Model worms - Professor Jonathan Hodgkin

12 May 2012

Interview with

Professor Jonathan Hodgkin, University of Oxford

Jonathan -  I and hundreds of other labs around the world, we work on a tiny worm called C. elegans - Caenorhabditis elegans -  which lives in the soil all over the world, but it turns out to be a wonderful organism for studying in a lab for all sorts of problems because it's just incredibly easy to work with, and geneticists love it because it goes through two generations a week, so it grows incredibly fast.  Work on this started about 40 years ago and it just kept on expanding.  So back then, which is actually when I started working, there was just one lab and now, there are about 800 around the world.

Kat -  So, who first thought this was a good idea to look at these tiny worms?  Where were they first found?

Jonathan -  Well, these particular tiny worms, the one we work on, they all come from one worm that was isolated on a mushroom farm near Bristol in the early 1950s.  One of the reasons it's a handy creature to work on is that it can reproduce by self-fertilization.  So, you can trace everything back to one worm.

Kat -  I understand they're quite handy as well.  You can pop them in the fridge, you can put them in the freezer.

Jonathan -  Absolutely.  That's a big, big advantage.  You can slow them down or you can speed them up.  Very importantly, you can just freeze them completely and keep them in liquid nitrogen or minus 80, and they will leave forever like that and then you just thaw them up and it's actually wonderful to watch them waking up after having been frozen for what, for them, is the equivalent to 40,000 years and they just go, "Oh!  Ahh..."

Kat -  "Here we are again."

Jonathan -  "Here we are again,"  Yeah.

Kat -  So, tell me a bit about how studies into these worms have told us about human biology because you might not think that there's an awful lot of similarity between a tiny worm and humans, but they have had a really big impact on our understanding of some processes.

Jonathan -  They certainly have.  One of the things that was originally intended in this process was to understand how you put together a nervous system. That's led to an enormous amount of basic understanding of how that happens.  Both how you make a nervous system, how you wire it up, and how it functions.  But then there've been all sorts of completely unexpected things that came out of this and two of those ended up as Nobel Prize-winning discoveries, and one was understanding cell death - apoptosis, which is absolutely crucial to health and to just everything that happens in your development, and all the time in yourself, cells are dying all the time.  They haven't really been appreciated and how important that was that there's actually a special programme that allows cells to commit suicide gracefully, and that was really all worked up because of the C. elegans worm.  And the other thing is this novel process called RNA interference which is a new way of turning genes on and off.  And again, we didn't expect that to be discovered.  It wasn't predicted.  It came as a complete surprise, but we were able to use the power of the experimental system to get to that point.

Kat -  And now, RNA interference is being used in all sorts of studies in human diseases and across the biological world.

Jonathan -  It certainly is.  Like every discovery, the initial dreams that people had didn't quite pan out but some of them did pan out, and there's still a huge amount of potential for using this RNAi process to control disease, to control viruses.

Kat -  One of the other things that you're interested is testing drugs on worms and presumably, these are not drugs that will have an impact on the worms, but these are drugs that may be useful or beneficial for humans.

Jonathan -  Well, worms are a good system for this, partly because they're so small.  I mean, a fully grown worm is only a millimetre long, you can barely see it, but that means you can grow it and keep it just in a tiny, tiny drop of liquid and that means that therefore, if you want to screen a million different compounds for their effectiveness as a drug, you only need a tiny amount of the drug in order to do the test.  And also, it's very easy to see what's going on because the worm is completely transparent and you can see what's happening inside it all the time.  So, if a drug has an effect, it's immediately dramatic.  As far as a lot of human diseases, what we can do is basically humanize the worm.  We can put human genes into the worm and then they can be given these human diseases and we can try and cure them in the worm.  So Alzheimer's disease is an example of this, where worms don't normally get Alzheimer's disease, but you can make them have it by putting the relevant human genes in there and then you can test for drugs that will be ameliorative for Alzheimer's.

Kat -  And as well as their benefit for humans, worms are also an agricultural problem.  They're an agricultural pest.

Jonathan -  They sure are.

Kat -  So, there are some ways that we can try and develop new ways of tackling them as a pest, as well as beneficial species.

Jonathan -  Yup, that's the other side of what we do and what I'm increasingly interested in my own work is that C. elegans is completely harmless.  I said we've found it in the mushroom.  It was found in a mushroom farm originally, but if anything, it's beneficial to growing mushrooms, but it's totally harmless but there are lots of other related nematodes which are very bad crop parasites and it's estimated that something like 10, 20% of all primary crop production is severely at risk with nematodes.  There are places where you simply can't grow tomatoes because of the nematode risk.  So finding new ways of attacking nematodes and particularly plant parasitic nematodes is very important and it's even more important because the main compound that was used for many years - methyl bromide  - to control plant parasitic nematodes - is quite rightly no longer allowed to be used because it's a very dangerous compound.  So there's a big gap and need for new drugs to control plant parasite nematodes.

Kat -  So maybe from these tiny worms, we could get new drugs for human diseases and new drugs to combat this agricultural side.

Jonathan -  Exactly!  Absolutely and we can also - as well as the plant parasitic nematodes, there are human parasitic nematodes which are a significant health burden in particularly the developing world.  Things like river blindness, things like elephantiasis, and then in more insidious things like hookworm. There are hundreds of millions of people who have got hookworm.  Hookworm doesn't kill you, but it makes you pretty unhealthy and finding new ways of controlling that would make an enormous difference in many countries.

Kat - That was Professor Jonathan Hodgkin, who was awarded this year's Genetics Society Medal for his work with tiny C. elegans worms.

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