Rosalind Franklin: the hidden story of DNA

20 July 2020
Presented by Chris Smith, Eva Higginbotham
Production by Eva Higginbotham.

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This week we're celebrating the hundredth birthday of DNA pioneer Rosalind Franklin and how her work helped to unravel the DNA helix. Plus, in the news: COVID causes heart damage, water shortages in England thanks to climate change, and magic bullets to make shellfish more nutritious...

In this episode

Image of heart rate signal

00:57 - COVID causing heart damage

Over half of patients in hospital with COVID show signs of heart damage

COVID causing heart damage
Marc Dweck, University of Edinburgh

Despite the fact that Covid is a respiratory disease that spreads - chiefly - through the air and causes lung infections, the repercussions of the disease are felt throughout the body, including in the heart. A new study out this week looking at patients admitted to hospital with covid has found that half of them had evidence of heart damage caused by the disease. British Heart Foundation cardiologist Marc Dweck led the study...

Marc - We know from other viral infections that viruses and other bugs can cause problems with heart function. And we know with COVID-19 that people who have preexisting heart disease are more likely to get COVID infections, and have more serious disease.

Chris - And does that mean then that COVID causes heart problems? Or is it just that we're seeing an over representation of people with heart problems who then succumb to COVID?

Marc - Yeah, that's an excellent question. I think it's a mixture of both. We did a study of more than 1200 patients from 69 countries across the world. And now, these were people with severe COVID-19 infection who had been admitted to the hospital. And when we looked at the scans of their heart that they had done, we found that half of the scans showed some form of abnormality in how the heart was pumping. Now, often this was mild. However, in one in seven patients, the heart damage was severe, meaning that the heart was struggling to effectively pump enough blood around the body. We then did another analysis where we excluded all the patients who have any form of history of heart disease. And when we looked at those people, just under half of them had some form of heart damage, and one in eight had severe heart damage, but they didn't have any damage registered before. And so our assumption is that that damage was new and related to the virus.

Chris - How do you think the virus is actually damaging the heart? What's it doing?

Marc - Yeah, this is the next question we really need to answer. And I think that is very important. There are several different hypotheses. One is that the virus is directly affecting the heart muscle, causing inflammation in the heart muscle that impairs its ability to pump. Another explanation is that people who have a very serious illness, develop a stress response in their heart muscle, where again, the heart fails to pump properly. The interesting thing about that is if you treat the other conditions that they have, then the heart goes back to normal. And finally people with COVID-19 are more likely to develop blood clots, and this can cause problems in the lungs and in the heart that can lead to impairment in how the heart pumps. So we really need to understand what the exact mechanism of the damage is. A; so that we can give people the right treatment, but B; so that we can understand what the longterm consequences of this heart damage is. Are people going to be left with heart failure in the future?

Chris - If as many as a half had signs of this happening, the half of the patients that you studied, is it actually very serious, the impact on the heart? Or is it one of those things, if it is reversible, it is going to recover that a person may not even know this has happened, and they just feel a bit out of sorts for a while, and then things get better and they think, phew, glad that's gone away?

Marc - Yeah. I think that's really important to understand. I mean, this study didn't address that question. It was in a very specific group of patients that were very sick with COVID-19 in hospital. The truth is we don't know how common it is for the heart to be involved in milder cases. Most people who have COVID-19 don't need a hospital, and we don't know how often their heart is involved. I suspect. And again, this is a guess, that in the milder forms of the disease, the heart isn't really involved. But what our study has shown is that if you have a very severe form of the illness and you're in hospital, then the heart can reasonably commonly, become involved. And we, as doctors should be thinking about that, because actually it's an opportunity. We have very good treatments that treat heart problems. And so there's an opportunity if we can pick these patients up, to get them better and out of hospital, back to a normal life,

Chris - To what extent do you think that COVID might just be bringing forward the inevitable for these patients that you've picked up with heart problems? I.E. given a little bit longer, they would have got to that point anyway, and it's just accelerated the pace.

Marc - Well, I think time will tell, I think, as we understand what actually causes the damage, we'll understand that better. I personally think that this is a response to the infection, that will largely get better as we treat the infection. So I don't think it's inevitable that these patients would have developed heart problems in any case. I think it is directly due to the virus, whether that's the virus affecting the muscle directly, or just the stress of having a really severe illness affecting the heart.

Chris - There's a group of people who are now dubbing themselves the long haulers. People who've had coronavirus infection, it's been documented and they've got through the worst of it, but it just seems to be going on forever. There are people who say, I used to run marathons. Now I struggle to run up the stairs. Do you think that in a proportion of these people and they're both young and old, that actually heart failure may be a sort of hidden element to this?

