Leading the Next Medical Revolution: Dr. Nazneen Aziz on Her Work in Genomics and Precision Medicine

This interview was conducted on February 13th, 2019, by:

Tahsin Tabassum, Tasmin Tabassum, Ridwan Hossain, Maliha Tanjum Chowdhury, and Jabale Rahmat

Juniors at the Schools of Life Sciences

Independent University, Bangladesh

Published on April 3rd, 2019

Dr. Nazneen Aziz, Ph.D., the President and CEO of Variant Genomics, Inc. Variant Genomics provides expert advice and guidance for implementing clinical genomic testing and precision medicine research in the community health care systems in the US as well as in developing nations. She is the former Executive Director of the Kaiser Permanente Research Bank and Senior Vice President and Chief Research Officer at Phoenix Children’s Hospital and the Director of Molecular Medicine at the College of American Pathologists (CAP).  Dr. Aziz has held executive leadership positions in the biotech/biopharma industry. In her industry career, Dr. Aziz focused on personalized medicine, biomarkers, genetic tests, and development of drugs for cancer and diabetes. Prior to joining the biotechnology industry, Dr. Aziz was an Assistant Professor at Harvard Medical School and Boston Children's Hospital where she discovered new genes and their role in polycystic kidney disease. She currently holds Adjunct Professorships in the School of Life Sciences at Arizona State University and in the Department of Child Health at University of Arizona College of Medicine.

Dr. Aziz received her Ph.D. in Molecular Genetics and MS in Biochemistry at the Massachusetts

Institute of Technology (MIT) and her BA (Honors) in Biological Sciences from Wellesley College.

She has several issued and pending patents. Her publications have been cited extensively in the

medical and scientific literature and she has been invited to speak at numerous national and

international conferences.

During a visit to IUB to conduct a highly informative and engaging seminar on precision medicine, Dr. Aziz graciously agreed to be interviewed by some of the students from the School of Life Sciences for the HERE BE DRAGONS blog. The following transcript of her interview contains amazing advice for students and early career scientists thinking about going into industry, as well as numerous insights on genomics and precision medicine, and the prospect of using such technology in Bangladesh.

Maliha: For someone who was in academia, how was the transition into industry? What are the similarities and differences you experienced between the two?

Dr. Aziz: A very good question. In my experience, as a faculty at Harvard Medical School for 8 years, I was completely independent. I had my own funding and my own lab while conducting research in discovering new genes and their functions in polycystic kidney disease. I loved interacting with my lab team – students, technicians, post-doctoral and medical fellows. We were one team and working the course of action that were my labs research objectives.  I loved that independence, the thrill of discovery research from large victories to small successes.  For example, the euphoria that comes with discovering a new gene associated with a devastating disease to the simple joy of running a successful electrophoresis gel. So really, there is great satisfaction and contentment in academic research. However I realized that if I stayed in academia for a very long period of time my focus would become too narrowed into my own specialized field. I  wanted to make a contribution to healthcare and not just be highly focused on getting another publication that may or may not translated into products or that would impact human health in the near term. This area of research is called translational research and it had a strong appeal for me.  I decided to move into the biotechnology industry which was growing rapidly in Cambridge, MA in early 2000 with spin-off companies being created from MIT and Harvard.

The biggest difference between the two worlds- academics and biotechnology- is that the research that you conduct in biotech is not solely determined by you but it follows the company’s greater goals and objectives. However, because I was in a leadership role in my biotech/biopharma career, I did have the authority to delineate the scientific and technical strategy of the company and the research direction. And I really think that my industry career has helped shape my strategic thinking and built my business acumen. I think the biotech industry experience has broadened my horizons as well. My discoveries and publications of my academic research  were certainly important contributions to the scientific community. However, the products that you create whether it is a drug or a genetic test ---things in the research and development realm or in the translational research realm in biotech have a more immediate impact on human health.  It is a gratifying experience.

Maliha: Students completing undergraduate and Master’s programs in fields like Biochemistry and Microbiology often want to go on to do basic science research in academia. How do you attract or recruit such people into the industry instead? And if you have to convince them, what advice would you have for them to succeed?

Dr. Aziz: I think academic research is a great choice for some but others may choose to go into biotechnology/biopharmaceutical industry to develop medical devices, medicine, genetic tests or consider a healthcare profession that could range from being a medical doctor to a medical technologist, genetic counseling etc.  However, the opportunities for these alternative careers has to be readily available. In Bangladesh, I am not sure how developed the biotech and health technology industry has become.  Industry leaders should open up internships in their organizations for students. Graduates of the life sciences should certain try to do internships in these alternative career paths  to see if that line of work appeals to them or not.

Maliha: Does your company currently have any collaborations with any academic institutions?

