Stanford Scientist, Dr. Bikul Das was recently in the news for his study on discovering altruistic behavior in embryonic stem cells. CureTalk reached out to Dr. Das and he was gracious to answer our questions through email and share his research journey with us.
Dr. Das began his career in molecular biology and cancer research after several years of clinical practice in Bhutan and India. His studies in oxidative stress and his concern for the impact of pollution on human health led him first to the subject of isopreniod antioxidants and subsequently to the Isopreniod Squalene, with its recently discovered importance in preventive medicine. His Ph.D. work involved work on cancer at the Hospital for Sick Children, University of Toronto, Canada, where he identified a novel signaling pathway of cancer drug resistance and metastasis. Following his Ph.D. training, he was a fellow in the stem cell and developmental biology program of the hospital he focused on isolation of lung cancer stem cells. He is currently continuing his research at the Stanford University Medical Center.
Read on for a wonderful journey of discovery of altruism with Dr. Das,
Me: When and how did the idea of altruism at the cellular level begin to interest you?
Dr. Das: Interesting question, but kind of difficult to answer! My father late Krishna Ram Das was a poet, and he wrote an Assamese poetry book, ‘Sonali Nakhar Jui” (published in 1991), where he attempted to describe altruism from a Vaishnavite philosophy. While I was (and still am) an atheist, and kind of belonged to rationalistic school of thought, my dad was into Vedantic philosphy, so we used to have heated discussions about altruism. I was then a 4th year MBBS student, read evolution in detail, and rejected my dad’s view on altruism. During 1991, our evolution books did not talk about altruism; it was all about survival of the fittest.
So, I rejected my dad’s idea on altruism as speculative and not possible for life to evolve (how could altruism or sacrifice help a species to gain fitness to survive? I thought and did not get any good answer). Nonetheless, years of heated debate on altruism with my dad made me read about the subject quite in depth so that I could debate with my dad, and reject his ideas. This is how I came to know about altruism. Dad died of cancer, and during that time, he again insisted that our own cells might be altruistic and so might fight against cancer. I brushed it off again as wishful thinking.
But then, during 1998-2000, while writing a book on antioxidants, “the Science Behind Squalene” in which my job was to make an argument that due to global pollution and ozone depletion, our antioxidant/oxidant balance experiences stress, and this stress is felt most intensely in our skin. In order to make a strong argument to defend my idea I looked for a candidate antioxidant highly present in our human skin, but not in primate skin. I found, squalene, an antioxidant abundant in human skin, but not in primates. So, I dug more into squalene, and found that squalene metabolism evolved in archae about 2-3 billion years ago.
I did intense literature search on the early evolution of unicellular life. The question was simple: how did these life forms survive the intense radiation and oxidative stress? This is when I started thinking about the potential of altruism as a cellular mechanism of early unicellular life. To describe altruism, I used a word, “cytoprotection” (my editor did not want to use the word altruism, as it was then considered mostly spiritual and philosophical). Thus, the idea of altruism at the cellular level began to interest me (I did not find a satisfactory answer about the early part of evolution of unicellular life).
Me: If I am not wrong, your studies found Glutathione to be the molecule that facilitated the altruism. What would be the other factors that can be credited with this benevolent behavior of human embryonic cells?
Dr. Das: Glutathione is just the tip of the ice berg! There is more into it. I am hoping to identify quite novel cellular mechanisms that do not depend upon growth factors or antioxidant alone. If you consider that altruism is quite ancient, I mean billions of years old, then, you know, we expect the cellular mechanism to employ some kind of robust mechanism that helped those cells to survive under the intense radiation. I do have some good ideas, and now waiting to get my own laboratory so that I could explore those ideas.
Me: Can your study be used as a cellular model/tool to investigate further altruistic tendencies in cells?
Dr. Das: Yes, the model that I use is extremely hypoxic, less than 0.1% oxygen, and then sudden re-oxygenation that generate very high amount of free radicals. I call this model as the “mass extinction” model in the lab. I did a lot of experiments with other models, but found this model as the best of the lot. The model puts the cells under enormous stress, kind of simulating the early unicellular life environment….and so, it probably evokes some kind of ancient coping system buried deep in the genomic and epigenetic memories of stem cells. Also, please note that I have not found altruism in differentiated cells, only in stem cells.
Me: How does the concept of altruistic cells help in the fight against cancer?
Dr. Das: Altruism is basically a biological force of regeneration, this is what I think at present. I read Ed Wilson’s book on Ant and human altruism, where altruism more or less serves as a defense mechanism for a community to survive by sacrificing some of them. I was expecting similar findings in my research. However, my findings were surprising. The altruistic stem cells first transformed themselves to a very cytoprotective and robust state. This transformation process is the key of cellular altruism.
But this transformation process could also transform some altruistic cells to cancer cells. If this is the case, studying altruism could help to understand the “big bang” or the early event of malignant transformation. Such studies could help in the early diagnosis of cancer.
Then, as I wrote at the beginning of this answer, altruism is also a biological force of regeneration. If this is so, is it possible that our healthy cells that surround cancer cells, or live inside the tumor might also exhibit altruism, try to regenerate, and in the process, inhibit cancer growth. After all, tumor is like a non-healing wound, and so, if a few altruistic cells within the tumor initiate a healing and regenerative process, that process might regenerate the normal tissue by killing or differentiating the cancerous tissue. Thus, this is the second way that altruism, by understanding altruism, we might fight against cancer.
The third one is this: what if cancer cells are hijacking the altruistic mechanism to repair and regenerate their own tissue. If this is the case, it could explain why it is difficult to treat cancer. They regenerate or relapse. We do not yet know how they do it. So, if we study altruism, understand the mechanism, then we might be able to know the secret of cancer regeneration. If we know the secret, then we may be able to kill the cancer.
I am quite optimistic about the fight against cancer. I think, for me, altruism is like a guide to the secret of cancer. By understanding the molecular mechanism of altruism, we might find a weakness in cancer…it is like the metaphor of Death Star in the Star War episode IV. Death Star was indestructible, but yet it had a small hole, a weak spot, and Skywalker shot through that tiny hole leading to the explosion of the death star. I believe my research on altruism will eventually help to find that small hole on cancer Death Star! It is quite wishful thinking, I know, but then you need to dream and imagine first in order to get going to discover something novel about cancer.
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