Sex discrimination was not yet ruled unconstitutional, and it had been just 16 years since the US Supreme Court ruled against segregation of schools. Fifty years ago, when Future Shock was released, cigarette TV ads were banned in the US, The Beatles broke up, the Apollo 13 spacecraft suffered an oxygen tank explosion en route to the moon, protests heightened against the Vietnam War, the Ford Pinto came out (later realized as a poor decision), Janis Joplin died at 27, and the EPA was established. Sex discrimination was not yet ruled unconstitutional, and it had been just 16 years since the US Supreme Court ruled against segregation of schools.
In the world of science, the Nobel Prize was awarded to the discoverers of neurotransmitters (the signaling molecules of the nervous system) and the famous photo of DNA taken by Rosalind Franklin was celebrating its 18th birthday. It would be another 15 years before the development of a pioneering technology known as polymerase chain reaction, or PCR, would allow researchers to edit, amplify, and detect specific DNA sequences.
Scientific expansion was happening in an exponential scale from astrophysics to biology. In 1970, exploring things to come in Future Shock, the author speculated about the expansion of a scientific discipline known as bio-engineering. With advances in medical technologies, patients were being saved from life-threatening injuries and genetic diseases—and life expectancy had increased 17 years over the previous 50 (between 1920 and 1970). Though lives were being saved and extended, clinics faced new challenges as a result of these improvements in healthcare. It became more common to see such things as degrading joints, organs slowly losing their functions, and traumatic loss of tissue that once would’ve resulted in loss of life. At that time, there was no organ donor wait list, and the practice of transplantation was still in the early stages. Since the organization of a standardized wait list and further improvement in medical care, there are now over 100,000 patients waiting for life-saving transplants.
Even in 1970, it was appreciated that future demand could lead to a black-market organ trade (which is a very real thing in the new millennium). Furthermore, transplanted organs are composed solely of human donor tissue. The recipient’s immune system, not recognizing the foreign tissue, will reject it in the absence of strong immunosuppressive drugs. Each cell of the transplanted organ is tagged for destruction by the patient’s immune system via proteins called the major histocompatibility complex (MHC) or HLA (human leukocyte antigen). If the donor had even one HLA form that differed from those of the organ recipient, then the organ would be rejected—and there are a lot of different HLAs out there.
A need outside of organ transplants and immunosuppression was thus recognized and the field of bioengineering emerged. The first of the biomedical implants to truly engineer the human body appeared in 1958 with the pacemaker, followed 10 years later by the first knee replacement. In 1970, it was predicted that within 15 years artificial tissue and organ replacements would be standard practice. This held true to an extent, with a rapid increase in total knee and hip replacements, as well as in synthetic heart valves and numerous pacemaker implantations. However, we definitely still have miles to go before donor transplants become a thing of the past.
In our current world, passing from the 2010s into the 2020s, we have seen advances in bioengineering that include nanoparticles, genome-editing technologies, and neural-machine interfaces. We have also experienced advances in wound care, including materials derived from biologic sources that work with our body to help regrow tissue with less scarring. However, we are still working to create materials that can reliably regenerate or regrow tissues and organs.
Moving forward, there is a growing contingent of researchers paying attention to a critical player in wound healing and tissue regeneration—the immune system. Mind you, I might be slightly biased because this is what I study. Nevertheless, our immune system is one of the most advanced and powerful parts of our body. Beyond our lymph nodes, our spleen, thymus, and our bone marrow, which generate immune cells that circulate throughout our blood and act as hubs of immune cell activation, each tissue has its own resident set of immune cells. In our liver we have Küpffer cells, in our brain we have Microglia, and every other tissue has cells that react specifically in ways that are regulated by the tissues they reside in. Therefore, whatever we do to our body, from implants to genome editing, can be affected by immune cells.
