Anita Harding, Co-discoverer of mitochondrial DNA mutation in human disease and of the concept of tissue heteroplasmy of mutant mitochondrial DNA.

Anita Harding, co-discovered the link between mitochondrial DNA mutation and human disease and the concept of tissue heteroplasmy in mutant mDNA

At least I won’t have to buy Windows 95” said Anita upon hearing she had a terminal condition. Anita was my first boss a very long time ago. Way back then I would never have imagined that I’d write an article to help her name be remembered.

The death of Roger Bannister at the weekend had the effect of reminding me of the untimely death of my first boss over 22 years ago. Bannister is remembered for being the first human to break the 4 minute mile record in 1954, but he was also a consultant neurologist in the National Hospital for Neurology and Neurosurgery. Brilliant Anita Elizabeth Harding made her name in the adjacent building in Queens Square, in the Institute of Neurology. She helped break down very different and far more important types of barriers.

Anita was my first boss. I briefly had the honour of working for one of those giants whose shoulders other great scientists stand on. Anita achieved many things in her short stellar career, but I want to express the enormity of one achievement in simple terms.

In complex organisms like humans, DNA is only found in 2 cellular structures, in the nucleus and in mitochondria. Anita Harding co-discovered the connection between mitochondrial DNA mutation and human disease. That alone should ensure her virtual immortality in the annals of science and medicine.

Is growing old the most common mitochondrial disease of all?
Anita Harding.

It probably is, but Anita never had the good fortune to experience that postulated disease. Hardly anyone knows who she is. And that saddens me greatly. Anita was a warm generous human being — and I feel compelled to write this for her. If some people from the world of neurology beg to differ with my assessment of how well known she is, I’m talking about the fact that she’s not known at all outside of that exclusive little bubble. It’s really up to scientists and medics from that male-dominated world to tell Anita’s story to a wider public.

The lack of references to Anita are an example of a form of historical devaluation which humans routinely assign to great women.

Just like Rosalind Franklin very probably should have won a Nobel prize for her work in visualising the twisted ladder (double helix) structure of DNA which Watson and Crick modelled and declared in 1953. They were subsequently awarded the Nobel prize. Just like Franklin, Anita didn’t get the credit she deserved. Franklin is now very famous and well-remembered for this crucial achievement, but it took time. And it’s well known that her work was crucial to the discovery of the structure of DNA. Anita is virtually forgotten. I’m not saying Harding’s contribution was as fundamentally ground-breaking as Franklin’s, but it was nevertheless a huge scientific discovery and a massive contribution to modern medicine. Both women achieved so much, despite dying so young from cancer.

Anita Harding died at 42.
Rosalind Franklin died at 37.

Rosalind Franklin in Birkbeck College

Rosalind Franklin in Birkbeck College

I was shown Rosalind Franklin’s x-ray photograph and, Whooo! that was a helix.
James Watson

“If ever there was a woman who was mistreated, it was Rosalind Franklin, and she didn’t get the notice that she should have gotten for her work on DNA.”
Ava Helen Pauling

I used to walk from the Institute of Neurology in the evening to attend lectures in comparative evolutionary biology in Birkbeck College – where Franklin completed her career doing ground-breaking work on the molecular structures of viruses. Little did I know that someday I would find myself writing this and connecting the histories of these two giants of molecular biology.

Anita forged a path for women to enter neurology back in an age where our ignorance relating to gender inequality was significantly worse than it is today. And 12 Queens Square was certainly no exception. Anita ran a ground-breaking neurogenetics research team. She co-discovered, with Ian Holt and John Morgan-Hughes, the “first identification of a mitochondrial DNA mutation in human disease and the concept of tissue heteroplasmy of mutant mitochondrial DNA”, published in Nature way back in 1986. The image below shows deletions of mitochondrial DNA in Kearn-Sayre syndrome — well known today, but it had a revolutionary significance at that time.

