I.In discussing emerging and potential future forms of longevity medicine, it is important to remember that not everyone alive today
has 30, 20, or even 10 years to spare waiting for advancements that might save their lives.
While I agree with many longevity advocates that techniques to
clean up and repair age-related damage in the body hold tremendous promise, the fact remains that there are many people alive today for whom those techniques (if developed) will arrive too late. My own support of longevity medicine and relevant research stems from the basic fact that I don't believe in putting an expiration date on anyone's value as an individual -- the way I see it, a 90-year-old has just as much of a right to effective healthcare as a 30-year-old.
It is therefore crucial (per my ethical position on these matters, at least) for those of us in our 20s, 30s, 40s, and even 50s to beware thinking of longevity only in terms of what might be possible for people
our age. Longevity medicine, if it is to be truly effective, must take into account existing demographic diversity and this will assuredly mean pursuing different simultaneous research avenues
1.
One such avenue is that of attempts to
replace nonfunctioning or poorly-functioning organs in people whose lives are threatened by disease, damage, or injury affecting those organs. Of course organ replacement can and does happen all across the human lifespan, however, it has particularly significant implications for people presently in their sixties and up.
II.My grandfather, who is in his 80s, had a heart valve replaced a few years ago -- the fact that he's still around (and will hopefully be around for many more years) really brings home the point for me that organ/tissue replacement is going to have to be part of any comprehensive longevity medicine enterprise.
The notion of replacing worn-out, diseased, or injury-damaged organs is far from new.
Artificial heart designs of varying clinical efficacy have been in development since the 1950s.
Kidney dialysis was developed in the 1940s.
Hip replacement surgery was first successfully performed in 1960, and prosthetic limbs have been around for thousands of years.
Note that all of the above examples entail the attachment of non-tissue parts (plastic, titanium, etc.) to human tissue. Whether these non-tissue parts are implanted (as in the case of artificial hips) or temporarily connected (as in the case of kidney dialysis), their capacity to sustain life and functionality is limited in ways medical science has yet to overcome. Human bodies did not evolve universal adapters at the interfaces between our various organs and tissues, meaning that even just attaching replacement devices where they are needed is generally invasive and mechanically challenging.
Furthermore, unlike healthy animal tissue, materials used in artificial parts do not yet possess self-repair mechanisms -- a fact which makes anyone who receives an artificial part subject to potentially numerous future surgeries and clinic visits. This is less of an issue for prosthetic
limbs (
the newer artificial legs used by athletes like Oscar Pistorius have been described by some as potentially
more optimized for fast running than "natural" legs), but one does not even need limbs in the first place to survive (however convenient they may be). This lends a certain amount of leeway to designers and users of artificial versions.
III. The same cannot be said, however, when it comes to parts like livers, and kidneys, and hearts. Without any of
these parts, or something capable of performing their precise functions reliably, a person will most assuredly not survive very long. So critical are these organs that technologies which replace their functionality via "non-biological" means are still considered substandard in addressing their injury and/or absence. This is why right now, the best a person with a failing heart or kidney can do is get a transplant.
Transplants are major surgery to be sure, but they are also one of the most intuitive examples of presently-feasible (and definitely lifesaving) replacement techniques. After all, doctors, scientists, and surgeons don't have to know how to build a working heart from the ground up in order to know that if someone's heart fails, the best thing to put in their chest to replace it is another heart!
Like the idea of parts replacement in general, the idea of replacing a missing or diseased part with a corresponding part from a donor (living or dead) is old news; a successful
cornea transplant was performed as early as 1905, and there is some speculation that skin transplantation occurred in second-century BC.
Throughout the 20th century and continuing into the 21st, many lives have been saved via transplantation of hearts, lungs, livers, kidneys, and other essential organs. A good transplant can lead to impressive survival -- heart transplant recipient
Derrick Morris died at the age of 75 in 2005, after having lived 25 years with a heart he'd not been born with.
