Early kindling of interest in health sciences

Growing up in North England both of Mark's parents were the first in their family to go to university. His father trained as an engineer and his mother studied mathematics. Right from his early days at secondary school Mark dreamt of becoming a doctor. In part this was driven by his fascination with understanding how the body works. But he was put off going down the medical route after he did some placements in hospitals while taking his A levels. Critically this experience made him realise that he did not really have the right personality to work with patients.

Not getting much help from careers advisors at his school, in the end Mark decided to take a biochemistry degree at the University of Sheffield. The first in his family to leave home to go to university, Mark says at the time he opted for biochemistry because he had little knowledge about what other subjects were available and the options proposed by his school's careers advisers were rather limited. But going to university exposed Mark to a much wider range of subjects in his first year. This led him to swapping over to doing a dual degree in biochemistry and genetics.

After his undergraduate degree, Mark went on to complete a doctorate in immunology looking at allergies and vaccine design. He was able to undertake the doctorate because he was awarded a BBSRC Co-operative Awards in Science and Engineering (CASE) studentship. These awards are designed to encourage partnerships between academic institutions and companies to help solve a scientific problem oriented to further a particular process or product.

First foray into industry

Eighteen months into his doctorate, Mark realised that he did not want to pursue a career in an academic research environment. He grasped this after spending six months in an industrial setting which was encouraged by his CASE award. This time away, he says, really opened his eyes to the range of careers he had previously had no knowledge about.

One of the areas Mark became fascinated in patent law. Patents can be taken out to protect the intellectual property (IP) of an invention. In the biomedical sector this might be for a new drug or medical device or it could be for a new way to solve a technical problem. Issued to an inventor, the patent excludes others from using, making, or selling their product or method for a set period. A patent enables companies to get market exclusivity for a limited period which is a way for them to recoup their investment in the invention. Patents usually last 20 years from the filing date of the application. Protection ends once the patent expires, at which point anyone can exploit the invention. Patent owners can give permission to, or licence, other parties to use the invention for an agreed sum or sell the patent on to someone else.

After Mark finished his PhD he was offered a placement to work with a company in York which gave him a chance to work in patent law. Working with the company for a year, Mark says it soon became clear to him that patent law would be too 'dry as a career and too far removed from science' for his taste. This was because it involved 'an awful lot of legal texts and legal arguments with the European Patent Office'. But the experience gave him invaluable commercial grounding.

Introduction into the diagnostics world

Not sure exactly what he wanted to do, Mark was offered a job with Launch Diagnostics, a company involved in the distribution of diagnostics from American, European and Japanese companies. Initially viewing the job as a way to temporarily earn some income, he soon realised that diagnostics was a 'really interesting area to work in'. Until that point, he, like many other people, did not appreciate just how important the diagnostic pathway is to making medical decisions.

Mark spent nearly five years with Launch Diagnostics helping to launch diagnostics produced by other companies into the UK market. During this time he got to see the introduction of new diagnostic technologies, such as protein and genetic testing, which had the potential to revolutionise how people got treated. One of these included a test for measuring calprotectin, a protein found in white blood cells, which gets activated when inflammation occurs. Where this can be useful is in the diagnosis and subsequent treatment of inflammatory bowel conditions such as Crohn's disease, ulcerative colitis or irritable bowel syndrome. These are very painful conditions that can have serious complications, including a high risk of surgery and increased risk of colorectal cancer. Monitoring calprotectin in faecal samples, for example, can help healthcare givers monitor the progression of the disease and how effective a treatment is and where it might be adjusted. It can also help reduce the need for time-consuming and invasive colonoscopies in suspected inflammatory bowel diseases cases.

Prenatal and reproductive health diagnostics

Excited by what he saw at Launch Diagnostics, in 2015 Mark decided he wanted to focus more fully on innovative diagnostics. As a result he took up a position at Elucigene Diagnostics, a company founded in Manchester in 2013, focused on the development of diagnostics for prenatal medicine and reproductive health based on molecular genomic testing. Such tests look for certain genetic changes known to be associated with specific health conditions.