I hardly feel qualified to write about her as I left that research team after a year and I was the most junior member, but I remember the experience as if it were yesterday. Anita had a mischievous side. She used to rib me about being Irish sometimes. At a time when being Irish was sometimes difficult in 80s London, she was not afraid to have a little fun. She’d mention how lucky we were not to be in Ireland on a religious holiday because all the shops were closed. I was an atheist from the age of 7 and had an allergy to the oppression of the church in Ireland, so I enjoyed laughing with her. Anita was born in Ireland, but brought up and educated in Birmingham. She travelled across the water constantly to drive around collecting blood samples. In those days families were still very large in Ireland and that made them very useful for tracking familial inheritance.

1989/1990 was a sensitive time to be a young Irishman in the heart of London. Ireland was still the corrupt Banana Republic that Bob Geldof had sung about 10 years earlier. Like many of my friends I was an economic migrant, but I couldn’t wait to get out of Dublin anyway. It was very friendly in those days, but it was also grey, unworldly and ultra-conservative. The standards of formal education of that generation compared very favourably with our UK neighbours, but Dublin was an isolated cultural backwater compared to the excitement, energy and openness of London.

She gave me a chance when I really needed it. I was one of 34 scientists applying for a role in reply to an advert in the New Scientist. I arrived at the interview with my jacket under my arm. I said it was the summer heat, but I was actually trying to obscure a small rip in the arm. Afterwards I walked home from 12 Queen’s Square to the little flat I was sharing in Leytonstone because I didn’t have the fare for the tube. A 3 hour walk if you take no wrong turns. Young, hungry and broke in a city of wealth – but the interview had gone well. I remember a spring in my step.

During the interview I distinctly remember the Chief Technician saying to me “You just want a good salary … that’s it … isn’t it?” It’s hard to believe today, but he actually repeated it every few minutes (with that annoying, grammatically incorrect “isn’t it?” grating at me). Eventually I stated very firmly that my biggest goal was working in mitochondrial genetics. I had actually completed a final project in college revolving around mitochondria – so this was the truth despite the fact I needed money too. That sort of questioning was irritating.

But I also remember Anita with a barely visible grin as she observed my annoyance. She subsequently hired me and I was over the moon.

I only stayed 12 months and did not get to use my brain an awful lot. Science in those days took an incredibly unhealthy pride in the idea of the ‘95% perspiration, 5% inspiration’ cliche. Utterly ridiculous. I was doing repetitive work almost exclusively and keeping my brain on life support with various studies outside of work. I remember one senior scientist in there asking me one morning “Have you been programmed yet.” I fumed at the unnecessary remark – exasperated by the fact that I did not consider the smart-ass who said it to be especially clever. But I was very skilled in the lab and focused on the one thing I had a license to excel in. I quietly enjoyed showing up one esteemed medic in particular (who had questionable lab technique at best, sometimes flawed understanding too) when it came to successfully extracting and amplifying mitochondrial DNA.

That medic took his lack of success in the lab very personally. I made it worse by immaturely declaring in advance of each mini-process that I would succeed where he had failed. I was young and full of hubris. I do remember Anita telling me it was “luck of course” in front of him. I seethed at the inaccuracy and apparent injustice of her statement. Later that day she winked at me knowingly and smiled. She said that it achieves nothing to knock his confidence.

Looking back that particular guy was a highly intelligent, dedicated medic that had committed many years to training as a consultant. Anita was right. I was working hard, but going through the motions at the same time. She knew that I wasn’t committed to a career. She displayed leadership and pragmatism in protecting him. I also remember a couple of high achieving male consultants that used to make jokes about Anita frequently. Like two public schoolboys. And that was very much a part of the culture in there. I’m sure they contended it was harmless fun, but you could tell they were envious. And that stuff is never harmless. It’s toxic and it crystallises into glass ceilings. We still have a long way to go, but it was so much more difficult for women to succeed in those days.

In the domain of Neurology, glass ceilings were set very low and thick. Anita smashed through several of them. Anita Harding’s greatest achievements can be summarised as follows:

* She was the first to identify mitochondrial DNA mutation in human disease, specifically Kearns-Sayre syndrome.

