Having echoed the reflexive, participatory spirit of The Final Rule ,today we seek to detail the emerging realities of life in the 21st century. We detail phenomenon brought on by the fourth industrial revolution that make human subject research this century dramatically different. Remarkably so to warrant authoring of the final rule.
In order to successfully unpack this environment in which 21st century science operates,a contextual feel of the relationship between science, technology and society is important. This is because science as an enterprise has come a long way. In the 20th century, the environment for scientific research was such that there existed a chasm between science,technology and society. As the following text explains, in the relationship between the three, change is the only constant.
The Science, Technology and Society dynamic
Today, the fourth industrial revolution emphasizes the need for science and society to be in constant dialogue. We insist on this dialogue as we are now more attuned to the maxim that the two are locked in a tango. As science and society evolve they do so in an intricate dance; impacting each other along the way.
While scientific advances are more dramatic and thus plain to sight,society morphs more subtly. As a result, it is often easy to forget that society too has come a long way. Consider for instance, that not too long ago humanity with great trepidation was preparing for an apocalypse event at the turn of the century (Y2K). Barely two decades on, the excitement is palpable when Elon Musk tells us that man in the 21st century will be a two planet species having colonized Mars.
Granted,things change. Rather,change is manifest. We have appreciated this as reality since Heraclitus,the Greek philosopher,credited with the phrase “change is the only constant in life.”
However, the phenomenon of change in the 21st century is like no other. Why is it so? To answer that, you will have to consider its nature i.e., the speed, scope and disruptive effects on systems of the fourth industrial revolution.
What Is The Fourth Industrial Revolution?
Never before has this been witnessed. Neither was it envisioned. Even Google co-founder Sergey Brin didn’t see a technology, artificial intelligence, that’s archetypal of the fourth industrial revolution coming. Hollywood with movies like “Metropolis” to “I Robot” kinda prepared us. But it’s Klaus Schwab, founder and executive chairman of the world economic forum,who best describes the times:
When compared with previous industrial revolutions, the Fourth is evolving at an exponential rather than a linear pace. Moreover, it is disrupting almost every industry in every country.And the breadth and depth of these changes herald the transformation of entire systems of production, management, and governance.
The short lived third industrial revolution, the digital age, presented man with agility thanks to the novel technologies of mobile (electronics) and internet. However, the fourth industrial revolution promises to kick more powerfully. This is because the 4th industrial age also packs in lessons from the other revolutons. From the 2nd industrial revolution (Read: power in mega proportions). And those of the 1st industrial revolution (Read: mechanization). What really sets the fourth industrial revolution apart from these other periods of human advancement is that it not only multiplies, but also deliberately harnesses all this accumulated know-how.
Man is now able to aspire more thanks in part to the ubiquity of mobile technology; democratization of information; accessibility to crazy processing power and improved ability to make power portable.
Having appreciated these disruptive characteristics of the fourth industrial revolution,we as stakeholders in human subject research we have to ask:
What does the fourth industrial revolution portend for human subject health research? In the subsequent text we percuss the situation as is and will potentially be
3D-Printing Technology, the Fourth Industrial Revolution and Human Subject Health Research
New Imaging technologies, particularly 3D-printing present new ethical dilemmas in human subject health research. First among them is how pluripotent cells that are critical 3D-printing will be sourced.
What bio-printing does is give us the structure of the organs we are interested in. With a 3D- printer, and using bioengineered materials like Gelatin, a computer prints out the organ structure. Think of this structure as the supporting beams, trusses and struts of a building.
Later, once implanted in the body, the 3D-printed organ has to be vascularised. Visualize vascularisation as the plumbing, electrical, gas and sewage works. Vascularisation is the process by which blood vessels grow into new tissue. Blood vessels supply oxygen and nutrients needed for survival while removing toxic waste from cell processes.
Of all these stages to 3D-print a biosynthetic organ, vascularisation presents the greatest technical challenge. A challenge that is more marked for larger organs of interest like the heart. But before even bioengineers get here, they have to be sure about where the actual cells that make the 3D printed organ will come from.
