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Column: In the heat of the moment - by Jenni Lawton

September 16, 2014 - 12:55 -- Ingeborg van Schayk

The column below was contributed by Jenni Lawton.

Scottish contributions to malaria research

 

With the Scottish Independence Referendum looming on the 18th September 2014, here we are all waiting with bated breath to see what the outcome will be. I thought this would be a good time to reflect on Scotland’s contribution to the understanding and treatment of tropical diseases, including malaria.

Last year marked the bicentenary of the birth of the famous Scottish explorer, missionary and anti-slavery campaigner Dr David Livingstone. To celebrate this anniversary, Professor Barrett and colleagues presented a series of events at Glasgow University, giving an interesting insight into the life and legacy of Livingstone and his contemporaries. To download the “The Scottish encounter with Tropical Disease” booklet by Barrett, Innes & Cox click here.

The relatively great number of contributions to tropical research by Scots can be partly explained by their different approach to education compared to their English neighbours. This was particularly clear during the Scottish ‘enlightenment’ which began in the 18th century, when education was available to anyone in Scotland, but remained a preserve of the wealthy in England. Scottish graduates without the financial support of affluent relatives were thus obliged to work, and many were drawn to expeditions and/or military campaigns in the tropics.

David Livingstone is an excellent example of the opportunities afforded in Scotland at the time; he was born to a poor family and worked in a Blantyre cotton factory from the age of 10. Showing great determination however, studying in the evenings, he was eventually able to enrol in medical school. As a medical missionary, Livingstone undertook extensive travels throughout Africa and news of these travels turned him into a Victorian celebrity. This was made possible in large part by his use of quinine to self-medicate against malaria. The formulation was later marketed by Burroughs-Wellcome as ‘Livingstone’s rousers’, contributing to the success of this pharmaceutical company. In turn, Henry Wellcome’s will founded the Wellcome Trust, which retains a keen interest in Tropical diseases, particularly at their Centre for Molecular Parasitology here in Glasgow.

Plasmodium I presume?

Since the causative agent of malaria was identified by the French physician Laveran [1], several crucial discoveries about Plasmodium and other tropical parasites were made by Scottish medics, most notably Patrick Manson and his protégé Ronald Ross, who was awarded a Nobel prize in 1902 for his demonstration that malaria could be transmitted by mosquito. [2] These pioneers were founding members of the London & Liverpool Schools of Tropical Medicine, respectively.

* Following these pioneers, research into malaria has continued in Scotland, below I have emphasized just a couple of highlights, including those that have inspired my own studies:

 - * Shortt and colleagues discovered the liver stages of Plasmodium cynomolgi, vivax and falciparum.

Where no references are given, please refer to: http://www.malaria.ed.ac.uk/history

- Walliker et al. used genetic crosses to demonstrate that the mammalian stages of the parasite lifecycle are haploid and that recombination could occur following mosquito transmission.
- McBride et al. performed extensive characterisation of the P. falciparum antigen merozoite surface protein-1 (MSP-1), to which substantial immune responses are made during infection.
- Brannan, McLean & Phillips demonstrated that antigenic variation / switching occurred in the murine malaria model P. chabaudi; and that different variants displayed different switching rates. [3]
- Hunt and colleagues have investigated the molecular mechanisms behind the development of parasite drug resistance.
- Rowe and colleagues have examined the phenomenon of infected and uninfected erythrocyte rosetting, as well as cytoadhesion to host endothelial cells, in order to understand their contributions to pathology during malaria infection.

More recently, exciting discoveries have been made in several areas that could aid anti-malarial strategies from all sides. Closest to human trials is a compound identified by the Drug Discovery Unit at Dundee in collaboration with the Medicines for Malaria Venture (http://app.dundee.ac.uk/pressreleases/2014/february14/malaria.html).  Another clear potential for translation is the use of highly polymorphic regions from the MSP-1 protein as a vaccine candidate, newly shown to protect Aotus monkeys from challenge with the FVO strain of P. falciparum. [4] Finally, the discovery of a ‘master regulator’ for gametocyte development [5] suggests numerous possibilities for interfering with parasite transmission, particularly if combined with drugs or vaccine strategies that target other stages of the parasite too. Clearly malaria research in Scotland in 2014 remains as strong as ever!

If Scotland votes for independence, will this affect our continued malaria research?

The repercussions of an independence vote for research are unclear and will largely depend on economic discussions and whether the British Research Councils are willing to continue their support for Scottish research. This has many academics worried, although others argue that there could be increased freedom (http://www.nature.com/news/scientists-split-over-scottish-independence-vote-1.15882). It is fervently hoped that whatever the outcome next week, our ability to continue the Scottish tradition of research excellence will not be affected, particularly in the tropical diseases that have remained so fascinating since the days of Manson and colleagues.

