The global shortage of organs for transplantation has long been recognized as a major public health challenge, and the World Health Organization (Geneva) estimates that only 10% of the worldwide need for organ transplantation is being met1. The data suggest that the organ shortage is among the greatest crises facing biomedicine today. Although few estimates are available of the total number of patients who could benefit from organ transplantation if supply constraints were removed, the commonly cited transplant waiting lists clearly fail to capture the organ shortage's true magnitude. For example, the number of patients added to US transplant waiting lists each year—roughly 50,000—is dwarfed by the ∼730,000 annual US deaths attributable to end-stage organ disease (Fig. 1)2,3. As one example, the true need for heart transplantation in the United States has been estimated at more than ten times the heart transplant waiting list4,5. It has been suggested that with all supply constraints removed, organ replacement could theoretically prevent >30% of all deaths in the United States—doubling the average person's likelihood of living to 80 years of age6,7,8. Similarly, estimates based on incidence of diseases that are potentially addressable by on-demand organ replacement place the true need at millions of transplant organs per year in the United States and Europe combined9.

Figure 1: The true lifesaving potential of organ transplantation. The roughly 50,000 US patients added to transplant waiting lists in 2011 were outnumbered over 14-fold by those who died from end-stage organ disease (http://www.perfusix.com/impact-of-ex-vivo.html), without counting cases where malignancies could have been treated with organ replacement168. This suggests that the true size of the organ shortage could be many times larger than is reflected by transplant waiting lists (currently 120,000 US patients). Full size image

The organ shortage is markedly worse in many other countries. For instance, the continent of Africa holds 16% of the world's population but performs only 0.5% of its organ transplants (Fig. 2). Moreover, in some of the countries with the least access to transplantation, a substantial fraction of transplant procedures are actually instances of transplant tourism10. In Pakistan, for instance, up to two-thirds of kidney transplants in 2005 are estimated to have been performed on foreigners10,11. The practice has widely been considered problematic because it creates opportunities for organ commodification and exploitation of vulnerable populations; the Declaration of Istanbul, signed by 157 representatives from countries across the globe, condemns the practice12. Healthcare infrastructure, national wealth, and sometimes cultural factors can each play a major role in the disparities in access to transplantation internationally. Yet over time, easing logistical burdens and increasing supply can lower the barriers to development of transplantation infrastructure4,5, and as discussed below, to equitable access to transplantation within countries.

Figure 2: The global unmet need for transplantation greatly exceeds that of the United States (see Fig. 1), which contains roughly 4% of the world's population but performs 25% of its organ transplants. By comparison, the continent of Africa contains roughly 16% of the world's population but performs fewer than 0.5% of its organ transplants (http://www.transplant-observatory.org/summary/; https://esa.un.org/unpd/wpp/publications/files/key_findings_wpp_2015.pdf). Full size image

The above considerations should place technologies that can substantially increase the availability of transplant organs at the top of our scientific priority list. Moreover, the need for these technologies is shared with many other major public health challenges. Banking of viable organs and tissues can transform cancer treatment for young patients and have a dramatic impact on precision medicine and research on diseases such as heart disease, cancer, and Alzheimer's disease. Ballooning costs in drug discovery are exacerbated by poor availability of human tissue models, which in many cases could provide more valuable data than the animal models currently used. Tissue transplantation faces enormous logistical barriers in emergency care because tissue is needed on such short notice. These challenges are magnified in contexts where large numbers of patients require care, such as the treatment of wounded service members and civilian victims of natural disasters or terrorist attacks. In these and many other areas, adequate techniques and treatments often already exist. However, their use is pervasively handicapped by the limited availability of organs and tissues, which are among the most precious resources in research and medicine. The aggregate toll on human health attributable to causes that could be addressed by increasing organ and tissue availability makes this problem one of the most important healthcare challenges of this era.

Developing an organ and tissue supply that can meet the healthcare demands of the twenty-first century requires the development of solutions to twin challenges: first, having enough of these lifesaving resources; and second, having the means to store and transport them for a variety of applications, each with distinct but overlapping logistical needs. Having enough organs and tissues to meet public health needs has been the subject of extensive efforts in science, medicine, and public policy aiming to increase organ donation13,14, improve donor organ utilization15,16,17,18, and gain the understanding needed to engineer laboratory-grown tissues19, bio-artificial organs20,21, and 'humanized' animal donor organs for transplantation22,23. The success of these efforts is intertwined with meeting the second challenge: preserving organs and tissues during procurement (or manufacturing), storage, transport, and other steps of the supply chain in order to meet logistical needs.

Despite its importance, the preservation challenge has received relatively little attention from funding agencies, the research community, and the general public. Taken together, preservation constraints place widespread burdens on efforts to use organs and tissues in transplantation, regenerative medicine, and research. Yet, although >80% of the budget of the US National Institutes of Health (NIH) goes to institutes with missions tied to unmet preservation needs24, and numerous other science agencies and stakeholder groups stand to benefit from preservation advances, no funding body has been charged with overcoming the remaining technical challenges common to the preservation of organ and tissue systems. As a result, the past half-century has seen only incremental and relatively ad hoc investments to advance preservation technologies.

By overcoming these institutional barriers and facilitating coordinated and cross-disciplinary research, it is now possible to dramatically accelerate progress in organ and tissue preservation using existing knowledge from a diverse array of fields. The past decade of progress has allowed us to understand and intervene in human physiology at the tissue and organ level as never before, with breakthroughs in nanotechnology, sequencing, imaging, omics approaches, and other areas. These technologies can be used to build on proofs of principle for organ cryopreservation6,7,25,26,27,28, discoveries from organisms that can enter 'suspended animation' at subzero temperatures29,30,31,32, rapid advances in perfusion technologies33,34,35,36,37,38,39,40,41, and other advances.

In light of these opportunities, a growing coalition of scientists, clinicians, policymakers, advocacy groups, academic institutions, and industry representatives is assembling to accelerate progress in organ and tissue preservation. This has led to an extensive dialog spanning more than a year, which has included the first global Organ Banking Summit at Stanford, NASA Research Park, and other locations7, a US National Science Foundation (NSF)-supported Roadmap to Organ Banking and Bioengineering Workshop6, a meeting hosted with the Defense Advanced Research Projects Agency (DARPA) leadership at the US Military Academy at West Point, New York, on a potential 'Organs on Demand' research program, a White House roundtable on organ banking and bioengineering, and a symposium and roundtable on emerging organ preservation technologies on Capitol Hill. At these events, stakeholders have begun to outline the vast public health needs, remaining technological challenges, institutional and infrastructural barriers, and untapped research opportunities surrounding efforts to eliminate preservation constraints on the use of organs and tissues in biomedicine25. These efforts aim to facilitate the advancement of preservation platforms allowing us to transport, repair, assess, bank, and even enhance the health and function of organs and a variety of tissues used in research and medicine.

The diversity of authors of this article, with expertise spanning organ and tissue procurement and transplantation, preservation research, bioengineering, economics, trauma care, and regenerative medicine, reflects the breadth of need in this area—and the widespread concern that until preservation breakthroughs are pursued aggressively, many medical technologies will not come close to reaching their lifesaving potential. In the sections that follow, we describe how organ and tissue preservation can meet a variety of major public health needs. We also outline recent discoveries indicating that a revolution in organ and tissue preservation is now achievable, propose a novel paradigm for preservation involving convergence of a family of existing approaches, and describe how technologies have the potential to make a new generation of preservation technologies feasible. Finally, we suggest ways that the research community can overcome institutional barriers that hinder advances, and we highlight recent progress toward a coordinated research effort.