Marc - I think that's possible. I think this is an area that is often difficult to understand. Some people feel extremely tired following a viral illness or indeed a pneumonia. And it can just be a response to that very serious infection that a patient has had. In a small proportion, it is certainly possible that tiredness, and in particular if that's accompanied by symptoms like breathlessness or ankle swelling, that that may be due to problems with the heart. And I think the heart should be looked at.

WATER-DRINK

06:59 - Water shortages set to strike England within decades

A lack of infrastructure means England is not prepared for future climate change-induced droughts

Water shortages set to strike England within decades
Vanessa Speight, University of Sheffield

A report submitted to the UK government claims that parts of England may run out of water - within decades. These water shortages will be thanks to climate change making our winters wetter and our summers drier. And at the moment, the country doesn’t have the infrastructure to store enough water to weather the droughts. Phil Sansom heard about the problem from water systems expert Vanessa Speight...

Vanessa - By 2050, certain areas will have a quite drastic decline in rainfall, which means a quite drastic decline in water supply that's available for people to use in their homes.

Phil - Is that a serious problem in terms of drinking water?

Vanessa - That is a serious problem. Summers might have 20 or 30% decrease in the water supply, which means we are going to have to have some alternative ways to provide supply, to keep using water the way we use it right now.

Phil - That's bizarre. Because here in the UK, you don't really think about water as a limited resource like that, do you?

Vanessa - No. There is a very common perception here that it always rains and it will always keep raining. But in fact, that's not going to be the case, and we've already seen some quite hot and dry summers in the last few years. So there's all indications that this kind of behavior will continue. Certain regions, particularly in the South and the Southeast will have a worse problem in terms of lowered rainfall, where other areas might actually have more precipitation in the North and in Scotland.

Phil - So are you saying that climate change predictions say that there's going to be overall just less rain?

Vanessa - We may have on an annual basis, the same average or the same total, but actually that will come in different ways. So we'll have potentially longer dryer patches without rain and then possibly long wet patches with lots of rain and the potential for flooding.

Phil - Ah, I get that it's an issue having those extremes, but if there's the same overall rain, then why is water supply going to be an issue?

Vanessa - The problem in the UK is really about storage. So, many countries that are very dry, have vast, vast reservoirs that they've built to collect up water. Sometimes over years. That kind of reservoir storage is not as significant in the UK. The reservoirs here are relatively small and it's a small country. There's not really a lot of room to build vast new reservoirs to store the kind of water that we might need .

Phil - Where does our drinking water come from at the moment then? Is it from the small reservoirs or do we have underground water or what?

Vanessa - Predominantly it's from the reservoirs, which is runoff from the rain that's collected up. And there are a lot of these smaller reservoirs around. So it's not that there's no storage. There's just not potentially enough. There are some groundwater sources, depends on which area you live. The East in Norfolk and some of the parts of the country have quite a lot of ground water. And that's also related to rain because it's relying on the rainfall, trickling down through the soil and recharging the groundwater storage.

Phil - Part of the reason I think, that water doesn't seem like, you know, it's not like a fossil fuel that you burn, is because, you know, we just, when we use it, we don't use it up. It just goes down the toilet, or the sink, or the bath. I mean, could that water not just get used to go straight back into what we drink? I mean, not straight back.

Vanessa - Yes. And it's a very common practice in other parts of the world to reclaim the water, or reuse the water from the wastewater treatment works. That's not a common practice in the UK right now, but it is a solution that could offer a lot of potential. Particularly if the wastewater discharges are going to the ocean and basically are lost, it could be used for lots of different uses for agriculture, for industrial uses. At the extreme, you can use reverse osmosis to reclaim water from sewage. And that's in fact what they use on the space station and on rockets. So it is technically possible. It's just a question of building that infrastructure, and thinking more creatively about how we use water that's matching the quality to the use that we want to have.

Phil - If there's this predicted time limit, then what was it? 20 years?

Vanessa - By 2050, possibly earlier.

Phil - Oh, okay. Well, if there's this urgency, what's the plan? What needs to happen?

Vanessa - There isn't a great plan yet. Each of the water companies do their own plan, but that doesn't necessarily take into account national issues. And so really now is the time to develop a serious longterm plan. And this infrastructure takes many, many years to plan for and build. So it's not something we can just snap our fingers and say, Oh, next week, there's going to be a drought. So we'll just install a new treatment works. It doesn't quite happen that quickly.

Mussels on the seashore

12:48 - Shellfish supercharged with vitamins

Vitamin bullets developed that load shellfish with extra nutrients

Shellfish supercharged with vitamins
David Aldridge, University of Cambridge

Researchers in Cambridge have developed what they’re calling ‘vitamin bullets’ - but they’re not for shooting, and nor will you find them at the pharmacists! These capsules are designed to be fed to shellfish to make them more nutritious. Joining us is the vitamin bullet farmer himself, David Aldridge…

David - Thanks very much, Chris. Well, a vitamin bullet is a tiny particle. It's about 20 microns in size. So you can get about 50 of these lined up along one millimetre, and inside these particles are nutrients. Things like vitamins vitamin A, vitamin D, which are wrapped up in a tasty coating. And the idea is that these particles are made just the right size and shape for mussels, and clams, and scallops, and oysters, to filter out of the water column. And by doing that, they concentrate those particles inside their guts. And then when we eat those shellfish, we get that nutritional benefit.

