This bizarre DNA event recording system can track cellular activity from birth to death

• This study proposes the creation of a synthetic DNA region in an organism’s DNA.
• The new DNA region would record cell activity throughout the life of an organism.
• The DNA event recorder could reveal secrets such as the origin of cancer in humans.

Life begins with a cell, but can you see how a single cell gives rise to a whole organism and then leads to other complex biological processes in its body over the course of time? There is no way one can watch such changes as they happen, but now a team of international researchers has suggested a method that involves recording these changes. They have proposed an interesting cell-embedded camera system made up of proteins, DNA, and RNA molecules to record cellular activity in mammals.

Currently, if a scientist wants to study the cellular changes occurring in an animal’s body at a particular stage of its life, then he or she has to kill the animal and destruct the cell to observe the changes. The current approaches have various limitations, for instance, if you dissect an adult bat and then you are able to examine the cellular changes that are visible at that moment. You won’t be able to observe how the cells changed their statuses and communicated in the complex biological system over time, to reach that particular stage.

To study the previous stages, you’d have to kill another frog. But what if you could record every cellular change happening inside the frog’s body throughout his life? The researchers claim that by establishing a high-content DNA memory system in a cell, they can record cellular activity and store the same using a process called DNA event recording.

What is DNA event recording and how does it work?

Using advanced CRISPR-mediated DNA editing and genome engineering techniques, scientists can introduce a synthetic DNA region in an animal’s DNA. This region contains “genetically encoded DNA barcode arrays” called DNA tapes that record cellular changes in the form of mutations. Later, these recordings can be recovered via DNA sequencing.

DNA tapes are just one component of the DNA event recording system. It also comprises a molecular machine (a molecular video camera) to sense what is going on inside and outside the cell, a writer system to transmit such information to the synthetic DNA tape by repurposing genome editing technologies, and a reader that reconstructs biological history (from the recorded mutations) using DNA sequencing and high-performance computing.

According to the researchers, this entire DNA event recording system targets the synthetic DNA regions and therefore, it does not affect the original DNA or the native biological system. Plus, it is also likely to solve the major problem related to studying cellular activity i.e. killing animals of the same species again and again to study the changes occurring at different stages of life. The cell-embedded recording would require us to sacrifice an animal only once at the endpoint to see previous event history information.

When asked about other applications of DNA event recording, one of the authors of the study and Director of research at the University of British Columbia’s School of Biomedical Engineering (SBME), Nozomu Yachie told IE, “We still do not know how a single cell creates our complex mammalian body structures, deciphering this is simply exciting. Also, such information will be a new backbone resource of biology like Google map where we can map and integrate diverse biological knowledge."

He further added, “the same idea can be applied to study cancer progression and metastasis too and will derive hints to regulate various cancer diseases.”

Can we implant DNA event recorders in humans?

DNA event recording could increase our understanding of human biology and help us solve many mysteries related to cancer and other diseases. However, Professor Yachie believes this idea will never be applied in studying human development from a fertilized egg because of the ethical considerations of genetically manipulating human embryos. This is also one of the major limitations of their research.

Although that does not mean this method can not be employed to study human cells. The researchers suggest that by combining DNA event recording with techniques like in-vitro organ culture, scientists could extract a great deal of information on human development. However, before conducting such experiments, more research is required to further develop the different technologies (DNA tapes, molecular sensors, etc.) involved in the recording system.

“Somebody needs to establish this approach. I also believe this is currently only the possible approach we can use to observe the long-term history of an animal/organ subject since we do not have a time machine,” said Professor Yachie.

The study is published in the journal Science.