IV. Still, despite its obvious efficacy, transplantation as a practice has plenty of technical and ethical issues it hasn't entirely worked through yet. Transplant patients generally need to take powerful immunosuppressant drugs (which are neither cheap nor devoid of side effects) throughout their lives -- a precarious situation to be sure.
There's also the fact that for many lifesaving transplants, one person needs to die in order for another to live. This puts transplant hopefuls (who are faced with the bizarre prospect of wanting to live but not necessarily wanting to want someone else to die),
disabled individuals (who may live in justified fear of someone "disconnecting" their life support in order to harvest their organs), and the families of individuals in (for instance) long-term comas in very unpleasant psychological territory.
Some transplants can be performed using tissue from living donors (a person can generally survive just fine with one working kidney), but not nearly enough to account for all the people presently in need of organs -- not to mention the fact that the growing underground "organ trade" almost certainly puts the poor in a position of increasing precarity and at risk of serious exploitation.
Furthermore, bringing this discussion back to the subject of longevity specifically -- elderly people are often at the bottom of the list, so to speak, when it comes to the prioritization of donor organ distribution. Some of this has to do with ageist (and likely ableist, and classist) prejudice -- there are, unfortunately,
some who insist that healthcare is a zero-sum game in which the elderly are "burdens" on the young. Some also has to do with the greater likelihood of physical frailty in older patients, and the fact that they are expected to survive for fewer years anyway even after a successful transplant.
Nevertheless,
more and more elders are getting transplants these days nonetheless, and doubtless doctors are finding it more and more difficult to refuse to perform transplants after seeing that both survival and quality of life
can follow those operations.
What is needed next, along with wider recognition of the lack of an expiration date on an individual person's value, is a means to replace worn-out parts that doesn't require nearly so many dead donors, and that doesn't pose so much danger to the recipient in terms of infection and immune issues. It will likely be a while before this becomes a reality, but there are definitely areas of research that look quite promising in this regard. One such area that has recently come to my attention is that of
bioartificial parts.
V.Bioartificial parts are essentially the products of the emerging science of
tissue engineering.
Wikipedia describes tissue engineering as:
...the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions. While most definitions of tissue engineering cover a broad range of applications, in practice the term is closely associated with applications that repair or replace portions of or whole tissues (i.e., bone, cartilage, blood vessels, bladder, etc.). Often, the tissues involved require certain mechanical and structural properties for proper functioning. The term has also been applied to efforts to perform specific biochemical functions using cells within an artificially-created support system (e.g. an artificial pancreas, or a bioartificial liver).
Of course applications of tissue engineering will benefit people of all ages (
bioengineered bladders have already been successfully implanted in several children), but the growing elderly population stands to benefit tremendously from
anything that makes effective replacement parts safer and more readily available.
Bioartificial parts could potentially take innumerable forms, but given the organs people really depend most on for survival (if you'll permit me to ignore the brain for the moment), it is definitely good to see that laboratory results (and in some cases, clinical/experimental trials) have been obtained for bioartificial arteries, hearts, livers, and kidneys.
VI.Cardiovascular structures are some of the most crucial in the body, and
are notoriously prone to malfunction as a person ages. Not only are veins, arteries, and other blood vessels susceptible to plaque-like buildups, clogging, and hardening, they also experience mechanical fatigue that can decrease elasticity and increase overall systemic fragility.
Hence, bioartificial arteries, such as those in development at the
University of Minnesota's Institute for Engineering in Medicine, will surely be a welcome addition to the medical arsenal.
UNM's informational piece,
Better bioartificial arteries, describes the project as follows:
Daniel Mooradian, an assistant professor of biomedical engineering, and Robert Tranquillo, an associate professor of chemical engineering and materials science, began developing the bioartificial artery as part of a collaborative tissue engineering project in 1992.
The two researchers have been exploring ways to grow smooth muscle cells that mimic both an artery's form and its internal structure by using three-dimensional collagen matrices as a framework for the cells.