Chris - Can you actually demonstrate though, that whatever's packaged up in your magic bullets is absorbed by the creatures and then gets into their bodies so their bodies become enriched for those substances?

David - Well, actually what' we've done is quite clever in that what we've designed these particles to do is to be dosed just at the end of the production system for commercial shellfish. So whenever people farm mussels, or clams, or scallops, or oysters, they have to go through, what's called a depuration stage. And this typically lasts about 48 hours. And this is the stage where ultraviolet light is shone into the water so that all the nasties, all the bacteria are removed from inside the bivalves. And what we've found is that if we just dose the particles at the very end, the last eight hours of that process, just before the bivalves are then removed and sent off to the shops, then the bivalves keep those particles in their guts. And because we eat the entire animal guts and all, when we eat bivalves, then we actually know for sure that those particles are going into the people that consume them. And another important thing with this is that by fortifying something where you actually eat the animal flesh and tissue, we know that that makes it much more bioavailable to the consumer than having it just added in a pill.

Chris - Will it work for any vitamins and minerals David, or are there specific ones that work best like this?

David - Well, the beauty of this technology. If you like, the world is our oyster, we can put whatever we like in these particles. I couldn't resist. We can tailor the nutrient profile that we put in these particles to whatever is limiting in a particular geographic location. So we know for instance, that vitamin A and vitamin D are particularly important nutrients in terms of global deficiencies. So for instance, over 85% of people in India are vitamin D deficient, and that can cause osteoporosis and rickets. So we know that perhaps if we target species in India, we should put vitamin D in, and actually even in North America, 40% of the population is vitamin D deficient, but there are other regional nutrient deficiencies globally. And we can tailor our formulation to whatever the local need might be.

Chris - Does it effect the creature itself, when it ingests these particles? Does it affect the flavour? That's very important, but does it also affect the health of the organism? And also in terms of storage, when we put these things into storage and transport them, are there any risks through doing this where it may have a health dis-benefit?

David - The products we use are a hundred percent food grade, we actually manufacture them on a plant that makes encapsulated particles for the food industry. So, there's absolutely no reason to think it would actually have a negative impact on the animals. And actually another avenue of our research is - actually relates to putting flavourings in these particles so we can make the bivalves more tasty.

Chris - What sort of flavours are we talking? Do your mussels come pre-loaded with garlic? Is this what you mean?

David - You could do whatever you like. Yeah. So we've actually tried garlic butter. Another potential thing would be to have chilli flavourings. So you could bring your mussels back from the supermarket and you could put them in some water and get some to take up chilli and have a game of Russian roulette with your mussels [giggle].

Chris - But more seriously, what you're showing is that this works across a repertoire of different things that you could put in. How much does it cost though? Because obviously if it hits the bottom line in a big way, it's just not going to be practical for people who are earning a dollar a day. Whereas if it's very, very cheap and it can sort out their diet, then that's wonderful. So what's the price?

David - Yeah, absolutely. That's the crucial thing. And for that reason, we’ve started from the top down and we actually manufacture our products on a commercial scale and have sort of tailored commercial scale systems down to meet our needs. And so we can produce 5,000 tons of product very cheaply, on our UK plant and because we only dose these products for eight hours, you need next to nothing. And so we estimate that perhaps our products might add less than one pence onto the cost of an oyster. And so it will be very, very acceptable. It's also been shown that actually in a lot of developing countries, that fortified foods carry an acceptable price premium, which people are willing to pay, much more so than eating a vitamin pill, which is less good anyway. A good example is nutrient-enriched rice for instance in a lot of the developing world, where people recognise it as being healthier and are prepared to pay a slightly higher premium, but the cost is really, really small.

A first place trophy.

World record breaking kidney transplant
Angela Dunn, France & Roy Calne, Addenbrooke's Hospital

This week, 50 years ago, a young woman had a pioneering operation that undoubtedly saved her life. It was one of the first kidney transplants, and it was performed by Cambridge University surgeon Roy Calne. Half a century later, her now world-record-breaking transplant is still going strong and she's in fine health. Chris spoke to her, and Roy Calne, to hear their remarkable story...

Angela - My name is Angela Dunn. I'm 74 years old, will be 75 next month. And I have had my transplant for almost 50 years, 50 years next week. I had scarlet fever three times when I was young, and also erysipelas. And then it was obvious that there was something seriously the matter with my kidneys. My health was deteriorating. I had a period when I was vomiting every other day, I had very high blood pressure, bleeding in my eyes.