Elucigene's tests were developed to diagnose human genetic conditions caused by chromosomal disorders. Generally most human cells carry 23 pairs of chromosomes, which contain all the genetic information necessary for growth, survival and reproduction. Any deviation in the standard number of chromosomes or mutations can cause repeated pregnancy loss, male infertility and congenital disorders in the baby such as cystic fibrosis (CF), Down's syndrome and other rarer diseases.

Until very recently the conventional method for identifying chromosomal abnormalities during pregnancy was to obtain foetal genetic material from either the placenta, using a procedure known as chorionic villus sampling, or from the womb, using a technique known as amniocentesis. But both tests are invasive and can be uncomfortable for the pregnant woman as well as stressful. They also carry a small risk of miscarriage. By contrast the prenatal tests can now detect chromosomal abnormalities in blood samples taken from a mother's arm which eliminates the need to remove any cells from the baby.

Mark helped oversee the company's development of a prenatal diagnostic test for CF, an inherited, chronic, debilitating and life-limiting disease. One of the major challenges with CF is that it can cause problems with breathing and digestion due to the build up of very thick and sticky mucus in the lungs and digestive system. This is caused by a mutation in the CF transmembrane conductance regulator gene which all of Elucigene's diagnostic kits are designed to detect.

Remaining with Elucigene for over five years, Mark gained a lot of experience in product development and sales. In 2017 he was appointed Chief Executive Officer (CEO), a position he held until April 2019 when Elucigene was acquired by Yourgene Health, another British-based molecular diagnostics company looking to expand its product portfolio within reproductive health.

Life as a portfolio CEO

Since the sale of Elucigene, Mark has worked for a number of companies helping them to develop their strategies for taking diagnostic products from the bench through to the market. Much of his work is with early stage life-science companies that have been spun out of the work of university academics which need someone from a pharmaceutical or diagnostic background to step in and transform their ideas into a viable product. Such companies are unable to afford a full-time CEO, so they tend to hire Mark on a part-time basis. This means that he often gives support to three or four companies at the same time.

Mark is one of about thirty individuals in the UK who spend their time assisting different companies. Most of these people, often known as portfolio CEOs, work for a couple of companies that are at different stages of development. Having a range of companies at different stages is important, because some will fail to get their product launched onto the market, in which case they will die. But in other cases they might be successful at which point the opportunity opens up to work as a full-time CEO.

A lot of Mark's time is spent working out the necessary steps that need to be taken to get a product to market and how much money each requires. He also helps work out what clinical pieces of work need to be carried out in order to move on to the next stage. This means his day-to-day work is highly varied, which is why he likes his job. One day he might be absorbed in the general management side of things, and other times he might be looking at regulatory processes and how they get rolled through into the business. He also gets involved in the operational side of things, looking at how to manufacture a product. Then there is the commercial side of things where he looks at how to get the product out into the market and the logistics of distributing them to different countries. Another important element of his work requires understanding the reimbursement process. Alternatively he might spend three months at a time out of the office working to raise funding. Sometimes he says this process is like being in 'Dragon's Den', a TV series where entrepreneurs present their ideas to a group of wealthy investors.

Supporting start-up companies

Having been in the diagnostics business for many years, Mark was not short of job offers after Elucigene was sold. The first one he supported was MicrosensDx, a molecular diagnostics company based in Cambridge, that successfully gained approval for a rapid test that can be used to detect multiple pathogens in real-time, such as norovirus, respiratory syncytial virus (RSV), influenza and the SARS-CoV-2 virus. It does this by extracting RNA from a patient's sample using a chemical-bead based solution which is then amplified and sequenced. The test can be performed on throat and nasal swabs taken from patients as well as their saliva and sputum. One of the advantages of the test is that it can be used both in mass testing laboratories and also in a minimally equipped laboratory close to a patient setting.

Mark now works part-time for two companies. The first one is GenoME Diagnostics, based in Belfast, Northern Ireland. Spun out of the Patrick G Johnston Centre for Cancer Research at Queen's University Belfast, GenoME Diagnostics is pioneering a platform that makes it possible to measure DNA methylation changes in blood. Such changes are particularly helpful to the early diagnosis of cancer.

