change their DNA. Looking at the DNA of one skin cell wouldn't tell the dermatologist a lot about the beach goer's history of sun exposure, but looking at the DNA at a thousand skin cells (out of tens of billions that make up the skin) might tell the doctor a lot.

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Analog, Not Digital

When retrons are analyzed in groups of cells, they begin to offer much more useful information. One cell's retron tells whether the cell has been exposed to an event or not. A larger group of cells retrons, studied together, may reveal not just whether a damaging event has occurred, but how long, and how much. Dr. Cameron Myhrvold at Harvard University's Wyss Institute for Biologically Inspired Engineering likens this effect to an old-style tape recorder. A digital recording captures a sound or doesn't, but a tape recorder captures the strength or weakness of the sound reaching it.

Retrons Could Revolutionize Medical Research

The discovery of how retrons work could lead to enormous strides in medical diagnosis. Biologists already know that retrons are active in animal cells, and presumably in human cells. Lu and his coworkers believe that the human body could be seeded with specially engineered cells that could later be recovered for analysis, much as wildlife researchers set up cameras to record the movement of animals in the wild.

A Monitor For Cancer

How would this work? Dr. Lu believes that the best use of these monitor cells would be to record the signals cells send each during disease processes. For instance, cell signaling and failures in cell signaling are important parts of the development of cancer.

They send out signals to cells to build blood vessels that provide them with additional oxygen and nutrients. They can help each other become "immortal," ignoring inflammation that causes healthy cells to stop multiplying, become quiet, and not replace themselves before they die.

A seed of genetically engineered monitor cells could be placed near a tumor. The retrons in these cells would record whether nearby cells send out signals to the tumor to stop it, and how strong the signal was. They would record the signals that cause the formation of new blood vessels during the process of angiogenesis, and how strong they were, and likewise they would record the effects of inflammation. These Removable cells would tell not only whether there was a presence of absence of cancer-causing or cancer-stopping factors, but how strong or weak they were, when they occurred, and when they were weakened or amplified.

An Explanation For Brain Function Or IBS

Likewise, retrons could be used to explain how neural networks form in the brain. They could record the changes in growth factors and neurotransmitters that accompany the formation of memories. (Most likely this research would be conducted in the laboratory with samples of human brain tissue, since it is highly unlikely that there is an ethical, approved approach for inserting packets of cells into the living brains of people who volunteer for research studies). Or retrons could be used to document the currently elusive changes that cause episodes of irritable bowel syndrome, also known as IBS.

Many technical challenges, of course, have to be resolved before retrons are a useful tool of medical research.

Dealing with the fact that cells mutate is another. It's possible that the genes that control the activity of retrons could change during the process of observation. And analysis of changes in retrons is not likely to be useful in studying processes that involve relatively small numbers of cells. Irritable bowel syndrome, for example, involves billions of cells in the lining of the gut. Changes in retrons would be easy to trace. The formation of a memory may involve a small number of neurons, and a small number of retrons may not capture the "intensity" of the cellular signals involved in the process.

See Also: How Skin Changes Warn Us About Health Problems

Scientists believe, however, that these problems can be solved, and retron analysis will provide useful information on not just the presence of certain cellular processes, but the importance of their intensity. Many of the technical problems with using the technique are already being resolved.