Next Level in Medical Genetics
India is swiftly moving towards being the capital in prevalence of non-communicable diseases, having secured the third position in congenital malformations and genetic disorders as the commonest causes of mortality in neonates in cities. The ability to identify these non-communicable diseases at an early stage lies in the hands of the genetic screening segment. Genetic screening, however, is still in its infancy and to realise its full potential there are many challenges that need to be overcome. Till date, we have just been able to understand its basic applications. At present, a huge percentage of people from the medical background, the public at large and government bodies all remain largely indifferent as well as skeptical toward the potential of medical genetics. How far this restraint is justified and how far it blocks the growth path for this field of medical sciences needs to be analysed on a serious note
By: Neelam Jhangiani
Diagnostics has become an integral part of most patients' work-up in today's scenario and with phenomenal advances in imaging, imageologists i.e. radiologists of yesteryears are now increasingly in demand. With an increased need to provide superior healthcare owing to the significant advancements in healthcare, genetic testing has become a highly attractive segment in the molecular diagnostics market. Genetic testing, which is an analysis of genes, chromosomes, or proteins helps predict the risk of diseases, its diagnosis, likely course of the disease and also identify carriers of disease (individuals not having the disease but having a copy of the disease gene). Congenital and hereditary genetic diseases are becoming a significant health burden in India, and hence there is a need for adequate and effective genetic testing and counseling services. "The market for genetics in India is expanding as more and more individuals and physicians are availing these services," says Dr. Abdur Rub, Co-Founder and Chief Technology Officer, Xcode Life Sciences. In India's urban areas, congenital malformations and genetic disorders are the third most common cause of mortality in newborns. Factors contributing to this high prevalence include consanguineous marriages, high birth rate, improved diagnostic facilities, and a lack of expertise in genetic counseling. While the global genomics market is estimated to reach around 23 billion USD, the Indian market is not yet as mature – both in terms of clinical and consumer genetics segment. It is expected that some of the divisions of genetics such as diagnostic testing, pharmacogenomics and personal genomics with new technologies like microarray and next generation sequencing (NGS) will significantly contribute to the growth in India. It is a trend that has shown an increasingly upward surge in the past decade. The availability of genomics is going to change the lives of the vast majority of the population. It will make people live longer and healthier. Today, in healthcare there is hardly any personalisation, but genetics is now changing this scenario. Genetic screening is becoming more customised, less expensive and we are now able to understand better and better what to look for. Dr. Ravi Gaur, Chief Operating Officer, Oncquest Laboratories Ltd., is very sure that the segment is now building up and with more understanding of the genetic code, is on its way to developing drugs that can target the genes and other applications. He says, "Though we cannot predict by when this will happen, we have definitely entered that path and the next decade would be very exciting." Although the awareness of genetic diseases is significantly increasing in India, very few clinics and labs are offering advanced cytogenetic, biochemical/metabolic, molecular and prenatal diagnosis services and genetic counselling as a one stop solution. Healthcare & wellness has become an integral part in today's age and citizens are willing to utilise these available genetic technologies proactively to ensure personal wellbeing. "A host of genetic tests such as premarital genetic testing, carrier testing, pre-implantation genetic testing, prenatal screening especially non-invasive prenatal screening (NIPS/T), prenatal testing, new born screening, pre-symptomatic screening, predictive screening, forensic testing, immune genetics especially in transplants coupled with genetic counseling, is benefitting a huge number of people across the length and breadth of the country," says Ameera Shah, Managing Director, Metropolis Healthcare Ltd. Unlike other inventions, genomic sequencing technologies are undergoing regular upheavals at unprecedented speeds. NGS is a great example of an innovation that is driving major positive changes in the market. The increased adoption of gene testing is being driven by the expanding applications of genomics in research and testing, advances in next generation and whole genome sequencing, declining cost of instruments and consumables, integration of genetic testing into a clinical/hospital practice, increasing government investments, increasing physician adoptions and most importantly the growing consumer awareness and adoption.
