Repairing DNA and fixing radiation treatment

Photo by Braňo on Unsplash

Our marker for success as a species comes with evolution, with millions upon millions of generations creating a life form we can define as us. The difference between us and our ancestors of eons past is with our DNA, or more specifically, the four letters that make up DNA.

AGCT

Dancing nucleotides

These four dancing letters are our nucleotides, or our building blocks for every single piece of DNA. This DNA is then transcribed, creating mRNA, and that mRNA is then translated to create amino acids, which create proteins that make up every part of our lives. Sometimes, there’s a mistranslation between DNA and RNA, and a chain reaction is started. For our purposes, let’s say that a single A gets turned into a C. Seemingly harmless, to where only one amino acid gets affected. This amino acid, however, can change the way that the protein folds, meaning that it changes the effect of what that protein can do. This mistranslation, over the course of billions of years, creates differences in everything, to the point where we can distinguish between species. These mutations created humans. However, simple mistranslations aren’t the only kind of mutation that can happen.

Radiation

Source

Radiation is one of the most extreme forms of mutation. The most common form comes with the Sun and UV light, where UV radiation merges two nucleotides together. To fix it, a whole chunk of nucleotides that have the merged nucleotides together are replaced. Here’s a fantastic video by the people at Ted Ed about it. While UV light has a high frequency and a short wavelength, gamma radiation has a higher frequency and an even shorter wavelength, meaning that it does more damage to the DNA. DNA is completely severed. A double strand break occurs, where the double helix of DNA breaks at both ends, splitting the DNA into two. With that, cell death is likely, because there is no template to create anything from. Luckily, our body has two solutions for it, one being more favorable than the other. If similar DNA is present, enzymes interlace the DNA until both strands of DNA have a full double helix. This is known as homologous recombination. The other option is to re-fuse the DNA together, removing amino acids and genetic code in the process. Known as non-homologous end joining, this is only used in the case where there is no similar DNA present. This is the worst case scenario for DNA double breaks.

Traditional Cancer treatment with Radiation

Photo by National Cancer Institute on Unsplash

Radiation is one of the primary tools for cancer treatment, but it in many cases is the nuclear option. Surgery is used when possible tumors can be removed safely, stopping the cancer all together. If the surgery fails or if the tumor grows in size, chemotherapy is the next option. The target for chemotherapy is always fast growing cells, which cancer falls under. However, chemotherapy doesn’t distinguish between fast growing healthy cells and cancerous cells, meaning that the body takes a massive toll to remove the cancer. This is why hair can start thinning, as hair cells are some of the fastest growing cells. External radiation treatment utilizes a targeting mechanism of gamma waves, which can shrink the tumors over time, but healthy cells often come into contact, where cell death can happen from double strand breaks. There is no perfect solution to cancer, where only cancer can be killed without harming the rest of the body.

Fixing radiation therapy

The Basics of Radiopharmaceuticals

The major problem with radiation therapy is with radiation harming healthy cells around it. For targeted radiation, skin cells, hair cells, and even the immune system could be damaged in the quest to destroy the cancer. To fix this, radiopharmaceuticals were developed. There are three main parts to radiopharmaceuticals: The radioisotope, the vector, and the target molecule. The radioisotope is the ‘killer’, as it is the mechanism that kills the cancer cells. The actual amount of radiation has to be small, in order to not have side effects similar to external radiation therapy. The vector is attached to the radioisotope, to which it can attach to the target molecule, in this case the cancer molecule. Shape determines function. A square peg doesn’t fit into a round hole, and with that same principle only a certain protein can match the receptor given by a cancer cell. We can kill cancer by using the cancer’s natural mechanisms for reacting with the world.

Improving Radiopharmaceuticals

The biggest problem with radiopharmaceuticals is the radiation itself. Once the radiation kills off the cancer, the radioisotope still remains in the body until the half life hits, and the radioisotope is, hopefully, removed from the body naturally, bringing radiation to wherever it goes. The side effects of radiation can still hit. For this, we can increase our protection against radiation, otherwise known as radioprotection.

Enhancing the Gut Microbe System

Photo by CDC on Unsplash

The gut microbe system is full of germs, but good germs. These germs protect us in the greatest way possible, and that’s to keep us healthy. They remove toxins and harmful bacteria, and have a strong relationship with our own mental wellbeing. So, how can we make this better, more specifically in helping remove radiation? There are two main bacteria that are in our microbe system that protect us from radiation: There are two main bacteria types in our gut that specialize in radiation protection: Lachnospiraceae and Enterococcaceae. Lachnospiraceae, among other things, has the responsibility of synthesizing short chain fatty acids. These fatty acids are key to the regulation of the system as a whole, but even more so in radioprotection. In mice, those with high production had a 100% rate of radioprotection, while those with a low production rate had around a 50% of protection. With the enhancing of SCFA production, we can protect against radiation in a better manner. A possible gene to target here would be 16S rRNA, although more research must be done to ensure the optimal production of SCFAs. If the 16SrRNA gene is overexpressed, then there is a possibility in an enhancing of radioprotection. For an increase in SCFAs, supplements of probiotics and foods that have a high fiber content, polyphenols, and fermented items can be administered.

Reverse Engineering the goal of improving Radioprotection in the Gut Microbiome

Learning from Extremophiles

There is a possibility for another case of gene editing to be used here. For this, we have to look to an even older bacteria in an extremophile, or an organism that can survive in environments hostile to most others. This particular extremophile is Deinococcus Radiodurans, and it’s claim to fame is it’s protection against radiation. The lethal dose to kill it is around 1500x higher than humans. There are many possible theories around how the bacteria is so effective against radiation, including it being alien life. The primary theory for it’s radiation protection is it’s protection against drying out, allowing it to survive in any conceivable scenario, even in outer space. The fewer proteins that dry out, the better the protection against radiation will be. This drying out is called desiccation. Compared to other bacteria, D. Radiodurans has a similar method of repairing double strand breaks. There are four main genes involved: DR1372, DRB0118, DR0105, and DR1172. These four genes all fight desiccation, meaning that they are the primary defense against radiation. These four genes protected D. Radiodurans against radiation, and if we can express them in our body in whatever way we can possibly do the same. An expression of these genes in our bacteria (or even in some of our cells!) can prevent radiation damage.

A possible method to test these genes

Credit: AACR

Granted, gene editing is one of the most controversial and possibly dangerous things to do against the environment around them. This has to be tested in a multitude of environments before this treatment can reach humans. However, if it does reach humans, it could function in a similar way to how CAR T-Cell therapy works. Here’s a step by step:

  1. Remove some of the gut bacteria already in the patient
  2. Insert the selected gene out of the four listed above
  3. Grow bacteria in silica
  4. Feed through mixing the bacteria in a food naturally containing healthy bacteria

Possible Drawbacks:

Any gene editing is dangerous and possibly life threatening. Safety has to be the first priority, and understanding how the environment in the body can be benefitted the most is key. The bacteria could stop functioning, the body could reject the bacteria, or the bacteria can mutate into something worse than the cancer to the body. There are a million things that could go wrong.

The future:

With that said, this could possibly revolutionize the environment around radiation treatment and radiopharmaceuticals. We can make life better and healthier for those undergoing radiation treatment, and save lives in the process.

Hi! I’m Aniket, and I’m interested in making the world better through biology. If you want to contact me about anything, here’s my Linkedin and Twitter.

I’m Aniket, and I’m interested in how we can make humans fundamentally better through better disease prevention and innovation.