Yes we have done it before..… but the wrong way!

Recent news from the US about transplant of a pig heart into a human made headlines in the media world over. There have been some posts going viral on Indian social media about how a maverick Indian doctor Dhani Ram Baruah from Assam had achieved this feat some 25 years ago and how he was ridiculed and punished for doing something which is being hailed and celebrated today as revolutionary! This self congratulatory attitude shows utter ignorance and wanton disregard to science! Some introspection is warranted before we adopt this holier than thou approach.

Successfully transplanting an animal organ into a human (Xenotransplantation) involves a lot of fundamental research in immunology, pathology, virology, human leukocyte antigens (HLA) system, genetics and physiology. A plethora of bench studies and animal laboratory studies go into this before one can actually contemplate a xenotransplant. A lot of tissue engineering and gene modification is required to minimise the possibility of rejection which is the most dreaded complication of such a transplant. These studies are published in peer reviewed journals. This is followed by experimental transplant of these genetically modified hearts into other non-human primates like baboons to study their survival. These are all bioethics of transplant science! Everything is then studied and approved by the institutional ethics committee which ensures that everything that is done is within the purview of law, ethics and science.

How was the heart genetically modified?

The genetically modified pig heart that was recently transplanted in the human had received 10 genetic tweaks. Three for preventing it from producing certain sugars which are rejected by human body, two for reducing inflammation, two for promoting normal blood clotting, two for reducing antibody response and one for reducing the chance of pig heart outgrowing human chest.

How was the patient immunosuppressed?

Even with these genetic modifications to the heart, to prevent rejection, patient is being given a strong immunosuppressant: an experimental antibody drug called KPL-404, made by Kiniksa Pharmaceuticals, Ltd.

Standard immunosuppressants used in human-to-human organ transplants aren’t effective if the immune system makes lots of antibodies against the organ, as surgeons feared would be the case with the pig heart. KPL-404 is considered a game changer.

How was the heart harvested and prepared for transplant?

Immune rejection aside, pig hearts transplanted into baboons seem to sputter out in a matter of days unless they’re perfused with a nutrient solution before the transplant. The mechanisms behind the hearts’ failure are unclear, though he speculates that being deprived of blood flow and oxygen when removed from the pig chest somehow depletes the energy-producing mitochondria in the organ’s cells.

The US team relied on a method developed by Lund University surgeon Stig Steen and commercialized by the Swedish company XVIVO for storing and treating the donor heart after it’s harvested. The heart is bathed in a circulating broth that includes water, hormones such as adrenaline and cortisol—and dissolved cocaine. Each shipment needs a permit (because of cocaine) from the US Drug Enforcement Administration.

In spite of these Herculean efforts, the prospects of survival of this patient are uncertain.

Compare this with what was done in 1997. At a time when transplantation medicine was non-existent in India with no immunosuppressant treatment, Dr Baruah managed to harvest a pig heart and shove it in the chest of a patient with heart failure. He flouted the norms and rules of Transplantation of Human Organs Act of 1994. He disregarded the law, ethics, morals and the science involved. It was rightly interpreted as a barbaric and savage experiment that was ruthlessly inflicted upon an unsuspecting poor patient. It deserved the punishment that was meted out to him.

The writer is Director, Cardiac Cath Lab and Interventional Cardiology

Kamalnayan Bajaj Hospital.