Deborah Dormady Letham, PhD

In Science and Medicine, Radiation is a Double-Edged Sword

Radiation is usually a concern for cancer, but it is also helping to treat it

My father is such a good patient, so when a new cancerous growth near his ear was found, he just “took it on the chin”, literally, since the treatment apparatus partially rests on his chin as it delivers powerful radiation to the affected area on his neck. His lesion is similar to one that was spotted in December 2018, and successfully treated. As I wrote about in my previous blog , this radiation therapy with follow up immunotherapy is the path forward for slow growing squamous cell carcinomas (and he is not eligible for chemotherapy with his known other health concerns). What is quite interesting is that they had a snowstorm last time too but were not deterred from treatments – they have MORE snow this time, 20 inches in fact, but are all dug out and ready to go for travelling locally for treatments. Even snow cannot stop the great healthcare folks and the crucial path forward for cancer patients.

Dad did actually stop his previous immunotherapy treatment follow-ups after the radiation treatment in 2019, not just because he was in remission after the first round, with a tremendous reduction in tumor size, but especially because my parents wanted to reduce outside travel due to the COVID-19 exposure concerns. Did the cancer come back or was this a new spot? It’s a new one, and there are now two spots, but only one is growing and so thankfully my mother spotted changes in it. Changes are a constant in life. Cancer, especially from the effects of the sun, is constantly nipping at our heals as we get older.

It sounds strange that we both appreciate and warn against radiation. But we are talking about a different uses of the word radiation! It was the UV radiation of the sunshine that likely led to cancer spots for my father (that and not enough shielding of a good hat!), and yet certain controlled radiation is also being used as a viable treatment option for cancer.

In early DNA sequencing, radioactivity was key

Dad’s radiation therapy got me thinking about my experience working with radioactive substances and a phrase any new scientist learned right away: Time, Distance, Shielding. It’s what we would repeat to demonstrate important safety tips around radioactivity experiments. The DNA sequencing experiments we perform now are fluorescent based, but in the early days of DNA sequencing radioactivity was key. Although the word “radioactive” would scare many people, it is also important to understand how useful a tool this was, and still is, for certain science experiments.

Radioactive isotopes won’t generate the next Spiderman™, but we do have to take super precautions, just as we would for any lab chemical that needs containment. I can remember from my graduate school days, using an isotope of sulfur in classic Sanger dideoxy nucleotide sequencing. Without fear but with appropriate precautions, I certainly used my share of isotopes over my 30 years in labs (so far). To me molecular biology is STILL new – but certainly the advances make my new so very old now. Back before we had “modern” kits for sequencing experiments to determine the pattern of individual A, C, G or T bases in sequence in a DNA sequence, we had separate ingredients and recipes to combine all the right ingredients like buffers and salts, a starting primer to bind the opposite strand of DNA and a polymerase enzyme to read the complementary strand and make a new strand with added four dNTP nucleotides (called deoxy-nucleotides).

In this mixture was included a small amount of a radioactive dNTP nucleotide to be incorporated into the growing strand. Then splitting the reaction into four reaction tubes, you add a di-deoxy (meaning missing an extra oxygen) nucleotide, halting the incorporation of the next base. All that from the completed reactions were separated on a giant gel electrophoresis unit - think the Plinko game from the Price is Right but made from Jell-O poured so thin in-between two panes of 3 foot by 1 foot window glass then dipped in salt buffers with 3,000 volts of electricity running through it. The electricity was MUCH MORE DANGEROUS than the radioactivity. In my postdoctoral laboratory, they posted warning signs in three different languages. Yes, SAFETY FIRST!

Planning out experiments and monitoring “Time, Distance, Shielding” minimized my risks. Time: you limit your time exposed by knowing what manipulations you are going to do, then go in and do them, thus minimizing your close contact. Distance: you keep a safe distance until you step closer to the material to do the work. Shielding: you block the radiation from traveling. Then there's physical shielding.

Sugar molecules and plant genetics

We developed our own methods for shielding us from harm while working with multiple radioactive materials. I stepped into classic plant physiology experiments while in my studies as an undergraduate and graduate student. Feeding cut stem sugar molecules that contained an isotope of carbon, 14C, you could trace sugar movement and storage in plants using X-ray film and now the modern version: PET scans, just like cancer patients get. To study the pH mechanisms in photosynthesis, the lab used tritium, a radioactive form of hydrogen, in "pulse chase experiments" – which was adding radioactive molecules, then cold non-radioactive molecules. Using Sulfur 35, the DNA sequencing experiments I performed in graduate school, we were able to decode a novel plant gene . For Phosphorus-32 and Phosphorus-33, gel Southern electrophoresis analysis detective work was useful for searching for sequence similarities. For those isotopes, we used clear plexiglass and tubes placed simply in water in a beaker, because it absorbs the radiation and shields the user. For Sulfur-35 or Carbon-14 or H-3 tritium, gloves on your hands were sufficient to shield exposure, and of course we always wore lab coats and goggles. Safety first.

When I used Zinc-65 as a postdoc, I had lead bricks in front of me. Come to think of it, my postdoctoral days were spent in the same USDA ARS laboratory building where Nobel Laureate Robert Holley discovered and described transfer RNA (tRNA), elucidating the mechanism of how nucleic acids are made into proteins. So many discoveries relied on the safe uses of radioactive materials. Thankfully, the regulations and safety considerations have now led scientists to suitable substitutions using non-radioactive methods for most of these types of experiments. In all, we wore our PPE and thought: “Time, Distance, Shielding.” Not everyone did in the very early days of radioactive work, not knowing it was a cancer risk.

The healthcare workers, including my dentist when taking X-rays, and these cancer-treatment professionals for my father, understand “TIME, DISTANCE, SHEILDING” and they step away behind a barrier for the short time of the “zap”. They are monitored with dosage badges as well that measure monthly exposure. My Dad will restart immunotherapy to slow further growth (immunotherapy is another medication made possible by using DNA sequencing tools in the development, and potential medications cross our computer screens in the DNA sequencing laboratories at CRL).

This is a good plan forward for my parents and us, even though it requires venturing out into the public (gratefully COVID-19 cases are dropping in the Northeast). The venturing outside to the hospital will always be weather permitting, of course. The weather is ALWAYS changing. Snow days (over 20 inches for them) are an automatic forced self-isolation of: “Time, Distance, Shielding.”