TeachableMedicalNews article 10222022

Teachable moment in classrooms:

  1. chemical basis of life chapter – genetic engineering can remove genes from, or add genes to DNA molecules (the chromosomes)
  2. cellular basis of life chapter – removing a gene removes a protein, while adding a gene adds proteins to the functional toolkit of cells
  3. hear chapter – blood pumping action of left ventricle delivers oxygen, nutrients to all organs
  4. immune system chapter – role of HLA proteins in the recognition of self and non-self antigens

The news item:  Recently the following news article was published:

Two pig heart transplants succeed in brain-dead recipients

Surgeons at New York University (NYU) have successfully transplanted genetically-engineered pig hearts into two brain-dead people, researchers said on Tuesday, moving a step closer to a long-term goal of using pig parts to address the shortage of human organs for transplant.

The article states that experimental transplantation of pig hearts into brain dead humans was carried out, and the hearts remained functional for the three days of the study.  The article also states that the transplanted hearts came from genetically engineered pigs in which 4 genetic alterations were done to prevent rejection, and 6 genetic modifications were done to prevent incompatibilities between pigs and humans.

So, Why Do I Care??  There are about 600,000 people in the US whose heart is about to give out (end stage heart disease), but there are only about 3800 heart transplant operations. Several people die each day because suitable donor hearts are not available for transplantation. If we could routinely transplant pig hearts into humans that would save thousands of lives.

Plain English, Please!!!  First, let’s talk about why people need a heart transplant. End stage heart disease happens either because of the degeneration of heart muscle from coronary artery disease or from viral infection, or because of heart valve problems.  Once the pumping efficiency of the heart drops to less than the half of normal, the flow of oxygen and nutrients is so slow that it endangers the life of the patient. There are mechanical devices that can provide temporary help, but eventually only a heart transplant can save the life of people with end stage heart disease.

Second, let’s talk about why the number of heart transplantations are limited. The simple answer is that the number of suitable hearts from organ donors is much fewer that the need. The suitable heart not only needs to function well, but, in addition, there has to be a reasonable tissue match between the HLA proteins of the donor and the recipient. HLA proteins are like a personal name tag on our cells, and our immune system attacks more intensely the cells (and organs) that have a name tag very different from ours.

Third, let’s talk about how we can make a pig heart suitable for transplantation into humans. To begin with, the anatomy, and the mechanical workings of the pig heart is identical to the human heart.  However, the HLA name tags on the cells of the pig heart are very different from human nametags, so the pig heart would be quickly rejected by a human recipient. During the genetic engineering process the long ribbon of DNA is reshaped by cutting four genes from the ribbon and adding six new genes, new segments of ribbons. The removal of four genes caused some of the antigen nametags of the pig cells to become invisible to the human immune system. The addition of six genes achieved that the remaining pig antigen nametags are more difficult to read by human immune system.  The end result is that a pig heart transplanted into a human recipient is not rejected any faster than a tissue matched human heart would be. If the experimental transplantations give promising data, we will see transplantations into living patients soon.

 

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