Dr NEIL VARGESSON

Dr NEIL VARGESSON
BSc (Hons)., Ph.D., FHEA

Senior Lecturer

Overview

Contact Details

Telephone
work +44 (0)1224 437374
Fax
fax +44 (0)1224 437506
Email
Address
The University of Aberdeen School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, Room 5.15.5, University of Aberdeen. Foresterhill. Aberdeen. AB25 2ZD. Scotland.

Link to “Primodos: The Secret Drug Scandal”, a Sky News Documentary which features some of my group's research findings. https://www.youtube.com/watch?v=7ZRkCNUQvBA&sns=fb

For a recent discussion on Primodos and its use as a hormone pregnancy test, please see the following article published in 'The Conversation':

https://theconversation.com/is-primodos-the-forgotten-thalidomide-50673

 

For a recent discussion about Thalidomide research and some of the goals we have please see the following article published in 'The Conversation' and the 'Independent':

https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330

http://www.independent.co.uk/news/science/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-a6772956.html

 

Guest Editor, Special Issue of Reproductive Toxicology  on 'Developmental Angiogenesis’. 
http://www.sciencedirect.com/science/journal/08906238/70

 

Biography

August 2013  Senior Lecturer, School of Medical Sciences, University of Aberdeen.

August 2007   Lecturer, School of Medical Sciences, University of Aberdeen.

2006 - Fellow of the Higher Education Academy (FHEA)

2005 - CASLAT (Cerificate of Advanced Study in Learning and Teaching), Imperial College

2004 - 2007    Lecturer. NHLI Division, Faculty of Medicine. Imperial College London.

2001 - 2003    Postdoctoral Fellow. Cancer Research UK, London. UK, with Dr Julian Lewis studying zebrafish gut development.

1998 - 2001    Postdoctoral Fellow. Department of Genetics and Development, Columbia University, New York. USA, with Dr Ed Laufer studying TGFbeta signalling in chick limb development (funded by HFPSO Long-Term Fellowship)

1998 - Ph.D (Developmental Biology), University College London (with Profs Lewis Wolpert and Cheryll Tickle)

1994 - B.Sc. (Hons) Human Biology, Kings College London

Research

Research Interests

Research in the lab is focused on determining the mechanisms underlying thalidomide-induced teratogenesis; identifying non-teratogenic forms of thalidomide; studying the actions of Primodos (was used as a hormone pregnancy test and alleged to have caused birth defects); screening drugs to identify their function/s and action/s; studying how blood vessels are involved in controlling normal and abnormal limb development; studying the role of the YAP signaling pathway in embryonic development; using the chicken embryo to produce a model of Clubfoot to understand how this common birth anomaly comes about; and understanding how birth defects come about in general.

For a discussion on Primodos and its prior use and history please see the following article: https://theconversation.com/is-primodos-the-forgotten-thalidomide-50673

 

For a recent discussion written for the public about Thalidomide and some of the goals we have please see the following article published in 'The Conversation' and also in the 'Independent':

https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330

http://www.independent.co.uk/news/science/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-a6772956.html

 

For recent discussions written for the public on other topics related to birth defects please see the following articles:

https://theconversation.com/proving-that-the-zika-virus-causes-microcephaly-53716

 

My research interests have also led to requests for scientific advice from the World Health Organisation, the UK Medicines and Healthcare products Regulatory Agency and the Canadian Parliament. I have also been interviewed by the media to comment on news stories including Thalidomide (eg: https://www.thetimes.co.uk/article/scots-race-to-develop-safe-form-of-thalidomide-f3gph3blkd5), Primodos (eg: http://news.sky.com/story/primodos-sky-news-exposes-pregnancy-drug-cover-up-10807338; https://www.youtube.com/watch?v=7ZRkCNUQvBA&sns=fb; Sky News Live interview 21 March, 2017) and also recently on Epilim. Interviewed by Sky News Live (26 Sept, 2017) to discuss the epilepsy drug, Epilim, and how it caused damage to babies born to epileptic mothers, and the new European Medicines Agency inquiry into a lack of information/warnings being given to expectant mum's.

Current Research

Primodos:

Primodos was used as a hormone pregnancy test between 1958-1978. It is alleged to have caused birth defects in children exposed to the drug when their mother was trying to confirm they were pregnant. We have investigated the actions of the components of the drug in Zebrafish embryos.

