Isotopic Resonance
How stable, heavy isotopes mediate growth.
Later this year, I will be undertaking a thesis project at Karolinska Institutet. I have been fortunate enough to get in contact with and lock in a project focused on Zubarev’s ‘Isotopic Resonance Hypothesis’ which is a fundamental approach to the biological significance of stable heavy isotopes. This hypothesis is vital not only for understanding the growth and regulation of biological systems, but also for understanding the origins of life. As it turns out, there are specific conditions at which life becomes more probable, where chemical reactions are favoured and complexity becomes an option.
I had stumbled on this opportunity by chance while I was looking for a meaningful project to be involved in. Given my relatively nichè interests, I was seeking a project that would not only be interesting to me, but one that would actually contribute to a deeper understanding of biology. By chance, Gàbor Somlyai had reached out to me about a new preprint of his, knowing how interested I would be. Gàbor’s work in deuterium (heavy hydrogen) depletion has fascinated me for many years now, so I asked him if he know anyone who might be interested in doing a nutrition-related project about deuterium. He immediately recommended his colleague Roman1, who is also at Karolisnka. Roman and colleagues were the first to demonstrate that deuterium depletion initiates oxidative stress, preferentially interfering with the function of malignant cells. A few days later, I met up with him in his lab to discuss a potential project, even though his lab does not take on master’s students.
Our discussion was riveting, with many incredible ideas being shared. We discussed his theory in detail, musing on the implications of it being proven. What has been most interesting to me is that there are well-documented biological effects of enrichment or depletion of stable, heavy carbon, nitrogen, oxygen and sulphur — not just hydrogen. While I had considered this in years passed, this was somewhat of an eye opener to me. Work on the biological effects of other stable, heavy isotopes has been going on for over 50 years. While I am yet to start working in the lab on our project, it has been fascinating reading into this concept of isotopic resonance and its potential to revolutionise our thinking around diet, environmental inputs and malignant growth.
Isotopic Resonance
The isotopic resonance hypothesis was born out of work done by Gao and Marcus which won them the Nobel Prize in 1992. Oxygen has 3 stable isotopic forms: 16O, 17O, and 18O. These can form ozone (O3) in any combination of these isotopic forms. However, they found that when synthesised in a lab or when formed in the atmosphere, ozone has a preference for monoisotopic forms. They showed that the formation of ozone as 16O16O16O, 17O17O17O or 18O18O18O was more likely than 16O16O18O or 16O17O18O or any other polyisotopic composition. This was explained as a reduction in quantum states, with the polyisotopic variants being less reactive than monoisotopic configurations, which were seen as “hotter”.2
“Statistically, 16O16O16O possesses, because of the symmetry of the symmetric ozone, one-half the number of quantum states that 17O16O16O and 18O16O16O do.”
This evolved under Roman and his team when they discovered what they call an “early life relict” in peptide mass distribution. When accounting for molecular weights, it is standard practice to use average molecular weight when considering both the weight and abundances of the stable, heavy isotopes. However, in biological and ecological cycles, averages are insufficient. Conventional thinking states that stable isotopes are distributed evenly throughout nature with no discriminating factors — ie. the isotopic composition of the human body reflects the isotopic composition of the diet 1:1.3 However, increasing and indisputable evidence continues to suggest that there are sophisticated methods of isotopic discrimination in both ecology and biology. In other words, we are not what we eat.