In 1998, Professor Haroun N. Shah led a team of young researchers in the development of a rapid, low-cost method for identifying human infectious disease pathogens, which drastically reduced diagnosis time from days to minutes. Using mass spectrometry, Shah innovated with new instrumentation and created the first database of mass spectral profiles of microbial pathogens that allowed the methodology to work. It is now used by some 3,000 hospitals in Europe and North America, and is fast being implemented in developing countries where the method’s accuracy and low cost are having a major impact on public health services.

NIHERST interviews Haroun Shah

Q: You spent your childhood in San Fernando before leaving to study in England where you have lived since. What was your early life in Trinidad like?
A: I grew up in Coffee Street at the base of the Naparima Hill which gave me a very carefree childhood. My father, a supreme court marshall in San Fernando, was also president of ASJA (Anjuman Sunnat ul Jamaat Association) and the one who proposed establishing ASJA Boys’ College in 1960. My mother was a teacher. They had eight children and gave us very strong family values. Education was of prime importance, for my mother especially, but they did not inhibit us from doing other things. I loved science and began experimentation from the age of six with my chemistry set. I built my own laboratory below our house. Later on, my brother, a petroleum engineer, would bring home crude oil samples for me to distill and fractionate. After Common Entrance Examinations, I was due to go to Naparima College but was the guinea pig for my father’s creation and had to attend ASJA.

Q: Did you do well there?
A: I barely passed my eight O levels. Science entirely consumed my interest, not languages. Luckily, being a new college, ASJA, unlike others, allowed me to pursue all three science subjects- physics, chemistry and biology. This had a great bearing on my career. I started A levels in Trinidad, at Naparima, and finished in the UK. By then, all my siblings had started emigrating, either to Canada or England. I was offered a place at McGill University but I had envisioned England with so much vibrant culture. The “Beatles” led me there in August 1967! Amongst my luggage on the 14-day journey on the S.S. Antilles was my tenor pan and guitar.

Q: Were you on a scholarship there?
A: (Laughs) I had been working since I was 15 in various stores in San Fernando and after my O levels I worked as a
teacher, eventually accumulating £1000 to study abroad. When I arrived in the UK, university tuition fees were £25,
but within three months, they increased tenfold! I was penniless in less than a year and forced to study part time,
working evenings and weekends to support myself from then onwards.

Q: What work did you do?
A: Every job I could find – in bakeries, on buses, post offices, pubs, restaurants, various factories. In winter, I offloaded night trains. I worked excessively and was so run-down at one point, I collapsed at university and was
hospitalised. Britain was now unwelcoming, racism was rife and my future looked dismal. It was one of the lowest
points in my life. I wrote to my mother asking to return home. Her response, in a ten-page letter, was swift and uncharacteristically brusque, pushing me to confront the challenges of life and citing examples from her own journey. Her words made me more determined than ever to succeed. In three years, I applied for 52 personal grants
that barely saw me through to graduation. The hard work paid off, though, as I got the university’s only first class
honours and the Dean’s prize.

After jobs at ICI (drug development), Royal Marsden (cancer research) and Kew Gardens (plant biochemistry),
I moved to the Biochemistry Department at the University of London’s Royal London Hospital Medical College in
1972. The challenge was to lead in the burgeoning area of “anaerobic microbiology” (life without oxygen). I worked
full-time and, after hours, pursued my PhD there on anaerobic bacteria in the alimentary tract. I studied the chemical makeup, physiology and biochemistry of many components of the microbial flora, publishing my first scientific paper in 1975. Japanese and European scientists later named some species, such as Prevotella shahii and
Leptotrichia shahii, after me, in recognition of work I had published in biochemistry, pathogenicity, systematics and evolution. I completed my PhD in 1981, binding six papers into my thesis, and was appointed as a full time
lecturer.

