Rosalind Franklin: the hidden story of DNA

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?

凡妮莎-这是一个严重的问题。萨默斯可能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.

菲尔——这是奇怪的。因为在英国,你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.

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.

罗伊-新闻是通过肾脏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.

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.

贝,绝对。如果曾经有过一个比赛, 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?

贝——所以罗莎琳德富兰克林来到吻ngs 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.

贝,绝对。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.

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.