SOLS Podcasts

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Peggy Coulombe: Hi! This is Peggy Coulombe, and welcome to "Science Studio." We're going to talk about stem cell research, nanotechnologies, gene therapies, and bionics and robotics with ASU School of Life Sciences ethicist Jason Robert, an assistant professor, and geneticist Kenro Kusumi, an associate professor whose research focuses on the early development of the spine, and elucidating the genetic causes of vertebral birth defects.

I don't know if you've seen the commercials for a new TV series that's coming out, "The Bionic Woman," based on an older TV series popular in the 1970s that starred Lindsay Wagner. In the '70s, the show was largely science fiction. Now, with new technology and new understanding of the human body, and the rise of things like nanotechnology, is such medical innovation and biomedical intervention so far off? Kenro Kusumi: Well, I think this is not anything new. I think it's just a matter of how visible these things are. You walk around and, especially in Arizona, there are a lot of people with implants or prostheses, whether it be an orthopedic replacements for hips or joints. There are people that are walking around with cochlear implants for helping with hearing.

We're all used to things that help that are on the surface; for example, eyeglasses and contacts. So we've all made great use of mechanical additions or replacements. Of course, there are people walking around with bypass grafts and all kinds of organic replacements artificial valves. I think, so far, the techniques have allowed us to somewhat replace the functionalities.

I guess the difference in "The Bionic Woman" and the "Six Million Dollar Man" is could they even be better and enhance what would be normal function? Now we see, as the technology is advancing, that perhaps it's not that far off, in terms of things that might be better than what we are already are equipped with.

Although, one should emphasize the fact that we [as human beings] are the outcome of a tremendously long period of time of developing [our own] unique structures. We are some of the most complicated machines, so to speak, on the planet. We're definitely quite an advanced machine ourselves. Jason Robert: It's interesting that Kenro focused a little bit on the enhancement issues associated with these technologies; that certainly was the big issue in "The Bionic Woman" and "The Six Million Dollar Man" in the '70s. Now, I think another thing that's different is not just that these devices are becoming more visible or, in fact, less visible when they're more deeply implanted but also that some of the new prosthetic devices have the potential for dramatic feedback with the body.

So, rather than just bridging a function that has failed so, for instance, by replacing a valve in the heart that's not working any longer now there's an opportunity, really, for much more feedback between the body and the device, a deeper integration of that device into the body, and even, potentially, for the device to learn how to help the body better repair itself, better stabilize, better maintain its functional state once a repair has been achieved.

These sorts of advances, I think, promise a really interesting future, not just for enhancement of human specializations, which, of course, is a very complicated issue, both technically and ethically, but also for much better, much more fluid, potentially much more expensive, manipulations of the human body through these bionic means.

Peggy: Jason, you have a book coming out based on chimeras, or part human organisms. Can you tell me something about it?

Jason: The book's almost finished. I got sidetracked by my involvement with the College of Medicine. The book is on chimeras, cyborgs, and the moral limits of science. So it's both about these bionic women, but also about part human, part non human animal combinations that are becoming increasingly prominent in scientific research, whether we're talking about very basic research, such as the implantation of human cells into non human animal hosts to assess the potency of those cells just to determine, say, whether those cells are pluripotent that is, have the potential to develop into many different cell types or, whether we're talking about something like the functional integration of human cells into non human animals, or non human animal cells into humans, this potential for crossing species boundaries again raises some of these interesting issues that the cyborgs raise.

Kenro's right, of course, that, with regard to bionic humans, these really are just there's not a whole lot new under the sun here; they're really extensions of pre existing technologies. The same is true of chimeras, that have been around in the sciences for a hundred years, and part human chimeras have been part and parcel of cell biology for the last fifty years or so.

But now the technologies have been perfected, new cell types have been identified, and the potential for a much greater functional integration than we've seen before is quite real and apparent. I use these both as examples of very controversial science that have terrific medical applications, but also raise significant social controversy and use them as an opportunity to discuss what the potential moral limits of science might be in a complex civilized society such as ours.