Chris - How did it then escalate, so that you ended up on a transplant waiting list?

Angela - Well, my condition deteriorated, I had very high blood pressure that was virtually uncontrollable, went into a coma and it was decided that the only thing to do was to take my kidneys out, and then I had to start dialysis.

Chris - What was that like?

Angela - Horrible. And I found it very difficult. But the worst for me was the limit on fluids. Five or 600 ml a day is not a lot for a girl from Lancashire who likes a big cup of tea.

Chris - Yes. I imagine that would be quite a wrench. So your quality of life was down. You were on dialysis regularly and fluid restricting. And feeling probably exhausted all the time, which for someone in their early twenties, that's not really living, is it?

Angela - No, no. It was difficult. And it was very difficult for my husband as well.

Chris - So tell us about that day, the big day when it all happened.

Angela - We lived about a mile from the hospital and so about seven o'clock at night, the doctor came to the door, my consultant, and said: "the kidney is on its way, pack a bag and come up to the hospital. And Professor Calne is coming from Addenbrooke's.

Chris - Addenbrooke's is Cambridge University's teaching hospital. And Roy Calne was professor of surgery there. And one of the pioneers of organ transplantation in the UK.

Roy - News came through that there was a kidney from a road traffic accident victim, and it was the right blood group for her. I went and saw her and she said: "you've got to do it".

Chris - But there was a very good reason why Roy Calne and his surgical team needed to come halfway across the country to Angela.

Angela - Because I was dialyzed in the same room as somebody who it was thought had hepatitis B. And hepatitis B at that time was absolutely terrifying for every renal unit and transfusion service in the country. And so Addenbrooke's would not have me through the door.

Chris - Luckily Angela's husband, Eric, came to the rescue.

Roy - Angela had a husband who was an RAF fighter pilot. So he asked if he could help. So I told him, well transport's the main thing. And he said that he could get my team there because he had access to an aircraft. So he was the taxi driver there and back.

Chris - So the RAF flew you and your surgical team to do the operation?

Roy - RAF Poulton.

Chris - So the RAF pulled some strings?

Roy - Very important strings.

Chris - Roy Calne did that surgery. Angela, luckily didn't have hepatitis B. And the outcome was a successful one.

Angela - It took eight days for the kidney actually to work. I have to say that after four months of not "spending a penny", it was quite a strange sensation.

Chris - That must've been one of the most welcome wees that you've ever had!

Angela - Absolutely. [giggle]

Chris - And how have you managed since? What has happened to you since?

Angela - A normal, healthy, happy life. And from 1978 onwards, I competed for Cambridge in the transplant games.

Chris - What was your event?

Angela - I ran the longer distances, and I swam. And I occasionally played table tennis.

Chris - Did you win?

Angela - Yes. Quite a lot.

Chris - You're now at the half a century point since this all happened. Does that put you amongst one of the longest surviving transplant recipients? Are there any other people who are further down the track than you?

Angela - I am told, but I have no proof of this, that my kidney is the longest cadaver kidney in the world.

Chris - So not only did you get a record on the transplant games, you're also in the Guinness Book of Records potentially for the longest surviving transplant?

Angela - Yes. I'm not entirely sure that I wanted an accolade like that actually! Not something I would seek.

DNA structure

24:53 - What is DNA?

What does DNA do in our cells, and what does a 'DNA sequence' look like?

What is DNA?
Eva Higginbotham

Coming up, we’ll hear about Rosalind’s life and work, including hearing from her younger sister, Jenifer, and where the DNA revolution she helped to kick start is taking us today. But first, what actually is DNA? Recently, Eva Higginbotham took a windy bike ride in the July sun down to the south of Cambridge, along a cycle path painted like coloured piano keys stretching into the distance as far as she could see...

