An Interview with Prof Nina Wedell

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Animals behave in ways that sometimes seem strange to us humans. But, fundamentally, everything they do is driven by survival and reproduction. They need to eat to stay alive, and they need to reproduce to ensure their line (and genetic information) survives once they are gone.

“Why do animals behave the way they do?” is the question that got Nina Wedell interested in science and now she is a top professor at the University of Exeter studying the evolutionary ecology of sex and selfish genetic elements. Reproduction is essential for all species, but there are many differences in sexual behaviour between different animals. Prof Wedell has looked at the genetic basis for these differences. In fruit flies, for example, she has shown that female promiscuity can actually prevent population extinction caused by a male-killing selfish gene found in these insects.

I spoke to Prof Wedell to find out more about her work on selfish genes and to get some insights and advice from a successful woman in science.

LabcoatLucy (LL): Let’s start off with the science! What is your most interesting discovery?

Prof Nina Wedell (NW): One of my favourites is an early finding which settled a long-standing mystery. In most species of butterfly and moth, the male produces two types of sperm: normal sperm and copious amounts of blank sperm with no genetic information in it. This blank sperm seemed to have no evolutionary value, or even to be detrimental to fertilisation. However, most insects can store sperm – to give an extreme example, bees and ants might store sperm for 30 years! I studied the green-veined white butterfly and found that the male butterflies produce all this extra dud sperm to fill up the female’s sperm storage tank. This tricks her into thinking she has a full sperm supply and so she doesn’t re-mate with other males. So, the dud sperm helps to ensure that it his good sperm fertilises the female, rather than another butterfly’s sperm. There is an evolutionary advantage!

LL: So, what are you working on now?

NW: Nowadays, I work on selfish genes that are present in all organisms, including humans. They violate equal inheritance: the selfish genes are more frequently inherited than other genes. Most scientists just ignore them and think of them as junk DNA with no real purpose, but how they persist and spread is fascinating. We use fruit flies (Drosophila) to study these selfish genetic elements. You can breed fruit flies rapidly and then follow changes over many generations.

But genes are not straightforward! ‘DTT resistance’ is a nice example of this… Some fruit flies carry a variant of a gene that makes them resistant to DTT, which is great for the fly. And in females it also makes them produce more eggs, so it’s a great gene to have. In contrast, males who have the DTT resistance suffer, they have lower mating success than those without the resistance gene. We call these genes sexually antagonistic: good for one sex, bad for the other. Looking at how this type of gene is inherited down the generations is very interesting!

LL: What is the biggest unsolved problem in your field?

NW: The link between genotype (genetic makeup) and phenotype (observable characteristics such as height and eye colour). For example, with height there is an interaction between different genes in the individual that determines height, but we don’t know how that works. To go back to fruit flies with the DTT resistance gene, there are clearly gene-gene interactions that differ in males and females.

LL: What first got you interested in science?

NW: As a child I was always intrigued by natural history. At the age of 4, I wanted to be a lion tamer. When I was a little older, I wanted to be an author and explorer. And now, as a scientist, that’s what I am! Science is exploration. I ask questions, discover the answers and then write about it! And I get to travel all over the world. I actually had a background in humanities up until the age of 18. As an adult I went back to study science as I realised that it was more than just an interest, but something I wanted to spend my life doing.

LL: So do you think your background in humanities set you up well to be a scientist?

NW: Yes! In science you have to come up with a precise hypothesis to test. The humanities taught me to be creative and articulate, which is essential for this. Clear thinking and good communication skills are vital in science, I would say more important than being clever. Very few scientists are real savants or geniuses, for the rest of us science is about slogging, being creative, taking intellectual risks, discussing our ideas with other people and not being too afraid or intimidated to consider a new idea. The humanities gave me a good start in those things. But maybe a science background would have given me the same, there was no control experiment!

LL: Of what achievements are you most proud?

NW: Well, apart from teaching… one of the things I am most proud of is a natural history discovery, rather than an evolutionary biology one. I found a brand new species in Australia, and it was actually named after me!

LL: That’s cool! Interesting that you say “apart from teaching”, so teaching is important to you?

NW: I get such joy from teaching! That moment when you watch the penny drop is brilliant. Nothing is so rewarding as teaching. A colleague once gave me some advice, “Everyone complains about teaching, but just embrace it.” And that was a game changer. If you decide that teaching is encroaching on your research, then you will just resent it. I call it positive self-deception: look on it positively and you’ll enjoy it.

LL: So, what advice would you pass on to younger researchers?