Peggy: I'm going to step back a bit here and ask Kenro something more specific about his research. Kenro, you study the development of the spine. There are 33 pairs of bones in the human backbone, is that correct?

Kenro: Yes.

Peggy: What made this system one that fascinated you?

Kenro: I had the chance to begin this project that, actually, I'm still working on, back when I was working on the human and mouse genome projects. It really stems from this interest of, most of the animals that we have around us, either as pets, or the animals that are the food and agricultural animals, are vertebrates.

So think about dogs, cats, snakes, fish; what makes each animal look the way they do? We all belong in this group called the vertebrates, and one of the key things is this backbone, or the vertebral column. So why does the snake have hundreds of vertebrae? Why do we have 33? Why do mice have 65 or so? Why do some frogs just have seven? A lot of that information, you would think that would be in the genome sequence, encoded in there. So as we get the human genome, we could find the aspects of "human ness" in there, or in the mouse genome, the "mouse ness."

So that's really set off this line of study of what regulates the number of vertebrae we have? What regulates what they look like and what they end up being shaped like? And that really forms the core of our body, the way we appear. That fascination is slowly being unraveled.

Our group, with other groups around the world, have been working on this. Really, in the last ten years, a lot of progress has been made, in terms of realizing that what was known to be this repeating process that happens again and again and produces the units that make up our backbone, is actually really being regulated by a very interesting set of genes that have a very fascinating pattern of expression.

Peggy: I think everyone's heard about the biological clock, but what about the segmentation clock?

Kenro: We have a lot of repeating processes in our bodies. We all know about the biological clock, or the circadian clock which means, basically, you wake up, you go to sleep, you wake up and go to sleep. Even if you were put in a cave, you would still be waking up and going to sleep at approximately the same frequency as you do based on the rising and setting of the sun.

There are other clocks that regulate our biological processes, and one that we study is something that really is a developmental clock. So you can think of these clocks as, really, drumbeats or pacemakers. Like rhythm like it's music, a beat that regulates and sort of serves as a timekeeper for other things that are happening.

In the circadian clock it's something that's happening every 24 hours or so; in the developmental clock, it's very specific to each organism. So again it comes back down to: What makes a human human? What makes a mouse a mouse? What we've found is that for the first time we have some clue as to what's happening in the human.

We know we develop very slowly; it takes us about forty weeks to basically get through gestation. Our clock is relatively slow, so the rise and fall of the genes, that are important in controlling the process of making the precursors to the backbone, go up and down every five hours.

Now, if you look at a mouse, a mouse develops much faster. In 20 days, their gestation is over. Their clock goes up and down every two hours. Chicks are about the same. They actually take about 21 days to hatch, and they also have about a 90 minute cycle.

But you can contrast this with very fast developing animals, like some fish that develop in two days, and their clock is 30 minutes. So again, I think some of the aspect is not only just the number of units that you make, but it's also the pace at which you go through it. It's interesting that different animals have different clocks.

What's interesting also is that there's evidence that these rhythms that are developmental rhythms aren't just restricted to embryological structures that clearly have this repeating pattern. We also see them going up and down in almost all the cells in our body, including the cells that make up our brains.

What are they doing there? Do they have some other function? That's something that we and other groups are very interested in. Do they have a regulatory clock like function outside this formation of the backbone? That's hopefully what the community will help to find in the next 10 years.

Peggy: Kenro, I understand you originally pursued an MD PhD, then changed to a PhD. Why was that?

Kenro: I have nothing but admiration for people that are MD PhDs, or MDJDs, who are able to combine everything. In my mind, it's a little bit like combining two very different things. Imagine having a TV show that combines both "ER" and "Boston Legal". It's really hard to make it work in some ways, partly because there are such different things happening, and there's such different pacings and storytellings.

I think that's a lot of the issue about the way medical practice works, versus research. I think some people thrive on juggling four balls at once. For myself, I wanted to focus on something, and coming out of the very fast paced and exciting research field of the Human Genome Project, I really wanted to focus on studying how the genetics and gene regulation affect the formation of our bodies, and how it shapes us. For me, that was the right decision.