Some of the Lab's work looking at the components of Primodos in zebrafish embryos was featured in a Sky News Documentary on 21 March 2017 entitled: “Primodos: The Secret Drug Scandal”. The full documentary can be seen at: https://www.youtube.com/watch?v=7ZRkCNUQvBA&sns=fb

Several short versions of the story featured on Sky News:

19 March, 2017: http://news.sky.com/story/primodos-sky-news-exposes-pregnancy-drug-cover-up-10807338

21 March, 2017: http://news.sky.com/story/uk-mothers-betrayed-pregnancy-drug-wasused-for-abortions160160-10809235

I was also interviewed on Sky News Live (21 March, 2017) discussing the lab's research on Primodos and discussing the Sky News documentary 'Primodos: The Secret Drug Scandal'.

Our Primodos research also featured in a news article in the German Newspaper 'Taz - die Tageszeitung' https://www.taz.de/Archiv-Suche/!5411785&s=&SuchRahmen=Print/ on 2 June, 2017.

 

I was also invited to discuss our Primodos research to the Medicines and Healthcare products Regulatory Agency (MHRA) in Oct 2016 and Aug 2017. The MHRA are currently investigating if Primodos could have caused birth defects - they will be publishing their findings in late 2017.

 

For a discussion on Primodos and its prior use and history please see the following article: https://theconversation.com/is-primodos-the-forgotten-thalidomide-50673

 

Thalidomide:
We have demonstrated (Therapontos et al., 2009) how thalidomide can cause limb malformations. The drug was used as a non-addictive, non-barbiturate sedative and was also prescribed to pregnant women suffering from morning-sickness (typically, but not exclusively, between weeks 5-10). Tragically over 10000 children were born with severe birth defects, notably, and commonly, limb malformations.

Using analogs and metabolic byproducts of the drug, we showed that the antiangiogenic action of the drug causes limb defects, through preventing blood vessel migration into the developing limb bud. We further showed how the drug exerts its antiangiogenic effect, through preventing endothelial cell proliferation and migration and thus, preventing vessel tube networks from forming. At the time the limb forms (which in humans is around 5-8 weeks) it has a highly changeable vessel pattern - whereas the rest of the body has a stable vascular network. Thalidomide therefore may prevent new vessel outgrowth, which then causes an increase in cell death and loss of limb signalling pathways, stopping limb formation.
 

Reference:

Therapontos C, Erskine L, Gardner ER, Figg WD, Vargesson, N. (2009). Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proc. Natl. Acad. Sci USA. 106, 8573-8578. DOI:10.1073/pnas.0o01505106.  
 

This work received wide spread media interest, including:

STV: http://news.stv.tv/scotland/95571-scientists-make-thalidomide-breakthrough/

BBC: http://news.bbc.co.uk/1/hi/scotland/north_east/8040535.stm

http://www.clickliverpool.com/news/national-news/124324-thalidomide-victims-welcome-research-breakthough.html

A large number of newspapers, including The Independent, The Daily Mail, The Scotsman, The Press & Journal, and several Radio stations.

The work was also featured in Nature News: 

http://www.nature.com/news/2009/090511/full/news.2009.462.html

 

Making safer Thalidomide alternatives:

We are also interested in identifying thalidomide alternatives that retain the clinical benefits of the drug (successfully used to treat Leprosy and Multiple Myeloma) with lessened or no side-effect (eg: birth defect, peripheral neuropathy). To this end we have compared the effects of Thalidomide with its structural analogs, Lenalidomide and Pomalidomide. We demonstrated that the minor structural changes in Pomalidomide make this compound more anti-inflammatory (and not teratogenic in chicken and zebrafish embryos) at lower concentrations than Thalidomide and Lenalidomide (Mahony et al., 2013). We have also screened fluorinated thalidomide analogs and demonstrated differences in analog activities (Beedie et al., 2015). These findings validate making structural changes to Thalidomide to try to find safer alternatives.


Following on from this work we have screened over 80 thalidomide analogs in our zebrafish and chicken embryo assays and identified several with actions that retain clinical advantages (ie: anti-inflammatory) with reduced or no observable teratogenic effects in zebrafish and chicken embryos (Beedie et al., 2016). Some of these analogs are being patented.


References:

Mahony C, Erskine, Niven J, Grieg NH, Figg WD, Vargesson N. (2013). Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic invitro. Proc. Natl. Acad. Sci USA. 110, 12703-8. doi: 10.1073/pnas.1307684110

Beedie SL, Peer CJ, Pisle S, Gardner ER, Mahony C, Barnett S, Ambrozak A, Gütschow M, Chau CH, Vargesson N, Figg WD. (2015). Anticancer properties of a novel class of tetrafluorinated thalidomide analogues. Mol Cancer Ther 14:2228-2237. doi: 10.1158/1535-7163.MCT-15-0320.

Beedie SL, Rore HM, Barnett S, Chau CH, Luo W, Greig NH, Figg WD, Vargesson N. (2016). In vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish and chicken embryo models systems. Oncotarget. 2016 May 31;7(22):33237-45. doi: 10.18632/oncotarget.8909.