NW:

  1. Try not to worry.
  2. Be in it for the long haul, there are no quick fixes in science.
  3. Do something that you find exciting. If you do something just because it’s trendy (i.e. other people find it exciting), you won’t enjoy it so much and there will be so much competition that a better financed lab will probably beat you to it.
  4. Believe in yourself.
  5. Ask for advice. Now, as a professor, I want to do what I can to help younger scientists, but it is virtually impossible to help you if I don’t know what you need. And getting advice gives you a network.

LL: Ah, you mention “networking”, a word many PhD students don’t quite understand and a great many fear! Do have any networking advice?

NW: Well, as a supervisor I feel that it is my duty to introduce members of my lab to other researchers as it is a crucial part of science. I’d say, start with your peers, you can share experiences with them and grow up in science with them.

Before a conference, target one individual: send an email beforehand telling them that you have a poster or are giving a talk and invite them to talk to you. One really rewarding interaction is better than ten rubbish ones. Also, do your homework, find out who is going to be there that might be interested in your work. People worry that networking is too much like self-promotion, but networking is fundamentally sharing information about research. That is why we all do science, because we are interested in the latest research, so we all want to discuss it! Some people don’t want to talk about their research because they are worried someone will nick their idea, but I say “so be it!”. Science in secret doesn’t work, we need to maintain a culture of openness.

LL: Who are your science heroes?

NW: Barbara McClintock is one of my all time heroes. She worked with corn which had differently coloured kernels and discovered that the colours were due to different transposable elements. She got the Nobel prize for that! Obviously, Darwin! I know it sounds a bit clichéd, but he was genuinely a fantastic scientist. Dame Linda Partridge who looks at the biology of ageing is amazing and I really admire Miriam Rothschild, a self-taught natural historian who kept working until she was almost 90.

LL: Quite a lot of those heroes were women! Do you think of yourself as a “woman in science” or just as a “scientist”?

NW: Both! There are shockingly few women at the top in science and there are many complicated reasons for that. So I don’t shy away from being a woman in science, I acknowledge it. And I acknowledge that the loss of great women from science is an issue. Almost two thirds of undergraduates in biology are female and at PhD level about half are female, but it drops off rapidly and there are hardly any female professors. Having half your talent not contributing to the subject further up the career ladder is terrible! And so I make an effort to show students that you can be a mum and a scientist. I spend a lot of time chatting to young women, encouraging them. Always being in the minority isn’t nice, we need to fix it. With more women, it is more fun for all of us! Women add creativity and different ways of thinking, and there is evidence that an equal sex ratio encourages a more collaborative atmosphere, which can only be good for science.


Thanks so much to Prof Nina Wedell for taking the time to talk to me! And thanks also to Lindsay Walker (@Linds__Walker) for suggesting Prof Wedell. Who would you like me to write about next? Leave your suggestions in the comments below, or tweet me @LabcoatLucy!

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Dorothy Hodgkin: biochemist and x-ray crystallographer

When you look at the world, what do you see? Nobel prize winner Dorothy Hodgkin (1910–1994) saw puzzles waiting to be solved. Using x-ray crystallography, Dorothy solved some of the most challenging puzzles of her time: the complex atomic structures of penicillin, vitamin B12 and insulin.

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So, what is x-ray crystallography? Put simply, it’s a method for discovering the atomic structure of a molecule by studying how x-rays bounce off a crystal of the molecule. The main requirement of the crystal is order. Like wallpaper which has a repeating two-dimensional pattern, a crystal has a repeating three-dimensional pattern. Once you have a good-quality crystal, you shoot a beam of x-rays at the crystal, they bounce off the atoms in the crystal and you record the resulting pattern made by the diffracted x-rays. From these patterns, you can work out the structure of the molecule (with the help of a lot of mathematics and a little imagination).

From a young age Dorothy was fascinated by crystals and as a teenager she was inspired to become a scientist by the 1923 and 1925 Royal Institution Christmas Lectures by Sir William Bragg, a pioneer in using x-rays to study the atomic structure of materials.

Dorothy went to Somerville College, Oxford to study chemistry. Luckily for her, the university set up its first x-ray crystallography lab just as she was due to start her undergraduate project. As I’m writing about Dorothy, I’m sure you can guess that her project was a great success. In fact, her thesis on the structure of thallium dialkyl halides was published as a short note in Nature. *Keep jealously under control*

Dorothy did her PhD at Cambridge, under J. D. Bernal. Working in Cambridge opened her eyes to the potential of x-ray crystallography to solve the structure of complex biological proteins. She carried out initial measurements on sterols and pepsin crystals (and published a lot!), but she returned to Oxford to focus on cholesterol. Soon Dorothy published the first structure of a steroid, cholesteryl iodide, with Harry Carlisle, but this was just the first of many biologically important molecules that Dorothy would solve.