But I've definitely been very encouraging of people who could go in both directions. I have had two students, actually, that are currently in MD PhD programs, that are very much thriving in that environment.

Peggy: What possibilities exist for treatments with bionics, stem cells, gene therapies or nanotechnology in your field, Kenro?

Kenro: Even though we now know that there are 26,000 or so genes in our body, we still really don't know that much about them. One of the gene families that's really important in regulating this embryological process that makes up our backbone is called the Notch Pathway, after the first gene that was found. It was actually the very first gene developmental characterized in fruit flies, back in the 1930s, and it was called Notch because it made notches in wings.

Well, that gene, as it turns out, is important in so many processes, including the key factors that regulate stem cells, and are important in gene therapy. It regulates how cells divide and continue to divide, and if they don't divide the right way, go on to form cancer. They regulate whether a cell becomes a neuron or a non neuronal cell.

You see this a lot of times in development, but the genes that are involved in regulating how we are normally shaped are also very, very important in these processes that you mentioned. For example, in stem cells. Or in later therapies, where you're trying to essentially guide cells to do your bidding, except now in the adult.

The fact is that we still know very little about them. In fact, many of the family members are still not identified. So really, the Human Genome Project has finally given us the tools to begin to do that. That will be something that will be quite interesting to see what comes out of it in the years ahead.

Peggy: Kenro, we hear more and more about personalized medicine. What does this actually entail?

Kenro: Personalized medicine is really applying the advances, both in terms of the genetic and genomic sciences as well as in the social sciences. Simply put, what's the best therapy for you? So the factors that might make one person, for example, you different from me, might be age, gender, the population group that we come from, ethnicity, and socio economic factors.

How can we tailor the therapies that are likely to be the most successful for you? Already there have been significant advances, especially in fields like pharmacogenomics, where drugs are clearly more useful in some populations than others, so that you get the treatment that is the most likely to give you success in the future.

Peggy: Can you explain what it would mean to put some aspects of medicine in the hands of citizens, and how it could change the practice of medicine and training of clinicians?

Kenro: So, it is clearly already having an effect in pharmacogenomics, or basically, what drug therapies are you getting. For example, one example is a drug that has been used for lung cancer. Its technical name is gefitinib, but its marketing name is Iressa. That is a drug that has very clear differences within different population groups.

So for example, what group you come from which you could determine by genetic tests or perhaps if you have a fairly clear ethnic background then you may be able to tailor the drug so that you have the best chance of having the best outcome from your therapy for cancer treatment, rather than just blind shotgunning drugs left and right.

So that is already having a strong impact; and increasingly, more and more of these types of factors, including for treatment for Type two diabetes, many, many things are taking into account who you are, and what is the best treatment for you.

It is sort of, basically tailored treatment, instead of just getting something off the rack, something that is tailored just for that patient.

Peggy: When I got to the doctor, I get about 15 minutes of their time. How does a person develop personalized medicine when the time you have with clinicians is fairly short?

Kenro: One of the key things that is important in the earliest steps of medical education is the value of the patient interview, or talking with the patient, finding out about themselves, their families, what they do, their jobs, and all these things, and I think that that is something that medical students early on definitely spend a lot of time doing.

As time goes on, of course, doctors have extreme time pressures and that interview process gets shorter. However, they do get better at taking these pieces of information, both from that interview but also from the increasingly, by informatics and computer technologies making a huge impact in terms of what you immediately have on hand.

So this is part of the patient chart or profile that that physician can look at, or see some of these factors that might make a difference in this therapy.

But of course, nothing replaces the importance of getting the skills for that patient interview.

Peggy: Kenro, I mentioned that your research revolves around spine development and birth defects. Would personalized medicine impact your field of study?