Pluripotent stem cells are precursors for the organs to be 3D printed. Pluripotency refers to their naive state as they are not specialized cells like cardiac muscle or the insulin producing beta cells in islets of Langerhans. Being naive means that in the right environment, they can be programmed to be whatever cells: heart cells, pancreatic cells etc.
Stem Cells
Stem cells, for health research have to be donated by other humans or even sourced from other animals such as pigs. But the best ‘quality’ stem cells are sourced from the person’s own umbilical cord blood, lab fertilized embryos and even genetically deprogrammed fat cells.
While vascularization presents technical challenge in 3D-printing of organs, the ethical issues of stem cells present key sociotechnical quagmire. Whenever we seek areas of convergence between issues, we tend to compare and contrast.
That is we flesh out the differences and highlight the similarities. It is a useful approach that’s served as well from our high school science essays days. Only that with this approach, the tendency is to be inward looking and look at the characteristics, components, functionality etc., of the phenomenon.
We rarely, for instance, expend in unpacking healthcare and banking and their challenges in serving the bottom of the pyramid. The fourth industrial revolution forces us to do exactly that.
On the other hand, 3D-printing makes new opportunities abound by making it possible for human subject research by use of lab cultivated organs.
Moreover, transdisciplinary research- a key tenet of fourth industrial revolution enterprise- is likely to flourish as demand for biomaterials requires new ground collaborative efforts from engineering, physics and medicine disciplines among others.
Information, The Fourth Industrial Revolution & Health Research
The ubiquity of mobile technologies like encrypted end-to-end messaging services have already found use in human subject research. as data handling platforms together with expanded mobile phone functionality such as the use of mobile phones as voice recording devices, have to be considered in light of attendant cyber security risks (DDoS) due to inherent internet & internet of things connectivity.
However, all is not rosy with information technology industry experts report a decline in accelerated growth in computing power as described by Moore’s Law. This 20th century norm in the world of computer processors was named after Intel cofounder Gordon Moore who observed in 1965 that transistors were shrinking so fast that every year twice as many could fit onto a chip, and in 1975 adjusted the pace to a doubling every two years has slowed down.
This has lead to an arms race in search of new way to pack computing power for 21st century needs of mobility, connectivity and large volume data analysis. This presents a risk to research programs reliant on supercomputers such as human subject dependent, multicenter clinical trials.
Jobs, Health Research & What It means to be Human in the Fourth Industrial Revolution
“For people with a disability, the Fourth Industrial Revolution will give us super powers.”
-Birgit Skarstein, Double paralympic athlete and World Rowing Champion, Norway
Careers and jobs in the fourth industrial revolution
Model thinking, design thinking, analytics,informatics etc.,are the new cool. Thanks to the fourth industrial revolution, rewarding careers are being built on concepts that were hitherto alien prior to the 21st century.
To be in demand as professional in the fourth industrial revolution, one has to be astute at integrating different types of data. In actual fact, as this inforgraphic shows, careers where data is rarely combined, mined, analyzed, or shared are at risk thanks to AI.
Like in any situation, the inforgraphic may understate the outliers. Health research is an example of industries that occupy these outlier positions. This is because although health research is complex and requires for high level skills, increasingly more aspects of conducting new medical research are being taken over by AI software.
Even the most human intensive bits of clinical research will be done by machines in the fourth industrial revolution
The best example of this paradigm shift in conducting clinical research is found in the process of getting informed consent. In the barest of definitions, an informed consent is negotiated voluntary leeway by the human subject in health research to take part in scientifically sound research well aware of the risks and benefits.
It is now universally agreed that informed consent is a central pillar in the ethical conduct of health research encompassing behavioral, social and even clinical trials. The central responsibility lies with the researcher to ensure that at any given time, the human subject is well informed of the research risks and benefits.