One of the company's most advanced products is a novel blood test for the earlier and more accurate detection of ovarian cancer which often goes undetected for years due to the fact that its symptoms are largely silent. Ovarian cancer is not usually picked up until it has spread throughout the pelvis and abdomen, at which stage the disease is far more advanced and far more challenging to treat. The advantage of the GenoME Diagnostics' test is that it is non-invasive so can be used to screen for patients who might have early ovarian cancer which is important to improving patient survival and outcome.

The second company Mark works for is Rosa Biotech, a company founded in 2019 to advance a new artificial intelligence (AI)-driven biosensing platform pioneered by Professor Dek Woolfson and his team at the University of Bristol. They were inspired to develop it based on dogs' highly refined ability to smell malaria, Parkinson's and other life-changing diseases. To do this they created a series of barrel-shaped proteins that resemble proteins found in the mammalian olfactory system. Made up of an array of different barrel proteins, each loaded with a dye, the sensing platform is able to detect faint chemical signatures given off by chronic diseases. This is picked up through the dislodgement of the dye in the protein when exposed to a particular sample, such blood. The resulting coloured patterns are then analysed using AI to determine healthy and diseased samples. One of the advantages of the platform is it is not reliant on pre-identified markers of disease, so it can detect illnesses not picked up with traditional biomarkers.

Rosa Biotech is currently testing the sensing platform for low-cost screening of a range of life-threatening diseases that remain difficult to diagnose. It is currenting testing it for nonalcoholic fatty liver disease (NAFLD), a long-lasting condition caused by the buildup of fat in the liver. NAFLD is now the leading chronic cause of liver disease worldwide. Nearly a third of adults in the general population in Western countries are affected by the disease. Moreover its prevalence is increasing which is putting significant burdens on healthcare resources. One of the major challenges with NAFLD is that it has no specific symptoms even at a late stage. This makes it very difficult to diagnose. If left untreated it can cause liver damage and increases the risk of developing type 2 diabetes and cardiovascular diseases.

The importance of keeping options open and being bold

When asked what tips he would give to someone looking for a career in the biomedical industry, Mark advises against being too 'narrow-sighted' early on. As he says 'I don't know anybody that's ended up in a field that they necessarily understood at the time that they left school.' He also points out the need to be prepared that 'ultimately the first career you step into might not be the one for you.' Many of the bioinformaticians he now works with, for example, originally did a degree in physics or computing and have no biological background. They only became involved in the medical side of things much later. From his perspective the key thing is 'to be bold enough to go and try something different and see whether you like it and not be too worried about whether it's the right one the first time around.'

Similarly Mark stresses 'don't be scared to admit something is not right for you'. He is highly familiar with the difficulties this can cause because of the failure he felt when he decided not to go down the path of patent law after he finished his doctorate. In addition, he has witnessed the emotional struggle of several new graduates who after some months of working with him realised that laboratory work was not for them. With some later becoming accountants, bioinformaticians or business analysts after finding out they much preferred dealing with data to the practicalities of life in a laboratory.

One of the major ways to find the right path forward Mark indicates is to talk to as many people as possible involved in a range of jobs to get a sense of what is involved. Finding opportunities to do work experience can also be helpful for understanding what is involved and 'getting under the skin' of the job. Talking to people at careers fairs can also be useful.

Mark highlights the many exciting career opportunities there are now within the biomedical industry which need people with lots of different skills. Within the diagnostics field he points to the major advances now being made in the development of non-invasive tests and sensing technology as a result of the coming together of different disciplines.

He is very optimistic about the recent progress in diagnostics which are shifting towards screening for the early onset of diseases such as cancer. Big headways are also being made in companion diagnostics. Such diagnostics can help identify which patients are most likely to either benefit from a particular drug or be at an increased risk for serious effects from certain drugs. They can also provide a means to monitor a patient's response to a treatment so that it can be adjusted to improve safety or effectiveness. Going forward Mark also believes AI will have a major impact because of its potential to improve the identification of better targets for diagnostics as well as treatments. All of these changes will not only require people with clinical training, but also expertise in computational biology and experience with big datasets.

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This article was written by Dr Lara Marks based on an interview with Dr Mark Street-Docherty on 10th August 2023.