* Co-discovered the concept of tissue heteroplasmy of mutant mitochondrial DNA. Most eukaryotic cells contain hundreds of mitochondria with hundreds of copies of mitochondrial DNA and it is common for mutations to affect only some mitochondria, leaving the majority unaffected. This influences the severity of mitochondrial diseases.

* She identified trinucleotide repeats in degenerative neurologic diseases e.g. Huntington’s disease.

* She ran a clinic where she had the unenviable task of telling about 50% of the patients who came in for testing that they would eventually die of Huntington’s.

* Anita was responsible for a huge body of work on the population genetics of disorders with ethnic distribution. I remember her travelling widely to get blood samples — particularly in Ireland where huge families were commonplace in those days.

* She published over 200 articles and edited 3 books. She jointly established, with Dr. Mary Davis (another great person I remember from those days), one of the biggest service labs for molecular analysis of neurogenetic disorders in the UK.

Anita should not only be remembered as a brilliant academic. She was a pragmatist who carried out research to improve people’s lives. She was no ivory tower researcher. Her discoveries served a lot more than curiosity. And she did all that in just over a decade. She was utterly amazing. Yet I could not even find a decent photograph of Anita online for this article.

She was a wonderful human being. That’s why I remember her like it’s yesterday. The day I told her I was leaving to go back to Dublin to specialise in another area of science, she took a huge interest in my motivations and in whether/not it was the right career move. I was a kid, the most junior guy in there. She was an academic of world renown. She made time for everyone. I called Anita a couple of years after I left to ask for a recommendation. She gave me an amazing reference, a far better one than I deserved. On that call she asked me to make up with an Irish scientist with whom I never got along. She told me that this scientist would really appreciate a call from me. I still regret not bothering to do that because Anita obviously cared about it and because it would have been the right thing to do.

Apparently in her final weeks Anita took a deep interest in the futures of her team and her peers and discussed their options at length. I find that very easy to visualise. Anita was also one of those pioneers that opened a lot of doors for women in science.

Here’s a tribute from an Irish woman who worked in 12 Queens Square from 1991 onwards (the year after I left). This woman is today one of the leading lights in clinical neurology and associated research.

“If I had to pick one person who has most influenced my career, it would be Professor Anita Harding. Her untimely death in 1995 at the age of 43 not only left a hole in Queen Square but also for me personally. I worked with her in the area of Familial Amyloid Polyneuropathy between 1991 and 1993 and after that had the opportunity to be her clinical registrar. She was a role model for me both as a clinician and as a woman in medicine. She was also an excellent clinical neurologist who was very intuitive in her clinical opinions.

What she truly excelled in was taking questions from the clinic back into the laboratory. She would try to address these questions, particularly for the genetic neuropathies, and it was from her that I developed my research interest in inherited neuropathies. As a woman she achieved new heights in Queen Square that had not been done previously and at no stage did she allow being female to limit anything she did. That attitude has stood me well. Finally she was great fun and her attitude to life was also how she approached her work; this clear enjoyment of her clinical and research work was something I admired and taught me how productive you can be if you enjoy your work.”
Professor Mary Reilly, President of the Association of British Neurologists (the first ever woman to hold that position).

In 1995 Anita Harding was posthumously awarded the Association of British Neurologists Medal for her contributions to the science of neurology.

Women invest up to 90% of their incomes back into family — they are the bedrock of society, wellbeing and the economy. The least humanity can do is write women back into human history. After all, they created half of it. We need to evolve to a place where it will be accurate to say that days like International Woman’s Day are patronising and serve no purpose. But for now we need to celebrate this day to constantly remind ourselves about the need for a world of equal opportunity.

We must honour memory fairly.

May Anita Harding be remembered for her brilliance, her strength, her sense of humour, her generosity of spirit, and the ever-enduring impact of her ground-breaking work.

The only decent published account of Anita Harding’s achievements that I could find online was this article by Professor Alastair Compston.

It’s a shame that this excellent source is a PDF hosted on a scientific journal and targeted only at specialists. Anita discoveries affect how we understand, research, diagnose and treat many inherited neurological diseases.

Her achievements are nothing less than heroic.

RIP Anita Harding, 1952 – 1995