The world’s foremost body in the funding of health research, NIH, demands that informed consent must be a continuous process. A timely, recurring process that reflects the fluid nature of risks and rewards in an experimental environment. Whilst echoing the principle that ethical research must be reflexive and participatory.
Responsible Research
You can imagine the amount of work a contract research organization has to undergo in order to be ethical by avoiding using human subjects as a means to an end. The back and forth would be enormous given that by virtue of research being experiments, there is no certainty on the outcomes.
For example, an experimental drug may have unanticipated adverse effect that is selectively observable in the human subjects participating in the clinical trial. The principal investigator in that clinical trial is obligated by the principle of autonomy that gives life to informed consent to inform all trial participants of these events.
The human subjects would then decide if they are still interested in continuing with the study or not. This should be done under no duress or coercion. At times, the events may have taken place in a similar study but not necessarily the one in question as can be the case in multi-center clinical trials.
Ad lib and it is easy to see how this process is vulnerable to violation not forgetting the ton of paper work involved. To this quagmire, enter medical research companies that have developed impressive informed consent software that rely on AI. Some these e-Consent technology have even been approved by the NHS. With the fourth industrial revolution e-Consent software that sit ready to be further unlocked as cyber physical systems develop.
What it means to be human in the fourth industrial revolution
Welcome to the creepy part. Klaus Schwab in the book, Fourth Industrial Revolution: what it means, how to respond, laments the possible loss of humanness.
To reveal how we are at risk of losing our humanness, requires us to imagine a world with more AI and cyber physical systems as will be the case in the fourth industrial revolution.
As it stands, AI and cyber physical systems will require even more man-machine touch points than is the case today with the digital age.
The National Science Foundation predicts that cyber physical system will not only revolutionize life in the 21st century, but redefine man’s interaction with engineered systems in ways more complex than the simple embeded systems of today.
In other words,if you are the type to sue your date for texting during a movie date, I pity you bro as advances in CPS technology might just usher more “threat to civilized society“. The sacrifice of human physical connections at the altar of constant mobile connectivity might just get worse with augmented reality and virtual reality.
Personhood
We are constantly on our phones connecting with others through social media. As a result, loved ones may be in the same physical location but otherwise disengaged thus killing compassion and cooperation. Klaus Schwab puts it as follows:
Similarly, the revolutions occurring in biotechnology and AI,which are redefining what it means to be human by pushing back the current thresholds of life span, health, cognition, and capabilities, will compel us to redefine our moral and ethical boundaries.
The implications of such a shift will be far reaching affecting our ethics and our definition of values like universal human rights. For example, should we all follow Mexico’s example and have broadband internet as a right?
Defining personhood is one of the central questions in bioethics. While bioethics has made some progress at least in expanding the scope of this debate, CPS technology and AI are still in their infancy.
But it’s not all gloom as Artificial intelligence now has the Asilomar AI principles to lean on. These principles can find applicability in with CPS technologies (basically AI +physical systems) as the name suggests, the Asilomar documents remain source material.
Here, our earlier suggestion of finding common ground in difficulty among disciplines, could prove helpful as health research has grappled with ethical issues over the years that lie in the path of the fourth industrial revolution.
New areas of Research in The Fourth Industrial Revolution
With the fourth industrial revolution,sophisticated computer software algorithms, better internet and mobile technology thanks to the potentiating abilities of CPS technologies new areas of research activity abound.
Particularly within behavioral health research. Exciting areas already attracting research funds include: neuroethics, autism and Alzheimer’s research.
Gene Editing Research & The Fourth Industrial Revolution
Early in the 21st century,completion of Human Genome Project laid the foundation for precision medicine today. This project is also seismic for altering health research by promoting an environment of data sharing. It also contributed a lot to and innovation in analytics and DNA technology.
Today, we explore the power of novel technologies like CRISPR. In a letter to the President Obama,the Presidents Council of Advisers on Science and Technology warned of CRISPR potential use as a biological weapon.