 

Media Interest

This work was mentioned in The Sunday Times, 4 August 2013.

http://www.thesundaytimes.co.uk/sto/news/uk_news/scotland/article1296248.ece?CMP=OTH-gnws-standard-2013_08_03

And on realradio.co.uk/scotland.

 

Review articles on Thalidomide History and Mechanisms of Action:  

Vargesson N. (2009). Thalidomide-induced limb defects: resolving a 50-year-old puzzle. Bioessays. 31(12):1327-36. doi: 10.1002/bies.200900103.

Vargesson N. (2013). Thalidomide embryopathy: an enigmatic challenge. ISRN Developmental Biology Volume 2013 (2013), Article ID 241016,. http://dx.doi.org/10.1155/2013/241016

Vargesson N. (2015). Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C Embryo Today. 105(2):140-56. doi: 10.1002/bdrc.21096.

 

 

Media Interviews/Discussions about our Thalidomide research:

2009 - The Material World (BBC Radio 4) - http://www.bbc.co.uk/programmes/b00k9hlz#synopsis

2010 - The Diane Rehm Show (US Radio) - http://thedianerehmshow.org/shows/2010-09-16/thalidomide-and-fda

2010 - The New York Times - interviewed by Carl Zimmer
http://www.nytimes.com/2010/03/16/science/16limb.html?pagewanted=all&_r=0

2011 - The Naked Scientists (BBC Radio) - http://www.thenakedscientists.com/HTML/content/interviews/interview/1785/ 

2012 - German Public Radio - http://www.dradio.de/dlf/sendungen/hintergrundpolitik/1917460/

http://www.dradio.de/dlf/sendungen/wib/1945008/

2013 - The Today Program (BBC Radio 4) - Thalidomide: Were more babies affected?

2013 - BBV TV News - Thalidomide: Were more babies affected? (Oct 14, 2013)

2013 - BBC News Website - http://www.bbc.co.uk/news/health-24472269

2013 - The Naked Scientists (BBC Radio) -

http://www.thenakedscientists.com/HTML/content/interviews/interview/1000545/

2015 - SHMU Radio - 'Talking Science' (Jan 27, 2015)

 

Some images of my thalidomide work is featured in a Fine Art Exhibition (and subsequent Book) by the renowned artist, Taryn Simon. The Exhibition is entitled: ‘A Living Man Declared Dead and Other Chapters’ and toured the world throughout 2011 and 2012.

 

Media articles about Thalidomide

2015 - The Conversation

https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330

2015 - The Independent

http://www.independent.co.uk/news/science/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-a6772956.html

 

Awards for Public Engagement

Winner, 2017 Principal's Prize for Public Engagement with Research - Senior Award.

https://www.abdn.ac.uk/engage/staff-students/2column-page-152-152.php

Some of the Lab's research on Primodos, a now disused hormone pregnancy test alleged to have also caused birth defects, featured in a Sky News & Sky Atlantic documentary  (https://www.youtube.com/watch?v=7ZRkCNUQvBA) and Neil was part of resulting interviews, including on Sky News Live (21 March, 2017) and news stories in national and international media. Neil also discussed the Primodos research and answered questions from MP’s and Lords at the Houses of Parliament at a special event where the Sky News documentary was premiered. In addition, Neil presented the Primodos research to an Expert Working Group of the UK’s Medicine and Healthcare Regulatory Agency who are determining if Primodos could have caused birth defects – their decision due in late 2017. Neil’s other research interest is understanding how thalidomide caused birth defects and identifying forms of the drug that retain clinical benefit without the spectre of birth defects. This work led to an advisory role to the World Health Organisation in 2014 which has contributed to advisory notices about the diagnosis and causation of thalidomide embryopathy from the World Health Organisation. In addition, Neil gave evidence to the Health Committee of the Canadian House’s of Parliament in 2017 investigating how the drug caused birth defects and the range of damage it induces, as part of the Canadian Government’s scheme of who and how to award compensation for thalidomide damage. Neil has also written several popular articles in 2015 and 2016 for the website ‘theconversation.com’ on Primodos (https://theconversation.com/is-primodos-the-forgotten-thalidomide-50673), thalidomide (https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330) and the zika virus and how it might cause birth defects (https://theconversation.com/proving-that-the-zika-virus-causes-microcephaly-53716).

