About science; About bioengineering vital organs

This is about science produced by the California Institute of Technology and originally broadcast by station KPCC in Pasadena California. The programs are made available to the station by national educational radio. This program is about bio engineering of vital organs with host Dr. Robert McGregor and his guest Dr. Sheldon Friedlander. Here now is Dr. McGrath there. We keep hearing more and more often. Sheldon the notion of artificial organs and in fact I've heard very recently the expression bio engineering and this is something which perhaps has grasped imagination some elements of the public. What does all of this mean on how we come to this particular state of affairs that people take an interest in these artificial things. BB I think there are a number of reasons why engineers have become interested in these medical and health problems.

In part I suspect it's a question of a guilty conscience because as you know that engineer is going to be remarkably successful. It comes to things like designing extremely destructive weapons for the military. They made tremendous contributions. Does your contributions which are often at times lead to air for air and water pollution and in addition of course they've contributed to biological and chemical warfare in the development of this type of weaponry. So there's a sense of responsibility developing. Professional community. Exactly I think they would like to see whether they think their invention just can't be used for perhaps more desirable. And but I think it's really only one part of the problem. That sounds like a kind of a negative side of the picture again I must be a positive side. Yes it's I think

that was positive in the sense that if it is you want to do some good. But I think it's really a purely natural development to a great extent in the sense that we have beef available to us now on technology and instruments which have not been available in the past we're kind of ready to play ready we're ready to avoid these two problems itself in medicine for example the case of the developer of the airplane this rest is based in part on the existence of a commercially successful method for producing aluminum that you need a technological base for any development and we have it in new plastics and you have electronic instrumentation and we can take those things and apply them to medical services. So we now have a concern about the amount of excitement building up in our professional community a desire to do these things and a technical readiness.

And what does our background of experience and working with artificial organs for the human body the of course the simplest types of artificial devices are things like false teeth and artificial limbs wooden legs for example and how to somewhat more sophisticated level as the famous are in London which was developed in the 1930s actually by old Fessor mind Professor sessile and there are two professors actually professors Philip and social drinker at Harvard filter who was a chemical engineer and he was a chemical engineer says the drinker was a pulmonary physiologist they're brothers and they collaborated in designing a device which of course is. It was tremendously useful and successful in the case of treating polio victims. It was a mechanical device. And you know in a sense it was just just one step

advance from things like a wooden leg or the false teeth or the joints weave some bones or. Exactly. And but it was the result of collaboration between an engineer and a medical man. So we thought in the beginning and this goes back some centuries of course. That's my take I kind of remember if my memory is in fact accurate that some figures in history have had prostate wooden teeth wasn't really that was you know they figured Washington as you know used wooden Faustino. So I thought in terms of mechanical devices which was easiest conceptually to handle. Well as our understanding of the physical processes and chemical processes has matured here. Has How has this come to play a role I what is the next step here of the development of these organs.

The next step is the development of devices like artificial learning and an artificial kidneys which while simple. From the point of view of their primary functions medically still for an engineer or somebody other than God is trying to make that represent a fairly complicated system to to reproduce. But some still do say simple Oh. Well they're simple in the sense that they they are they involve primarily a limited number of involve a limited number of chemical substances which we want to exchange from between the blood and the environment in some way for example in the case of the lung. But of artificial or real we're interested in getting oxygen into the blood and carbon dioxide out of the blood. So it's simple in the sense that there's a simple chemical exchange process

which has to take place in a particular organ. I want to see another example here and in the case of the kidney However we have a somewhat more complicated situation here we're trying to remove potassium mind and condition a variety of products for the metabolic processes which is the waste products of the tribalism of the cells and you're right I think we'll hear I guess in cracking your ear. But when we can identify up to a certain point the substances the substances that we want to remove. And in that sense the both of these devices are relatively simple as the lung the artificial one for that matter of life and the kidney I might add that in the case of the kidney the situation is not quite as simple as we'd hoped it would be

because the physicians have actually done experiments in which they have used they have they have used artificial kidneys with in such a fashion by putting your ear into the fluid which believe the kidney they were able to prevent the removal of urea from the kitty and from from the from the circulating blood it and found that there was no deleterious effect no Marple effect on the patient. So apparently it's not the buildup of urea which you would think would be primarily responsible for damage to the patient but it's actually trace substances most of them if you don't identify which are causing damage. And so when I say these devices just simple Oh they're relatively simple. Even in the simplest cases they still ask more complicated than we can understand.