In the context of regenerative medicine—where we try to regrow missing or damaged tissue, this interaction becomes very apparent. Not only will our immune system react to the implant that is put in to help regrow this tissue, but it also regulates how our tissue develops. The proteins that are secreted by immune cells can interact with stem cells and affect how they behave, either making a functional tissue, or instead resulting in dense scar tissue. This same issue happens when scientists try to create integrative prostheses. When any part of a synthetic prosthetic interacts with our body via connections that break or pass through the skin barrier, our immune system responds to that synthetic implant as something that isn’t supposed to be there, and it will be walled off with scar tissue. This can be avoided by integrating muscular contractions via patches that sense electrical activity but do not go through the skin barrier. If further integration is to be accomplished, though, the immune system will have to be considered. Advances in integrative prostheses and synthetic organ mimics (both clinically and in the laboratory) are very promising and have great potential to improve a patient’s quality of life.
Toffler predicted that the future human body will become “modular,” wherein parts of the body that are non-functional or do not meet a set standard can be replaced with new components. This interestingly parallels a philosophical thought experiment known as the Ship of Theseus. In this scenario, a ship sailed by Theseus (mythical king of ancient Greece and founder of Athens) was aging. As parts of the ship wore down and compromised the integrity of the structure, they were replaced with new components to keep the ship seaworthy. As time passed, more and more old pieces were removed and new pieces were added to the ship. The question then became, at what point does this ship cease to be the original ship? Is it when there is one piece changed? Most would argue, of course, that it’s the same ship. Just because I got the tires changed on my car doesn’t mean I got a new car. Half of the ship? Well, which half? What pieces from the original structure remain?
Now of course, a human body isn’t an inanimate ship, but this gives us something to think about. Is a human body still a human body after half of its tissues are made of synthetic materials? Most people would argue that a human is still a human as long as neural cognition is intact. But what if we take this a step further. With advances in computing, artificial intelligence, and high-powered computers, could it be possible to one day transfer the electrical impulses generated by our body into a synthetic, computerized storage system? And then, would we still be considered human? We will not face such an enigma in the near future, and if we do get to the point that missing or damaged organs can be quickly and easily replaced synthetically, we will have recognized a fantastic level of medical treatment.
Moving into the year 2020, it is foreseeable that these advances in integrative prostheses and regenerative medicine continue to progress through the convergence of different scientific fields, such as bioengineering, immunology, mechanical engineering, polymer chemistry, and molecular biology. As these fields interact, we will see increases in therapeutics to help treat traumatic injury, decreasing the presence of scar tissue and increasing the regrowth of functional tissue. We might see prosthetics that integrate with the body to the extent that they provide sensory information from their surroundings, enabling us to “feel” with a synthetic limb. We could see increases in the use of bioreactors that are able to grow tissues and organs in the lab. I, for one, am excited about the next generation of research and how we will leverage expertise from different scientific fields to further medical discoveries and innovations.
Dr. Kaitlyn Sadtler, PhD is currently an Earl Stadtman Tenure-Track Investigator and Chief of the Section on Immuno-Engineering at the National Institutes of Health. She recently finished her postdoctoral fellowship in the lab of Dr. Daniel Anderson and Dr. Robert Langer at MIT, studying how our body interprets medical device implants as “foreign” and how to prevent the subsequent inflammatory response. During her time at MIT, she was the recipient of a NRSA Postdoctoral Fellowship for her work on immunoengineering in the context of soft tissue trauma, a TED Fellow whose TED talk was listed as one of the top 25 most viewed in 2018, and was recognized in the Forbes 30 Under 30 list in Science for 2019. Prior to MIT, Dr. Sadtler completed her PhD at the Johns Hopkins University School of Medicine, where her thesis work describing a specific type of immune cell required for biomaterial-mediated muscle regeneration was published in Science magazine. Dr. Sadtler received her BS summa cum laude from University of Maryland Baltimore County, where she was named an Outstanding Graduating Senior in Biological Sciences, prior to a postbaccalaurate IRTA at the National Institute of Allergy and Infectious Disease in the Lab of Cellular and Molecular Immunology. Learn more about her via the following links: www.go.ted.com/ kaitlynsadtler (TED Talk), https://scholar.google.com/citations?user=N4Zcv00AAAAJ&hl=en (Scientific Publications), https://twitter.com/KSadtler (Twitter)