[MUSIC] There are a range of ethical issues raised by Synbio based medical applications, but I'm going to focus almost exclusively on those related to human subject research. There have been a range of documents, international and domestic related to human research subjects protections. These often go back to the Nuremberg Code from 1947 which came out of the Nuremberg Trials or the Nazi Doctor Trials, related to the unethical research that was done on many people during that war. The Declaration of Helsinki by the World Medical Association was developed in 1964 but has been revised multiple times over the years. And here in the US, the document on which most of our human subjects protections policies are based is the Belmont Report from 1979. The Belmont Report laid out three ethical principles that needed to be taken into account in human subjects research. These were respect for persons. So the recognition of a person as an end in and of themselves and not a means to your ends, and protection of those who weren't able to exercise their own autonomy. Such as people in comas for example, children etc. The second principle is, ethical principle is beneficence, so there are two general rules that are sort of expressions of beneficence. One is do no harm, which will be familiar to you from the medical world. And the second is to maximize possible benefits and minimize possible harms. The third ethical principle is justice. So appropriate, fair distribution of risks and benefits. The Belmont Report was later developed into something called principalism, which also holds great sway in certainly in biomedical ethics in the United States but elsewhere as well, and there a fourth principle was added which was no-maleficence. So which is more explicitly do no harm. The Belmont Report, turned as I said, is the basis, largely, the basis for the human subject's protections here in the US. Now, I will talk about this more in the governance lecture. But surprised to say here that the Common Rule governs federally funded human subjects research. And again, more about exactly what constitutes human subjects research in the governance lecture. And the informed consent process, which is the primary response to respect for persons. All right, if individuals are ends in and of themselves rather that means to your ends they should have the opportunity to make decisions about what happens to them, right. They should have the ability to express their autonomy to make their own decisions. So we informed consent process, includes importantly disclosure about what the research is. What you are planning on doing. What are the risks and benefits of that research and alternatives to participating in research. You need to facilitate understanding, so you don't just hand someone a form, the informed consent document that is that disclosure. Don't just hand it to them and say, okay, you need to facilitate understanding. So actually have a conversation with them. Informed consent as a process, not just a document, so facilitate understanding of the content of the research and the risks and benefits and promote voluntariness. So there should be no kind of coercion or bias or anything like that. You need to try to promote an environment which the individual can make a voluntary decision. And again, more on the policy itself later. But there are many ethical issues beyond informed consent. These include safety issues. This has been a tremendous concern when it comes to genome editing and in particular, the possibility of germline genetic modification. How do you determine when a technology is safe enough? To be used in humans, which brings us to first in human trials, where in you are deploying a new technology in research trial for the first time in humans. And it's hard to anticipate what the risks might be of that research. And human germline genetic modification in particular, and there's this question about consent of those future generations, right. If it's germline modification that means that is a modification not just to the person in front of you, but to all that individuals descendants as well. Is it okay for us to be making decisions now about the genetic constitution of generations to come? Science in the spotlight, this is a set of concerns around very high profile or research. Right, the first time for example that a stem cell based therapy was done and it was done in spinal cord injury. And very shortly after that first person was enrolled and treated with the experimental therapy there was a newspaper article about him. So if you are doing a clinical trial with a brand new therapy in an environment where lots of people are going to know immediately what's happening in that trial, how does that affect the science itself? And how our scientist and research participants conduct themselves in that context? There are with most things do not extra search in particular as it relates to humans. Concerns about playing God. Is it our place to be making genetic modifications to humans to eggs and sperm or embryos that are going to become humans. This is not a concern that everybody has but it's a concern that many have, and how do we take that into account when thinking about research going forward? Concerns about environmental impact, this is not human subject research, but if you're talking about for example the genetic modification of mosquitoes to try to prevent Zika Virus transmission or Chikungunya or West Nile Virus. There are environmental concerns associated with that as well, even though it's focused on human health. And then also with genetics frequently in humans there are concerns or discussions about the use of the genetic technology for enhancement. So not just to correct a genetic mutation that causes disease, but in fact to sort of gain a function in humans. [LAUGH] So giving a human a trait that they could not otherwise have, but for that mutation or that intervention rather. So, one example of this might be to do germline genetic modification that introduces the CC or five mutation that makes you basically resistant to HIV infection, that would be an enhancement. It would be an enhancement that exists, a trait that exists in a human population naturally but it would be a trait that that individual would not have but for that intervention. So, these are some of the issues that are raised. With the use of synthetic biology, technologies including and certainly, recently most, sort of controversially genome editing. But there are others as well that are related not to interventions in individual humans, but rather to genetic research on tissue samples from humans. I just want to talk through one quick example of this, because I don't want you to think that ethical issues are, Present only when you're intervening directly with a human a friend of you. So this is a case from 2010, Havasupai tribe in Arizona in United States, they participated in research. That they thought was focused on diabetes, which was a very serious problem in this tribe. So they gave blood samples to researchers, who went off and presumably, did their research. Much later it was discovered by a member of the tribe that those blood samples had been used not just for diabetes research, but also for research on schizophrenia and for research on the history and migration patterns of the tribe. At these uses were the people were involve in the research did not think that they had given permission for these uses that were not related to diabetes. Further, they were very concern about those other uses themselves. So research on mental illness can be very stigmatizing, and research on the tribe's origins actually conflicted with the tribe's own origin story. So the tribe, in this case, took the researchers to court, the University of Arizona to court. And it ended up being settled out of court so we don't know the details of what happened there. But it's important to note that even though there was no direct intervention with a human subject, rather there was no clinical trial, right? You were to putting anything new or testing anything on human subjects in front of you, it was the taking of a blood sample and research on that tissue that led to a whole host of ethical issues that led to a whole host of ethical issues that need serious consideration.
