For the first time, scientists have been able to successfully grow monkey embryos containing human cells.
Researchers at the Salk Institute for Biological studies in California, working in collaboration with Chinese scientists, grew the embryos in a dish with some surviving up to 20 days.
Their research, published last week, immediately ignited debate over the ethics of such an endeavor and sparked fears of human-monkey hybrids.
But Insoo Hyun, a leading bioethicist at Case Western Reserve University in Ohio and the director of research ethics at Harvard Medical School, says such fears are misplaced.
Below, a Q&A with Hyun, edited for length and clarity.
As a bioethicist, when you heard about what these researchers have done, did it raise any ethical concerns for you?
I had known about this study as it was ongoing for quite some time, so it wasn’t a situation where I, along with everyone else, read the news and reacted to it. I had quite a bit of time to process what was going on and to understand the rationale for the research. In my role as a bioethicist for the International Society of Stem Cell Research I had known about it for a couple of years.
I can certainly see how for many people when they hear this news for the first time it is quite shocking. I definitely understand that. My perspective is starting from a much earlier point and having a longer time to think about it. I have more background than the average person about this area of science, so I can understand why they wanted to do it. These are teams who are also involved in the very aspirational goal of eventually, one day, who knows when, developing human transplantable organs in livestock animals that are normally raised for food. Sheep and pigs. I’ve known for years that that research has stalled out because the human cells do not survive and do not proliferate in the pig or sheep embryo. For this organ transplantation work what they had to do was to take the embryo of, for example, a pig that has had its ability to make, say, a pancreas or a liver or anything of interest disabled. And then that void is filled with human stem cells that will make a human-specific organ in that animal.
Why do they want to do that?
Because bioengineers don’t know how to make an entire human organ outside the body, but nature somehow knows how to build these things during pregnancy. So, when they transferred the human stem cells into the embryos of pigs or sheep they didn’t last long. And that is understandable because pigs and sheep are so evolutionarily remote from humans. I knew about these frustrating failures and I knew that they need to better improve strategies for cell survival of human cells in another species. So it was not surprising to me that to optimize their approach they wanted to use a much more closely related species such as a monkey. Not for gestation or to attempt to grow an organ in a monkey, but just to study how the cells talk to one another across different species.
You say the researchers have been very mindful of regulations and ethical issues. What regulations actually govern this kind of research? Do regulations vary from country to country or is their international regulation of this kind of research?
This type of research involves two types of oversight. One is for the use of animals for biomedical research and the other is in relation to the use of human stem cells for biomedical research. There are international standards for both. There are international standards for the humane treatment of animals for research and all of the facilities involved in this study were part of this international standards network. So they had to make sure that the sperm and the eggs were humanely derived from donor monkeys. And they were. No monkeys were harmed in the process of procuring the sperm and the eggs. The sperm and the eggs were united in a dish. So the removed sperm and eggs never went back into a monkey’s body, it stayed in the dish.
The next step was to use human stem cells. For the human stem cells step there has to be oversight and standards met for the use of human stem cells in experiments — even in experiments that only happen in a dish. So for that we have the International Society for Stem Cell Research which has guidelines. Both institutions involved in this research, the Salk Institute in California and the Primate Research Center in China, had careful review of this work, including the executive directors of both institutions. Normally the executive directors don’t get involved in reviewing protocols. The Salk team also consulted with well-known bioethicists – not me but people I know — in the design of this. Not only did they follow the animal research guidelines, but they went above and beyond by involving the directorship of the institutions and external bioethics advisers.
Some articles seem to imply that because this is a joint project between American and Chinese researchers it was taking advantage of less stringent Chinese regulations regarding this type of research. From what you’ve said, it sounds like that’s not the case.
Yes. There’s a very good reason why the American team wanted to collaborate with this group in China. One, they have the facilities and the expertise to deal with monkeys where you have to remove sperm and eggs for assistive reproductive research like IVF. There are few facilities that have enough monkeys and the right conditions for their care. They are few and far between in the U.S. But probably more importantly, the reason they wanted to collaborate with the Chinese was that there is a researcher there who was able to culture monkey embryos for 20 days – longer than anyone has ever done before. So they needed his help. That expertise doesn’t exist in the U.S. So it wasn’t a case of trying to skirt any rules, these rules are international so you can’t really escape them by going to another country.
From what you’ve said, the idea is not to create a human-monkey hybrid but to better understand how the cells of different species communicate with each other and then, using that knowledge, to make, for example, the experiments that have been done with pigs work.
That’s correct. And just to clarify the terminology. Some people have been calling these hybrids, but they are not hybrids because hybrids would be a 50/50 split of two species by uniting the sperm and the egg of two different species. These techniques create what are called chimaeras that are far from 50/50. That’s just transferring a few human cells into another animal and hoping these cells will integrate. And of course, depending on how many cells you transfer you’ll get varying percentages of human contribution. We’re not talking close to anything like 50/50. In the case of the monkey embryos in this research, they got up to a maximum of 7% human cells contributing to the embryo.
This story has attracted a lot of interest because of the sci-fi movie scenario aspect of this — “Planet of the Apes” or “The Island of Dr. Moreau,” etc. But from what you have said the reality is far from that.
That’s what makes it a great news story because people are so interested in it and wondering, “Why are they doing this?” And then you realize there is actually a humanitarian angle to this. Everybody knows somebody who suffers from some kind of organ failure.
Are there any issues of experimentation on primates vs. other animals such as pigs and rats? Are different ethical concerns raised when it comes to primate research vs. research on other animals? Are their different regulations and guidelines depending on what kind of animals you are using in your research?
Yes, there are. The more complex the animal species is, the more scientifically justified the study has to be and the closer scrutiny it deserves. So monkeys are going to be the “highest” form of animal you can use in medical research. And by monkey we aren’t typically talking about apes – gorillas, chimpanzees, etc. – what we are talking about is a little bit further away from humans than that. These are all non-human primates with tails — Macaque monkeys, Rhesus monkeys — these are typically monkeys that under the right justifications are used for biomedical research. We cannot use chimpanzees, gorillas, orangutans – the great apes – we cannot use them for invasive biomedical research. You can do behavioral studies, but you can’t do anything invasive that would hurt them. They have protected status. And in some European countries great apes actually have personhood status.
What about fears that a rogue scientist might go too far?
There is always that concern of people breaking the rules and going rogue. In this case, what I think, for me, is of ethical concern is not so much that somehow human dignity has been harmed by crossing the line too far or that any human being is somehow worse off, it’s rather the well-being of the animal that is used itself. I’m more concerned about the welfare of the more intelligent animals used for biomedical research. And if they are used in an unjustifiable way then that is the waste of a life and brings unnecessary burden and suffering on the animal. So when I worry about some kind of rogue work, I’m actually more worried about the actual physical treatment of the animal.
Note: This story will be updated with video.