Hi, I’m Aastha, and welcome to Live Longer World, where I interview scientists researching the frontiers of longevity science and write about health & longevity practices.
Genes are king. Or are they?
I was recently at a longevity retreat where a professor gave a talk on creating artificial organs using stem cells. Stem cells are undifferentiated, which means they are not yet specialized for specific organs. One of the challenges in using stem cells for creating specific organs like the kidney is that we need to ensure the stem cells differentiate into kidney cells and not liver cells. The professor spoke of his approach to do so, which was to identify specific genes for kidney cells, ensure each of the kidney genes transcribe into the correct proteins, silence some of the other genes, and so on.
As someone without a formal degree in biology, my head was spinning. The approach involved twisting every single gene-protein interaction to get to the right combination. I couldn’t help but wonder: “What if we manage to get every single gene combination right and still not get the right organ?” Or even if we do get every single gene combination correct, what if there is a simpler way of controlling the shape of organs, as opposed to micromanaging every gene?
Other questions flooded my mind: “What if we need to be looking beyond genes? What if genes don’t hold all the keys to organ function and shape? Are we being too narrow-minded by not broadening our thinking beyond genes?”
I’m of course not the first one to be asking these questions. Several biologists have started to voice the fact that contrary to prior beliefs, genes do not hold the answers to many questions in biology, and we need to be looking beyond them.
After Watson and Crick’s discovery of the structure of the DNA, the gene-view has occupied center stage in the realm of biology. By gene-level view, I mean biology’s inclination to herald our genes as the most important code to decipher and solve major questions. From the human genome project to scientists trying to understand every gene-protein interaction, the first thought that crosses our minds when we encounter most biological problems are questions like, “What genes are responsible for it? What genes are impacted by it? What genes can we silence? Was there a mutation in the genes?”1
In fact, genes and DNA are held in such importance that the gene language has permeated life outside of biology too. It’s common parlance to speak of a “company’s DNA” or utter statements like “It’s in your genes” or “She must have a genetic gift for it.”
Looking beyond our genes
Earlier I gave the example of the professor trying to perfect every gene-protein combination in order to create the right organ. Micromanaging every gene-protein combination seems akin to what computer programming was like when it first started – it involved manipulating the system at the hardware level. Now, all programming is done at the software level. It’s possible that in biology we are still stuck at the hardware level of programming by controlling the knobs that are our genes.
Furthermore, controlling at the level of genes strikes me as a reductionist approach, which may not yield the answer even after twisting every gene knob. A reductionist approach such as this also does not account for the idea of emergence in biology. Emergence here means that the outcome of larger systems cannot be predicted by the lower-level causal explanations.
“We are good at manipulating molecules and cells. We are a long way from control of large scale form and function. Biomedicine is about digging into the molecular level hardware, so genomic editing, pathway rewiring, protein engineering, all of these things are about the hardware. And if you think about the trajectory that computer science took this is what programming looked like in the 1940s and 50s, to program you literally had to manipulate the system at the level of the hardware. But now its all software.”
-Dr. Michael Levin in this talk.
But what if biology has a software layer too, which lies outside the hardware of our genes? In that case, we’d have to take seriously the levels of biology that reside outside our genes.
For, what if the answers don’t lie merely with the genes? What if there is significant code to crack outside the level of genes? What if we should be asking questions outside of genes? And what if there are other elements that might in fact be more important than genes and control our genes? Dr. Alfonso Martinez Arias says that genes are not the blueprint of life.
Let’s take a specific example to show that genes don’t contain all the answers. There is no information in our DNA that tells us how the shape of organs should develop and where in our bodies they should develop. How then do most of us end up with the same set of eyes, nose, ears, organs, and other body parts, and in the same place in proportion to our bodies? Why don’t some of us grow eyes on our hands or ears on our legs? How do our bodies know where our eyes should be when the DNA contains no information about it? Surely, they must be receiving some other signal that lies outside of the DNA.
The human genome project was launched with one of the promises being that this will help us map the genes responsible for causing deadly diseases. But this promise was not fulfilled. Not necessarily due to a lack in mapping. But because genetic risk scores are not useful in predicting disease. Biologist Denis Noble says that “what this tells us is that genes are too low a level to see [biological] functionality. We need to get back to network analysis and what we were doing before the genomics revolution.”
I’m not trying to discount the importance of understanding the genetic code. I think it is incredibly important. However, perhaps we should be asking more questions outside of genes too. And this is exactly what a growing number of scientists are now beginning to do.
Bioelectricity
Bioelectricity is one such realm of biology that dares to look beyond the gene-level view. It’s a view of biology that asks questions about our bioelectric code, i.e. the electricity in our bodies and its significance.2
Pop-science articles tend to make us associate electricity in our bodies to the firing of neurons and electric currents in our brains. A select few of these articles might extend the electric signals in our bodies to muscle cells as well.
However, neurons and muscles are not unique in their potential to pass electric signals. Electric signals run through every cell in our body. Neurons and muscle cells exhibit rapid transmission of electric signals, whereas the transmission of these signals in other cells is typically at slower speeds.
Bioelectricity is about the study of electric signals in our cells and their significance. Research shows how bioelectricity could have enormous implications in anatomy (the shape our cells take), wound healing, embryonic development, regeneration, cancer and aging.
I was first introduced to bioelectricity when I interviewed Dr. Michael Levin for Live Longer World. Mike Levin is one of the pioneers of bioelectricity and his lab has done some incredible research showing how bioelectric signals shape morphology (the shape our cells take), regeneration of limbs, and could be a cure for cancer. Yet, in a biology world dominated by genes, bioelectricity remains an underrated and small, but fast-growing field.
Another reason bioelectricity remains underrated is because people don’t grasp the biophysics that underlies the electric signals in our body. It sounds fascinating and even woo-woo to some extent, but without a deeper understanding it is hard to appreciate the field. Contrast this with the decades of information we’ve been given on genes and DNA. They are central to every biology book, have been brought to the forefront by many popular biology books, and are part of everyday conversation. All of this makes it easier for people to relate to genes and have a better understanding of them.
For more people to appreciate the true beauty of bioelectricity, we need media and information that explains not just the significance of bioelectricity, but also how bioelectricity works. What does it mean for our cells to be electric?
In my next essay, I will introduce you to these wonders.
To living longer,
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Perhaps it’s not fair to see that biologists assume genes to be central to everything. They of course look at other factors. But it’s fair to say that genes have been the most dominant vantage point for a lot of biology research. Comparatively far fewer scientists question whether genes should be such a dominant paradigm and look at what some of the other paradigms are.
I’m not suggesting that bioelectricity is the only other area exploring territory outside of genes; there are others too. There is an increasing group of scientists beginning to look beyond the gene-level view of biology and bioelectricity is one of those realms.
Hi, interesting read again :) nice work. Also, epigenetics is an interesting topic in this context :)