Heart transplantation at 50+: Celebrations and challenges

[first paragraph of article]This year marks the 51st anniversary of the first human heart transplant operation by Christiaan Barnard at the Groote Schuur Hospital in Cape Town. This event has had a profound effect on Science, Medicine and Humanity, almost beyond expectations. The anniversary calls for celebrations, and evaluation, as with maturity comes accountability. We here attempt to summarise the reasons for celebrations, and highlight the remaining many challenges and expectations. Regarding the celebrations, this anniversary exemplifies and calls for celebration of at least four human attributes; courage, innovation, compassion, and human spirit.

This year marks the 51st anniversary of the first human heart transplant operation by Christiaan Barnard at the Groote Schuur Hospital in Cape Town. This event has had a profound effect on Science, Medicine and Humanity, almost beyond expectations. The anniversary calls for celebrations, and evaluation, as with maturity comes accountability. We here attempt to summarise the reasons for celebrations, and highlight the remaining many challenges and expectations.
Regarding the celebrations, this anniversary exemplifies and calls for celebration of at least four human attributes; courage, innovation, compassion, and human spirit.

COURAGE
According to Sir Winston Churchill, courage is the most important human attribute, if present, all other desirable attributes follow. The definition of Courage, given by Sir Winston, is ''to do what you think is right, even if you know it could harm you''. This applies to many acts in life, and performing the first heart transplant is certainly an example. Progress in science is achieved through a series of imaginative leaps, to be followed by scrutiny. Thus, the initial enthusiasm for heart transplantation was followed by extensive debate and criticism (refutations) resulting in a 'moratorium' for a period of time.

INNOVATION
Creativity or innovation is essential for progress, and has been defined by Sir Peter Medawar as ''producing ostensibly, out of nothing, something of beauty, order or Significance''. With all the benefits of Science, Medicine, and Humanity, heart transplantation is a strong reminder of the need for innovation. It also shows the importance of being conscious of finding an answer to the question ''innovation at what price?'' to patients and Society.
Following a period of intensive debate, studies aimed at establishing the risk benefit ratio and cost effectiveness of heart transplantation has helped to establish and refine the procedure. Formulating rules and regulations for innovative medicine, while essential, should not be restrictive. A constant open dialogue between scientists and Society should be strongly encouraged, to resolve such issues as brain death criteria in adults, infants with anencephaly, and presumed consent.

COMPASSION
Another important human attribute to celebrate is compassion. This is manifest in society, welcoming the concept of organ donation, as a gift of life. However, the application of these principles are extremely variable and needs to be addressed. This applies to the global application of modern medicine, and specifically cardiac surgery.
Taking cardiac surgery to the people Extensive discussions of this topic took place at the Celebrations of the 50th anniversary of the first heart transplantation, organised by Dr Peter Zilla and his colleagues in Cape Town. This meeting was attended by more than 200 participants, representing professional societies, industry, and academic and popular press. A detailed plan for addressing the unacceptable inequalities was formulated, and the ''Cape Town Declaration'' will be published, and hopefully implemented, in the very near future.

HUMAN SPIRIT
Another closely related reason for celebrating is ''human spirit'', which is both unifying and combines many of the attributes discussed above. This was clearly obvious during the Cape Town meeting.

CHALLENGES
The future of cardiac transplantation depends on solving the current challenges, none of them insuperable. The four main challenges include scarcity of donor organs, chronic rejection, complications of immunosuppressive drugs, and gross inequalities in global access to transplantation.

Scarcity of donor organs
Currently, this constitutes the most important limitation to organ transplantation, with a wide variation in the numbers for organ donation, varying from 0-35 per million in different countries. In addition, a very high number of donated organs (up to 70 percent) are simply not used, due to inadequate care of potential donors. Efforts to deal with these problems are being made through increasing public awareness, introduction of new legislations, such as presumed consent, and adoption of tested programmes like the 'Spanish model'. The use of donors after circulatory death (DCD) is also being explored and is gradually expanding. The use of methods to enhance donor preservation, including ex vivo perfusion of donor organs, is very promising and needs to be explored further

Xenotransplantation
In theory, xenotransplantation offers the opportunity of having an unlimited number of donor organs, and therefore continues to to be the focus of intensive research. The use of primates is ethically unacceptable, and carries the risks of introducing a very large number of simian viruses. In contrast, the use of hearts from genetically modified pigs, was thought to be ethically justifiable up until recently. However the risk of transmitting, the integrated pig retrovirus PERV, which carries a small but definite risk of being transmitted to and from the recipient, remains a major problem. The recent introduction of gene editing with CRISPR-Cas9 technology has had a dramatic effect in this field. The same technology may now be used to prevent rejection of the xenografts.