So in this second stage of the evolution of artificial organs. For the body we think in terms of chemical exchange processes and organs which empower simple chemical exchange. Now the medium of this exchange is what the. Well the this might be a wall or a membrane or something. Yes it would just be an exchange of these gases or substances chemical species. In passing right in in the case of the kidney. This has been the only method use one separates the blood from a say on a solution on unwanted materials chemical substances are allowed to create that membrane and move from the blood into the US in fact salt water which is flowing either side of the membrane. While in the case taken out one way when in case all along you need a membrane which can pass the oxygen one way only common outside the other.

Yes and actually we've been interested at Cal Tech in the design of artificial lungs membrane lungs but the devices which have been used by physicians in the past have had for the most part not been membrane lungs that is they simply exposed the blood to the gas directly it directly that bubble the gas pumps oxygen through the blood and producing a bloody mess. And from this this is very effectively exchanging serious you just off the carbon dioxide very easily and the oxygen gets into the blood very effectively. But unfortunately there seems to be a tendency for the blood to deteriorate under the circumstances. So you start and you need a membrane. So if there is a good experimental evidence which indicates that when you use a membrane to separate the blood from the gas you produce less damage. And people think this is true. They still

try to establish it seems not to be true because we know that by bubbling gases through protein solutions we can effectively strip out the proteins and after all the blood plasma is an effective approach a solution and it seems like. An undesirable thing to do just a bubble pass through it. So the girl or the objective will be researching on this level of understanding than it is to understand the processes or the characteristics of membranes or membrane materials and eventually develop a new membrane materials that can be used in this kind of situation. Yes there are that's one important part of the whole exchange problem is the development of the membranes which pass the chemical substance fast enough and which at the same time don't damage the blood don't produce a breakdown of the constituents of the blood. But we found in our work at Cal Tech is where it was done by one of our graduate students in engineering and in

its space edge found that the controlling resistors to gas exchange was not the membrane but thin film of slowly moving blood which passes over the membrane. One of these exchange devices come upon really are about to Arafat. That's right. Concentration back to where existed and so the membrane is not as crucial now and you know these membranes that once we use were silk of rubber membranes which. You were named by the General Electric Company and there are just about a thousandth of an inch thick and a block of film is actually look at this and doesn't pass the oxygen as effectively as the silicone rubber membrane so it's a case of two resistances in series you know you have a large resistor is a small one large resistance being that blood film a small one being the membrane and there's not much point in working on that

membrane is more resistance reducing it because it will increase they'd be like the current so to speak through that system. So the discovery of proper suitable membrane materials is not so difficult a problem that understanding the processes that go on in the boundary layer. In the case of the design of artificial of membrane lungs at this point. This seems to be the crucial problem but you know are these engineering problems scientific problems have a strange way of oscillating back and forth you get like one bargain and you will have to. Do you and your difficulties in arise in another area you look at that and suddenly the only problem somehow becomes what you thought you had licked and you did it in the former context. Suddenly crops up to plague you again. Yeah well it is a kind of the nature of the problem that spawn really a problem of this film problematic card shall.

Be the oxygen in the case of the artificial on the oxygen gases. Perhaps I should backtrack a bit and say what we have is oxygen. If you're on one side of the membrane which is that thousandth of an inch in thickness and on the other side we have blood which is flowing over the surface it's going in the course of passing from one side of the patient from the from the base citation to the actuarial side. These devices by the way are used during the course of heart surgery and I think we mention since we use the NISA temporary devices 90 the artificial on this temporary device used during heart surgery. There's the artificial kidney is maybe used for years in fact our case isn't a real replacement then well in that sense it is not replace these sensors. They're portable. This is one of the things we're shooting for. Possibility of. Developing designing

