King Solomon’s Mines

The biblical Solomon, a king of Israel and son of King David, was renowned for his wisdom, power and his fortune, often described as one of the largest in the ancient world. But while Solomon’s famed wealth is a story as old as the ages, the popular fascination with locating a portion of this fantastic fortune is a far more recent affair. The idea of mines full of riches was first introduced in the late 19th century by author H. Rider Haggard in his adventure novel, King Solomon’s Mines, whose publication coincided with a boom in archaeological discoveries of ancient sites in the Middle East and Africa.

The treasure then was gold, silver, and gems. Today the most precious treasures are genes, genomes, and genetics. Genetic research is a scientific discipline that investigates the role of genes in human disease. If we can decipher the precise gene or sequence that is responsible for a particular disease, we can develop more targeted and specific treatments. It is the potential applications of this knowledge that has research groups and big pharma investing a great deal of time, money and effort into identifying the genetic mechanisms underlying disease. With the advent of newer technologies that enable us to introduce targeted changes in genomes to correct defects (gene-editing), genetics has moved from science fiction into reality.

Traditionally, scientists have genetically engineered mice to ‘knock out’ genes in order to evaluate their function. Once they have discovered what the gene does, it is possible to make new drugs that can either block a gene (if it is harmful), or enhance its positive functions (if it is useful). However, while such research is informative, evidence from studies in animal knockouts often does not hold for humans. Genetically engineering humans to study genes is not possible, however natural human ‘knockouts’ exist in different populations around the world.

Consanguineous marriages, which are common in Pakistan, are much more likely than unions between unrelated people to result in human knockouts. With growing interest in genomes in this part of the world and knowledge that such research has caused ethical challenges in other countries, it is important to evaluate the status in Pakistan to identify gaps so that we can ensure safeguards and good practice for future studies.

“Mirror, mirror on the wall…who is the most ethical of us all?” is the title of a study that I conducted three years ago to understand if there were ethical guidelines available for genetic studies and to then analyse and describe the extent to which researchers in Pakistan comply with existing ethical standards. Pakistan’s National Bioethics Committee (NBC) has published several clinical ethics guidelines and listed a review of genetic research studies. However, it has issued no guidelines for genetic research, gene therapy or gene editing studies.

I consulted ‘The International Compilation of Human Research Standards, 2019 edition’ compiled by the Office for Human Research Protections (OHRP), U.S. Department of Health and Human Services, to identify local, regional and international standards for genetic research. Once I had identified the guidelines, I searched for research studies published from January 2017 to December 2018. These studies were assessed for a number of ethical standards: informed consent, conflict of interest, and IRB review. These categories were complemented by author, institution, the disease studied, study type, and NBC review. This analysis of ethical standards included a total of 52 studies. According to the data I collected, over 90% of the research was conducted through international collaborations. 19/52 publications were first author studies by a Pakistani researcher based at a Pakistani institution, but most (39/52) were collaborations with either a UK or US based institution. Funding for 57% of the studies was solely from an international funding agency.

The highest number of publications were related to blindness, deafness, neurological and developmental disorders (24/52), with 45% conducting whole exome sequencing. No gene editing or gene therapy studies were identified. Many of the genome-wide association and consortium studies using biological material or genetic data from Pakistan had not been submitted for IRB review, and no study mentioned a review by the NBC or a material transfer agreement. No genetic counselling was offered to support participants in any of the studies. There was no clear reference to any community engagement activities or awareness sessions. Although informed consent was mentioned in most studies, a blanket statement that “consent was taken” does not indicate the quality or understanding of the process.

International research guidelines presuppose an established system of accountability and oversight. However, Pakistan, like many LMICs, does not have strong internal or national oversight and accountability. There is an overwhelming expectation about the integrity of the researcher and his/her familiarity with ethics. Many of the guidelines tend to focus on individual obligations. Discussions of institutional imperatives, broad social goals or collective responsibility are rarely concrete.

Although no human gene therapy or gene editing studies were identified, gene editing technology is being explored in agricultural research in Pakistan. Applications of this tool will transition to microbial and human genetics and it is vital that we establish systematic changes for compliance, oversight and accountability. The findings from my study provide a foundation of behavioural practices for researchers. It is a starting point to develop systematic changes.