Dr. Aziz: Yes, indeed.  Variant Genomics’ business is to advice and provide guidance to help community healthcare organizations in the USA to implement precision medicine in the care of patients. That involves keeping very deep connections with numerous academic professionals as well as the biotech/genomic healthcare industry. My company uses a number of consultants in these different sectors for various projects.  Precision medicine also referred to as genomic medicine has been growing and evolving at a rapid pace. This excitement has attracted many from the academic sector to seek opportunities in the precision medicine industry.  There is an intense appeal of this burgeoning and cutting-edge diagnostic technology that requires a merging of research and clinical care. In the USA,  there are many examples of how academics, healthcare and genomic industries are working closely as there has been a keen awareness that it takes diverse skillsets to deliver the benefits of genomic technologies for patient care.

Maliha: How much experience would a student who completed their Master’s degree in biological sciences need in order to work in companies like yours?

Dr. Aziz: It really depends on the position you want to hold in those companies. For example, if you want to be a medical technologist, you would need to learn how to operate cutting-edge instruments such next generation sequencing machines. The same is true for bioinformaticians who would need to be proficient in next generation data analysis. Interpretation scientists to understand and create knowledge databases.  Therefore, I would say that for these entry level jobs, one would not need too much previous experience other than internships and learnings through coursework in the Master’s degree since they would receive comprehensive training on the job.

Jabale: Doctors have not traditionally been trained in genomics. How might doctors and medical professionals in Bangladesh and similar countries be trained on the use of genomics and precision medicine?

Dr. Aziz: This is one of the bottlenecks in the implementation of precision medicine. Even in the US, doctors do not get intensive education or training in medical genetics in their medical curriculum even though in recent years that has changed. With genomics bursting into the clinical care scene around 2010 it is a bit overwhelming for doctors everywhere, not just in Bangladesh, to understand how to approach it.  As you know, genomics is based on the concept of genetics except that it involves a much greater volume of data.  Most physicians do understand that this new field is coming close to home and yet they don’t have the time to learn a whole new science which leads to certain level of fear of the unknown. Therefore, there is a great need for companies like Variant Genomics and other genomic companies to develop tools, services and products to make it seamless and easy for doctors. All physicians need to do is to understand the power of genomics in patient care by educating themselves. They do not need to learn the complexities of next generation sequencing, data analysis and interpretation but that they should be aware of where to order genomic tests for the care of their patients.

In the USA, there is the requirement for medical doctors to take Continuing Medical Education (CME). CME can be fulfilled in a variety of ways, for example, attending a medical or scientific conference, taking an online course. It is important for Bangladesh to consider something of this nature so that doctors can keep up with the new research and new advancements in medical knowledge and how they can implement these new advancement in healthcare in patient care.

Jabale: How often do you find Single Nucleotide Polymorphisms (SNPs) in non-coding DNA regions like satellite DNA or any other repetitive DNA that actually are associated with disease?

Dr. Aziz: There are 3 to 4 million variants within individual genomes. The majority of the SNVs are in non-coding areas. The monogenic diseases (more serious types) are due to SNVs or structural variants that are generally found in the coding regions of the genes. These SNVs tend to disrupt the protein code and so they are rarer in frequency in the human population.

Many of the variants in the non-coding regions are benign. Recently, there is a greater appreciation regarding the role of noncoding SNVs in complex genetic diseases, e.g., hypertension and type 2 diabetes.  Complex genetic diseases are a different category of genetic disease than the monogenic (Mendelian) types. More and more research is leading to our understanding that SNVs in non-coding regions of our genome are associated with complex genetic diseases. For example, if a SNV happens to alter a gene regulatory motif in the promoter region, or in enhancers within introns and in intergenic spaces they can aberrantly regulate the expression of the gene which can lead to disease.  ENCODE was a big project funded by the NIH that investigated the function of non-coding regions of the human genome.

Tahsin: Do you expect there to be challenges to setting up precision medicine in a country like Bangladesh?

Dr. Aziz: Perhaps it is important to emphasize that precision medicine is not as difficult as the name suggests. A simple way to think of the field of precision medicine is to call it genomic medicine-- a specialized field that utilizes a new high throughput and cost effective DNA sequencing technology, called next generation sequencing to analyze a patient’s DNA. The DNA analysis provides insights in to the patient’s disease and how they should be managed based on their genetic profile. There are molecular diagnostic labs in Bangladesh that does simple genotyping and PCR tests. Precision medicine or genomic testing is just a much large scale version of singe gene analysis.

Certainly, there will be some challenges in the initial phases of setting up clinical genomics in Bangladesh, especially since the higher education in the new field of human genomics in this country is somewhat lagging behind other developing nations. However, a challenge is always an opportunity. I would find it exceedingly satisfying if my efforts can help pave the first steps towards implementing precision medicine in healthcare. What my company, Variant Genomics, intends to do is to make genomic tests easily available for patients in Bangladesh. These tests are being used in many aspects of clinical care. For example, in cancer, NGS tests can identify and match targeted drugs for patients. In pharmacogenomics, tests can identify if patients will have adverse reactions to certain medications. In inherited disease, NGS identify the genetic causes of diseases.

