Editorial 1: Reform can address India’s kidney transplant deficit
Context
- India’s organ shortage when it comes to kidneys is alarming. In 2022, over two lakh patients needed a transplant, but there were only about 7,500 transplants (about 3.4%).
The Need
- Due to the prevalence of diabetes, malnourishment, overcrowding and poor sanitation, there is a high prevalence of Chronic Kidney Disease (CKD) in India, affecting about 17% of the population.
- CKD often leads to end-stage renal disease (ESRD). A kidney transplant is often the best treatment for ESRD.
- Specifically, transplant is often better than alternatives on almost all dimensions that matter: quality of life, patient convenience, life expectancy, as well as cost-effectiveness.
- These are four main ways a patient can obtain a kidney. The first is to get a kidney from a deceased person. This is constrained due to a lack of donations, the particular conditions required on the nature of death, and the infrastructure needed to collect and store kidneys.
- The second is to request a relative or friend to donate. However, donor and recipient have to be compatible in terms of blood type and tissue type; such relative/friend donors are often incompatible.
A case for changes
- Thus, regulations for kidney exchange are needed as kidney exchange must often occur across family units.
- But the argument is that these regulations need urgent reform to unshackle two innovative kidney exchange methods: kidney ‘swaps’ and kidney ‘chains’.
- Our research shows that there are barely any swaps and almost no chains in India. This is because of legal roadblocks. And this is a significant opportunity missed with terrible consequences.
- Consider swaps. Swap transplants are legally allowed in India with due permission, but only near-relatives are allowed as donor-recipient pairs.
- Exceptions to this restriction are Kerala, Punjab and Haryana, where High Court judgments have recently allowed non-near-relative donor-recipient pairs after verification.
- Further, unlike national, regional, and State lists for direct transplant from cadavers, there is no national coordinating authority for swaps. This is again a huge lost opportunity, since larger and more diverse pools make it easier to find compatible swaps.
- While there are occasional swaps in India, there are almost no kidney chains.
- The lack of kidney chains is possibly an even bigger opportunity missed than swaps.
- While participating in swaps, families demand nearly simultaneous operations of all donors and recipients since no one wants to lose a kidney without gaining one.
- But in chains, each patient first receives a kidney and only then does their relative donate.
- Thus, chains, compared to swaps, involve significantly lower hospital resources and uncertainty for participants.
- Needlessly harsh laws regulating swaps and chains have contributed to a proliferation of black markets for kidneys.
- These black markets endanger all their desperate participants since these operations are conducted ‘off the books’, without due legal and medical safeguards.
At a slow pace
- Reforms of kidney exchange laws have been slow.
- The Transplantation of Human Organs and Tissues Act 1994 set the ball rolling by recognising transplant possibility from brain-stem death.
- In the 2011 amendment, swap transplants were legalised, and a national organ transplant programme was initiated.
- The government’s recent reforms (February 2023) allow more flexibility in age and domicile requirements while registering to obtain an organ.
- But these reforms leave the fundamental issue of inadequate kidney supply largely unaddressed.
- This is why it is beneficial to allow and encourage altruistic donation, non-near relative donation for swaps, and to improve the kidney-exchange infrastructure.
Conclusion
- India does not need to innovate in order to reform chains and swaps. Sufficient precedents have been set globally. ndia’s real challenge, therefore, is to learn from and replicate such existing successful regulations to improve the lives of several thousands of citizens.
Editorial 2: Nipah virus outbreak: What are monoclonal antibodies?
Context
- Last week, India reached out to Australia to procure monoclonal antibody doses to combat the Nipah virus outbreak in Kerala. India is expecting 20 more doses soon.
Monoclonal Antibody
- Monoclonal antibodies are laboratory-made proteins that mimic the behaviour of antibodies produced by the immune system to protect against diseases and foreign substances.
- An antibody attaches itself to an antigen – a foreign substance, usually a disease-causing molecule – and helps the immune system eliminate it from the body.
- Monoclonal antibodies are specifically designed to target certain antigens.
- Niels K. Jerne, Georges J.F. Köhler and César Milstein were awarded the medicine Nobel Prize in 1984 for their work on the “the principle for production of monoclonal antibodies”.
m102.4 Antibody
- According to research published in The Lancet journal of Infectious Diseases, m102.4 is a “potent, fully human” monoclonal antibody that neutralises Hendra and Nipah viruses, both outside and inside of living organisms.
- The antibody has passed phase-one clinical trials — which means that researchers tested it with a relatively small number of people to estimate the right dose of treatment that also doesn’t cause side effects.
- As of now, the drug is used on a ‘compassionate use’ basis — a treatment option that allows the use of an unauthorised medicine under strict conditions among people where no other alternative and/or satisfactory authorised treatment is known to be possible and where patients cannot enter clinical trials for various reasons.
The working of Monoclonal Antibodies
- Monoclonal antibodies are specifically engineered and generated to target a disease.
- They are meant to attach themselves to the specific disease-causing antigen. An antigen is most likely to be a protein.
- For instance, most successful monoclonal antibodies during the pandemic were engineered to bind to the spike protein of the SARS-CoV-2 virus.
- The binding prevented the protein from exercising its regular functions, including its ability to infect other cells.
- Dr. Köhler and Dr. Milstein, used this principle to describe the hybridoma – a fusion cell made up of B cells (white blood cells that produce antibodies) and myeloma cells (abnormal plasma cells).
- These hybrid cells allowed the researchers to produce a single antibody clone, which came to be known as a monoclonal antibody.
- The initial technology of producing hybridoma in mice was unsustainable.
- Today, these antibodies are made using recombinant DNA technology.
- Here, the gene that codes for the monoclonal antibody’s binding region — also known as the variable region — is isolated from a B cell or synthesised in the laboratory.
- This antibody is then introduced into a host cell, often a bacterium or a mammalian cell, using recombinant DNA technology (which involves manipulating DNA material outside an organism to obtain specific traits or characteristics).
- The host cells, called bioreactors, produce large quantities of the monoclonal antibodies which are extracted, purified, and readied for use as desired.
- The m102.4 monoclonal antibody binds itself to the immunodominant receptor-binding glycoprotein of the Nipah virus, potentially neutralising it.
Conclusion
- Despite their significant benefits, monoclonal antibodies can have limitations, such as high production costs and the potential for immune responses. Advances in technology, such as the development of humanized antibodies (antibodies with human components to reduce immune reactions), have addressed some of these challenges.