Eva -Although the path was created in 2007, the metaphorical foundations for this path were laid back in 1953 through the work of somebody whose birthday it is on the 25th of July, who would have been 100 years old - Rosalind Franklin. You see, this is the DNA cycle way, and Rosalind Franklin’s research was part of what set us on the path to really understanding DNA. DNA is the material unique to each of us that lives in our cells and contains all the instructions for not just what that cell has to do, but for how to build your entire body. Now DNA stores this incredible amount of information very elegantly in the form of a long sequence of different molecules called nucleotide bases and there are 4 types: adenosine, thymine, guanine, and cytosine, A T G and C, and just like the path, where the bases are represented by the different colours, they are in a long sequence one after the other, in what appears at first glance to be random order, but is actually not random at all, because it’s the order of these As, Ts, G, and Cs that makes up specific genes, which in turn codes for the specific proteins and other products which make up our cells. In fact, if I kept going south, I would come to the Sanger Institute, a research institute named after Fred Sanger who invented the first method to figure out the order of bases in a piece of DNA in a process called sequencing. The path I walked on goes on for over 10,000 yellow, green, red, and blue ‘bases’, and represents the genetic sequence of the BRCA2 gene, mutations in which can cause breast cancer. It’s also rather busy, and next to the railway tracks. Rosalind Franklin sadly died at only 37 of ovarian cancer, but it’s partly down to her research into the structure of DNA that we know that not only does DNA have bases, but is actually made of two long strands of molecules called phosphates with the bases stuck in between, and those two strands stick together because the bases like to pair up with each other. A’s bind with Ts, and Gs bind with Cs. You can think of it like a ladder, where the horizontal rungs are the bases and the vertical bits are the phosphate backbone. Apart from DNA is more like if you twisted the ladder to form a sort of corkscrew, in other words, a helix. The reason we know DNA is a helix is thanks to Rosalind Franklin’s experiments using a technique called X-Ray crystallography, but the story of that discovery isn’t exactly straightforward. So as my walk down the DNA cycleway came to a close, let’s walk back in time to find out more about Rosalind’s life and work. And what better place to start than in Cambridge, where Rosalind got her start as a scientist.

Bookshelves in a library

29:18 - DNA structure: a history

How does Rosalind Franklin fit in the DNA story?

DNA structure: a history
Birgitta Olofsson, IST Austria

So what's history behind the science of DNA structure? Neuroscientist Birgitta Olofsson, who is also making a documentary about Rosalind Franklin’s life and her role in the DNA story, spoke to Chris Smith...

Birgitta - So DNA in itself was not much of interest to a biochemist. It was mostly protein. But Jim Watson and Francis Crick were very keen to understand the genetic basis for heredity. That is what is information that's passed on to the progeny? And Jim Watson, being a geneticist, had very little understanding about chemistry, but in terms of chemistry, the structure of DNA, so the actual chemical structure of the DNA, had been known since a number of years. It was also postulated that the DNA was in fact the genetic material that's passed on into the offspring. And that was done in a set of elegant experiments, where a bacteria was infected by a virus, much like the coronavirus that we talk about a lot these days. And the virus consists of a protein structure and the DNA. And by selectively labelling the protein structure versus the DNA, they could show in these experiments that only the DNA that's taken up by the infected cells and then passed on in the progeny of the virus.

Chris - So they knew that DNA was critical to heritability, but they didn't necessarily know how. And they didn't know how the molecule was organised. And that's really the breakthrough of the early 1950s was working out that there actually was a structure there that could carry  heritable information?

Birgitta - Yeah. So it was generally believed that DNA was too simple a molecule to be of this importance. Because in DNA there is only four letters, so to speak. The A, T and the C and the G. Meanwhile in a protein, a protein can be built up of 20 amino acids. So the complexity in the proteins favoured that proteins were in some combination with DNA, the genetic carrier. So it wasn't uniformly accepted that DNA was indeed the genetic carrier.

Chris - And what was the thinking at the time? There must have been rival groups. It wasn't just Watson and Crick's game, was it? There were presumably many other scientists who were all trying to understand this all at the same time and they must have all had rival theories.

Birgitta - Absolutely. So if there ever was a race, the race was not between Rosalind Franklin and Morris Wilkins in Kings in London, and Francis Crick and Jim Watson up in Cambridge in Cavendish, it was actually between Linus Pauling, a protein chemist in the US, and the group at the Cavendish. It was postulated by both Linus Pauling, and Francis Crick and Jim Watson, that DNA could be a three strain molecule where the DNA bases were facing the outside and the phosphates facing the inside. And that would not be chemically and physiologically possible.

Chris - Why though was solving the structure so critical to all of this?

Birgitta - Well, by knowing the structure, you could immediately understand how the DNA could be replicated. That is that one DNA strand makes two new DNA strands in the progeny.

Chris - Where then did Rosalind Franklin enter the equation? Why is she so important to all this?

Birgitta - So Rosalind Franklin came to Kings in 1951 and she was on her own fellowship. So she was not an assistant to Morris Wilkins who was there already working on DNA, but she was really an excellent chemist, a physical chemist, and she knew how to treat specimens. So she was able to see that the previous x-ray crystallography photographs that had been made was really a mixture of two forms of DNA. And she was able to separate out these two forms. So then you can study these two forms separately. And we know that one of those forms is the physiologically relevant, that one that is in our cells and that's called the B form.

Chris - So she managed to separate the DNA  into a form that could then produce very nice pictures. And it's those pictures that were the insight into the structure.

Birgitta - Exactly. From those diffraction patterns on these pictures, you could see that it was a helical structure, repetitive units, and you can also see how many base pairs per turn in the unit and the diameter of the helix. But it was really Francis Crick and Jim Watson who worked out the antiparallel structure. So the two strands of DNA are going in the opposite direction, plus this base pairing. So hydrogen bonds between these letters, so to speak, in the ladder of DNA.