a portable TV. Instead of going through the rather inconvenient kind of treatment that the patient with chronic kidney disease has to go through now. What do you have to do now is to record several times a month to the hospital for where he's been for a period of hours goes through the dialysis the cleaning out of his blood and His Will up. This is been now or this this process as it existed for a number of years and we have patients now who have been using artificial lungs for up to five years. Arshad can either start pushing kidneys up to five years because of the artificial lungs pretty different. This is just extremely temporary device to use during heart surgery. And one of the reasons it's temporary is that big blood did deteriorates during the passage through the device and you know you don't attribute this to the membrane it sounds or do you know it's

primarily due to the very large surface area that the blood. It has to flow over including the in order to make the exchange which make exchange because in the case of the lungs he entire blood supply has to pass through the line to get enough oxygen. Where is the case of the kidney. We only need to take a relatively small fraction of the blood any time to exchange but right now what is the nature of this deterioration do we understand what causes. Bobbie remember injuring proces be the two most serious are the clotting of blood and the interface to blood on my right above the membrane or the blood and the rest of the experts call the extra full system through which circulation is taking place. Clotting is one and the other problem is the destruction that

formed elements in the blood and the foreign elements. The red cells white cells and platelets there are three major shaped bodies which are floating in the clouds which pass through the blood and these are destroyed when passing through foreign devices. So how do we understand are both mechanisms and bargain factories are the predominant on. One of the. The problem is that my physician friends told me in the in the case of extra poor circulation is that you really between the devil and deep blue sea because when the blood passes through the external circuit it tends to clot. Now in order to prevent the break to break up the clots the body and the blood passes back in the bloodied but the body releases certain enzymes which reduce clotting

and prevent the corrective action for action right. So what happens well on the one hand you're busy forming clots on the outside and the other hand inside your busy producing insanity to break down parts and then actually to produce bleeding that is if there are cancer you have little breaks in the servitor system you get bleeding through the through the brakes because you have this financing which is preventing the class from forming. So in theory the position of the surgeon is in a difficult position and he has to in order to steer is his course properly. He's forced to to use measured doses of heparin at one end to reduce clotting and another chemical which neutralizes heparin in the protein to prevent the. The heparin from persisting is just a very fine balance though to find out exactly. Where face the loss of these balances as I and I were talking about

the the problem of the two problems of cloud formation and red cell destruction. He we've seen in recent years the several groups at Johns Hopkins Hospital and Patel Institute in Ohio have developed methods for reducing the clotting preventing services from for producing clots and amped up from Virginia gauges with their materials because it's cool they have a very clever method. Doing is what they do is to is to introduce introduce. Could turn really annoying insults into the membrane or the plastic material which is composing the artificial circulatory device. And this serves to bind on this they can attach heparin which is

a an anti-coagulant and a heparin then is linked to the surface of the of them on the coffee plastic material and prevents the clots from forming just dandy. And it really works very effectively apparently. However it is an unfortunate side effect because at the same time this other problem crops up the problem of the destruction of the red cells seems to become seems to be aggravated worse by but that's not why this happens we don't know. But we managed to solve one problem with the cooperation we aggravate the other. The destruction of the red cells. So we are continually and this fine balance trying to handle this this is tough. Flu is not like turpentine or water or jet fuel. Barbara it's we'd like it to be that way and that blood as we're shooting this we were shooting for we like to be live like be able to Him we do water

alcohol or jet fuel or some other substance grappling with it. Problem can you separate out the side effect of the film our boundary layer from the effect of the surface itself. The there are this actually is related to the problem of ritual destruction there are people who have hypothesized two possible explanations for why the red cells are destroyed. One group argues well we have high shear rates by sheer fields we were pushing We looked through it pretty rapid rate valves and things in our system and it's breaking down because of the shear It's just like. Oh breaking up this question of breaking up

chocolate. We make hot chocolate. This is you know we do we want our high she reveals that we can break down the the aggregate of you know the chocolate and can get it mixed into a liquid and we say well maybe ice which produce they argue people argue that was producing the destruction of red cells. Other people of course the academics as likes to think that if you like to offer How do you manage directly that it's a shared chemist on the other hand people think immediately of the chemical organ he said with the say well the red cells are new services and they're bumping into the surface and there's a chemical process chemical process which perhaps links the membrane of the cell to the surface momentarily and then in the sheer field perhaps of its more loose and the. The membrane breaks and spilling the contents is difficult to decide which one it is in this primarily responsible for this.

