Podcast transcript
Manipulating the molecules of life
Professor Nick Hoogenraad
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Transcript
- Matt Smith
Hello there. This is me, Matt Smith, welcoming you, the listener, to a La Trobe University podcast. Who are we hearing from today I hear you ask. Well, that’s a very good question. It’s Professor Nick Hoogenraad. He’s the Head of the School of Molecular Sciences at La Trobe University and the Executive Director of the La Trobe Institute for Molecular Sciences. Did Jurassic Park teach you anything? I hope so. And that would be, don’t mess with the molecules of life. For those of you who want to know what the molecules of life are, that’s where this talk with Nick comes in.
- Nick Hoogenraad
I’m often asked by people who are not trained in biology, what is it that makes life? And of course, life is based on just a relatively small number of molecules. They’re both large and they’re small. I think the most fundamental aspect is, that the molecules of life are based on the atom carbon, and carbon has this wonderful property to actually join together, in four different positions. So you can get almost infinite shapes and long chains and everything else and this was very suitable to base life on a molecule like carbon. And then there’s hydrogen and there’s oxygen and nitrogen, that form the fundamentals of what we call organic molecules. Organic means based on carbon. So all living processes are based on carbon.
- Matt Smith
It’s the structure and the way that they bind that defines a function?
- Nick Hoogenraad
Yes, so a nice way of looking at function is that function is dependent on three dimensional shape. You can have a motor car, which can look very different from one another, and they function because they have an engine, which can look different from the engines in other cars. But in living species, structure is ultimately the determinant of activity of function, so if the shape changes, even in a very minor way, the function will stop, and in fact, a way living cells have found a way to get function is to go from one shape, which has no function, to a shape which has function, so it can switch things on. It’s almost like a switch like a light switch, just simply changing the shape, which you can do by binding hormone for example, on to a molecule, it can change its shape and makes it active, and before the hormone’s bound, before the finger’s gone on the switch, if you like, the shape is different and it’s inactive.
So the basic unit of living species is the cell. And the cell either in bacteria has no compartments inside it, or in anything above yeast, has compartments like a nucleus where the DNA is found. So one of the molecules of life, which everyone knows about, is DNA, and it’s made of the same atoms, carbon, nitrogen, oxygen, and DNA is a very large chain that codes for proteins, which is another molecule of life, if you like. So DNA is the genetic material, proteins are the machines of life, and the structural elements. So, all the structures of all living species is largely based on proteins, except for plants, I can come to that in a minute, and the functional molecules, which we may call enzymes, or even hormones, or receptors, sensors if you like. They’re all protein molecules and they’re coded for by the genes.
- Matt Smith
So how much diversity is there of molecules, say from a human down to an ant?
- Nick Hoogenraad
It’s remarkable that from the lowest form of animal to the humans, we have about 30,000 genes. Of those 30,000 genes, all living species might share 20,000 of them. So even bacteria, we have extraordinarily similar. We make our energy, we extract energy from food, and have the same chemical molecule called ATP, which is the energy for muscle contraction, for thinking, for all of our function, and indeed, when we stop being able to make ATP, that’s when we die. It’s remarkable how similar we are, and in fact this is the basis of scientists using even bacteria as a model to study human beings. Now we are a bit more sophisticated and we would use a more advanced animal species as a model for a human being, maybe a mouse nowadays. But people still use yeast, for example. Many of the processes are so very similar, the way we replicate DNA, the way we convert the message into a protein molecule and the way the protein molecule is actually made in the cell and how it folds in its exquisite three-dimensional shape. That’s all the same in all living species.
- Matt Smith
You said there was a difference with plants.
- Nick Hoogenraad
One of the fundamental structures in plants that give it strength – the plant’s cell is fundamentally the same as the cell of a human being but there is an element of difference and that is surrounding that cell there’s a very hard shell, made out of cellulose, the cell wall. This provides strength to the plant, to its structure, whereas our strength resides in our skeleton, if you like. Whereas plants have an exoskeleton, and outside skeleton if you like, and then trees and woody plants have lignin, that’s carbohydrate molecules fundamentally, in cellulose’s carbohydrate, molecules that add strength and become woody because it becomes impregnated with chemicals. There I’ve spoken about proteins as a molecule, I’ve spoken about DNA as a molecule and I’ve just mentioned another critical molecule, which is carbohydrates, and these are polysaccharides, so they’re complex carbohydrates that make up the structure of plants, but we have complex carbohydrates in our cells, so if you have a meal at 6 o’clock at night let’s say, you will digest that food and you will store the energy in the complex carbohydrate called glycogen, which is almost identical to starch, that plants make, to store energy. And that’s a very dynamic molecule, the glycogen, because by about midnight, you start running out of all of the nutrients that are readily available like blood glucose, and you have to replenish blood glucose, because your brain needs glucose all the time. So you start breaking down that glycogen that you stored after a meal. And by the time you wake up in the morning, the glycogen’s nearly gone, and so you need another meal to refill it. And if you don’t have a meal, you’ve got to get your energy from somewhere else. So you break down fat. We have a finite capacity to store carbohydrate in our cells, and glycogen, so glycogen deposits can only get so large. But fat, we have an infinite capacity to store fat, as you notice by looking at populations, and fat’s a very rich source of energy.
Fat’s another molecule I’ve just mentioned, because we call them triglycerides because there’s actually three chains, high in energy, that are attached to a glycerol molecule.
- Matt Smith
So on a molecular level, what happens when mutation happens?
