Xenotransplantation

in the Y2K

~

" If I Only Had a Heart "

~

Frank P. Horvat

Scientific Session

April 16, 1998


Xenotransplantation in the Y2K


In episode AM-117, Theme of Life, Ally McBeal takes on a case about an attractive surgeon accused of performing an unauthorized, controversial transplant procedure.

Xenotransplantation in the Y2K


Some day it might be easier for us to get a new heart than it was for the Tin Woodsman in the Wizard of Oz.

Xenotransplantation in the Y2K


There are not enough of these vital organs for all the people that desperately need them. Viable human organs are scarce and the waiting lists continue to grow.

Xenotransplantation in the Y2K


In the spring of 1996, the National Institutes of Health awarded a $500,000 research grant to a team of scientists from the University of Missouri to develop the first strain of transgenic pigs whose organs could be routinely used for human transplantation.

Xenotransplantation in the Y2K


"Hundreds of patients die each year waiting for a heart or kidney transplant. The swine heart is similar in size and capacity to a human heart and would be a suitable model."

Xenotransplantation in the Y2K


Animal physiologist Randall Prather and his team aim to create pure transgenic pigs whose hearts, lungs, kidneys and livers could be transplanted into humans without the danger of rejection.

Xenotransplantation in the Y2K


They hope to accomplish this feat of immune response hoodwinking by implanting human genes into the pig's DNA--creating a genetic chimera with molecular characteristics of both.

Xenotransplantation in the Y2K


PORKY BABE GORDY




Xenotransplantation in the Y2K


"If we can go in and genetically modify the DNA so that human molecules are expressed--or we take the pig molecules and get rid of them so that when the organ is transferred into a human, it will either be recognized as self or at least not recognized as foreign."

Xenotransplantation in the Y2K


Collaborating with Boston based BIOTRANSPLANT INCORPORATED, Prather's team will use their NIH grant for phase one development of genetic constructs which, when injected into a single-cell pig embryo, will modify its immune system.

Xenotransplantation in the Y2K


Prather's team aims to alter swine leukocyte antigens with human genes to produce a complete human histocompatibility complex on the surface of the pig organs.

Xenotransplantation in the Y2K


In phase two, the researchers will remove several pig embryos at the single cell stage and inject each cell with modified human DNA. After culturing the cells in vitro, they will expose them to UV light. Those that glow will be the chimeras, having incorporated the new genes into their DNA.

Xenotransplantation in the Y2K


It's here Dr. Prather's team is facing difficulties. Once the chimeric embryos reach the eight cell stage, their human genes fail to incorporate into all of the cells, creating a "mosaic" chimera with unpredictable results.

Xenotransplantation in the Y2K


catman

Xenotransplantation in the Y2K


To bypass this problem, the researchers must remove those cells that are purely transgenic from the "mosaic" animal and reculture them into new embryos.

Xenotransplantation in the Y2K


These fully transgenic embryos will be implanted into the sow's womb where they will grow into individual piglets, carrying the human histocompatibility. Once mature, their organs would be viable for harvesting and transplantation.

Xenotransplantation in the Y2K


Dr. Prather says that once his team develops a foolproof method for producing pure transgenic pigs, it will take about four years to produce a "founder generation" to breed test animals.


Xenotransplantation in the Y2K


Even if everything works perfectly and if FDA approvals proceed as planned, it will still take ten to fifteen years until experiments with humans are begun.

Xenotransplantation in the Y2K


Discussion


Xenotransplantation in the Y2K


What are the barriers, dangers and disadvantages to xenotransplantation?

Xenotransplantation in the Y2K


It just doesn't work


Xenotransplantation in the Y2K


Kidney Heart Liver Pancreas


Xenotransplantation in the Y2K


The overwhelmingly unsuccessful track-record of xenotransplantation is due to the biochemical, physiological, anatomical and immunological differences between humans and other animals. In general, discordant xenografts - where the source animal is more distantly related to humans - were a greater failure than concordant (nonhuman primate to human) xenografts.

Xenotransplantation in the Y2K


What are the barriers, dangers and disadvantages to xenotransplantation?

Xenotransplantation in the Y2K


Unknown Viruses


Xenotransplantation in the Y2K



LONDON, Feb 25 (Reuters) - Australian scientists have sparked new fears about the safety of animal-to-human transplants after they discovered an unknown virus in pigs. Virologist Peter Kirkland and scientists at the Elizabeth Macarthur Agriculture Institute in Camden, New South Wales, found the virus that caused deformity and stillbirths in pigs and also infected two workers, New Scientist magazine said on Wednesday. Concerns about the possibility of introducing animal viruses into humans led scientists to call for a moratorium on cross-species transplants last year.

Xenotransplantation in the Y2K


But proponents of xenotransplantation -- the use of organs, tissue or cells from one species to another -- claim the organs can be screened for viruses. "But you can't screen for disease agents that you don't know about," the magazine quoted Kirkland as saying. He and his team traced the virus that swept through a piggery near Sydney to a colony of fruitbats that lived nearby. The virus only attacked pig fetuses, which were either stillborn or had defects in the spinal cord and brain. The two infected workers recovered and the virus was not found in pig products or other people who may have been exposed to it. Although the virus was contained, Kirkland said there were no guarantees that it would not break out again.

Xenotransplantation in the Y2K


What are the barriers, dangers and disadvantages to xenotransplantation?

Fiscal - Poor use of Resources
In 1994 nearly $3 billion was spent on organ transplants. This cost does not include the expensive follow-up care. The average costs for the doctor/hospital care in 1994:

Heart $140,677.00

Liver $138,382.00

Kidney $ 51,877.00


With xenotransplantation the costs are even higher! The success rate is zero, insurance in not available and the surgery benefits an extremely small number of people. Using limited research dollars on experimental surgeries wastes dollars that could be spent on expanding basic care to the medically underserved populations utilizing physician extenders.



Xenotransplantation in the Y2K


What are the barriers, dangers and disadvantages to xenotransplantation?

Ethical / Religious
Aside from the fact that of human beings kill other living creatures for food, the question of "soul" is raised. As we increase the percentage of DNA that the porcine cells contain, do we increase the percentage of "human-ness" and does this new "entity" have a fractional soul?


Xenotransplantation in the Y2K


Questions?


Xenotransplantation in the Y2K


Thank You for your kind attention!