David Mitchell and telomeres – an endless love story

I love David Mitchell. Proper love him. Ever since the first episode of  his sitcom, Peep Show, I’ve harboured an ill-advised crush that has been the cause of much hilarity amongst my friends. I loved him through the podgy phase, the slightly sweaty phase, the endless-voiceovers-on-dubious-tv-ads phase. My persistence paid off when he emerged, circa 2010, like a butterfly from a chrysalis – thinner, beardier, handsome, presenting left wing TV shows and marrying girls’ girl Victoria Coren. I was smug. I thought he could do no wrong.

sultry david

He could. He did.

In a baffling rant in a recent column in the observer (ok, not so recent, but I’ve been busy, yeah, so deal with it), David Mitchell went crazy over the ridiculousness of telomeres (we’ll get to what telomeres are immediately after the ranting has finished). From what I can make out from his ramble, the main problem seems to be that they’re too ruddy complicated. Damn you, science! In a rather incoherent outburst, Mitchell first attacked journalists who attempt to simplify science with metaphors, then went on to bemoan the fact that science language is so complex that he can’t follow it. I think, although I can’t be sure, that his basic point is this – ‘I’ll never properly understand science, so what’s the point in trying? And why should I care anyway?’

But David – telomeres are amazing! Telomeres keep you alive! Telomeres won a Nobel prize for heavens sakes! And here’s why I think they’re so cool.

Telomere is the posh word for the bits of DNA at the end of each of your chromosomes. It comes from the Greek words telos, meaning to end or complete, and meros, implying a part or segment. So telomeres are simply the ‘end segments’ of the chromosomes. If you cast your mind back to GSCE biology, you might remember that DNA is made up of long strings of four different molecules called ‘bases’, which biologists have given letters – A, C, G and T. The order in which the bases are lined up in each chromosome – the genetic code – determines what genes are present and when these genes are turned off and on. As such, the genetic code determines almost every aspect of how each cell in the body behaves. Telomeres are different from the rest of the genetic code because in these end segments small subunits of bases are repeated over and over again. In human telomeres, the repeating unit is TTAGGG. The repeating units of the telomere are pretty irrelevant for much of a cell’s life, but become very important indeed when that cell is dividing.

Telomere

Telomere (Photo credit: Wikipedia)

When a cell divides into two daughter cells, all the DNA in the cell must be copied exactly, to prevent mutations that could cause cancer or stop important genes working, and to make sure that each and every gene is present in both daughter cells. But the cellular machinery responsible for this DNA replication is big and clunky, and so when it attaches to the end of the chromosome, it can’t copy from the very first base. This would be a BIG problem if the first base indicated the start of a gene, but luckily, this is where telomeres come in. Each time the DNA is copied, one TTAGGG unit is lost from the telomere. The rest of the DNA can then be copied unhindered. To exercise an over-used, David Mitchell-bashed metaphor, the telomeres act like the plastic bits on the end of you shoelaces – protecting the rest of the DNA from gradually unravelling and being lost over time. Sorry, David, but it really is an excellent metaphor. The older a person gets, the more cell divisions they have undergone, and so the shorter the telomeres in their cells are. Older cells have shorter caps, which makes the genes of the chromosome shoelace more vulnerable during replication. In cells with shorter telomeres, mistakes during DNA replication are more common, increasing the chance that cancer-causing mutations will arise, or that the cells will die. So the length of your telomeres is intimately linked to the aging process.

But wait! I hear super-attentive readers cry. You’ve told us before that there are 100,000,000,000,000 cells in the human body, which all came from one fertilised egg. Are there enough repeating units of telomeres for all those cell divisions?* Well, no. Although human cells generally have between 3000 and 8000 TTAGGG repeats (more than enough to make 100,000,000,000,000 cells all being equal) some cells are responsible for making huge numbers of daughters – for them, 8000 repeats wouldn’t cut it. So how do cells do it?

This question bugged scientists for ages. The answer won Liz Blackburn and Carol Greider a Nobel prize (although, according to my research, they made the all-important discovery on December 25th. This led me to imagine how peed off I’d be if I’d gone into work on Christmas morning and NOT ended up with a Nobel prize. Is the temptation worth the risk??). As is often is the case in nature, it turns out that the solution is beautifully simple. In growing embryos, an enzyme called telomerase is produced. The job of telomerase is to stick telomere repeats back on the DNA ends at the same time as replication is occurring.  It does this using a template from a DNA-like molecule called RNA, which tells the telomerase which bases to reattach. This keeps the plastic bits of the DNA shoelaces at a reasonable length, preventing cells from dying before their time. If developing cells can’t make telomerase, the result is diseases of premature aging such as dyskeratosis congenita, which can cause early death. Generally speaking, once the initial period of growth is over, telomerase production ceases. Without telomerase, telomeres gradually become shorter and so the cells age over time.