Chris - And is that the basis of this so-called famous photograph 51? Is that the one that's the very famous picture we see in textbooks and things, it almost looks like a zebra crossing in three dimensions.

Birgitta - Absolutely. So photo 51 was called photo 51, simply because it was number 51, and it's of the B form. And it was Rosalind's PhD student, Raymond Gosling, who took that. And when Rosalind was about to leave to Birkbeck from King's College, he showed that to Wilkins who later showed it to Jim Watson. So they had access to this photograph.

Chris - And once she took that amazing photograph - and we will learn a bit more in a second about the technique that she used in order to take that photograph that was the clincher that revealed the structure of DNA, as you're saying - did she carry on doing this sort of work? What happened to her after this?

Birgitta - So Rosalind was at King's only two years. And then she continued at Birkbeck where she used x-ray crystallography to solve structures of viruses. So she was in fact with her group, the first person to solve a viral structure, which was the tobacco mosaic virus. And her tombstone does not tell anything about DNA, it's for the virus work.

Titanium aluminium

What is X Ray Crystallography?
Megan McGregor

The key to the breakthrough of understanding genetic inheritance was understanding the structure of DNA, and, to solve this, Rosalind Franklin used a technique called X-Ray crystallography. This enabled her to figure where the individual atoms are in DNA. But how does it actually work? Materials scientist Megan McGregor explains...

Megan - Rosalind Franklin used x-ray crystallography to create photo 51, a black and white picture showing an X shape made up of spaced apart, black splotches. And it was thanks to this photograph that the structure of DNA as a helix was figured out. This was a picture of crystallised DNA, but what is x-ray crystallography? Lots of materials from ice cubes to steel girders are made up of crystals. Each crystal is composed of a repeating arrangement of atoms with well-defined spacing like soldiers marching in formation. This repeating arrangement gives distinct layers of atoms and the spacing between them can affect many material properties from strength to conductivity. X-ray diffraction is one way to measure the distance between the layers. An X-ray diffraction experiment shines a beam of x-rays onto a material and varies the angle between the beam and the material surface. At certain angles, we can detect a very strong X-ray signal being re-emitted from the surface, like light being reflected off a mirror. Father son team, William and Lawrence Bragg realised that with a bit of maths, these angles could be related to the spacing of the atomic layers in the material. Why? At certain angles, the distance an X-ray travels between the atomic layers matches up perfectly with the wavelength of that X-ray. So if you know the wavelength of the X-rays, and the angle they hit your sample at, you can work out the spacing of the atoms inside the material based on the pattern of reflections you get. Each crystal will generate a unique pattern of strong reflections at certain angles, like a fingerprint that can be used to identify that crystal structure. This is why X-ray diffraction was so useful to those trying to figure out the structure of DNA. Working backwards from the unusual X-ray reflection pattern in photo 51, scientists were able to work out that the atoms of oxygen, hydrogen, carbon, nitrogen, and phosphorus could only be arranged in one way, the famous double helix.

Newnham College

38:48 - Jenifer Glynn: remembering Rosalind

Rosalind's sister, Jenifer, has many fond memories of Rosalind

Jenifer Glynn: remembering Rosalind
Jenifer Glynn

Regrettably Rosalind’s scientific career was sadly cut short when she died from cancer aged only 37. Greatly missed by her loved ones, she came from a big family with 4 siblings. Speaking with Eva Higginbotham her sister, Jenifer, has many fond memories...

Jenifer - My name is Jenifer Glynn, I'm the younger sister of Rosalind Franklin. I think it was always clear from the start that she was going to be a scientist. She loved developing photographs at home. My grandparents had a dark room she could use, and my mother was keen on photography, developing photographs. She enjoyed actually using the chemicals and doing it was a great pleasure to Rosalind as a child.

Eva - Rosalind's enthusiasm for science took her all the way to Newnham college at the University of Cambridge. One of only two colleges at Cambridge at the time that was open to women.

Jenifer - Rosalind went to Newnham in 1938. Everyone was delighted. Even my grandfather, who was perhaps the most conservative member of the family, gave her a present of five pounds, which was a lot of money in those days. I went to see her in her first year, went with my parents. And I, sorry to say that I was only eight, and all I can remember is the baby ducks on the river. But I did stay with her for a weekend when she was a research student. And she was a marvellous hostess thinking of everything that a 12 year old might enjoy. And it was a very memorable weekend. We saw all the standard Cambridge sites and went on the river. Being imaginative she also took me to see the Newnham baker stirring a great vat of dough, which I also remember with tremendous pleasure. She worked very, very hard at Newnham, but being outside was always important to her: hockey and tennis and cycle rides and skating she was very keen on. But most of her time really was spent on very hard work. She was very perfectionist in her nature, was always determined to do extremely well. It may be surprising to find how very nervous she was about exams, very unsure of herself in that way, right from when she thought she wouldn't get a school scholarship right through to university exams, and even her PhD, she thought would fail. Of course she always did extremely well, but it was a worry. Never anything came easily to her. She always worked very hard for it.