Bangladeshi healthcare systems have implemented very complex technologies such as MRI, CAT scans, PET scans including complex surgical procedures and therefore it would be a natural evolution for Bangladesh to develop the field of precision medicine next. It would give patients access to genomic tests that are routinely being used elsewhere in the world. I do not think it would be enormously challenging to bring this genomic testing technology to Bangladesh especially since India, Thailand, and other developing nations have already implemented genomic testing in healthcare.

Tahsin: Do you think doctors attending seminars and conferences are enough to help them understand and execute precision medicine?

Dr. Aziz: It is not enough, but it creates awareness.  The physician will be aware that there are better options than chemo and radiation for their cancer patients.  They will know the right questions to ask when they come across patients who are suffering from genetic diseases or patients who respond adversely to many medicines. Doctor don’t need to understand how to conduct the genomic test but just be aware that this new technology exists and where to order the test. The reports for these tests lay out the interpretation of the results and guides the physicians with knowledge available on how to manage the patient based on their genetic profile.

By going to conferences and seminars, physicians become aware of the latest advances in medicine and diagnostics.  Wouldn’t you want your doctor to provide you the most effective medicine or the best test available in case you were the patient being treated in Bangladesh?

Tasmin: Is there anything related to genomics that you are working on currently in Bangladesh?

Dr. Aziz: I want to start with bringing awareness that genomic testing labs are needed in Bangladesh. Hospitals and diagnostic labs are well aware that patient samples are being sent abroad for testing in large numbers.

My goal is to bring this technology to Bangladesh and to spread awareness that inherited diseases and cancers can be due to ethnicity specific mutations. Therefore, there is a huge need to bring this technology to this country in order to look at patient’s genetic profile from the context of ethnicity.

Ridwan: If precision medicine was to become the norm, that could lead to a contraction in the market for individual drugs. How will pharmaceutical companies handle this? Will the drugs become more expensive because they are for specific people and not everyone can use it? In the long term, will it become a problem?

Dr. Aziz: This argument of shrinking market size for a drug is now proving to be without merit and had raised concerns for the pharma industry initially.  Pharmaceutical companies have traditionally tried to create blockbuster drugs which will make them $1 billion annually called “block buster drugs”. They have had very little success in marketing blockbuster drugs in recent years, so the industry is becoming very aware that they need to adopt a different approach.

I look at the precision medicine area with optimism.  Incorporating precision medicine will allow pharmaceutical companies to manufacture and sell many more classes of medicine.  There will be subgroups of patients who will match medications because these drugs will actually work in that group of patients  and a simple genomic test can find that match. Wouldn’t we want to know if the drug is actually helping the patient or that it can harm the patient?  Pharmaceutical companies actually do want their drugs to be efficacious and to lead to fewer adverse events. In the US and in Europe, they are now doing clinical trials and investing genetic markers of people who respond or don’t respond to new investigational drugs during the development phase.

Regarding the price of these targeted drugs for cancer, there are over 200 or more that have been approved by the FDA and over 650 drugs listed that have a pharmacogenetic associations and it has not led to any significant increase in pricing or availability. It is just a safer and effective use of drugs for patient care.

Ridwan: Will the availability of these drugs all around the world be an issue?

Dr. Aziz: Targeted oncology drugs are becoming available all around the world. Pharmaceutical companies market their drugs all over the world. If an effective medication is there it will ultimately make it to patients around the world.

Ridwan: What are you currently finding out about the possibility of using precision medicine in this country?

Dr. Aziz: I am exploring whether healthcare and academic leaders understand what precision medicine is all about. I am actually happily surprised to see how receptive they are to implementing this technology. I think Bangladesh has gone through some remarkable achievements in recent years and has now been classified as a middle income nation. With the expanding middle class there is also greater expectation of the population of access to better healthcare– drugs that are efficacious and diagnostics that can precisely identify the cause of the disease.  Therefore, Bangladesh is poised to implement this powerful technology because it is cost effective in the overall scheme.

Ridwan: A recent population genomics study showed that African-Americans showed more elevated inflammatory responses to pathogens than European-Americans as a result of differences in their genomes. Can you explain to our readers how precision medicine can help to more effectively treat diseases that occur differently between populations?

Dr. Aziz: I am not aware of this particular study you mention.  In general the more we understand about genetic differences in health and disease in different ethnic groups, the better prepared we are with that knowledge to manage patients of different ethnic groups.

Ridwan: Could studying the differences between different ethnicities lead to more discrimination?

Dr. Aziz: It is good to study genetic diversity. It shouldn’t lead to racial discrimination with the proper regulatory framework in place. In the USA, there is a law called GINA (Genetic Information Nondiscrimination Act) which was passed in 2003.  Every new technology needs appropriate policies in place. Genetic differences among patients with different ethnicities should only be used  for maximizing its benefits in their medical care. In the USA and Europe researchers have focused genetic studies heavily with European Caucasians recruits and therefore at this time we have realized that we do not fully understand genetic diseases in minority populations. Therefore much effort is being expended for equitable health access and in studying the minority populations in the USA through the All of Us program initiated by President Obama. It is just as important to develop understanding here in Bangladesh of the genetics of the Bengali populations.