Q: You then went on to the University of Kuwait. How did that come about and what was your experience there like?
A: Around 1984, the University of London was in financial crisis and unpaid sabbatical leave was being granted to
academics. I was offered a two-year posting at Kuwait University. At that time, my marriage had broken down, so going abroad with my two little girls, who were seven and five, seemed the right thing to do, in spite of the risks
posed by the war between Iraq and Iran which threatened Kuwait several times. I knew applying for research
funding when I got to Kuwait would take months. So I successfully applied for a £250,000 grant from the UK’s
Medical Research Council [MRC]. This allowed me to travel between Kuwait and London to procure laboratory
equipment, chemicals, consumables, etc. to set up my laboratory immediately. The Dean challenged my team to deliver at least one scientific paper in an internationally recognised journal. We published four and the Emir
himself thanked me on my departure. Ironically, it was in Kuwait that I encountered the London-based Nostalgia
Steelband which was on tour, and began playing again! I became, and remain a director of the steelband.

Q: You then returned to the University of London in 1987?
A: Yes, and I was promoted to senior lecturer. It was my golden period, having landed seven major research grants,
worth several million pounds, from the MRC. Between 1987 and 1991, I published 42 papers and received several
commendations including an MRCPath degree. I went to Canada for family reasons and also for having received a Canadian MRC grant of CAN$1.3 million for research at Dalhousie University. I returned to England after two years, having been offered a post at the Eastman Dental Institute. The institute was aspiring to become part of the renowned University College London (UCL) but was barred because of its low rating of two. Universities are ranked
from one to five, based on an extensive research assessment exercise. One of my duties was to improve Eastman’s score but, after a year, the task seemed insurmountable.With support from the Dean, Saheer Gharbia, my second wife who is a Molecular Biologist, joined me to take on this prodigious exercise. Working insane hours – 15 to 20 – daily for two years, restructuring the scientific focus and obtaining MRC and Wellcome Trust grants, we achieved the seemingly impossible. Eastman became the first institute to be elevated from two to five, which sanctioned its amalgamation with UCL. But the exercise left us utterly worn out and I left academia to pursue a new career at
Public Health England (PHE) in 1997.

Q: Was your work at PHE very different from your research at the university?
A: Yes. PHE’s work directly impacts patient care whereas university was more academic. My main duty initially was
to establish a new laboratory, the Molecular Identification Services Unit (MISU), to analyse emerging, atypical and rarely isolated pathogens that eluded conventional diagnostic methods. Little was known about their pathogenicity, transmission, stability or source. Despite considerable opposition from some of my peers who felt my experience was too academic to undertake this challenge, within one year, MISU was running the first such service and remains fully operational today based on the same methodologies I established. Saheer also joined PHE to establish the new Applied and Functional Genomics Unit. We combined genomics and proteomics (designated “proteogenomics”) and
led PHE into a new era of science.

Q: Why could the pathogens not be identified with existing methods?
A: Traditional methods did not have the accuracy to identify such unusual pathogens that were referred to MISU. I began to explore new technologies, especially mass spectrometry (MS). MS instruments have been used for a century by physicists and chemists to study the nature of matter. Their application in biology, however, posed major obstacles and had to await the development of techniques that enabled very large molecules, such as proteins, to change their state to a “gas” so they could now travel in a charged field for analysis. There are numerous types of mass spectrometers. The one we first used was Matrix-Assisted Laser Desorption/Ionisation Time of Flight Mass Spectrometer (MALDI-TOF-MS) at a company in Manchester. In the method we used, a bacterial/matrix admixture placed at one end of a tube under vacuum, was bombarded using a soft laser to create a plume of ions or charged fragments. These travel at rates – milliseconds – that are inversely proportional to their mass/charge ratios to reach the detector where their electrical signals convert them into the mass spectrum that give a characteristic MS fingerprint of the bacterial pathogen. Our initial success was dramatic. I held the first such conference at PHE, to explore potential applications of this novel technology on 27th October, 1998. I expected about 30 scientists but over 150 people turned up including from CDC in Atlanta.

