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Frederik Pruijn
Frederik Pruijn
Frederik Pruijn obtained his PhD in Pharmacochemistry at the Vrije Universiteit in Amsterdam. Since 1992 he has been affiliated with the University of Auckland, New Zealand, and is a Senior Research Fellow in the Auckland Cancer Society Research Centre.


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The Two Most Fundamental Questions: How Did It Start and How Does It End?

May 22, 2011 5:17 am
Categories: limits of science

On the day that the world was to come to an end it seems appropriate to ponder the most fundamental questions that have plagued us for ages. At first it may seem that the questions posed in the title are not the most fundamental ones; one could ask many others, e.g. what’s the meaning of life? Why are we here? What makes us human? Many other questions could be phrased, depending on personal preference, however, one would not want to overcomplicate these matters and the two suggested ones will have to do.

Just a few days ago Stephen Hawking gave a talk at Google Zeitgeist 2011 in which he apparently (I have yet to watch the video, which can be found here) reiterated that there’s no afterlife. At the same time he believes that the M-theory will be the right and, in fact, only answer (to what?). I know next to nothing about M-theory, string theory, the theory of everything or TOE, and the Grand Unified Theory or GUT. A quick (!) look on Wikipedia gave me the two (I like to keep it simple today) most important facts: 1) there are 11 dimensions (or more or less); 2) nobody knows what the M in M-theory stands for!? Like most earthlings I have considerable difficulty coping with 4 dimensions and stringing my shoelaces in the morning (stiff back) so I’ll leave it at that except to say that these theories and their esoteric particle names quite often invoke associations with fiction, e.g. Tolkien’sone ring to rule them all”; this could be fodder for a couch session if I needed one but more likely it shows that science is starting to cross over to fiction…

It seems that Stephen Hawking does also not believe that the Higgs boson will be found by the Large Hadron Collider; the particle that other scientists hope to find by the end of next year. A small fly in the ointment? It is clear, however, that the Universe may have started (if this is the right word) by (or with?) the Big Bang; quantum fluctuations shortly (?) after the Big Bang may have been the origin of stars and galaxies (see figure). Some time (?) after that life emerged. Again, there are many theories about the origin of life so it appears that once again the fundamental question of how it did start remains unanswered. Assuming it did start it evolved and this is still ongoing. So, where where will it end? One person who tried to answer this and bridge the gap between science and religion was Pierre Teilhard de Chardin. He was a Jesuit priest, a philosopher and a trained and experienced palaeontologist & geologist. He developed an explanation for the beginning and end of the Universe; the end being to so-called Omega Point. As such, his explanation was an all-encompassing one, which appears to have a certain (aesthetic) attraction: a theory for everything. Obviously, there are many other thoughts on how the Universe might end.

Timeline of the Universe. Courtesy of Wikimedia Commons. Credit: NASA / WMAP Science Team.

A question that keeps many scientists and medics busy is: how does cancer start? This is a question that many of us unfortunately will grapple with during our lifetimes unlike the beginning and end of the Universe or the origin of life. The process of how cancer starts is called carcinogenesis or oncogenesis. The generally accepted theory is that it starts with mutations in DNA followed by a complex progression of those cells by natural evolution in the body. This evolutionary process bears many similarities to Darwinian evolution except that it takes place within the body and on a much shorter time scale. It is very important to keep in mind that at all times cancer cells are one’s own cells by origin and they are in many ways virtually indistinguishable from normal cells. This is one reason why cancer is so hard to treat. Anyway, getting back to theories or models for the origin of cancer, it is not surprising that a complex disease such as cancer has alternative models. Interestingly, one of those alternative models, the tissue organisation field theory (TOFT), does not appear on the Wikipedia page. A recent editorial in the journal Bioessays introduced a scientific debate between the somatic mutation theory (SMT) of cancer and the tissue organisation field theory (TOFT). It would be great to see more of such debates appearing in the literature. The accumulation of DNA damage (mutations) is also one of the fundamental concepts in theories of aging, which is yet to be fully explained by science.

Cancer is in many cases fatal if left untreated although spontaneous regressions do occur. The treatment of cancer is blunt & harsh, as we all know. It is perceived as getting rid of a foreign or alien parasite, like in the movie Alien, often at great cost to normal tissues and the body as a whole. Cancer research (NB one of the more disappointing Wikipedia pages) is aimed at better understanding the causes of cancer, the process of carcinogenesis, and the development of better curative therapies. Cancer research is conducted at all levels of complexity. Many experiments involve experiments of isolated DNA or proteins in an Eppendorf tube (the modern day equivalent of a test tube). The next level of complexity is the use of cells and cell cultures. Usually, these are immortalised human cancer cell lines grown as monolayers in T-flasks. One example are HeLa cells, a cervical cancer cell line, established in 1951 and grown in labs all over the world ever since. This raises one important question: how much does it resemble the original cancer after all these years in culture? The next level of complexity is to grow these human cancer cell lines as tumours in immune-compromised (immunodeficient) mice such as the nude mouse, the SCID mouse, and the RAG-1 mouse. Although the cancer cells are human in origin the blood vessels, the supporting tissue (stroma) and the invading immune cells are not. Again, this raises questions regarding the validity of findings obtained with such models. The final level of complexity is cancer in human patients. In this situation all cells are human, there are many interactions at many levels between the cancer cells themselves, with other surrounding cells, and even with distant tissues. One might wonder how this level of complexity is adequately accounted for by the experimental models described above. Going one step further, one might wonder whether something important is being missed or overlooked by scientists in their reductionist approach to cancer, whether the right question(s) is being asked. This may be better left for another time though. It is obvious though that the War on Cancer is far from over. Recently, the landmark review from 2000 The Hallmarks of Cancer has been updated by Hallmarks of Cancer: The Next Generation (Cancer 2.0). You’ll be shocked by how much is known about cancer but there are still so many unknowns and gaps in our understanding that we can look forward to next update in 10 years or so.

As mentioned before, HeLa cells are immortal. Apparently, this is because they actively and efficiently maintain the length of telomeres. In a new twist on genetic screening a new commercial OTC (over-the-counter) blood-based test is about to be launched that measures the shortest telomeres in order to predict how long you will live (actually, how fast you’re ageing). So, you may not only know how and when your life started (ask your parents) you may now also be able to find out roughly when it may end, which is good to know for insurance.

It is obvious that science does not and most likely cannot provide the answers to the those two most fundamental questions regardless whether these apply to the Universe, the origin of life and evolution, the origin of cancer (at least at this stage), why we age and die, etc. If this is indeed the case perhaps we should ask ourselves what to do with the time between beginning and end? Maybe this question should be the most fundamental question anyway since it can be asked by each and everyone of us and only be answered by each and everyone of us.

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