An opinion piece published on Livemint by Sandipan Deb claimed that COVID-19 will not affect Indians as they have the genetics for a sturdier immune system.
The Nature Asia article (2008), based on the research study by Du and colleagues (2008), published in the journal ‘Genes & Immunity’ was conducted by a team of scientists from the University of California in Los Angeles (UCLA), USA, All India Institute of Medical Sciences, India (AIIMS), and National Marrow Donor Program (NMDP), USA.
‘More immunity in Indian genes’ – The title of Nature Asia magazine article.
“Our bodies have one of the toughest immune systems in the world. We have grown up surrounded by so much filth and pollution that our natural resilience is much stronger than people in the developed world.” – Sandipan Deb in Livemint.
1. The Livemint article is based on a superficial understanding of the title of the Nature Asia, not its text.
The Nature Asia article is titled ‘More immunity genes in Indians’. However, the article itself does not make any such claims that, on the basis of the research study quoted, that Indians will be protected from the coronavirus pandemic or other infections due to their biologically inherited ‘resilience’. It simply states that Indians may have more genes linked with immunity as per the data. Also, one of the authors of the article and the research study Rajalingam Raja wrote, “Whether having more activating KIR genes is an advantage or disadvantage for Indians remains to be elucidated.”
This means that the genes tested through this study are not a piece of conclusive evidence that the contested tougher immunity will be an advantage for Indians in any way.
2. The Nature Asia article is based on a research study based on a single gene polymorphism in various ethnicities.
The Nature Asia article is based on a research study which relies upon a single gene KIR2DL5 polymorphism in many ethnicities including Indian, East Asian, white (Caucasian) and black (African Americans), suggesting that the gene is not unique to Indians only. Also, no evidence suggests that the presence of gene translates to gene expression or phenotypic change (e.g. higher immunity) in this case.
Nature Asia article based its claim on a gene polymorphism study by Du and colleagues (2008). Genetic polymorphism is the occurrence of multiple forms of a single gene which is expressed in the same population as a trait or a phenotype (Bull, 2004). It is similar, but not the same, as varying levels of pigmentation in eyes, hair or skin colour.
The study quoted showed the nature of polymorphism of one gene KIR2DL5 in four ethnic groups: Caucasians (European race, mostly white), Asian-Indians (South Asians), African-Americans and Asians (East Asians, i.e. Korean, Vietnamese, Japanese and Filipino).
KIR2DL5 (or CD158f) is the last identified KIR gene (the inhibitory receptor expressed on the surface of immune cells), with KIR2DL4, it makes up a structurally divergent lineage conserved in different primate species such as humans. The percentage frequency of this KIR2DL5 gene in Indians is used as an indicator of higher immunity.
The graph from the research study illustrates that the percentage frequency of KIR2DL5 (A and B, polymorphic forms of KIR2DL5 gene) is higher in Asian Indians than the other ethnic populations studied. However, the graph below from the same study suggests that the Individuals carrying the KIR2DL5 gene vary substantially among populations ranging in frequency from 35-85%. Thus, as per the author’s conclusions, higher immunity can be found in every ethnicity ranging from 35-85% population, not just in Indians.
Hence, with such large variability in genes in each population, it is impossible to deduce that the researchers certainly found the KIR2DL5 gene more frequently in Indian ethnicities, as compared to other ethnicities.
Also, the research paper doesn’t claim that this higher frequency in Asian-Indians population is linked to a better immune system or more natural killer cells in the body. In fact, there are no conclusions drawn on any ethnic group being genetically superior or inferior regarding immunity.
3. Is the occurrence of genes (KIR2DL5 gene) linked with immunity synonymous with its traits (tougher immunity)?
The occurrence of more genes in a population isn’t always synonymous with better traits. This is mainly because a greater amount of genes doesn’t always translate to a protein abundance, which consequently becomes a trait. That is, the presence of genes doesn’t always lead to the presence of characteristic traits related to the expression of the gene.
Sometimes, polymorphic changes in natural killer cells can also be associated with a susceptibility towards certain diseases (Orange, 2002). Thus, more correlative studies should be conducted where a higher frequency of KIR2DL5 gene results in an increased immunity regardless of ethnicity.
4. Smaller sample size
The beneficial effects of higher frequency of a polymorphic gene in a population can only be established after detailed protein, genomics and evolutionary studies with large sample size. But in this study, only 96 Indian genomes were studied as opposed to 250 Caucasians. Hence, these higher percent frequencies of polymorphs KIR2DL5 gene could also be an artefact resulting from a smaller sample size.
Only 96 non-randomised samples for the Asian-Indian group were sourced from New Delhi, which is a minuscule representation for the Indian population. These sample sizes were further reduced after identification of KIR2DL5 positive individuals.
Also, the Nature Asia article further claims that Indians gained the activating KIR (killer cell immunoglobulin-like receptors) genes because of natural selection to survive the environmental challenges during their pre-historic coastal migrations from Africa. This conclusion is not based on any evidence.
Similar claim in ‘The Print’ opinion piece
Dr Mehra, former Dean of AIIMS, in his opinion piece in The Print mentions the results from the same study that includes SK Sharma of AIIMS, to make his claims about the genetic advantage of Indians over Caucasians with respect to immunity against the coronavirus. Additionally, Dr Mehra also included other factors that may give Indians advantage – broad-based immunity due to overexposure to other pathogens, and epigenetic factors such as environment and consumption of Indian spices in cuisine. However, since the novelty of the virus and the increasing pathogenesis of SARS-CoV-2 in India, these claims remain without any research or evidence in Science.
The Nature Asia article published a misleading title on the basis of a genetics study which was termed inconclusive by the authors in their own research study. This title formed the basis of the Livemint article by Mr Deb.
The Nature Asia authors generalised their misleading article about Natural Killer cells (NK) to “immunity genes”. Natural killer cells are a small component of what makes up human immunity, not the expansive immune system.
Later, in the Livemint article, the Nature Asia article was used to claim a blanket superiority of the immune system of Indians. Mr Deb stated that Indians’ immune system is more robust than the people in the developed world to tackle the coronavirus pandemic.
Such dangerous opinion pieces with no understanding of the genetics of immunity have the potential to drive people to be careless with the protocols issued by the government on social distancing and other precautions or to encourage reckless behaviour during a critical situation.
Du, Z., Sharma, S. K., Spellman, S., Reed, E. F., & Rajalingam, R. (2008). KIR2DL5 alleles mark certain combination of activating KIR genes. Genes & Immunity, 9(5), 470-480.
Bull, L. (2004). Genetics, Mutations, and Polymorphisms. Molecular Pathogenesis of Cholestasis, 77-95.
Estefanía, E., Flores, R., Gómez-Lozano, N., Aguilar, H., López-Botet, M., & Vilches, C. (2007). Human KIR2DL5 is an inhibitory receptor expressed on the surface of NK and T lymphocyte subsets. The Journal of Immunology, 178(7), 4402-4410.
Orange, J. S. (2002). Human natural killer cell deficiencies and susceptibility to infection. Microbes and infection, 4(15), 1545-1558.