Dr Heinner Guio is the leading expert in research projects in genetics and is the founder of INBIOMEDIC, the first private research center, certified in Peru for molecular biology, genetics and hereditary studies. He was the Principal Investigator in the Peruvian Genome Project developed at the National Institute of Health of Peru. In the interview below, Dr Guio elaborates upon the unique genetic heritage in Latin America, strong sides and challenges to its genomic research and practice, what to expect soon, and what new genomic based healthcare service are expected to be provided in Latin America in 10-15 years.
Latin America has a unique genetic heritage with high levels of mixture from African, European, and Native American ancestral source populations. What challenges does it present for genomics?
The perception that Latino Americans have high levels of admixture from African, European, and Native American origins is relative. The genomics studies began in countries of the north hemisphere and subsequently added some countries from Africa and Asia. If the first studies would have started in Latin America the history would have been different. The ancestry tests currently depend on the databases that do not usually consider Latin American populations. Some biomarkers have been proposed in populations living in different environmental conditions. For example, people living above 3000 meters above sea level (m.a.s.l.) are diagnosed and treated following guidelines and studies from people with another physiologic background, i.e. low m.a.s.l. This is important due to the effect of altitude on the cardiovascular, kidney among other physiological aspects. These approach disparities are also seen in genomics.
What are the strong sides of genomics in Latin America, in your opinion?
Genomics is the information contained in a person’s DNA, product of millions of years of evolution and thousands of years of migration. There are native communities in Latin America that remain isolated and settled down since they migrated to those places, centuries or thousands of years before nowadays. These are the last populations where the evolution and effects of migration can be studied compared to studying populations that live in cities where the admixture is high as a result of conquests, wars or migrations consequence of sociopolitical problems. Therefore, each day that passes is one less day of opportunity to study these populations that keep in their genome the effects of migration and adaptation. Thus, studying these native or less admixed populations could help to underpin the human genome diversity and the knowledge of the human evolution.
You have been a medical doctor for 30 years; a significant part of your professional experience is in genetics. What has changed in genetics in Peru in this time, perhaps you can describe major developments in your country?
An important requirement to generate knowledge in the genetic and genomic area is the scientific basis. To generate information in the genetic area, technology, bioinformatics knowledge and, of course, training are required, not only for researchers but also for supervisors of the project, including ethics committees and public health stakeholders. We have lacked this experience for many years, limiting ourselves to collecting samples and depending on foreign protocols with different objectives for our local needs. In 2010, the Peruvian human genome project was proposed at the Peruvian National Institute of Health in which I can highlight 3 challenges. The first challenge was to create the research protocol trying to concatenate other local research projects needs to consequently make the monetary investment helpful and including previous lost opportunities not otherwise considered. For instance, a key component was the ethical consideration to protect the identity of participants from the 17 native and 13 mestizo communities in the Peruvian genome project. A second challenge was the training of a research team, which included analysis from a not complex genomes (bacterial and viral) to the implementation of a microarray platform for human genotyping at the local level. Researchers were trained in bioinformatics centers as part of their doctorate and post doctorate courses. Collaboration with Dr. Timothy O’connor (University of Maryland) and Dr. Eduardo Tarazona (University of Mina Gerais) was very important for the training, analysis and interpretation of the data. A third challenge was the collection of samples which meant the approval of our protocol for up to 4 instances until the final consent of the patient and the travel of our research team to places of difficult access of up to 3 days of travel (by air, river and road) remembering that the research originality in population genomics is farther from our homes.
Explaining to the ethics committees or those responsible for approving the project in each community was also a challenge. How to explain the concept of DNA to a native community or how to explain to a methodologist that the sequencing of a sample of people is very important to study population genomics knowledge; and we do not require the usual “sample size statistics”
This first project generated 800 genotyped samples from Peruvians by microarray analysis, 150 with complete sequenced genomes, and identification of 2 million new genetic variants. The analysis of these data is being oriented to the identification of important variants in local genetic diagnosis as well as in the area of pharmacogenomics. In genomics there are no geographical barriers, so these data will also be useful to other Latin American countries.