Although the awareness of genetic diseases is significantly increasing in India, very few clinics and labs are offering advanced cytogenetic, biochemical/metabolic, molecular and prenatal diagnosis services and genetic counselling as a one stop solution
India contributes around 20% to the world population but DNA sequences of Indians make up only 0.2% of the genetic databases worldwide. "We can partially attribute this to the lack of awareness and poor ease of availability," Dr. Rub says. Awareness has to start at the root-level believe experts in the industry. Dr. Gaur is of the opinion that a nation-wide campaign should be run to make users aware of its utility. Once the actual users understand the benefit, the demand will automatically go up. Furthermore, he believes in sharing additional knowledge for faster acceptability. For example, we need to share the knowledge and its applicability with doctors who are undergoing training; this would help them reap benefits in their practice in future. As a country, we are in a transition phase and need more medical genetic specialists and genetic counselors.
"I can see the genetic diagnosis moving from a probabilistic analysis to a more deterministic or rule-based approach that could provide the doctor directly with the correct advice," Dr. Gaur says.
Most major players in the industry are leaving no stone unturned to raise awareness about issues concerning genetics testing. Xcode Life Sciences has been conducting numerous courses on different aspects of genetics throughout India for several years now. A course on nutrigenomics for clinical dietitians in Bangalore was organised very recently by X code and they have plans to take this to Mumbai during summer and other cities across India this year. "It is a slow process and is the responsibility of companies like us who have access to both experts and consumers to do this," says Dr. Rub.
Celebrity endorsements have also played a big role in bringing about awareness for genetic testing, (e.g. Lance Armstrong, Lisa Ray, Yuvraj Singh etc.). However, they do not effectively target the populations that need the greatest of such services. In 2013, Angelina Jolie's public disclosure about having undergone chemo-preventive surgery of her breast and ovary bought about an increase in BRCA1 and BRCA2 testing.
"Some of the other awareness campaigns including medical camps, social media awareness (e.g. the ice bucket challenge), marathons, fund raisers, newspaper articles, interactive sessions by doctors have resulted in a boost in genetic testing in India," says Zoya Brar, Co-Founder & Managing Director, CORE Diagnostics. On the other hand, Ms. Shah of Metropolis points out the importance of detailed counseling letters and tele-discussion of reports to help change the existing situation. It will also help the population to choose a proper genetic test, she adds. Strong network for logistics is another area pointed out by Ms. Shah that holds equal importance in genetic testing so that samples reach the laboratory in stipulated time.
Mass screening for most common genetic diseases prevalent in certain geographic locations or tribal populations with the help of government bodies and healthcare institutions such as Beta Thalassemia, organising more and more CMEs/conferences, webinars and training courses in genetics to science graduates and medical doctors are some of the other strategies to raise the level of awareness for genetic testing in our country.
Metropolis Labs walks that extra mile for patients who come from rural and peripheral parts of the country. As a policy, a detailed counseling letter is sent to patients whose samples are received for genetic testing if a face to face meeting is not possible. Metropolis is also well positioned with its network of labs across India, collection centres and a seamless logistics team that makes it possible for samples to reach in the stipulated time.
Once the analysis and reporting of the sample is complete, every opportunity is taken to discuss the case with the referring clinician and after obtaining detailed medical history, counseling letter addressing to the doctor is issued in the best interest of patient/family. There are several aspects in the marketing of genetics believes Dr. Rub of Xcode, which are to a great degree dictated by the nature of the product. Clinical products need a field force and training and consumer products require more of training and education. It has been noticed that consumers better accept the concept more in therapeutic and prognostic but are susceptible of its utility in productive assays.
Preventive healthcare & genetics testingPreventive healthcare plays an important role in increasing the demand for genetic testing. The market potential for genetic testing is tremendous given the need for preventive healthcare. The primary markets that are picking up within the country are pharmacogenetics and nutrigenetics. A growing understanding of human genetics holds the promise to dramatically change healthcare through customised preventative care and treatments. Our genes play an important role in our health. The billions of genes in our biological code shape who we are and tapping into this information can reveal a lot about our potential health and future well-being. Understanding the way specific genetic variants influence disease risk can lead to reduced healthcare costs and a new approach to a healthy lifestyle. "If we know our genetic predisposition even before the first symptom manifests itself, we can adjust our environment and lifestyle so that we avoid certain risk factors and prevent the development of disease," Ms. Brar says. A disease state is interplay of our genetics, behaviour and environment. Some diseases are entirely genetic. That means that even if a person has a genetic predisposition towards the disease there is a lot one can do behaviorally to prevent it. "Most of the hereditary genetic conditions, though not treatable, are preventable. In genetic practice, using prevention as the cure may not be surprising," says Ms. Shah. It is a well-established fact that preventive medicine is by far the best and least expensive medicine. With time to come, disease prevention will gradually become the responsibility of the patient as well where they would recognise the consequences of smoking, unhealthy food habits or for that matter a sedentary lifestyle. The risks will be more personalised based on one's genetics. Experts opine that though in India, genetic testing would be more in the curative space initially, but it's preventive role will catch up soon.
