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20th Jul 2008
Discovering Drugs
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Drug Discovery: On this week's Naked Scientists, drug development goes under the microscope as we explore two new ways to find the treatments of tomorrow. We find out why size is important when it comes to chemicals that can kill superbugs, and how soil bacteria hold the chemical clues to the next generation of antibiotics. Plus, how sheets of carbon can be used to reveal single atoms of hydrogen beneath the microscope, how scientists have homed in on the part of the brain linked to obsessive compulsive disorder, and why electronically tagging jellyfish can tell us a sea turtle's secrets. Plus, in Kitchen Science, we make strange and unexpected shapes with bubbles!
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Kitchen Science
We discover a surprising feature of bubbles using only bubble mix, wool and a coat hanger!
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Question of the Week
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I’d like to know if there are any life forms: plant, animal, fungus, whatever that are effectively immortal?
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Questions

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How does coconut milk get inside the coconut in the first place?
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There’s an issue here because coconut milk is actually slightly different to coconut water. It’s coconut water that you find inside a coconut. That’s not water that’s got in from the outside, it’s created by the coconut itself. It’s actually what we call the endosperm of the coconut plant. That’s the stuff that gives the nutrition for the developing seed, a bit like the flesh of a banana. As the fruit ripens the coconut water gets converted into the solid fruit that you find in there. If you have an unripe coconut the water will be quite sweet and very nice. The riper it gets the less pleasant it gets to drink.
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Are there any mental or psychiatric conditions that are known to be hereditary other than OCD?
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Yes. Schizophrenia – we know that the risk rises very much so if you have a first degree or near-relative with the condition. Also bipolar disorder. They’re two very common conditions. They affect between one and two percent of the population.
Scientists are now beginning to apply the power of molecular biology to try to find out what the genes are that are linked to these conditions. They’re using something called single nucleotide polymorphism analysis or SNP analysis. What this involves is a big group of people who have the disorder, a group of people who don’t have the disorder and then you look across their DNA for these little molecular markers called SNPs to see if they crop up more often in certain places of the genome in people who have a condition than people who don’t. That gives you a kind of flag sign or a way-marker to say this bit of the DNA might be important in this condition. Then you can focus your attention much more closely in that area. The same analysis has proved that there are various other genes that, in addition to the ones we knew about, are linked to things like genetics for breast cancer and diabetes in the last twelve months. I think we’ll probably see quite a lot of fruit being borne out by that procedure quite soon.
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I have a brand new iPod. It’s never been charged and has no data put on it. Will it weigh more after charging the battery and filling it with music and pictures?
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It will, Neil, if you fill it with heavy metal (!)
But really, the answer’s no. The way in which an iPod works depends on which one you’ve got. If you’ve got the one which is solid state memory then all it’s doing is binary data. It’s just a memory chip which is storing information as digital information. If you’ve got the older, bigger iPods that have hard-discs in them this is magnetic binary data. In each case it’s either storing a 1 or a 0 by having something pointing in one direction – a piece of magnetism pointing one way or the other, effectively. You can think about it like that. That doesn’t actually matter whether it’s actually got anything stored on it or not because storing nothing still weighs the same as storing something. It’s not like a cupboard that you’re putting tins into. On our forum, Madidus Scientia, put this very well when they said it’s a bit like having a handful of coins and they’re either heads or tails. That’s like the 0 or 1 in digital binary. They weigh the same whether they’re all showing heads or they’re all showing tails. There’s no reason to think there should be a difference in the actual weight.
However, When you charge the battery you are adding energy and there is a relationship between energy and mass...
As Einstein said E=MC2 so when you boil your kettle or, this is the best excuse for not doing P.E. at school, when you run in both cases the hot kettle or you running have more energy. When you’re running faster you have more kinetic energy. Because E=MC2 – that’s E, energy, equals M, mass, times the speed of light, C, squared. Since the speed of light, C, doesn’t change if your E, energy, goes up your mass must go up. So a hot kettle will weigh more and when you run in P.E. you will gain something like 10-14g. This is not a prodigious weight-gain but it is nonetheless weight gain due to taking exercise. You could use this as an excuse for not doing exercise.