A friend a good friend in engineering Dr. Blackshear at the University of Minnesota has been trying to separate the two effects and he tries to do it by setting up a sheer field in which there is no surface present. He does this by injecting a light solution which it forms a jet of Salem solution into blood to flow into fluids around the blasphemies. And this way he's set up a shared field without a surface being present right. And he's found that the destruction of course he's probably helped in A.S. I think it was the disappointed to find that the damage destruction and I think of course important point but he's demonstrated is that sheer probably is not so terribly important and that it's as well likely to be the chemical some kind of interaction reaction surface that produces it down. So we've been talking about the law. On the one hand it

looks relatively simple because there are only two particular chemical components that have to pass oxygen and carbon dioxide in it and in both directions. In the case of the kidney you have just a number of materials that have to pass from one side to the other only is one more difficult than the other. You can't can you speak in those terms at all. I think that the conceptual way to learn is simpler for me as an engineer visualize to work actually on studying the rate at which oxygen carbon dioxide which I exchange with blood I think can lead to the rational design of these devices what we've done is to develop equations which describe the rates of transfer which would permit us to sit down and design a and or fish or fish along just as you use it to design a jet engine.

Clear rational basis no rational basis for designing these things sort of tailored. Home to what the requirements are ultimately right we can if we want to design for a minimum surface area which seems like what we like to do. We can do that because we know what the equations are now coming from you understand the physical chemical processes so you can actually. Attend or design literally design artificial Argan you know for a heart a brother for a long or for a kidney. It's alright knowing I was that I was going to distinguish between a lung and a kid alone. Seems simpler conceptually as we see it too these are the important things we are thinking and in the case of the kidney we have all these trace this identify trace ages which are so much maturing and we only know that if we remove your ear we usually get rid of these trace agents which are undesirable perhaps because they're the same molecular nature they will pass through the membrane. But from the jury point of view I think that you probably would agree with this it's so good and satisfactory to just

say well we're moving we don't know what we're shooting for but we don't we get rid of the real you're probably OK you're getting an effect we are quite understand that that makes you uneasy it's right. So from that point of view I would say the kidney is tougher but we've had more successful kidneys because for one thing we don't have to that we don't have to take hold all the blood and pass it through a kidney. Yes continually what you do is we're not alone. Right now you talk to her and this present level of understanding and development of a temporary organ so in the case of heart surgery and sometimes a replacement for the kidney can anyone envision a situation some years in the future as our knowledge increases so for literally portable devices that would be part of your system. This is what we are eating for about the National Sport Institute. Put out a call for

ideas on how to design and produce these devices portable not only portable kidneys. Well the hardest to permit early interested voices relate to the heart like the Ordovician hearts and. Longs as well. The other two other divisions of the nationalist who felt very interested in the design of artificial kidneys and the bookcase of the kidney and the heart. We are seeking to make them portable. In neither case are we really great success. If one goes beyond I at this present level of progress. We went from a mechanical to the simple chemical problems and evolved a sex change process through a membrane. What do you envision as the next level of sophistication of

artificial organs. I thought about that. Well I'm not a physiologist and sometimes I enjoy leafing through medical physiology books and I'm always flabbergasted overwhelmed when I look at the things which are done by organs like the pancreas or the liver and these seem to be one when I think of maybe for maybe the next step after the kidneys lungs and hearts would be to go to other more complicated organs are complicated in what sense. Well but they do their function is to produce a variety of hormones and enzymes that are quite complicated. I think many of them I'm standing are NOT have not been worked out many of the functions have not really been worked out and I you know

I think that this is certainly a problem which is the next step now how much successful the next step I don't know I think. Probably 50 years ago the possibility of constructing workable lungs and kidneys looked very difficult to us this was about science with host Dr. Robert McGregor Lee and his guest Dr. Sheldon Friedlander. Joining us again for our next program on another subject of interest to scientist and layman will be discussed. About science is produced by the California Institute of Technology and is originally broadcast by station PPC Pasadena California. The programs are made available to the station by a national educational radio. This is the national educational radio network.