A natural polymer-like collagen offers many advantages, explains Tranquillo. Not only is collagen in ample supply, it also provides an excellent natural substrate for cell growth that can be reabsorbed into the body.
So far the UNM researchers have succeeded in producing a "cell-populated matrix" shaped like an artery, which is certainly a step in the right direction. However, the resultant matrix was still lacking in necessary mechanical strength. Experiments are ongoing, and so far the researchers have noted some potential in techniques that involve fabricating cells in a magnetic field -- the field causes the cells to align in ways similar to those in actual arteries.
Clinical trials are still a ways off, but laboratory proof-of-concept results are definitely looking interesting so far. If methods such as those being studied by the UNM team are successful, it could lead to tremendous benefit for patients needing
small-diameter arteries replaced in particular, as these often cannot be replaced with synthetics the way larger-diameter vessels can.
VII.Bioartificial kidneys are a bit further along than bioartificial arteries -- in fact, they've already improved the conditions of several seriously ill people
in a recent study trial conducted by the University of Michigan.
The device is described as follows:
The bioartificial kidney includes a cartridge that filters the blood as in traditional kidney dialysis. That cartridge is connected to a renal tubule assist device, which is made of hollow fibers lined with a type of kidney cell called renal proximal tubule cells. These cells are intended to reclaim vital electrolytes, salt, glucose and water, as well as control production of immune system molecules called cytokines, which the body needs to fight infection.
Right now the bioartificial kidney must still be connected to patients the way traditional dialysis equipment is -- however, there are plans in the works to eventually produce a "wearable" (and, ideally implantable) version. The addition of actual kidney cells to the dialysis cartridge makes it possible for the procedure to perform many more of the chemical-balancing functions of healthy kidneys -- a feature which stands to greatly enhance survivability in patients whose systems are already weaker.
While again this technology will benefit people of all ages, it is particularly relevant for elderly persons as the
average age for starting dialysis was 62 in a 2006. Bioartificial liver devices (some of which were
already in clinical trials by year 2000) work on similar principles to those of bioartificial kidneys. That is, at present the filtration occurs outside the body, but with the aid of actual liver cells that enhance the effectiveness of the process. The
Extracorporeal Liver Assist Device, for example:
...is a “metabolically active” hollow fiber dialyzer analogous to cartridges used in kidney dialysis. The dialyzer is a two-chambered canister, mechanically very similar to a kidney hemodialyzer – like a container full of microscopic straws. The dialyzer cartridge’s extracapillary space is inoculated with a patented, cloned, immortalized human liver cell line. The cartridges are incubated in an automated cell culture, which works to deliver oxygen and nutrients to the cells housed in the cartridges. During a three-week maturation process, the cells replicate and attach to the outside of the cartridge’s capillaries.
Current bioartificial liver devices are not intended to permanently replace malfunctioning livers -- but rather, to permit the patient to survive long enough for transplant or (if possible) regeneration of his/her own liver. Permanently-implantable bioartificial livers
may emerge somewhere down the line, however, liver tissue tends to regenerate on its own more readily than kidney tissue, so it remains to be seen how far this technology will need to be developed.
VIII.It's not surprising that heart disease remains the
leading cause of death in developed regions, and the third leading cause of death in developing regions despite impressive medical progress in many areas over the last century. Of all the life-sustaining organs in the body, the heart stands out as one of the most difficult to replace -- not only do all heart transplants entail the death of the donor, but few to no options exist for long-term artificial maintenance of patients with life-threatening heart malfunctions.
Surgeons can temporarily
stop the heart during surgery in order to operate with less risk to the patient, but of course the patient is unconscious during this time and can only be kept safely without a heartbeat for a few hours. People can also sometimes survive for much longer periods on
heart-lung machines, however, these machines aren't exactly portable and expose the patient to risks including clotting, infection, and air embolism.