Similarly, in your iPod when you charge it up you’re putting energy into the battery. It will weigh a rather tiny amount more. One statistic I did hear is that a thumb print applied to the front of the iPod in the form of, say, the grease on your thumb will weigh thousands of times more than the weight of the battery will increasing due to charging it!
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You mentioned earlier that we measure things in Daltons. What actually is a Dalton?
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We put this question to Dr Harren Jhoti:
Harren - Basically a Dalton is just a measure of weight, it’s a measure of mass. It’s a very, very small measure of mass: something like micrograms or grams people refer to but at a kind of microscopic level, if you like. Daltons are basically very single units of small mass.
Chris - So when you’re down at the molecular level you can’t use grams or even thousandths of grams? You need to use much smaller molecular units.
Harren - That’s exactly right. That’s the most commonly-known unit which people refer to when looking at small molecules.
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Different people react differently to different drugs. Would you say there are different body types in the population and therefore should we be looking for them?
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We put this question to Dr Harren Jhoti:
Harren - Yes, I think this is a very interesting question. It really touches on what’s happening in a broader sense in the pharmaceutical industry. People are really talking about personalised medicine. This issue that body types or different types of people, often due to their different genotypes or genetic make-up - it’s going to be very interesting to see how drugs actually are metabolised by different types of people and whether those drugs show different levels of efficacy in different types of people. There’s a huge push in the industry now to see whether we can’t try to predict up front by reading the genotype of a particular person and whether that person is going to a) respond to the particular treatment and b) whether they’re going to have a higher chance of having detrimental side-effects due to some toxicities. There’s a big push in this whole personalised medicine. It’s based on body types and genome sequencing. It’s all part of the same issue.
Chris - It’s very interesting, isn’t it. If you go into a shoe shop you expect to get a pair of shoes that’s the right size for you. But you go into a chemist and you’re given a drug which millions of other people take and it’s expected t o fit your molecules in your body just perfectly even though you might be totally different from the next person.
Harren - Yeah. That’s a reality today because we simply haven’t had the technologies to be able to segregate people into these different groups. Genome sequencing is a very recent development and many of these drugs were actually discovered and developed ten or fifteen years ago. I think going forward molecularly-targeted agents which try to target subgroups of patients is going to be very much the focus.
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How do you train antibodies to attack skin cancer?
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We put this question to Dr Melanie McCullagh:
Melanie - Monoclonal antibodies are a very interesting new way of treating cancer and one of the really clever things about them is that they target specific receptors on the surface of the cancer. What we know about antibodies is that their structure is like a lock and key. They fit very closely onto the receptor and are very specific to where they take the activity of the antibody. In melanoma, which is a particularly serious form of cancer with some really quite poor outcomes, there’s some really great work going on at the moment looking at making the antibodies target those receptors much more specifically and much more clearly to the cancer itself.
Chris - Do you see this as being a massive growth area now? Are we going to see people that are better at doing this in future?
Melanie - I think it’s really important and there’s a lot of companies working on how to develop new forms of antibodies with a greater specificity for cancer but also with different types of activities. Even ones that can carry other cancer therapeutics directly to the site of the tumour, which is very interesting.
Chris - It’s very important too since one person in every three will ultimately in their lifetime die of cancer.
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Is it possible to create an intelligent vaccine or a drug that could evolve with the ever changing strains of the disease?
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We put this question to Dr Melanie McCullagh:
Melanie - That’s a very interesting question. I’m not sure that you would actually want a vaccine to evolve too much just in case once you set it loose in the wild you would risk some kind of a vaccine epidemic. I think what you can definitely do is apply selection pressure to the bacteria to change the types of molecules that they produce. That’s a similar kind of concept.
Chris - I would think that probably this is going to be big business in the future. We’re only just beginning to understand how molecules actually look. By turning this round in this way we can now start with what we want to end up with and then go back to the gene and tweak that. That’s quite a novel thing to be doing. Probably going to be a major way of doing this in the future.
Melanie - There are some real advances in technology at the moment that I think will enable us to expand greatly what we can do with genetically engineering the bacteria that produce these polyketides. Biotica’s a very small company but I think there’s a really big area for us to build into with increasingly novel technologies as things move on.
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