Titans of Science: Jane Carlton

0:11Chris Smith:Hello,

0:17Chris Smith:welcome to the Naked Scientist podcast. This is the program that brings you the biggest breakthroughs and also talks to the major movers and shakers in the worlds of science, technology and medicine. I'm Chris Smith. Today we're putting one of the world's most pernicious parasites under the microscope, malaria, and titan of science Jane Carlton is going to be our guide.

0:45Chris Smith:Jane Carlton was born on the 7th of January 1967 in Scotland's capital, Edinburgh. She attended St George's School for Girls and then completed a degree and a PhD in genetics at the University of Edinburgh, graduating in 1995 before moving to the US to take up a research position at the University of Florida where she used her skills in molecular biology to produce the world's first full genome sequences of the malaria parasite. Since then she's worked at NIH in Maryland and at New York University. Jane was recently elected as a fellow of the American Academy of Microbiology and she was also awarded the American Society of Parasitologists Stoll Stoncard Memorial Award in 2010, made a fellow of the American Association for the Advancement of Science in 2012 and named honorary fellow by the London School of Hygiene and Tropical Medicine in 2024.

1:40Chris Smith:She's now director of the Malaria Research Institute at Johns Hopkins University in Baltimore, Maryland, a post she took up in 2023. That is quite some CV, Jane. It's wonderful to speak to you today. The focus of your career has mostly been malaria, which is one of the world's highest impacting parasitic infections. So why don't we begin there? What actually are parasites? What's the definition?

2:05Jane Carlton:Parasites are fascinating organisms. They live in or on a host and usually to the detriment of that host. That can be through making the host unwell or perhaps reducing the ability of the host to reproduce or even changing the behaviour of the host. And the parasite that I work on in particular, the malaria parasite, is a protozoan, a single-celled organism. What took you down that path though?

2:32Chris Smith:Tell us a bit about the young Jane Carlton that got interested in parasites in the first place. How did that happen?

2:38Jane Carlton:It wasn't initially parasites that I was interested in actually, but genetics. And that's because my brother went to university and he came back with this new book all about genetics. And I really liked the front cover, which shows some chromosomes. And I thought, well, how cool is that, that the biology of an organism can be determined by these things called genes, and then how they're inherited can really affect their biology. so it was really through genetics and through my brother that I got first interested and then when I went to the University of Edinburgh there was quite a well-known and well-thought-of group that worked on the genetics of malaria parasites and that's really when I got into into the world of parasitology.

3:26Chris Smith:But how old were you when you picked up that genetics book then?

3:29Jane Carlton:Actually I was I think I was about 10 years or maybe eight years old I can't remember I still have it actually.

3:36Chris Smith:You're stole it?

3:38Jane Carlton:I did. I've actually stolen a few things from my brother over the years, as he knows.

3:44Chris Smith:But you must be pretty unusual. There are not many eight to 10 year olds reading genetics books. I mean, that singles you out as a bit special.

3:52Jane Carlton:Oh, well, I don't know. I mean, there's an interesting interpretation of the word special, isn't there? But no, I think my brother was the special one, bringing the book home. And that he actually taught me an awful lot about the world that we live in. So no, I put it down to him, not me really.

4:10Chris Smith:But obviously that must have inspired you because presumably you then followed a science track through primary school, secondary school, that would enable you to apply to Edinburgh University to do, because you did genetics there, didn't you? So how did you end up in that degree course? Was it just because of that book and then pursuing science at school?

4:29Jane Carlton:Well, it was always an interest in the natural world around me, actually. So I was always a very much an outdoorsy girl. And I loved riding and going off by myself and investigating things. And so then it was really wanting to know more about the biology and the kind of ecology of many of the organisms that I came across and the plants in the real world and then knowing how those developed and the role of genes and genetics that's how I really got interested and and decided to take that degree at the University of Edinburgh.

5:09Chris Smith:And it was that degree that then turned you on to malaria because you were applying that genetics interest to the malaria parasite because at this time this must have been what the mid-90s and although we take it for granted these days I'll just sequence that and we read the genetic code of everything we come across, don't we? In those days, the Human Genome Project was still, what, five or six years away from reporting its initial draft. So this was very early on in the game.

5:35Jane Carlton:Yes, it was. I was very fortunate at the University of Edinburgh and in the Department of Genetics that there was a very large group, very well-known group of malaria researchers that used genetics to study the malaria parasite. And so that's really how I got involved and did my PhD doing genetic crosses between different parasite strains that had different susceptibilities to anti-malarial drugs. And I had to generate the first genetic map of a particular malaria parasite species because the genome had not been sequenced. And that was very painstaking. And it wasn't that greater map. And that's really when I started to hear about news, especially in the United States, of an initiative to sequence the human genome.

6:29Jane Carlton:And I knew that there was a group at the University of Florida that was planning to sequence the malaria parasite genome. And so I jumped at the chance to try and join them.

6:40Chris Smith:And that's what took you to the States?

6:42Jane Carlton:Yes, that's right. It took me to University of Florida. And I think many British people seem to have an attraction to Florida because of the wonderful weather. I went there both for the weather, but also because of this great group who were tagging the genes of certain species of malaria parasites.

7:03Chris Smith:There's more than one type of malaria, isn't there, that hits humans?

7:07Jane Carlton:Yes, there are about six different species of human malaria parasite. The most prevalent, Plasmodium falciparum, which infects primarily children under the age of five in sub-Saharan African countries, is the most deadly as well and causes about 280 million cases each year and about 600 ,000 deaths. But there are other species as well. Plasmodium vivax, for example, is found in South America, but also Southeast Asia. And the really fascinating thing about that parasite species is it has a dormant liver stage. And so people can be walking around feeling perfectly healthy with this dormant stage, and that can then pop out years, months after an initial infection and cause the disease.