Hence, it is encouraging to see that
a prototype bioartificial heart was recently grown and activated by University of Minnesota researchers:
The team took a whole heart and removed cells from it. Then, with the resulting architecture, chambers, valves and the blood vessel structure intact, repopulated the structure with new cells.
"We just took nature's own building blocks to build a new organ," says Dr Harald Ott, a co-investigator who now works at Massachusetts General Hospital. "When we saw the first contractions we were speechless."
These experiments used pig and rat hearts, and the hearts observed to be contracting within four days and pumping within eight days were grown mainly from rat cells. Professor Doris Taylor, the principal cardiovascular research director at UNM, believes that growing a heart for humans using similar methodology is already technically feasible -- but unfortunately prohibitively expensive. However, researchers and doctors are nonetheless excited about the prospects for this research, given the unfortunate number of people who die as a result of insufficient donor organ supply.
While current proposals for bioartificial hearts do not entirely solve the problem of requiring the deaths of donors altogether, anything that could make better and more effective use of existing organs stands to reduce demand pressure and lead to more lives being saved. And, of course, it is possible that advances in this general direction could merge with advances in bioartificial arteries and other structural components -- eventually negating the need to start with the scaffolding of a donor heart altogether.
IX.In concluding this discussion of parts-replacement (and bioartificial organs in particular), I would like to reiterate the point that a lot of the most promising potential rejuvenation developments are
still likely out of reach of many alive today. It's obviously not always possible to predict what areas of research will advance first, and serendipitous discoveries can sometimes shorten development timeframes beyond anyone's expectations -- but one certainly cannot rely on this happening.
I'm personally quite excited about possibly seeing some of the types of therapies suggested by the
Strategies for Engineered Negligible Senescence platform come to fruition -- however, given the still-theoretical nature of many
2 of those therapies, people heading into their sixties and beyond are almost certainly going to need to take advantage of nearer-term developments.
Bioartificial liver and kidney devices, after all, already exist and are already helping people who would otherwise be dead survive, and it's important for more people to become aware of the options that do exist so that they can more realistically plan for their own and their loved ones' long-term healthcare.
I know some longevity advocates are strongly attached to particular research paradigms, funding pathways, etc., but I've never been able to "put all my eggs into one basket", so to speak. The sheer range of different bodies, configurations, and precarity levels would seem to demand varying approaches to research and development, and I am very happy to see things moving along in the bioartificial arena.
Finally, I would also like to emphasize that there's a lot more to making the world better for all types and ages of people than simply growing functional organs in a laboratory. Many infrastructural changes are desperately needed already in order to allow existing people to access existing lifesaving care.
Attitudinal changes are also in order -- I've noticed, as of late, a rather disturbing trend toward promotion of "survival of the fittest" and "life is a zero-sum game" mentalities amongst some folks, some of whom stand to make very significant decisions about other people's lives. E.g., moves toward
harvesting the organs of patients without consent are being seriously considered by some officials, which understandably has a lot of ill and disabled people (and their families) worried that they or their loved ones might be "sacrificed" without sufficient conclusive proof that they are absolutely beyond the capacity for a valuable and meaningful existence.
One reason I'm so supportive of bioartificial (and even fully artificial) organ and part substitute development is because I think people are going to find it a lot harder to justify convincing themselves that someone is "really dead for all practical purposes" when they
honestly don't know that the sooner we have substitute organs and parts available that don't require anyone to die. I'm not saying anyone today who receives donor organs should feel guilty, and I'm well aware that dead-donor transplants are likely to be around for a long time still -- but I definitely hope to see more work in the direction of developing better, safer, less expensive, more easily maintained replacement parts than in the direction of trying to narrow the definition of who is actually alive.
1 - Here I am referring to both technical and social research avenues -- many of today's oldest old, for instance, would probably benefit most immediately from care reforms and improved services, particularly services offered outside dangerous, depressing, understimulating "nursing home" environments.
2 - See AGE breakers for an example of an existing implementation of the "clean up the damage" principle lately popularized by SENS media.
