We had a lot of great questions/comments posted in the comments section of the youtube video released a month ago. I’ve copied and categorized all the relevant questions and comments in this entry. There were a lot of people asking the same questions, so I’ve also filtered the questions for redundancy (what do you expect from the computer guy -Aziz). We will answer them as we get to them. Check back often for updates to this Q/A.
Q1. So as long as the original worm is allowed to divide, the act of division regenerates its own dna in the process? That is quite amazing, and enough for me to classify it as ‘immortal’, as naturally it could live forever as long as it doesn’t die of other causes unrelated to aging. One problem though. Although these guys potentially could have a small chance of mutations on each division, is that enough to produce genetic variation? Is this why sexual reproduction dominated? As it allowed for more variable mutation and quicker adaptation? (rich1051414)
A1. Thomas Tan: Sexual reproduction does indeed generate more variations and allow better adaptations, therefore it is not surprising that ageing might have been evolved as a mechanism to remove older individuals and prevent them from dominating the gene pool. Although asexual clonal reproduction could also generate variations by mutation and mitotic recombination, a recent study in seagrass has found no detectable somatic mutations after thousands of years of clonal propagation. In lab culture sexual worms are generally fitter and more resistant to bacterial infections.
Q2. If those worms are asexual then are all the individuals of that species genetically identical? (Elpmek)
A2. Thomas Tan: Clonal asexual reproduction is expected to produce genetically identical “offsprings”. However mtutations and mitotic recombination may occur in cells within individuals, resulting in differences betweeen worms of the same clonal lineage. These processes are thought to be extremely rare. To my knowledge no work has been done at the moment to compare gene or genomic sequences between aseuxal individuals, although in my PhD thesis (published online) I did find a possible recombination event between two haplotypes of the asexual Smed_Tert gene.
Q3. Is there a way to kill it? (lakloplak)
A3. Thomas Tan: All methods that abrogate the survival of cells can kill the worm, such as freezing, heating, poisoning etc. The worms can also die of bacterial/fungal and possibly viral infections.
Q4. Sorry, I don’t really understand how they are immortal. Is this not just asexual reproduction? If this means they are immortal, would it not mean that all animals, fungi, bacteria etc that reproduce in this way would also be immortal? Or am I missing something? (RobertStyx)
A4. Thomas Tan: Many asexual organisms have limited capacity to reproduce by purely asexual means. For example, clonal ascidians become senescent after a number of asexual generations, and need a round of sexual reproduction to “rejuvenate”. This also applies to uni-cellular fungi like yeast. Most Bacteria do not have linear chromosomes like the eukryotes do, and are not subjected to factors that affects longevity in eukaryotes.
Q5. How many animals are known to science that are potentially ‘immortal’? (TadaGanIarracht)
Q6. I believe the key of this matter is if they truly don’t age when dividied artificially. My intuition tells me that DNA chains will get damaged anyway after some period of time. Probably because of lack of material/energy to properly regenerate. (damianpaz)
Q7. What would be really interesting (IMO) is to find out how the flatworms avoid cancer even though the rejuvenation process can potentially be infinite. That is, how come they don’t just split again right after a split, like a cancer cell? (GeekProdigyGuy)
Q8. Dr Aziz , what hapens with trees, you cut a branch and reborns, the DNA also has in part the capability as those worms to replicable ?. Trees do die as we know . Hope your work may one day open a clue for men can make grow a loosing arm or leg, not to be tragically immortal. Thanks for your work! (Marylisabon1)
Q9. I seem to remember reading that as a foetus humans have incredible regenerative abilities and even as very young babies if they lose the tip of a finger it can re-grow it. So, is the worm in a perpetual almost foetal like state? Do the worms get ever cancer? (wobblycogsyt)
A9. Belen: That’s right, developing embryos have a large number of “embryonic” multipotent stem cells that can form almost any cell in the body, and therefore have very high regenerative capabilities. Planarians also have a large pool of stem cells that are responsible for their regernative ability, but what makes them different from embryos (and quite exciting to study!) is that these stem cells are adult pluripotent stem cells. That means that even though they form part of the adult animal they can still form any cell in its body. When an animal is cut these cells divide and make all of the missing structures in the animal.