Even with such caveats, the promise of gene editing technology continues to be manifest. Recent happenings in the UK in reproductive technologies whereby we now anticipate the world’s first three parent baby illuminate the way.
What does the fourth industrial revolution portend for gene editing research then?
- Shorter turn around times as DNA, billions of bytes of data, will now be be faster and better sequenced and analyzed.
- More reproducible research models as the numerous machine-man touch points will allow for better medical monitoring and real-time analysis
Big Data & The Fourth Industrial Revolution
Theranos mojo arose from its promise to effortlessly accurately sift through tons of data with minimal fuss for the patient. For that, investors bet $900 million and the market valued at $9 billion.
The aftermath of its fall 11 years on read like a soap opera script riddled with lies, lust and presumptuousness. I have always maintained that if Theranos had been what it claimed to be, then it would have been the 21st century feat right alongside discovery of fire, the wheel, electricity and the Guttenberg press.
Lessons: the fiasco of Theranos teaches us that it is not enough for an organization’s value preposition to be clear. The potential value of acquiring ability to productively
mine large sets of data such as those generated by genome sequencing presents astronomical value way beyond Theranos
peak valuation.
However, the research is of value only if we are ethical by minding issues of data integrity as it is transmitted across networks to physical locations far removed from the human subjects and also design delivery systems for health technology to human subjects who bore the greatest burden of the research.
Evidence Based Medicine
In the quest to solve 21st century healthcare by reducing healthcare costs and providing value to the patient through a combination of safety+ efficacy+ awesome experience, practitioners have called upon research.
Clinical research differs from traditional health research that occurs within the controlled confines of a research protocol. In shifting the setting of research from the pious environment of say a clinical trial, to clinical care settings portends new ethical dilemmas.
For instance, clinical research often involves the combination of research data and clinical data. Now to obtain consent for collecting research data differs from collection of clinical data as the threshold or extent of informed consent differs with the later requiring less rigor.
Moreover, with conduct of research in clinical settings there is the added risk of therapeutic misconception as the recipients of the experimental intervention are likely to heavily discount risk. This may lead to poor health seeking behavior especially where subpar or adverse effects of the experimental intervention arise.
Bio-banking
Though cultural considerations have made bio-banks a distant reality in low and middle income countries, in other settings, biospecimen repositories and large databases have made it easier to do research on existing biospecimens and data.
The risks here are the ethical concerns of injustice arising from the possibility of widening the 90/10 gap in health research given than 21st century treatments that are products of this kind of research are likely to be highly specific for certain genetic makeup (precision medicine). This may inadvertently turn out to be discriminatory by leaving out many who might benefited from the medical technology.
IT in health:
Technology leaders in the fourth industrial revolution, Microsoft and, Apple have poured mega money in wearable devices for health and sophisticated software programs to run healthcare enterprises.
The goal here is to allow easy flow of patient data across care givers; allow for timely remote intervention of caregivers on daily health decisions of their patients; collect and analyze real-time health information of clients with the aim of providing patient centric health promoting advice and act as clinical aids to caregivers in facilitating care informed by latest research.
The challenge facing information technology in health has been the lack of inter-operability of different electronic health record platforms that arose from the silo mentality driven 21stcentury arms race for that killer software.
Democratization & Devolution of research:
In the same manner that emergent technologies like distributed ledger technologies (block chain) create new platforms for people to engage, transact and coordinate away from government and devoid of the middleman; the architecture of human subject research design, conduct and governance is at threat from the same influences.
As is the norm with the fourth industrial revolution, within this distributed framework, issues that need policy and regulatory address are beyond the slow top-down approach that currently characterizes public administration to demand a more agile approach.
Moreover,with democratization of opinion shaping in the 21st century, the risk of stifling bureaucracy is real. Especially when attempts are made to desist from marginalization of the now louder minority positions. At the same time, as envisioned in the shift to reflexive innovative research that is stakeholder driven, human subjects now continually demand an active role in research.
Additional Reporting: technologyreview.com, weforum.org, wired.com,federalregister.