Kenro: There are so many areas of medicine where, really, we don't know a lot about what causes it, how does it progress, and what is likely to be your prognosis. I actually work in the field of studying scoliosis, which is a curvature of the spine in either the left or the right direction, which is quite debilitating.

One of the key things that is really, in a form called idiopathic and idiopathic is just a glorified term that says we don't know in idiopathic scoliosis, one of the mysteries is that we know that, if you follow patients, some progress and they really need further intervention to prevent their curves from getting quite severe, and others actually don't really progress, so that monitoring just is making sure that that patient is being looked at. We know that idiopathic scoliosis has major genetic contributors, and in fact, some of the first genes are starting to get identified for that disease.

So it would be good if we could know ahead of time, "Oh, you belong in the category that you really are going to need much more therapy, " versus, "Oh, you are probably OK. We will keep monitoring you, but you probably are not going to need a lot more intervention." As with many diseases, even just having that knowledge ahead of time, or having some certainty, allows you to make plans and allows your physician to really tailor the therapy towards you.

So in that field of scoliosis, we hope that these types of applications of personalized medicine will make a big difference in the lives of children and adolescents that are dealing with a disease that still is quite mysterious.

Peggy: Jason, what sort of new ethical issues could arise as a result of personalized medicine?

Jason: In general, I don't think that there are very many new ethical issues, ever. I think, instead, we see some old ethical issues arising in new contexts. So to think of personalized medicine as an example, one of the concerns that many people have is that when you focus very much on trying to tailor treatments or potential cures to individuals, based on genotype and other information, you might be missing a profound opportunity though a less lucrative one to try to prevent disease and disorder in the first place.

So some people are concerned that to focus too much on personalized medicine will take the focus away from these more, kind of group based strategies that could make a bigger difference down the road.

Another concern, of course, has to do with some of the clinical integration issues that you have already raised with Kenro how, in fact, we will be able to maintain an emphasis on the person and her context in personalized medicine, which sometimes focuses more narrowly, not on the person herself, but really on her genetic background and makeup.

So that is a concern that some people really do have, that personalized medicine might, in fact, be taking the person out of medicine rather than focusing on her centrally.

Peggy: We have all heard the controversy around stem cell research and the use of tissues derived from embryos. How do you believe we can bridge such differences, balancing the needs of medicine and the directives of society?

Jason: I'm one of these people who believes firmly that any good policy decision and any good, really, policy relevant discussion, has to take place on the basis of sound scientific knowledge. This is the reason that my job is in a School of life sciences, rather than in a philosophy department, and at the University of Arizona College of Medicine, in partnership with Arizona State University, my position is in basic medical sciences rather than in some other department. I think that one of the things that goes a long way is making sure that people are talking about the same thing.

Scientists can be just as evasive and political as regular people can be, when it comes to controversial science, and one of my major research areas is, how should scientists and ethicists and regular people deal with science that is widely or even only occasionally deemed to be controversial. Stem cell research is a good example, brain sciences emerging brain science is another, where we see the opportunity for a dramatic conflict between the scientific research and medical research imperative on the one hand, and whether political or religious or other values based concerns on the other.

I think it is possible to have rapprochement between divergent views, but it requires a lot of good will, a sound scientific basis, and a real opportunity to express what the conflicts and values actually are.

Peggy: Can either of you give me an example of a medical treatment that was not considered acceptable, that now is?

Kenro: Most findings, at first, can be controversial, or people just don't believe it. Actually, I remember in the first year of medical school there was research pointing to fact that ulcers were caused by bacteria, and I remember at the time people thought that was just crazy. But of course it is now true that that is a major factor in the development of ulcers, and of course one of the therapies is to fight those bacteria.

So here is a therapy that people would have just been shocked at just a year prior to that, but of course now is part of the established therapies, and there are many things like that, where either because it is a new finding, or it might come from a different tradition for example, alternate, like acupuncture, if you had asked the medical establishment 50 years ago, it would have no place, and now of course it does have a role in pain reduction, and there are many things like that.