Q: How did you go about developing the methodology using that instrument?
A: At the conference we demonstrated that the identification of a pathogen, which normally took hours to days through analysis of the various carbohydrates metabolised by bacteria was now possible in two to three minutes by switching to protein analysis by MS. I retained the instrument in my laboratory for a month and my PhD students began experimentation, devising a plethora of protocols based first on fractionation of bacterial cells, and then eventually using whole cells. After considerable work, we developed a method in which each pathogen, e.g. for TB, cholera, pneumonia, etc., yielded a unique “mass spectrum” or electrical “finger print”, based on the makeup of their complex proteins.

The company was so excited by our results they let us keep the instrument for a year. We redesigned a new automated instrument which was built and delivered in 2000. The challenge was now to assemble a database of several thousand bacterial species to act as a reference source to compare unknown pathogens. The accuracy of identification of a species and its variants by this method is entirely dependent on having a comprehensive database of representative MALDI-TOF MS profiles.

Q: How was the database built and how big is it today?
A: We reported the first database in 2004 in a scientific journal. But there are major companies who assemble and market these databases, which now contain over 100,000 spectral profiles. More specific databases are also being developed. Our group is currently involved in an EU project to assemble a unique database of over 600 anaerobic bacterial species.

Q: Did the system get tested in the field?
A: Yes. Field-testing new technology to assess its robustness is essential. While the MS technology was being employed routinely in my laboratory, Saheer and I were awarded a new grant in 2005 for nearly £2 million to explore new forms of MS such as electrospray ionisation, orders of magnitude superior to MALDI-TOF MS for protein analysis but far more complex and cumbersome to field-test. I felt it necessary to field-test MALDI-TOF MS as the method for rapid diagnostics. I contacted numerous hospitals but all except my former employer, The Royal London Hospital, refused permission. With a few PhD students, we analysed over 600 isolates blindly and compared
results with those obtained by the hospital. All results, except for the hospital-acquired pathogen, Clostridium difficile, were highly successful. We collaborated with a German group, AnagnosTec, to resolve that problem,
exploring more potent organic solvents to disrupt the extracellular polymeric layers of the cell prior to MALDITOF
MS analysis and was immediately successful.

Q: How else is this diagnostic system being used today?
A: In the past, mass spectrometry focused on human diseases such as cancer, diabetes, multiple sclerosis, etc., by analysing surrogate markers for these diseases. These were seen as lucrative markets and took precedence. Today, microbial diagnostics has surpassed these applications, driving the technology globally and extending applications into diverse areas such as agriculture, aqua/marine farming, manufacturing processes involving microbes, environmental studies such as antibiotic resistance monitoring in rivers, sewage, etc.

Q: What research are you doing now or hope to be doing in the future?
A: Much of my time is spent taking the technology to developing countries where I believe implementation
will have immense impact on healthcare. In 2013, I spoke at CAREC (now CARPHA) in Trinidad and suggested a
group comprising UWI, Eric Williams Medical Sciences Complex, CAREC and others be set up to take the lead for the Caribbean and Latin America. Two local persons were trained in my laboratory at PHE in 2014.

Since leaving PHE in 2015 and moving back to university, I have the freedom to experiment and help in the design
of new instruments. One very new form of MS, referred to as “Top-down” proteomics, is rapidly pushing ahead. Led by ThermoFisher Scientific, with whom we have been collaborating over the last four years, I presented our initial
findings in April 2015, showing areas where it is superior to MALDI-TOF-MS. I am convinced these technologies will make the most incisive breakthroughs in diseases of all types. Saheer and I are also compiling our second book, “The Triumph of MALDI-TOF Mass Spectrometry and New Developments in Tandem Mass Spectrometry for Clinical
Microbiology”. My dream is to see my home country get involved immediately and become a leading global
pioneer in this revolutionary, futuristic field.