Seems simple enough, right? So what exactly did Mitchell get his knickers in a twist about?  Of course, as with all science, it’s not as straightforward as it seems. For example, you might reason that, if shorter telomeres causes cells to age, then lengthening telomeres in cells could reverse the aging process. In fact, some adult cells do retain active telomerase. These include stem cells, which need to be able to replicate indefinitely. However, scientists have found that it’s not necessarily a good idea for normal adult cells to produce telomerase. Cancer cells, like stem cells, are defined by their ability to keep dividing infinitely. In many instances, the cancer cells do this by turning telomerase back on to keep telomeres long enough to prevent the cell from dying. So, it seems that a balance must be maintained – too short and your telomeres can’t protect the DNA properly, leading to cancer; too long and cells will divide over and over, causing cancer via a different route. Actually, what’s complicated here is not telomeres, but the many different ways in which cells can become cancerous. But I’ll leave that for another time.

If you’ve understood this blog then you DO understand the basics of telomere biology. Pretty cool for less than half an hour’s work. Sure, there will always be more to learn about telomeres, but this applies both for those who’ve never come across the term before and for Nobel prize-winning experts in the field. David Mitchell may think that this means there’s no point in trying, but I think the eternal quest for knowledge is exactly what makes science so fascinating. The day that we understand all the mysteries of life will be a sad day indeed.

*If anyone wants to work out how many rounds of cell division is takes to get to 100,000,000,000,000, cells from one, I’d be very impressed. First in wins ‘Geek of the week’.

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13 thoughts on “David Mitchell and telomeres – an endless love story

  1. I wish to know how long does cell division takes on average? Also the average size of a cell. Then I can create a machine that can tell you how long it will take for a single cell to take over the world.

    • Excellent question, Edd! Unfortunately it’s not easy to answer. There are many different cell types in the human body and they are many different sizes and shapes, and they also divide at different rates, both from each other and in different environments. For example, an intestinal stem cell in a healthy gut barely divides at all, but if the gut is damaged, it leaps into action! People have been trying to use programming to mathematically model the growth of an embryo for years, but it’s notoriously difficult to make accurate models. Let’s have a go anyway!

      Let’s start with size. Although cells are many different sizes we can take a (very very) crude average from the smallest (a sperm, at around 5 micrometers) and the largest (an egg, about 100 micrometers, or 0.1mm), to give an average diameter of 52.5micrometers for a human cell.

      Give me a mo do to a bit of research and I’ll get back to you on average division…

      • Ok, totally unverified sources repeatedly tell me that when a human cell is going for it, it will divide once every 24 hours on average. This is because it’s good for the cell cycle to keep in sync with the other processes that are using up energy in the body. Makes your calculations easier too! Cant wait to hear the answer.

  2. Clearly I’m working hard. Noone can prove otherwise…
    Let’s do maths!
    SA of the Earth = 510,072,000 KM^2 or x(1000^”) 510072000000000 M^2 or x(1000000^2) 510072000000000000000000000 µm^2
    SA of a cell assuming it is a perfect circle which it isn’t = pi x (52.5/2)^2 = 2165 µm^2
    So to cover the Earth you need 235599076212471131639723 cells.
    That doesn’t seem that many.
    To create 235599076212471131639722.86374134 cells from a single human cell that divides every day you need log 2 235599076212471131639722.86374134 divisions = 77.6 divisions
    So in 78 days a single human cell can create enough cells to cover the entire earth assuming none die… That seems wrong. But where?

  3. Assuming each cell division works perfectly (so no cells are lost), then it would need 47 divisions to create 100,000,000,000,000 cells from the original single cell (using the same log method as Edd above). When are you going to send the blog to Mr Mitchell for his education and edification??

  4. I read him and thought he was a bit out of touch – but the shoe lace metaphor is overused! Maybe it’s a bit like knitting, where you cast on and cast off, although no one comesalong and adds more stitches when you need them! (apart from the fairies – maybe telomerases are like the fairies?)

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