Molecular model of Penicillin by Dorothy Hodgkin, c.1945

In 1940, Dorothy wasn’t the only future Nobel laureate working in Oxford. Howard Florey and Ernst Chain were culturing penicillium mould to extract the new and powerful antibiotic, penicillin. The day after their first historic experiment showing that penicillin could protect mice against streptococcal infections, Chain ran into Dorothy “in a very excited state” and promised her some crystals. Easier said than done. Penicillin proved to be extremely difficult to crystallise. At first, Dorothy and her research assistant, Barbara Low, could only work on smaller, breakdown products of penicillin such as penicilliamine and penicillic acid. In 1943, they started working with penicillin crystals, and in 1945, with the help of an early computer, they finally had the structure which contained (for the chemists out there) a thiazolidine ring and a β-lactam ring, much to everyone’s surprise. If you think you’re having a slow month, take heed! It took almost five years to discover this one structure. As Dorothy herself noted,

“I seem to have spent much more of my life not solving structures than solving them.”

But the effort paid off, and the discovery of penicillin’s unusual structure led to the development of a whole new class of β-lactam antibiotics. Dorothy’s model of penicillin was featured as Google’s Doodle on 12th May 2014, her 104th birthday.

Dorothy was an encouraging mentor to many enthusiastic young researchers. The most notable, perhaps, was Margaret Thatcher (then Roberts), the first female prime minister of the UK and the first with a degree in science (interestingly, she was said to be more proud of the latter)! Thatcher spent a year in Dorothy’s lab trying to determine the structure of the antibiotic gramicidin B (which wouldn’t be solved for another 30 years). It turned out that x-ray crystallography was not for her, but the pair maintained a warm relationship, and later Thatcher installed a portrait of the scientist in 10 Downing Street.

Dorothy herself was very politically engaged, but far to the left of her famous student. Dorothy’s husband and many of her close friends were Communists and, although Dorothy was never a card-carrying member, she was denied a visa to the US for her left-wing views. She later became President of Pugwash, a group which campaigns for nuclear disarmament (and itself won a Nobel Peace Prize in 1995).

After the war, Dorothy’s lab continued to churn out papers on a huge variety of molecules. In 1948, the new problem was vitamin B12. This vitamin is essential for the normal functioning of the brain, and had recently been discovered to treat pernicious anaemia rather effectively. Two rival pharmaceutical companies, Merck and Glaxo, were very interested to discover its structure. Dorothy was working with Glaxo, but she discovered that John White, a British scientist working at Princeton, was also working on vitamin B12 with Merck. There was an understanding in the x-ray crystallography community that different groups did not compete over the same structure, and so Dorothy suggested that they keep each other informed over their progress. She noted later that Glaxo must have thought her wholly unreliable, but she thought it was the honourable thing to do.

Dorothy’s group was making progress, but the complex structure was proving extremely difficult to untangle, as the mathematics involved was so computationally intensive. A group in California stepped in to lend a helping hand with their new, speedy computer, and together they solved it!

This discovery was huge and in 1964 Dorothy Hodgkin won the Nobel Prize for Chemistry, but she still wasn’t finished in the lab. Dorothy had decided to solve the crystal structure of insulin in 1934, but it was 35 years (and a Nobel prize) before she actually published the structure. The technology was just not advanced enough back then, but with continued effort (just a bit of an understatement) Dorothy and her lab discovered the structure. Dorothy’s own words make it clear how important this final major discovery was:

“I used to say that the evening I developed the first x-ray photograph of insulin in 1935 was the most exciting moment of my life. But the Saturday afternoon in late July 1969, when we realised that the insulin electron density map was interpretable, runs that moment very close.”

Dorothy Hodgkin’s story is not one of a triumphant but lonely, female figure who had to sacrifice everything to be a scientist in a world built for men. On the contrary, she was married with three children. Somerville, her forward-thinking women’s college at Oxford, even gave her paid maternity leave (a first for the college and the university). Her colleagues (including many women) admired her and sought her advice. She was an extremely successful scientist and that is how they saw her, irrespective of her sex. It is certainly how she saw herself.

Thank you to Vicki Hughes from the Nuffield Foundation for suggesting Dorothy Hodgkin. Who would you like me to write about next? Please leave your suggestions in the comments below, or tweet me @labcoatlucy!


Dorothy Hodgkin: A Life by Georgina Ferry (1998)

The University of Oxford’s Bodelian Library has an incredible collection of Hodgkin’s notes and data.