Can We Live Forever?
When machine components deteriorate beyond repair, they are replaced. Can 3D bioprinting enable the human body to be maintained like a machine?
I have spent the last 7 years studying, designing, and building machines. With proper care, machines can “live forever”. Perhaps humans can too.
Humans and machines physically deteriorate throughout their lifetimes. When a mechanical component deteriorates beyond repair it is replaced. Amazingly, we have the ability to replace some human components too, but the replacements we currently use are not perfect and are not abundant. In 2016, over 7,000 people died in the United States while waiting for a lifesaving organ transplant. There are currently 115,000 people on the organ transplantation waitlist, but only 13,000 donations have been made this year to date. [1] Tissue engineering promises to eliminate the need to wait for a limited supply of donor tissues, solving the organ transplantation crisis and extending human life expectancy. This technology will allow us to develop human tissue, in vitro, on demand, and using a host’s own cells, reducing the risk of immune rejection. [2]
Organovo was founded in 2007 around the research of Dr. Thomas Boland at Clemson University and Dr. Gabor Forgacs at the University of Missouri–Columbia. [3] Dr. Forgacs and his partners built NovoGenTM, the first 3D bioprinter that enabled precise placement of cellular aggregate – also called bio-ink – to form simple tissue structures. [4] Though the printing of smaller tissues in the form of tubes, patches, and organoids is possible today, the printing of whole replacement organs remains a medium to long term goal of Organovo. [5] The science is still years away.
In the short term, the company is solving another momentous problem for the pharmaceutical industry. Organovo’s 3D printed tissue provides researchers the opportunity to test drugs on a functional human model before ever administering the drug to a living person. Prior to Organovo’s breakthrough innovation, pharmaceutical companies could test on animals or human cells in a 2D architecture before moving to clinical trials. Neither of the prior models function in the same way as human cells in a 3D architecture, resulting in high failure rates of drugs during clinical trials that had been successful in preclinical testing. [6] A 2016 study reported the cost of clinical trials to be between US$20 million and US$80 million. [7] Another 2014 study reported that only 10% of drugs pass clinical trials and make it to market. [8] Organovo’s 3D printed tissue is positioned to increase the success rate of drugs in clinical trials, saving pharmaceutical companies millions of dollars and months of time in research and development.
With so much potential in the short and long term, what is there not to like about Organovo and the future of 3D bioprinting? It seems likely that only wealthy subgroups of developed countries will be able to afford the technology in its early days. It’s possible that a tiered system of organ replacement will emerge with those who can afford to pay for 3D printed organs living longer and enjoying a significantly higher quality of life. Others will have no choice but to continue to wait until a human organ donor becomes available and then have to rely on medication for the rest of their lives to prevent rejection of the transplanted organ. [9] Further, a “designer babies” problem may arise. Individuals may try to enhance themselves with 3D bioprinting if they can get an advantage. [10]
Some legal authorities suggest that 3D bioprinting does not fit within the current frameworks for regulation on medicine or conventional 3D printing. This could lead to new forms of exploitation such as a new black market in 3D bioprinted organs. [11] Given the severity of the ethical and legal concerns surrounding 3D bioprinting, I suggest that Organovo work proactively with the proper medical and legal authorities in the short and medium terms to ensure a positive future for their technology.
While 3D bioprinting of whole organs will likely begin with the kidney, liver and heart, the ultimate key to extending human longevity is the brain. Projecting into a future where brain transplantation using 3D bioprinted brains is physically possible, how do we maintain brain-body history and proper brain-body function? [12] If we can develop the ability to repair or replace all components of the human body, including the brain, what would be the extent of human lifespan? Can we live forever?
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References
[1] United Network for Organ Sharing, “Data”, https://unos.org/data/, accessed November 2018.
[2] F.G. Heineken, R. Skalak, “Tissue engineering: a brief overview”, J. Biomech. Eng. 113 (2), 1991, p. 111-112.
[3] Organovo, “History”, https://organovo.com/about/history/, accessed November 2018.
[4] Organovo, “Scientific Origins”, https://organovo.com/science-technology/bioprinted-human-tissue/scientific-origins/, accessed November 2018.
[5] Organovo, “3D human tissues for medical research & therapeutics”, https://organovo.com/tissues-services/3d-human-tissues-medical-research-therapeutics/, accessed November 2018.
[6] Organovo, “About Organovo”, https://organovo.com/about/about-organovo/, accessed November 2018.