Selecting it right
There is a plethora of tests in the market, which confuses the common man. Here, medical geneticists and genetic counselors come to play. They are trained healthcare professionals that help patients and their families get the care that's right for them. They understand a patient's needs and guide them accordingly. Onquest Diagnostics have created a skill driven central customer care desk where every patient is counseled. Though generally it is still a prescription-based test where clinicians play a major role of educating the patient. In addition, they have created an organ-based profile for instant recollection. X Code mostly covers consumer genetics wherein anybody can opt to take the reports without a medical recommendation. "Identifying the right test is better left to other healthcare professionals like physicians and wellness professionals," says Dr. Rub. Metropolis opts for pretest counseling to collect detailed medical, obstetric and family history based on which specific test is suggested to the patients. "In post-test counseling, we discuss the test report findings and explain the risk to patients and other family members, along with options available to avoid 'passing on' to the next generation. Also, to make it more cost effective we suggest targeted testing," Ms. Shah informs.
Genetic testing needs to be looked upon as an investment rather than an expensive affair, opine experts in the industry. Dr. Rub is of the view that a genetic report costs the same price as an average smartphone. Recently, Forbes reported that there are 1 billion smartphone users in India, which is half the population who can afford to pay 10,000 INR. A DNA kit purchased once provides a wealth of information, which makes the cost factor negligible, as per some experts.
Genetic tests performed to screen for a disease differ from the ones conducted to establish a diagnosis. While diagnostic tests are intended to definitively determine whether a patient has a problem, they are generally complex tests and commonly require sophisticated analysis and interpretation. They can be expensive and are generally performed on people believed to be at a risk, such as patients who already have symptoms of a specific disease. In contrast, screening is performed on healthy, asymptomatic people and often to the entire relevant population. A good screening test is relatively inexpensive, easy to use and interpret, and helps identify which individuals in the population are at a higher risk of developing a specific disease. By definition, screening tests identify people who need further testing or those who should take special preventive measures or precautions.
"Testing of the genetic code has come a long way, from a whopping 3 billion to a few thousand dollars," says Ms. Brar. When there is awareness, the demand increases, which in turn leads to an increase in sample size, thus reducing the cost to perform, hence reducing the overall cost. "Some measures to minimise the cost barrier include appropriate test selection, identification of appropriate candidate for testing, targeted testing approach for other family members, customise panels with reflex strategies and algorithmic testing by following the standard guidelines," shares Ms. Shah.
Newer & more eased applications, fast advancing technology, along with increasing volumes are additionally helping in bringing down the cost substantially. Government needs to play a proactive role here by helping out the devices & the diagnostic industry by providing better incentives, grants and offer other cost reducing measures. Genetic testing is currently seen as a premium product for the affordable class, but a right push from the government can make it happen for the general masses, which will bring down the cost drastically.
Interplay: Radiology and Imaging
Traditionally, radiology has been an important part of the algorithm for the diagnosis of a number of genetic disorders. Radiological and imaging findings are one of the important indications for genetic testing. For example, analysis of X-rays of the skull, spine and extremities is used in the diagnosis of skeletal dysplasias such as mucopolysaccharidosis. Additionally, certain neurogenetic syndromes, which include dysmyelinating diseases such as leukodystrophies and storage disorders require MRI scanning both for diagnosis and follow up.