Q10. I have a question: What is the minimum number of cells which allows it to regenerate a whole worm. May be he could regenerate from one cell? (giltine002)
A10. Belen: Thomas Morgan (the famous fly geneticist) found in 1898 that you could cut a worm into many very small fragments that would regenerate into full (though smaller!) animals in 14 days. He found that the smallest he could cut the worms so that they survived was roughly 1/276th of their initial body size. This is now known to be a minimum of about 20 000 cells.
A recent paper by Reddien’s group in MIT has shown that just one stem cell is sufficient to repopulate all of the stem cells in the planarian. What they did was irradiate a worm, which kills all of its stem cells or neoblasts, and then inject a single stem cell from a different animal into it. After time this worm replenished it’s stem cell population and survived happily (the uninjected animals die because they don’t have stem cells so can’t replace “old” cells). So in a way, yes, just one cell of the right type is enough to regenerate the whole animal.
Q11. I wonder what happens if you cut a worm lengthwise, but without cutting it completely, from the tip of the tail to just before where the head is. Would the wound just heal and close up? How would it heal? How would the cells from one tail half of the worm “know” how to get back to the other half? Or would both halves of the tail grow back its other half separately, resulting in a freak two-tailed worm? Or would it force the worm to split up? I hope a worm isn’t reading this… (FrankieSmileShow)
A11. Belen: That’s a really interesting question, which Thomas Morgan also asked himself over 100 years ago. Most of the time the two tail pieces fuse and the wound closes and heals, resulting in a normal worm. However, sometimes you get two-tailed worms. Equally, if you cut a worm lenthwise through the middle of the eyes, often you get double headed worms too. This was observed as early as 1828 by Duges. Have a look at these drawings that Morgan made about this in his paper “Regeneration in Planarians”.
Q12. How do they produce their stem cells? (Typho0n86)
A12. Belen: They are born with their stem cells, and they are just quite good at maintaining them! A big part of the way they do this is that they can maintain telomere length and so their cells don’t age like ours do.
A12 Aziz: Probably as the embryo develop some cells retain “pluripotency” and then later these become adult stem cells. Although we don’t know this for sure. It maybe that pluripotent cells that give rise to neoblasts are induced late in development. Very difficult to test this in planarians as the embryos of most of them are tough to work with.
Q13. Others may have asked this, but is it possible to trigger the telomere rejuvenation process without actually cutting the worm? There is presumably some kind of chemical signal that triggers the rejuvenation process after the worms are cut, so it would be interesting to see if that could be mimicked. If so, the obvious question would be whether a similar rejuvenation process could be induced in human cells. (cavalrycome)
Q14. Why can’t humans take special “telomerase pills” or a retrovirus that would induce telomerase prouction? Can we take genes that make the flatworms chromosomes stay intact and make transgenic, immortal organisms, i.e. lab rats ? (LechuCzechu)
Q15. How does the cell know when to activate telomerase activity after the DNA reaches a certain length? Maybe the end of the DNA code for a protein that, when its gene is cleaved, will be made not functional. This not functional protein, normally, may in fact regulate a set of activators that turn on telomerase activity. Since the protein no longer works from a cleaved gene, then the activators are no longer inhibited so they can now turn on expression of telomerase. I wonder if you can test this (emadrio)
Q16. On another more philosophical note, does the new head produced have all the memories of the previous head or does it have to re-learn everything? It would be very interesting if Aziz would look at brain function and games with these worms to see if cutting off its head changes the worm or if the worm maintains its memory and past self. Amazing video!! (TheeImmortalPhoenix)