[7] A. Sertkaya, H. Wong, A. Jessup and T. Beleche, “Key cost drivers of pharmaceutical clinical trials in the United States”, Clinical Trials 13 (2), 2016, p.117-126.
[8] M. Hay, D. Thomas, J. Craighead, C. Economides and J. Rosenthal, “Clinical development success rates for investigational drugs”, Nature Biotechnology 32 (1), 2014, p.40-51.
[9] N. Vermeulen, G. Haddow, T. Seymour, A. Faulkner-Jones and W. Shu, “3D bioprint me: a socioethical view of bioprinting human organs and tissues”, Journal of Medical Ethics 43 (9), 2017, p.618-624.
[10] S. Suter, “A Brave New World of Designer Babies?”, Berkeley Technology Law Journal 22 (2), 2007.
[11] J.L. Tran, “To bioprint or not to bioprint”, North Carolina Journal of Law & Technology 17 (1), 2015, p.123–78.
[12] R. Lozano, L. Stevens, B. Thompson, K. Gilmore, R. Gorkin, E. Stewart, M. Panhuis, M. Romero-Ortega and G. Wallace, “3D printing of layered brain-like structures using peptide modified gellan gum substrates”. Biomaterials 67, 2015, p.264-273.
One question I had was the consumer appetite for 3D printed organs. Looking at the current resistance to self-driving cars such as Tesla, I think that people may have a similar reaction to 3D printed organs. Perhaps in a life or death situation, people may care less about whether their organs are natural vs. 3D printed. However, I wonder whether that tipping point is within the medium-term horizon and whether Organovo has the cash flow to support themselves until that tipping point.
I found your post to be simultaneously insightful and thought-provoking.
In particular, after reading it I can’t stop thinking about the thought experiment about the Ship of Theseus (https://en.wikipedia.org/wiki/Ship_of_Theseus), which gets to the question of at what point an object that has its individual components gradually replaced over time ceases to be the original object. In this context, at what point do I stop being me if each of my individual organs are gradually replaced? Conventional wisdom would probably suggest that once my brain is replaced, I cease being me and instead take on some alternate identity. But, given recent research on things like the gut-brain connection (e.g. https://www.health.harvard.edu/diseases-and-conditions/the-gut-brain-connection), perhaps this conventional wisdom is somewhat myopic. Interesting stuff.
I love that you brought up the Ship of Theseus! The curveball in this case is that all of the replacements are derived from the host’s DNA so, arguably, they are just as much “them” as the originals.
To your other point, the brain is a mystery. All the more reason to study neuroscience!
This leap in technology and innovation is incredible! This reminds me of an episode of Grey’s Anatomy where they were testing out 3D printed blood vessels (I think?) — at the time I thought there was no way that 3D printing could complete such a feat. Of course, I was wrong!
I really like how the author explored not just the challenges the company faces with successfully developing and launching this product, but also the ethical issues that this technology would pose on society. With leaps in current technologies to improve the human lifespan (cord blood banking, in-vitro fertilization and stem cell research), these ethical concerns will only become more and more important in the face of 3D printing organs, with wealth being the ultimate decision driver of who can and cannot obtain the new technology or service. For example, cord blood banking is the process of freezing a newborn infant’s umbilical cord, which is rich with stem cells. There is a small chance that the stem cells in the umbilical cord could help save the child’s life down the road (e.g. if the child gets cancer and needs bone marrow transfusion). There is a blooming industry now that preys on insecure parents’ fears of the small probability that the child would need the cord blood. After all, which parent wouldn’t want to give everything they can to their child? Of course, this potentially-life-saving technology comes at a hefty price that only the wealthy could afford. The “initiation fee” is a few thousand dollars (and not covered by insurance) and the annual fee is a few hundred dollars. While cord blood banking technology does not have as broad of an impact as 3D printing organs, it illustrates a problem that organovo should consider as it continues with its product development.
Very interesting! Thank you for your thoughtful commentary.
A few more questions come to mind: Will the broader scientific community be able to reach a consensus about the best methods and expected outcomes of 3D bioprinting? Who might own these organs; how does one issue IP around something like this? In the medium-term, could there be more of an appetite for ‘organic’ transplant offerings — for example, using CRISPR to modify pig organs?
There’s no doubt that we’ll have to grapple with the ethical implications of such innovations sooner rather than later. I wonder if we have the foresight to understand the long-term implications of such advances in science, and how we might live to regret the methods in which we first introduce such technologies. Nevertheless, I am a firm believer in pushing forward with such research! I have high hopes for what companies like Organovo can accomplish.
