Modern medicine has produced many kinds of high-tech miracles, among them gene therapy to correct malfunctioning genes, electrical stimulation devices to restore significant function after traumatic spinal cord injury, and robotically-executed surgery.
Another sector of medicine that desperately needs breakthroughs is transplantation of solid organs. There is a severe shortage of organs: Currently, more than 100,000 Americans are waiting for transplants, and due to a shortage of hearts, lungs, livers, and kidneys, at least 17 die each day. Currently, donated organs — from a living or deceased donor — must match the recipient’s tissue type and size, and often, they are not perfect. [HD1] Nonetheless, these organs provide many years of additional functional life for thousands of recipients.
We are making progress in addressing the organ shortage, but too slowly. Two new high-tech approaches to providing organs for transplantation might ultimately eliminate the need for organ donors and reduce the risk of tissue rejection. But there is also a low-tech approach that would require only a tweak in healthcare policy.
Organs produced by 3D bio-printing
The first of the high-tech approaches is three-dimensional (3D) bioprinting, which uses “bio-ink,” a printable material made from a patient’s own cells, to print layer upon layer, creating tissue that will not be rejected by the recipient. But in progressing from tissue to a complex organ, one critical challenge has been how to get blood to flow to keep the cells alive, and researchers have devised a number of approaches to this. They include threading tiny channels through the organ, where blood vessels develop when implanted in animals, or seeding channels with the endothelial cells that line the inside of blood vessels.
An exciting advance was reported by a Swedish research group attempting to create human lungs by 3D printing. According to the lead author of the study, “We started small by fabricating small tubes, because this is a feature found in both airways and in the vasculature of the lung. By using our new bio-ink with stem cells isolated from patient airways, we were able to bio-print small airways which had multiple layers of cells and remained open over time.” Bottom of FormTop of Form
Bottom of FormBeyondBeBeyond the daunting technical challenges, healthcare executive Daniel Troy has described the regulatory lassitude at the FDA that has discouraged commercial interest in the field. “Bio-printed organs are one-of-a-kind creations, tailor-made for each patient,” he observed, a reality that clashes with the agency’s routine methods of evaluating the safety and efficacy of mass-produced therapies and medical devices. The FDA has long promised regulatory guidance for such products, but it has not yet materialized.
Organs from genetically modified pigs
A second approach to providing a sufficient supply of organs for transplantation is via genetically modified animals — most often, pigs — so that their transplanted organs will not be rejected. In effect, it uses genetic engineering to grow “humanized” tissues and organs in animals. There was a breakthrough with this approach in 2018, when scientists used gene editing to create hybrid embryos containing both human and sheep cells.
Another milestone occurred in December 2020 when the FDA “approved a first-of-its-kind intentional genomic alteration (IGA) in a line of domestic pigs” called GalSafe, which may be used for food or human therapeutics. Alteration of the animals’ genome eliminates the gene that makes α-Gal, a sugar molecule found naturally on the surface of porcine cells. It is the source of allergy in some people when they consume certain meats, and it also is involved in tissue or organ rejection after transplantation into humans. Additional modifications of genetic material in some pig lines may enhance organ acceptance.
Research is underway to create lines of pigs for transplantation, but it is accompanied by substantial controversy, including broad ethical and technical questions, including the extent of genetic modification necessary to avoid rejection and ensuring the absence of harmful pathogens. Two separate, very small clinical trials have already been performed – a pig heart transplanted into a patient with terminal heart disease, and a pig kidney implanted in a brain-dead patient. The heart transplant patient died two months post-transplant (the cause not announced), and the kidneys worked well until the experiment was terminated after three days. Experts regard these as encouraging early results, but much additional work remains to be done before this approach becomes clinically feasible with a high likelihood of success.
The low-tech policy approach
Although friends and relatives and even the occasional “good Samaritan” donor can donate a kidney, they cannot receive compensation for their generosity. (They can, however, get related expenses reimbursed.) Under section 301(a) of National Organ Transplant Act of 1984 (NOTA), it is a federal crime for “any person to knowingly acquire, receive, or otherwise transfer any human organ for valuable consideration for use in human transplantation if the transfer affects interstate commerce.”
Tragically, altruism is not enough. The yield from public awareness campaigns, the organ procurement teams that meet with families of the recently deceased and the reimbursement for donors’ expenses has leveled off. Moving to an opt-out system, under which we would recover people’s organs at death unless they had earlier indicated they didn’t wish to donate them, can do only so much — relatively few people die in circumstances that leave their organs suitable for transplantation.
An obvious solution is to allow potential donors to be rewarded for saving a life.
Therefore, we endorse a $50,000 refundable federal tax credit plan for living donors willing to save the life of a stranger by donating a kidney and a $5,000 federal tax credit for deceased donors of kidneys, intestines, pancreases, livers, and lungs.
The credit would be universally available – refundable in cash for people who do not owe income tax, not phased out at high income levels, and available under the alternative minimum tax. There would be no change in NOTA’s restriction on payments by organ recipients and other private individuals and organizations – it would still be illegal for recipients to buy organs.
A qualified organ donation would be subject to stringent safeguards. Prospective compensated living donors would be carefully screened for physical and emotional health, as all donors are now. A minimum six-month waiting period before the organ could actually be donated would filter out impulsive donations and donations by financially desperate individuals seeking instant cash.
In addition to saving lives, the credit would save the government money, perhaps $14 billion per year, by reducing expenditures on dialysis. Thus, donors would receive financial compensation from the government for both contributing to the public good and bearing the risk of a surgical operation to remove the organ. This would be compassionate and pragmatic policy. Moreover, it could be implemented immediately, clearing much of the backlog of Americans waiting for organs in advance of the longer-term high-tech approaches.
The organ shortage kills thousands of Americans every year. We must do all we can to alleviate it now.
Henry I. Miller, a physician and molecular biologist, was a Consulting Professor at Stanford University’s Institute for International Studies and the founding director of the FDA’s Office of Biotechnology. Sally Satel, a psychiatrist and senior fellow at the American Enterprise Institute, is a two-time kidney recipient. She and economist Alan Viard developed the tax proposal in depth.