7:58Jane Carlton:So yes, there are actually about 200 different species of malaria parasite. Which other animals get it then? Lots of mammals, so non-human primates and monkeys. Also reptiles, lizard malaria is a huge issue too. And then also birds. So certain species of malaria parasite have been decimating those beautiful populations of colourful birds that you find in Hawaii.

8:27Chris Smith:Given that it's in so many different species and even reptiles then, does that mean that in evolutionary terms this is a really ancient bug?

8:37Jane Carlton:It is. It's an ancient parasite. It was first described or known to have been described by Hippocrates, for example, who was the, you know, they call him the father of modern medicine. And he described the symptoms of malaria and the fact that people tended to come down with it. if they were close to marshes. So it's been known for a long time. There have been some very notable deaths due to malaria. So Alexander the Great died of malaria. George Washington had many episodes. Lord Byron. More recently, George Clooney actually had malaria too, I think, when he was traveling in Ethiopia. And it was great because he then used his illness to highlight the severity of the disease.

9:25Chris Smith:What's the actual process of malaria? I mean most people know it's connected to mosquitoes and it's something to do with blood but talk us through the actual process of how malaria does what it does.

9:36Jane Carlton:Well it's a really intricate life cycle. So malaria parasites are transmitted by female mosquitoes of a certain species called anopheles and that's because it's female mosquitoes that take blood meals. They need blood in order to produce eggs. So malaria parasites get transmitted from the bite of a female mosquito in the saliva into the skin and then those parasites migrate to the liver and in the liver they undergo cycles of reproduction and then they burst out of liver cells into the blood and it's actually those stages in the blood that really cause the symptoms and the diseases, fever and the muscle aches, the headaches, the chills that really lead on then to more serious conditions as well.

10:29Jane Carlton:And then in the blood stage as well, the parasite can form these sexual stages, like gametes, male and female gametes. And so when an uninfected female mosquito takes a bite, those stages will then move back up into the uninfected mosquito and they multiply and then the parasite moves to the salivary glands and so the whole life cycle is is complete so incredibly complicated if you can think about it because all of those different stages we have to study we want to know what genes are turned on and off and that can be quite challenging because you can't necessarily grow the parasite for all of the different species.

11:13Jane Carlton:It's a very complex life cycle.

11:15Chris Smith:It certainly is and to think that that one parasite can get into all those different cell types that insect cells, liver cells, blood cells grow in there and also evade the immune system at all these different stages both in the insect and in the person it really is quite extraordinary isn't it? Can you actually see it though? When we look down a microscope can you see malaria? inside these cells?

11:40Jane Carlton:Yes, you can. You do need a microscope, but you can see it in the red blood cells, for example. It's actually quite beautiful. I know I shouldn't say that for a parasite. So the ring stage of a malaria parasite looks just like a diamond ring, if you can imagine, with the big diamond and then the sort of platinum band as well. So you can see that quite visibly in red blood cells. And then you can see it in other stages too. So there's sort of a sausage crescent shaped stage, which is one of the sexual stages before it's taken up by the mosquito. And then actually in the mosquito itself, there are certain stages called the sporozoid.

12:22Jane Carlton:They're very interesting too, because they're very motile. So they sort of glide along a bit like a snake.

12:29Chris Smith:So how does it actually make people ill? When a person's got this thing, Obviously, they've got something growing in their cells, which can't be good. But how does it actually translate into illness, all of this?

12:40Jane Carlton:Well, it actually doesn't translate into illness for several weeks. And that's, you know, for all of your listeners, if this is the one take home message, if any of them go on holiday somewhere and then come back, if they're sick, two to three weeks afterwards, perhaps when they've forgotten about their holidays, to remember that they went to a malarious country because when they go to their doctor to tell the doctor, I've been to a malarious country, and that will immediately trigger in the doctor an alarm that potentially this person could have malaria. And the reason for that is that the malaria parasite takes a good two weeks or so to develop in the liver and then in the blood before a person starts feeling sick.

13:27Jane Carlton:And then that sickness tends to be a bit like flu-like symptoms but it's very important that people you know seek the doctor's advice and get treatment because it can spiral out of control pretty quickly and then about one percent of cases it can go on to convulsions and major organ failure and then that can lead to coma and to death.

13:51Chris Smith:Is that because it's killing cells or is it irritating the body in other ways?

13:56Jane Carlton:It's a combination of all of those actually. So in fact the immune response against malaria parasites can form a very big inflammatory response which sometimes is not helpful. But also cerebral malaria is when the parasite travels to the brain and causes blockages in the brain and brain swelling too and that's really what can cause the death.

14:21Chris Smith:I'll come on in just a second to how we treat someone in that position, how the drugs work. But you mentioned that with Plasmodium vivax, that can stay in the body for long periods of time. But once a person gets better, does that mean the parasite is gone? And are they immune after that? So in a bit like if I caught measles, I would be immune for life for measles. Do I then have immunity against malaria? No need to worry in future.

14:46Jane Carlton:Yeah, very good question. So for So children living in African countries, once they get malaria several times, they will be immune. But as soon as they move away, their immunity can drop. So people who are not in endemic countries won't have natural immunity to malaria. They won't have that built up unless they're going back to those countries many times. so immunity is not very well understood at all.

15:20Chris Smith:This is the Naked Scientist podcast with me Chris Smith and I'm in conversation with Jane Carlton who's director of the Malaria Research Institute at Johns Hopkins University. Coming on then to how people actually manage it, what do the drugs do?