This was super fascinating – appreciate you choosing a topic that is clearly so many years out, with its full potential still uncertain. Even looking at the nearest term use case—the drug testing on an artificial human tissue—you can see the challenges that arise in the application of 3D technology to human beings. Even for drug testing, I think it will be so challenging to disassociate the lived human reactions to a drug, which can have psychological or system-wide impacts. If Organovo was to expand out to organ replacements, I think the trajectory (if it exists) would be much longer than any 3D application in the manufacturing world. Humans are so much more complicated than machines and the interplay between all of our bodies’ parts can never be fully understood, particularly as the parts of deteriorate over time as we age and there aren’t good replacements. A brain transplant in particular raises a lot of questions for me of how our personality and life history could ever be replicated in an artificial organ.
A fascinating topic indeed and I agree with you that in addition to the technical challenges of extending human life, there are also ethical boundaries that we must consider. As we learnt in TOM, there are breakthrough/moonshot projects which have great potential to disrupt the status quo, but I also believe that there is a potential danger in the blind pursuit of innovation without thinking through the consequences, especially from an ethical point of view.
Nuclear energy is one such example, which unfortunately manifested into the development of the atomic bomb, two of which were dropped on my country in 1945. Humanity may be good at innovation, but the innovation could serve not only for the betterment of our race but also towards harmful uses.
Organovo reminded me of the work being done by futurist Ray Kurzweil (see: https://www.nytimes.com/2013/01/27/magazine/ray-kurzweil-says-were-going-to-live-forever.html). While I believe he has been overall quite accurate in his predictions of the types of innovations that we expect to see and share some of his enthusiasm for what’s to come, I am wary of society not keeping apace of the ethical boundaries that we need to consider as we mull the impact of these innovations upon our society.
Very interesting topic. I think however that the choice of manufacturing process (i.e. 3-D printing vs. traditional manufacturing techniques) largely has nothing to do with the underlying issue here, which is that scientific advancements have allowed for the production of life-like organs on which useful experiments can be run. In fact, given that one of the key issues with AM (at this point in time) is a limited set of “printable” materials, perhaps we are unable use material which might more closely resemble human tissue. It would be ironic if AM were actually constraining the otherwise groundbreaking technology of developing and utilizing artificial organs.
Bioprinting has made remarkable progress in recent years, with Organovo making faster strides in the engineering of solid organs than many had predicted (1).
As Alexandre mentions, the rate of progress may have exceeded the ethical and regulatory frameworks concerning bioprinting. Artificial organs and tissues offer numerous benefits such as reduced use of animal testing, greater success in clinical trials, personalized drug testing and disease modelling (2). With this comes a number of ethical considerations in the use of living cells.
With regards to neural tissue bioprinting, the long-term applications are more likely to be for tissue insertions to facilitate repair of the CNS (regeneration or replacement of damaged cells) from neurodegenerative or traumatic injuries (3), rather than whole lobe or brain transplants.
With regards to the ethics of such treatment and specifically its impact on personal identity, it is important to consider the relationship between the anatomical structure of the brain, i.e. its structural identity, and its neurophysiological and psychological functions, i.e. its functional identity. Specifically, structural brain identity does not necessarily imply functional identity and vice versa. As an example, patients can suffer severe anatomical lesions without detectable functional alterations. Conversely, there are diseases of “functional identity”, which – at least as of yet – have no identifiable structural cause, such as certain psychiatric disorders (4).
Within this context, I think that the emphasis should be on accelerating the development of these technologies with the promise of much benefit in the near term. It is important to ensure an appropriate framework to deal with the more pressing ethical challenges such as access issues and stem cell management. Managing some of the media hype and more far-fetched considerations will help the public to understand the value of these advances.
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2. Ong CS, Yesantharao P, Huang CY, Mattson G, Boktor J, Fukunishi T, et al. 3D bioprinting using stem cells. Pediatr Res. 2018 Jan;83(1–2):223–31.
3. Hsieh F-Y, Lin H-H, Hsu S. 3D bioprinting of neural stem cell-laden thermoresponsive biodegradable polyurethane hydrogel and potential in central nervous system repair. Biomaterials. 2015 Dec 1;71:48–57.
4. Northoff G. Do brain tissue transplants alter personal identity? Inadequacies of some “standard” arguments. J Med Ethics. 1996 Jun 1;22(3):174–80.