- Nick Hoogenraad
So what happens with a mutation – it can be a silent mutation, because about 99% of our DNA doesn’t code for proteins, so we have mutations all the time. We don’t notice an effect because it’s in non-coding regions but if you have a mutation in a gene that is in the region of DNA, which codes for proteins, then we are highly likely to get a change in the building block of the protein that’s coded by that part of the DNA. Now those building blocks are another molecule, are called amino acids, and if you change twenty amino acids in proteins, and they all have different shapes, and so depending on what order you have in the amino acids that are joined together, you’ll finish up with a different three-dimensional shape of the protein. You could have no effect, because it’s minor, but you can have a major effect, so that the protein no longer folds correctly. So as people stay older, we get more mutations, and we get more aggregates forming, you find diseases like Alzheimer’s Disease or Parkinson’s Disease, so mutations can cause loss of function.
- Matt Smith
What about mutations that are done intentionally? I’m thinking about modifications here, whether they be good or bad.
- Nick Hoogenraad
Yes. You’ve raised a very good point. Mutations can actually improve the protein molecule. Equally they can reduce its function. Most of the mutations are negative, but evolution has occurred by getting mutations which improved a molecule, and then when you combine that, as Darwin proposed, with a way of selecting, in other words, as a benefit from that improvement, a reproductive benefit, then you eventually will get improved function. And you can do that deliberately because we can manipulate DNA so easily these days, so we can make mutations in DNA.
- Matt Smith
How does this apply to the practice, like genetically modifying food, or making modification to maybe animals, so that they produce more meat that we like, or practices like that? Do you think that there’s something unnatural about doing things like that?
- Nick Hoogenraad
I think what you should realise is that the agricultural revolution started many centuries ago by actually selecting plants with improved qualities. The original grapevine produced tiny little fruit, just good enough for it to produce seeds to reproduce it. But somebody found in a hedgerow somewhere a grape plant that had larger berries, so they selected that, they took that, then they selected berries that got larger and larger, or better tasting fruit and so forth. So in time we learned how to actually cross plants, make hybrid plants to get improved function. All we’re doing by genetically modifying food is we are speeding up the process, and we’re doing it a lot more deliberately. So, for example, we apply chemicals to crop plants and so forth. We spray – cotton’s a prime example, one of the most polluting crops you can grow. If you can produce a cotton plant which doesn’t need chemicals on it, because you’ve engineered into it a gene that makes it defend itself against insects or a fungus, then you’ve just done very quickly what you could do by selection over a longer period of time. But you’re also very quickly helping to clean up the environment, by not needing to use chemicals. It drives a lot of those sorts of things as well, rather than more altruistic things.
- Matt Smith
Do you think that there’s an unnecessary stigma attached to genetically modified goods then?
- Nick Hoogenraad
Yes, I was actually around, I was in Stamford University in the early ‘70s when the first genes were cloned, and when that was done, the scientists themselves felt very nervous about what they were doing, and they actually got together and decided on a moratorium, which went on for two years. And during that moratorium period, they developed strains of bacteria that couldn’t live outside a laboratory. And we still do things under very carefully controlled conditions. But for a lot of the work, it’s got no constraints on it, because it’s proven to be totally harmless if you like. Of course, you know when the first genetically modified crops were made, particularly when they made crops that were resistant to glyphosates, or Roundup, so they could spray for weeds on the crop without affecting the crop, people were very concerned about that, that that gene would actually get into wild populations and you wouldn’t be able to control very dangerous weeds. It turned out to be true, and so some of this work can cause problems. But it’s very difficult to halt it. I think mostly there are very rigid rules in place, certainly in Australia, where you can’t do certain work. I remember well a scientist publishing in Nature, he discovered a new way to make evolution happen very quickly, by the way they did the mutations. So you could segregate good mutations from bad mutations. And so you could clearly select the better mutation, and the way he decided to test that – he mutated bacteria to see if he could get better antibiotic resistance. He finished up with a bacteria that was massively resistant to penicillin and although Nature published that work, they got an agreement out of the scientist that he would destroy his material and never do those sort of experiments again. Not with bacteria. So all I can say is, that scientists have consciences but that doesn’t mean to say that people with ill intent, couldn’t do things like that. And I’m sure there is biological warfare work being done in many countries, and that’s a great concern.
- Matt Smith
Meddling with the molecules of life. Do you think that we’re playing God too much?
- Nick Hoogenraad
Look, it’s so incremental that no one is playing God. There isn’t some character who is trying to make a super species. Look, we’ve been through this in the most painful ways. Eugenics has reared its head, it’s reared its head during the Second World War, and we’ve well and truly rejected the notion, as we have freedom of speech etc, people will come forward with wild ideas of eugenics, how to improve our species. But they’re in a minority and never get anywhere. I think we’ve learned lessons. So you did need recombinant DNA technology to play games in eugenics. I think that’s the thing that’s often forgotten. We have the plans, we have to reduce weed etc, due to genetic selection – selecting from mutations if you like, that are beneficial, and we can just do it more conveniently now and perhaps do it quicker. But the process in the end is exactly the same. We need very high ethical standards and we have to train people that get into this area the importance of ethics, and we have to have public safeguards and we need to discuss these things in public, so the public’s aware of it.
- Matt Smith
I suppose the most visible example in the Western world that we have, is domestic dogs and see how far they’ve come from a wolf to something in a handbag.
- Nick Hoogenraad
Yeah, I mean I think that’s a wonderful example. Basically we have, using not genetic engineering, but selection, we’ve selected on a few traits, we’ve developed bulldogs that can hardly breathe, dogs that people love because they have malformations that we would never tolerate in human beings, and we wouldn’t want to see people suffer that way. We’ve done it for our own vanity’s sake. Who needs genetic engineering to do things that probably ought to be unacceptable?
- Matt Smith
And that was Professor Nick Hoogenraad. If you have any questions, comments or feedback about this podcast or any other, then send us an email at podcast@latrobe.edu.au
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