Eva - The university had come a long way in how it treated students who were women, but there were still remnants of the past to contend with.

Jenifer - There were occasional lecturers that would still address their audiences as gentlemen, quite regardless of who was there

Eva - After completing her degree in 1941, Rosalind was awarded a research fellowship at Newnham, and she worked for time at a physical chemistry laboratory at the university. But, the second world war was in full swing and she had to do some war work, which she was very keen to do. She worked for a firm called the British Coal Research Association, where she investigated the structure of holes in coal, which helped in the manufacture of gas masks. The work she did there counted for her PhD.

Jenifer - She was very fortunate in getting a post in France. She loved France, and she was lucky enough to find a post in a French lab, which was investigating the structures of coal and was doing it with the technique of x-ray crystallography, which she was able to learn there. It gave us sort of continuity to her researches because it was always connected with the structure first of coals, then later of DNA, and then of viruses. And although she was not a biologist by training, but a chemist, it was the same techniques that she was then able to apply to biology.

Eva - After four very happy years in France, Rosalind took up a position at King's College London, where she did her famous work on DNA. However, being a woman in science didn't come without its challenges.

Jenifer - It was certainly male dominated. You have to work even harder and be even more sure of what you were doing. That possibly may have inhibited her from guessing in the way that say Crick and Watson did. You had to be terribly sure before you published anything, she did find the male atmosphere that King's uncongenial to say the least.

Eva - I asked Jenifer if she thought Rosalind would be surprised at the attention that her life story and family story have received over the years.

Jenifer - Yes. Simple answer. I think she'd have been totally amazed actually. She would have been very amazed at the idea that she became a sort of feminist icon. It was not, I think, anything in her mind at all. She was just a scientist who wanted to do it all she could in that way, although nothing would please her more than the fact that it perhaps encourages girls into science.

Genes and DNA

What's new in DNA structure?
Zoe Waller, University of East Anglia

So far we’ve dwelled on the history of DNA, but what about the present and future? Since 1953 we’ve decoded all 3 billion letters of the human genetic code, learned to read DNA sequences incredibly fast, found ways to transfer genes from one organism into another to make vaccines and drugs rapidly and safely, and now we’re moving into the realms of editing an organism’s DNA. But scientists still remain very interested in the structure of DNA itself, because it has some special chemical properties, speaking with Chris Smith from the University of East Anglia, is Zoë Waller...

Zoë - So Rosalind Franklin, the data that she got showed that the structure of DNA was helical, it's composed of two strands, and these run in opposite directions to each other, and that the helix was not completely symmetrical. So one strand was slightly offset from the other. Using that data, Watson and Crick proposed a model, so what they suggested was only a model of DNA. It was widely accepted to be correct, but it wasn't actually shown in full detail until the 1980s where they used detailed X-ray crystallography structures to actually determine a more detailed vision of what the DNA molecule is. And then that showed that actually that model was pretty much spot on.

Chris - Obviously cells have something of a problem with their DNA though don't they? Because if one were to look at how much DNA is in a cell it's measured in meters, but the size of a cell is measured in fractions of a millimetre. So how do cells get around this?

Zoë - That is true. If you lined up all of the DNA in one cell, it would be about two metres long. Being able to compact the DNA enough to get it to fit inside the cell is a magnificent feat of biology. The DNA is wrapped around proteins and it's very, very tightly wound up. So what happens is when the DNA needs to be used or read, that unwinding, it's a bit like winding up a an elastic band for example. If you wind it again and again and again, and then you try and pull it apart, you'll find that that tension actually causes other parts of the elastic band to kind of crumple up and the DNA will do the same. And it actually forms other structures as well when this happens.

Chris - Does that affect how genes can be read or not? Because if you've got your elastic band analogy, a band wound up very, very tightly, if I wanted to see what was written on the inside surface of a bit of my elastic band, I'd have a hell of a job pulling it apart so I could actually see. And I suppose when you want to read a section of your genome, if it's wound up tight as a spring, that's going to be a problem.

Zoë - There are particular enzymes and proteins that help unwind the DNA. Even when those are working, the DNA needs to pull apart to become two separate strands. And it's when that happens, that DNA can actually form into alternative structures. And those are some of the ones that we are interested in my research group.

Chris - Like what?

Zoë - We are particularly interested in four-stranded structures. So when DNA contains a lot of one single base, for example, the base C or cytosine, that can form into four-stranded structures. Which are very much like a, almost like a knot these are called i-motifs, we're very much interested in that. And these form when cytosine, instead of base pairing with guanine or C base with G, actually base pairs with itself. So it forms an interaction with itself. And then this can actually result in different structures forming.