Sadly, independence has not proved to be a blessing so far for the newest country in Africa: South Sudan. Since their secession in 2011, the South Sudanese have suffered enormous conflict, and the refugee camps in neighbouring countries have become breeding grounds for many infectious diseases, not least malaria (http://www.malariaworld.org/blog/column-how-fragile-we-are). Instability due to conflict and epidemics like the frightening spread of Ebola across West Africa, have many countries asking for more support from the international community. If the UK is to be split up, would this limit our ability to help or would it be possible to mount a faster response? Distressingly, the people who are in the midst of such crises do not have the luxury of waiting whilst we prevaricate.

References
[1] Laveran A. 1880. Note sur un nouveau parasite trouvé dans le sang de plusieurs malades atteints de fièvre palustres. Bulletin de l'Académie de Médecine. 9: 1235.
[2] Sinden RE. 2007. Malaria, mosquitoes and the legacy of Ronald Ross. Bulletin of the World Health Organization. 85: 894.
[3] Brannan LR, Turner CMR & Phillips RS. 1994. Malaria parasites undergo antigenic variation at high rates in vivo. Proceedings of the Royal Society B: Biological Sciences. 256: 71.
[4] Cavanagh DR, Kocken CHM, White JH, et al. 2014. Antibody Responses to a Novel Plasmodium falciparum Merozoite Surface Protein Vaccine Correlate with Protection against Experimental Malaria Infection in Aotus Monkeys. PLoS ONE. 9: e83704.
[5] Sinha A & Hughes K, Modrzynska K, et al. 2014. A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature. 507: 253.


Jenni Lawton is a post-doctoral researcher at the University of Glasgow, UK. Her research interests focus on the interactions between Plasmodium infected red blood cells (iRBCs) and the host; dynamic processes which are still incompletely understood. The behaviour of iRBCs may have important implications both in generating effective immune responses and in the escalation of some malaria infections towards severe complications. This will be her first foray into communications and she hopes to provide some interesting perspectives from the lab to the Malaria World community!

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Comments

Submitted by Nayna Patel on

Thank you Jenni for an excellent account of the Scottish contribution to mosquito and malaria research, especially the part played by the provision of free education available in Scotland. If only free education was available to peoples of many more/ALL countries! Now that Scotland has voted 'No' to independence, how do you see us all contributing and working together to eliminate vector borne diseases? How can we all best work together? It's an excellent first communication!

Submitted by Jenni (not verified) on

Dear Nayna,
Thanks very much for your thoughtful comments!

- I absolutely agree that free education would make an enormous benefit to communities across the world and especially would benefit the developing countries whose endemic diseases cripple their own populations. But how to encourage governments to invest in open access to education when in many places (England included) it often seems that those from privileged backgrounds are more likely to have these opportunities and are precisely the people then making such policy decisions?

- As Bart & Inga mentioned in their blog this week, it is poignant that the international community has only recently begun to respond to the frightening Ebola outbreak, despite warnings from the scientific community much earlier. Understanding more about malaria and other infectious diseases is crucial for developing therapeutics, which the research community has been striving to do since the discovery of these pathogens. Nonetheless, many potential parasite and vector control measures that we already know of fail to be implemented in a coherent manner, which our colleagues are urging governments and those financing large-scale initiatives to improve. This is a problem in the UK as well, where scientific advice is often sought and then ignored in policy making (see an excellent book by Mark Henderson: “The Geek Manifesto”). Perhaps the scientific community needs dedicated advocates who are able to promote the most effective strategies to the policy makers?

- Dr Manuel Lluberas recently pointed out that many of the measures that were historically successful in malaria control today would not be allowed due to tight regulations and safety fears (http://www.malariaworld.org/blog/column-will-current-global-malaria-programme-pass-cochrane-review). [In fact the successful first uses of Zmapp™ were only permitted by the WHO due to the enormous mortality associated with this Ebola outbreak. A safety and efficacy trial has just begun, with GSK hoping to begin delivering treatment to health-workers in West Africa before the end of this year (http://www.theguardian.com/society/2014/sep/17/ruth-atkins-first-british-volunteer-injected-trial-ebola-vaccine-oxford)]. Of course these restrictions have been imposed for safety reasons but as costs of developing new drugs and / or vaccines soar, there may come a point where such rigorous testing is not financially sustainable. Then we would have to weigh the possible adverse risks of new therapeutics against the likely ravages of disease without them.

- I wonder what our MW colleagues think?

Finally, may I just say that however people are feeling after the No vote, Scotland’s referendum has been an unusual example of widespread political engagement in a world where too few people have the opportunity to vote in democratic elections, and those that do often fail to bother. We are very lucky to be able to have a voice and the access to education when sadly these should not be down to luck at all.

Best wishes,
Jenni