Research Grants

2015-2017 PI, Sarcoma UK Project Grant

2012-2016 PI, Wellcome Trust/NIH funded PhD Scholar

Teaching

Teaching Responsibilities

Degree Programme Co-ordinator - Human Embryology and Developmental Biology

 

Course Co-ordinator - DB3006 Principles of Developmental and Reproductive Biology

Course Co-ordinator - DB4002 Evolution and Development

 

Teach on SM2001, SM2501, SM3002, DB3006, DB3804, DB4002, DB4002, PA4005

Further Info

External Responsibilities

-Editorial Board Member, Reproductive Toxicology (2015-2019).

http://www.journals.elsevier.com/reproductive-toxicology/editorial-board


-Guest Editor for a Special Issue of Reproductive Toxicology entitled 'Developmental Angiogenesis'

Published June, 2017.

http://www.sciencedirect.com/science/journal/08906238/70


 

-Editorial Board Member, Integrative Physiology, a speciality of Frontiers in Physiology (2017 -  )

 

-Organiser, 14th International Conference on Limb Development and Regeneration to be held at the University of Edinburgh between July 23-26, 2017.

http://www.ed.ac.uk/igmm/news-and-events/events/latest-events/limb-development-2017

 

-Member, Sarcoma UK Research Advisory Committee (2016-2019) - which oversees Grant Application reviewing and funding.

https://sarcoma.org.uk/research/research-advisory-committee

https://sarcoma.org.uk/about/people/rac

 

-Public Engagement/Impact and Media

Advisor, World Health Organisation 'Diagnostic Criteria and Mechanisms of Action of Thalidomide' - Feb 2014.  Meeting report with recommendations:   http://www.who-umc.org/graphics/28280.pdf

Advisor, Medicine and Healthcare products Regulatory Agency (MHRA) - Oct 2016 and Aug 2017. Discussing our research on Primodos effects upon embryonic development.

Advisor, Canadian Parliament, Standing Committee on Health, 'Thalidomide survivors compensation programme' - May 2017.

Interviewed by Sky News Live (21 March, 2017) discussing the lab's research on Primodos and discussing the Sky News documentary 'Primodos: The Secret Drug Scandal' - https://www.youtube.com/watch?v=7ZRkCNUQvBA&sns=fb

Interviewed by Sky News Live (26 Sept, 2017) to discuss the epilepsy drug, Epilim, and how it caused damage to babies born to epileptic mothers, and the new European Medicines Agency inquiry into a lack of information/warnings being given to expectant mum's.

 

 

Admin Responsibilities

Elected Member, University Senate (2008-2013) (2016-2020)

Senate Assessor to University Court (2009-2013)

Member, Governance and Nominations Committee (reports to University Court; 2012-2013)

 

Member, IMS Athena SWAN Team for Bronze Award (2015-present)

 

Awards

Winner, 2017 Principal's Prize for Public Engagement with Research - Senior Award.

https://www.abdn.ac.uk/engage/staff-students/2column-page-152-152.php

Some of the Lab's research on Primodos, a now disused hormone pregnancy test alleged to have also caused birth defects, featured in a Sky News & Sky Atlantic documentary  (https://www.youtube.com/watch?v=7ZRkCNUQvBA) and Neil was part of resulting interviews including on Sky News Live (21 March , 2017) and news stories in national and international media. Neil also discussed the Primodos research and answered questions from MP’s and Lords at the Houses of Parliament at a special event where the Sky News documentary was premiered. In addition, Neil presented the Primodos research to an Expert Working Group of the UK’s Medicine and Healthcare Regulatory Agency who are determining if Primodos could have caused birth defects – their decision due in late 2017. Neil’s other research interest is understanding how thalidomide caused birth defects and identifying forms of the drug that retain clinical benefit without the spectre of birth defects. This work led to an advisory role to the World Health Organisation in 2014 which has contributed to advisory notices about the diagnosis and causation of thalidomide embryopathy from the World Health Organisation. In addition, Neil gave evidence to the Health Committee of the Canadian House’s of Parliament in 2017 investigating how the drug caused birth defects and the range of damage it induces, as part of the Canadian Government’s scheme of who to and how to award compensation for thalidomide damage. Neil has also written several popular articles in 2015 and 2016 for the website ‘theconversation.com’ on Primodos (https://theconversation.com/is-primodos-the-forgotten-thalidomide-50673), thalidomide (https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330) and the zika virus and how it might cause birth defects (https://theconversation.com/proving-that-the-zika-virus-causes-microcephaly-53716).

 

Positions available for PhD students.

 I am looking for motivated, self-funded PhD students to join my group. Projects are available to study:

1. Mechanisms of thalidomide teratogenesis

2. Identification of non-teratogenic forms of thalidomide

3. Clubfoot

4. Mechanisms underlying limb proximo-distal outgrowth and pattern

5. Control of vascular patterning in the embryo

6. Role of YAP signalling in embryonic development

7. Action of Primodos in the vertebrate embryo

Publications

Publications 

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