Chris - I'm just trying to get my head around that. So I'm envisaging two strands of DNA. And then in one place in the DNA, there's going to be this long chain of Cs, the letter C, one after the other. And you're saying that because of the chemistry of that long run of Cs, that those Cs can sort of fold out and distort and stick to themselves rather than what they should be doing. And this produces these rather strange knots in the DNA.

Zoë - Yes. So if you imagine a single strand or even a piece of string and then wrap it around twice around something, that's the kind of type of structure that you've got. It's a four-stranded structure, so you need to loop it round twice. Instead of having DNA, or double helical DNA, I like to think of it like a twisted ladder - so you imagine a ladder, twist it round - instead of having that type of structure, an i-motif is intercalated and that's what the I stands for. If you criss cross your fingers or intersect your fingers so they form a cross shape, that is what you have in the middle of the core of this DNA structure. So instead of it being like a ladder, it has crosses in the middle. So this structure is very tightly compact, and it's also much smaller in size compared to the equivalent single strand or double stranded DNA.

Chris - Are these common in cells? Do you see this normally? And what do they do?

Zoë - Well, that is a big question and one that we are very interested in. It is only a couple of years ago that these have been shown to exist in cells. It's thought that these structures play a role in how genes are read. Some evidence has been shown that if you help try to form the i-motif structure, you can actually help switch a gene on, but we're still learning about these things. And this is one of the reasons why we are very excited to work on it.

Chris - If you look at cells that have diseases, and I'm thinking particularly of genetic diseases like cancer, do you see more or fewer of these things? Might they be a hallmark of a cell that's going down the pathway towards cancer, and may they also therefore be a way in which you could control genes in cancer and potentially turn a cancer cell off?

Zoë - This is absolutely one of the things that people are interested in. One of the things that we are working on and we've been looking at is how these sequences that contain a lot of cytosine actually change as we age. As we get older, these cytosines are quite often deleted or mutated, so that means they're no longer a cytosine, they might be changed to a different base. This will change eventually the structure of DNA as well. So we're looking at how that affects aging and how it affects the structure of DNA and how this could potentially affect how genes are read. But then also through the progress of disease as well, diseases such as cancer, but also we are looking at diabetes as well.

a hairdresser washing someone's hair with shampoo

QotW: Do you really need to wash, rinse, and repeat?

Phil Sansom's been getting down and dirty to answer Julie's question...

Sally-Ann - There is actually science behind the double hair wash method, and it is not a ploy to get you to buy more shampoo.

Phil - That is Sally-Ann Tarver, who is a trichologist - someone who studies and treats the hair and scalp. And while Sally-Ann says this ‘wash, rinse, repeat’ isn’t just marketing hocus-pocus, it’s also not always necessary.

Sally-Ann - It is really dependent on how often you wash your hair. If it’s short and you wash it every day, then no, you don’t need to shampoo twice, as your hair hasn’t had time to get oily. If you use a lot of product, you haven’t washed it for a couple of days, or it’s long or thick, you will need to wash it twice.

Phil - Now the reason has to do with how the soap or cleanser in the shampoo works.

Sally-Ann - The soap or cleanser molecules, micelles, can only hold so much dirt. Micelles are molecules that have one end electrostatically drawn to dirt and the other end drawn to water. As you shampoo your hair the micelles are attracted to the dirt / oil / product and kind of engulf it. Then when it’s rinsed out, the water loving micelle end is drawn to the water and the dirt is rinsed away with it.

Phil - The micelles can only hold so much dirt at once - so to really get at that stubborn oiliness, you might be better off doing two washes, just with less shampoo.

Sally-Ann - The first shampoo you may not get a lather but those micelles are attracting a lot of dirt which is then rinsed out. The second shampoo removes any remaining oil, product, etc.

Phil - Eva Proudman from the Institute of Trichologists agrees - and she says the advice changes depending on what you get up to.

Eva - If you love hair products and lavish them on your hair then two shampoos will most probably be required to ensure that they are fully removed. If you wear a hat or head covering all day, or work in an environment that produces pollution, then again, the 2-stage shampoo is for you. Those who suffer with dandruff, seborrhoeic dermatitis or psoriasis - regular shampooing can help to manage the scalp environment, so it’s a must. If you are  experiencing a flare up in symptoms, wash, rinse, and repeat can really help to calm the flaking, itching, and inflammation.

Phil - Thanks Eva Proudman and Sally-Ann Tarver. Next time we’re digging through the dump - to answer this question from Johnny:

Johnny - Does burying paper in a landfill sequester carbon?

Eva - Can you help out with Johnny’s question? you can ask via our website by going to nakedscientists.com/question, email chris@thenakedscientists dot com, find us on Facebook, tweet @nakedscientists or join in the debate on the forum - the naked scientists dot com slash forum.

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