We are currently generating other genomic projects at INBIOMEDIC research Center where we try to understand mechanisms of adaptation and immune response of the human being in high Andean places, as well as ancient populations using the DNA of 5000-year-old coprolites
How would you describe the current state of genetics in Latin America in comparison with other continents?
There are two factors that researchers in genetics face every day. Firstly, research activities in Latin America is at least 3.5 times more expensive than in countries of the northern hemisphere. Second, there are limited funds from the government for the development of these areas. Data generation (sample collection and sequencing) is more expensive than analysis. The COVID-19 pandemic has demonstrated the importance of genomic technology not to only understand the pathogen through the search for the best genetic regions for diagnosis, but also for potential targets of treatment and vaccines development. The best prepared countries identified the new genomic variants of SARS-CoV-2 in a record time to generate the appropriate epidemiological alerts. The countries of Latin America have the same problems and limitations to carry out projects in genetics and genomics, they are forming different collaborations and initiatives with different objectives, anthropological, studies of rare diseases, population migration, etc.
What major relevant developments to expect in the near future?
Undoubtedly, genetic panels will better guide annual medical check-ups. Pharmacogenomics will be a tool to guide chronic treatments and/or rationalize very expensive therapies such as in cancer, for example. In public health, the development of genomic epidemiology will be used to predict diseases and new outbreaks when a new pathogen or variant is identified. This will greatly help guide the development of vaccines for each epidemiological reality.
What is your vision to genetic based healthcare services to be provided in Latin America in 10-15 years from now?
Without a doubt, the cost-effectiveness analysis of the implementation of genetic tools in the clinic will be clearer, as well as the quality controls for genetic tests. Genomic tests at birth and/or prenatal tests will be used as routine in medical centers with greater infrastructure or funding; I think most private clinics. We will have different genetic panels for each specialty, however, the indication of clinical exome analysis for having additional information for what was indicated will be an added value of this test.
In oncology, studies on the DNA of the patient and of the tumor will be a reality, as well as the follow-up of the patient by liquid biopsy (Test that is carried out on a blood sample in order to look for cancerous tumor cells that are circulating in the blood or pieces of DNA from tumor cells that circulate in the blood). Likewise, it will increase the evidence of the role of the microbiome in human diseases. However, one of the limitations will be the lack of local studies in each country to validate and monitor the new variants and the “pathogenic status” of the variants identified in a different context from the country where it is to be applied and, as always, the criteria of implementation could be taken based on what has already been created, in a population different from ours.
What challenges are on the way to this vision?
Scientific evidence taken into daily clinical practice is very important to establish public health policies. Each researcher in the genetic field does what they can in the absence of a national program for genomic medicine. However, there are several initiatives in Latin America that are proposing collaborative work between nations to overcome difficulties. With the aim of reducing costs, these initiatives range from strengthening human capital to creating centers for genome sequencing, analysis and interpretation: establishment of genomic medicine. Despite these difficulties we are also already seeing projects targeting single cell sequencing which examines the sequence information of individual cells with optimized next generation sequencing (NGS) technologies, providing greater resolution of cell differences and a better understanding of the function of an individual cell in the context of its microenvironment.
In your opinion, how shall these challenges be addressed by health authorities and by medical communities of Latin America?
Medicine should be more oriented to predict and avoid diseases, medical genomics is an important path to achieve these aims. However, if health authorities don’t understand what We are asking for (cause) then their support will be limited (effect). The concepts and scope in genetics are still not very well understood. The last epidemic introduced not only “new” genetic terms to help health authorities to understand the state of the epidemic to make right decisions and transmit properly information to the population. Genetics and genomics should be understood and considered as a transversal specialty to other clinical specialties.
Universities, research centers and professional colleges are called upon to consider genetic training in specialties and to support the need for this area towards public health decision-makers.