So, many things, at the very first hearing, with good reason, meet with skepticism, and then some of course then pass through and are brought into the fold of traditional alopathic medical treatment.

Jason: So, a very nice example is in 1978, when the first so called "test tube baby," Louise Brown, was born. So this was the first baby who was brought to term through the process of in vitro fertilization, so fertilization of an egg with a sperm outside of the human body, and then transferred into the uterus, and then gestated and born, so far as we know, a relatively healthy baby, who is now almost 30 years old.

At the time there was significant outcry, both from religious people but also from people who were really concerned about the secular sanctity, if that makes sense, of natural reproduction.

Now many jurisdictions, including in Australia, for instance, fully support with state funds the use of in vitro fertilization for infertile people. It is certainly covered in some jurisdictions by medical insurance, and in vitro fertilization is widely believed to be an appropriate means for infertile people to be able to have a baby that is genetically related to them.

At the same time, it still raises lots of ethical controversies including, for instance, what do you do with the extra embryos that you produce in in vitro fertilization procedures. Typically they are frozen, potentially for later use in reproductive projects, but possibly also for research, say, in stem cell biology.

At the same time, other concerns about the safety of in vitro fertilization, especially for the pregnant woman or to be pregnant woman who has to undergo ovarian hyperstimulation in order to retrieve enough egg cells to begin the process in the first place. Lots and lots of ethical issues, but by and large the public outcry about them and the unnaturalness of in vitro fertilization has dissipated over time.

Peggy: How do these shifts in perspectives come about?

Jason: Sometimes time passing is enough. Other times, in the case that Kenro mentioned, it is really just further studies that show either the reliability of the initial finding, or the effectiveness of an intervention that gets people to sort of feel a little bit more comfortable with the technology.

Sometimes it is just the process of familiarization with something that seems so incredibly new, that is based on education, that is based on the passage of time, that is based on, sometimes, people's own personal intimate experiences. These are the kinds of things that make all the difference in the world. Sometimes ethicists help, too.

Kenro: When you look back at past medical therapies for example, if you look at the 18th century, state of the art would be bloodletting, and things that would just cause horror now. What we want is that in the future, people look back at therapies now and say, "They pumped these people full of, just, toxic chemicals to treat cancer," or, "They just put chemicals in that were trying to fight psychiatric illness, " that these would seem equally as horrific in the future.

So I think that as we understand how things work better, the attitudes will change, and I think that the therapies get much more refined and much more targeted. So we have a long way to go, but a lot of the process of change of perspective, it's increase in knowledge. We look forward to making many of the current therapies seem equally as archaic and primitive.

I came from the oldest medical school in the United States, and now, coming to the newest medical school in the United States, it is a tremendously fun exercise, because you don't have to say, "Oh, it is always done this way." We're the ones who are creating the very beginnings of how things are done, and instead of having an 18th century medical education, now we can look at a 21st century medical education and bring in the best practices of 2007 and beyond.

Peggy: Thank you for joining us today, Jason and Kenro.

Kenro: It's a pleasure talking with you.

Jason: It really has been. It makes me even more excited than I already was for what we are about to embark on.

Peggy: Jason Robert and Kenro Kazumi are just two of the five faculty members from the School of Life Sciences that will become adjunct professors with the University of Arizona's College of Medicine, Phoenix, in partnership with Arizona State University. They will be joined by School of Life Sciences researchers Jean Wilson Rawls, Alan Rawls, Doug Lake, and five others from the College of Liberal Arts & Sciences. Together they will fill out the 24 members of the teaching staff.

We wish them all the best of luck in this new collaborative and creative venture.

This is Peggy Coulombe, and you have been listening to School of Life Sciences podcast, "Science Studio." You may have noticed that we have acquired theme music. Our music comes from the web site Magnitudes. It was composed by Jongen from the collection "Moonrise." The School of Life Sciences and the College of Liberal Arts and Sciences are on the Tempe campus of Arizona State University.

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Clinicians and Cyborgs (Part II)

Transcript - [Printable PDF format]

SOLS Podcasts 2007