Radiogenomics is a new and rapidly evolving branch of radiology, which integrates advanced imaging and pathologic-genetic analysis of tumor biology into a collaborative approach that allows for more specific diagnosis of tumors as well as better understanding of tumor behavior including personalised therapies. Imaging genomics/radiogenomics can be used to create imaging biomarkers that can identify the genomics of a disease, especially cancer, without the use of a biopsy. Various techniques for dealing with high dimensional data are used to find statistically significant correlations between MRI, CT and PET imaging features and the genomics of disease, including SAM and GSEA. This branch of medicine has shown promising results in determining the MRI phenotype associated genetics of glioblastoma (highly aggressive type of brain tumor with low prognosis). Similar positive results have been reported in liver cancer genome from non-invasive imaging features and the approach has been successfully app lied in breast cancer as well.
"Simply speaking, radiology and imaging helps to identify high risk cases for genetic condition," says Dr. Arjun Kalyanpur, CEO and Chief Radiologist, Teleradiology Solutions. Genetic testing in such cases can help the confirmation of clinical diagnosis and many a times not only helps the patient but other family members who stand a risk of acquiring a particular ailment. So as a screening tool, the role of radiology & imaging is highly crucial and this can be further maximised by use of teleradiology and technology for the benefit of patients at large.
Genetic diseases are typically rare and complex that calls for a heightened need for specialised analysis and the number of radiologic specialists with expertise in this analysis is small; this is where teleradiology comes to the rescue. Speaking on the benefits of teleradiology in genetic testing, Dr. Kalyanpur points out that it enhances access to this expertise by transmission of images to a specialist with a long-standing experience and technical knowhow in analysis of these conditions. Use of technology in the form of machine learning and Artificial Intelligence is helpful in forming databases of information that can be used to train computer neural networks in the analysis and processing of this complex data to assist radiologists in diagnosis as well as treatment planning.
Barriers to growth
Medical genetics has seen an accelerating growth in recent years and the success of genetic testing in India depends largely on how major challenges are managed around this field. Since India is one of the emerging markets and being looked upon by the global players as a key niche for growth, it is time that the caveats that might affect its growth are well understood and taken care of.
Factors such as the authenticity of reports being questioned due to lack of credible standard procedure is one of the major dampener affecting the growth of genetic testing market. In addition, individuals are concerned about the high cost associated with testing and accessibility to these tests. Currently, genetic testing is accessible only to those living in a metropolitan city and the market in smaller cities and rural areas is still untapped. The aim is to spread awareness of gene testing and its role in predictive and personalised medicine. It is highly important to make genetic disease related services accessible along with adequate, well equipped, full fledge genetic laboratory setup and effective genetic counseling services. Dr. Gaur points out the need to collaborate between scholars, government and the industry. Traditionally, scholars or institutions are involved in developing new knowledge and the industry then takes it up for further development. "The gap between scholars, gover nment institutions and industry should be closed. The government and the industry have to provide financial support to roll out the disruptive innovative genetic testing and make it affordable. Also, we need to change our approach to scientific R&D and to education where interdisciplinary approach will dominate and replace in many ways the traditional, discipline-oriented approach," says Dr. Gaur.
Where the future lies
The current approach to treatment i.e. 'one size fits all' is now coming to an end and we are entering a new era known as 'personalised medicine' where the treatment is tailored according to the patient's molecular/mutational profile. The mechanism will drive the development of new drugs, which will be individual specific and of rational use. The broad-spectrum approach to prescribing medicines will probably get over or be restricted to a greater extent. This will help in more targeted treatment and reduce the cost with better outcomes. Human genome is highly complicated with 30,000 genes known to play a role in our health and well-being. Genetic testing has a different application in practice. On one hand it serves to confirm a suspected diagnosis (e.g. CFTR gene in cystic fibrosis) or can be of use for risk assessment of first degree relatives (BRCA1 & BRCA2 gene-breast cancer). While some genetic findings represent an absolute fate for the patient's health, others only show an increased risk of developing a disease. As medical/digital health technology matures, we can expect to see healthcare evolve in conjunction with growing consumer awareness. This evolution in healthcare and awareness will result in a dramatic change in the way we approach genetic disorders and healthcare management plans for individuals and families. The future of genetics is very bright especially with new technologies like array and NGS and there is a definite consensus that genetics will be the first line of investigation in laboratory medicine in the near future in clinical, cancer pharmacological, infectious disease and in almost every fraternity of medicine. firstname.lastname@example.org