More on Transplanted Pig Organs – Xenotransplantation

Although xenotransplantation has not progressed far enough to allow transplanting a pig organ to a human, there are other exciting opportunities in the works for xenotransplantation in the not to distant future.

Individuals that develop liver failure often die before a suitable donor can be found or before the damaged liver can heal on its own. There is no artificial liver comparable to the dialysis machine for kidney failure. But using a specially develop pig liver outside the body to cleanse the person’s blood of noxious compounds is a possibility. There have been some positive results using a normal or a genetically modified pig liver for such “extracorporeal” perfusion until a donor organ is available or until the patient’s liver recovers on its own.

Progress has also been made with genetically modified insulin-producing pancreas islet cells for treating diabetes. One approach is to place the transplanted islet cells into a “capsule” that allows insulin to exit out and nutrients like glucose to enter in yet keeps immune cells that would destroy the islet cells at bay outside the capsule.
Further progress in xenotransplantation is likely but there are significant barriers to success. Genetic modification of the pig is possible but it is not yet clear all of the modifications that will be necessary. Concurrently, work is progressing to develop immune modulation with drugs just as is done to suppress the immune system with human to human organ transplants. Further development of encapsulation may aide the process, especially with islet cell transplantation for diabetes.

Despite all of the progress to date, the barriers to success are very real and only time will tell if xenotransplantation will become a truly viable path to organ replacement

Transplanted Organs From A Pig

There are many more individuals with end stage kidney failure, heart failure, chronic lung disease, or liver failure who would benefit from a transplanted kidney, heart, lung or liver than are available. Similarly, there are many people with unstable, difficult to control diabetes that could benefit from a ready source of pancreatic insulin-producing islet cells.

Today the only option for more organs available for transplant is to encourage more individuals to pre-certify their desire for organ donation should they die in a traffic or other accident.

But another approach, still in the future but gaining traction, is to use organs from an animal – known as xenotransplantation.

Most efforts in xenotransplantation focus on the pig, in part because the organs are near to the same size as humans and the physiology is similar. Very real progress has been made in recent years. The steps required to make this approach effective include genetic modification of the pig so that the human immune system will no longer “reject” the transplanted organ. This has included removing the genes that produce the most important pig carbohydrate antigen that human immune cells recognize. Another step has been to add genes that create certain protective proteins in the complement regulatory system (another part of the body’s mechanism to eradicate “foreign” materials like bacteria, viruses or a cancer.) So far, these steps have been major advances but not sufficient so further efforts will be necessary in order for say, a pig heart or kidney to be successfully transplanted into a primate and eventually into a human. But the progress is real, exciting and promising. Stay tuned.

Thought Controlled Artificial Limbs

I wrote about the possibility of brain-controlled artificial limbs in “The Future of Medicine” but now there has been real progress. At Johns Hopkins Applied Physics laboratory, scientists have progressed with their design of an artificial limb that will have a brain controlled interface. The model came about through a contract with the Defense Advanced Research Projects Agency (DARPA) which has been looking for a prosthetic arm that would be many leagues advanced from those in use today and which in fact date back to the World War II era.

Not all that much progress has been made over the past few decades in artificial arm development. Perhaps it is because losses of legs are much more common than losses of arms. But the loss of an arm is especially devastating to the individual and a truly useful replacement is of critical need.

The new device will have remarkable dexterity with the degrees of freedom of a human wrist and the ability to control individual fingers. Look at your wrist. It can move in six different directions or “degrees of motion.” When you consider the entire arm, there are 27 degrees of motion and the new limb will have about 22 of them included. It weighs just eight pounds which is about what an average arm weighs yet can hold up to fifty pounds. The motive power comes from a rechargeable battery. These are advances of some great import indeed but the next step is the amazing one – brain control. The first step is to use outputs from the nerves in the shoulder that used to control the arm before the injury and loss. These nerves carry outputs from the brain that can be accessed to drive the various internal motors that operate the artificial arm. Later, the plan is to develop microchips to implant in the brain that will sense the “thought” to, say, “lift the arm” or “push that button.”

Johns Hopkins APL is engaged with multiple other groups to bring this work to fruition. One of the major hurdles is to develop the algorithms that take the signals from the brain or the nerve and convert them into mechanical activity. Signal analysis algorithms have now been developed that take outputs from the motor and the premotor cortex of the brain and decode them into specific dexterous movements such as grasping that can drive the electro-mechanical apparatuses in the limb.

The research needed to move this project ahead are daunting but the principals believe that the technology exists and can be turned to good use here. Perhaps one of the first types of patients to be tested will be quadriplegics because to offer such an advance would be dramatic for the involved patient. It sounds like science fiction but instead it is the result of the combined efforts of many engineering and computer scientists along with rehabilitation physicians and others. 

Are Physicians Knights, Knaves or Pawns?

An interesting article in JAMA [Sept 1, 2010] by Drs. Jain and Cassel referred to the British economist Julian Le Grand who suggested that public policy “is grounded in a conception of humans as knights, knaves or pawns.” Basically, are we motivated by virtue, by self interest or are we just passive victims? The authors suggest that this is a good question not only for physicians to contemplate but for our politicians and the general public to consider as well along with the implications of the answer.

Physicians need to examine whether we are working for the greater good and especially the good of our patients; and if so, then to consider why society generally does not think we are. Or do we work with our own income and other gains in mind as the foremost driver of action and work? Or perhaps do we just go about our daily efforts as unfortunate passive victims of insurer and government dictums?

Often the individual likes their physicians and thinks of him or her as a “knight.” This is the belief that the physician has the patient’s best interests in mind at all times and takes the needed steps to be sure that the patient is always placed first. But society overall does not think this way of physicians. To most, physicians have long ago lost their “Marcus Welby” status and instead are driven by the desire for a high income, reduced work load and less attention to the patient and the patient’s needs. With this sort of attitude, society through its elected officials and through the insurance apparatus erects many polices and procedures to guard against the “knave” doing harm, reaping too much income, etc.

Many physicians think of themselves today as just “pawns” in a large bureaucratic maze, unable to practice medicine as they believe it should be practiced; unable to earn a reasonable salary given the work burdens and the work content; and overwhelmed with paperwork and needless regulations. Unfortunately, society has indeed put the physician all too often in this setting and established regulations that presumably will ensure that the physician does what is needed.

There was a time in the clouded past when physicians were thought of as knights, when they looked upon themselves as members of the middle class with a special and higher calling, and government largely left them alone. But as costs of care have risen, as more safety lapses have been recognized, as quality has not been forthcoming commensurate with new knowledge, the public has come to believe that the physician is the problem and not the solution.

I would echo Jain and Cassel’s urging that physicians need to “thoughtfully consider whether and how they contribute to the perception that they are knights, knaves or pawns.” It is time to look in the mirror and, if the vision is not as desired, then to take the needed actions to make mid course corrections. To do nothing is to allow the system to characterize physicians as “knaves” and then to push them into the role of “pawns.”