Mhm. Yeah, well, good afternoon ladies and
gentlemen, thank you for coming and welcome to the
Lyric Theatre and our first ever distinguished lecture on regenerative
medicine. Our talk today would not have been possible
without the generous support of the College of Agriculture and
Life Sciences College of Liberal Arts and Human Sciences in
the Virginia Maryland College of Veterinary Medicine and the interdisciplinary
graduate education program, or hijab in regenerative medicine.
Regenerative medicine is a promising new medical paradigm that envisions
the use of stem cells to repair or replace tissues
that have been damaged by injury, disease or congenital
defect. This approach has particular promise for treating irreversible
tissue damage caused by strokes, heart attacks, traumatic
injuries and even auto immune diseases like juvenile diabetes.
Virginia tech side and regenerative medicine is designed to train
future leaders in the promising and growing field In this
uh using an in traditional culinary approach that involves 15
faculty and 30 graduate students from the college of veterinary
medicine, Engineering, liberal arts and Human Sciences and
business. Our students research ranges from cellular reprogramming and
the engineering of bio materials based cellular scaffolds to bioethics
and entrepreneurship, basically what it takes to generate stem
cell based therapies in the lab and bring them through
the market to the patient's bedside. That said the
field of regenerative medicine and all of its potential and
promise and indeed our own graduate program would not likely
exist today, but for our guests insight, hard
work and leadership that ultimately led to the birth of
Dolly the sheep. Some 20 years ago. Ian
Wilmut was born and raised near Coventry in England.
As a boy. He worked weekends as a farmhand
, which influenced his decision to major in animal agriculture
at the University of Nottingham and to pursue graduate studies
at Cambridge, where he earned a PhD for his
work on the deep freezing of pig sperm no stranger
to first in biology. Right out of the chute
, as we might say in animal science, Dr
Wilmot is the first to freeze bovine embryo for an
extended period of time, then thought out transfer it
to a surrogate cow and produced the first calf from
a frozen embryo, whom he appropriately named Frosty That
was in 1974. And the freezing technique pioneered by
Dr Wilma is now a mainstay in the cattle industry
and has contributed greatly to the genetic improvement of cattle
worldwide. That same year, Dr Wilmot moved from
Cambridge to the animal breeding research organization at Rosslyn in
Scotland to study reproductive efficiency in livestock, in particular
things affecting growth development and the survival of embryos during
early pregnancy. Then in the mid 1980s, as
it so often happens in science, a new technology
burst onto the scene that board great promise for the
benefit of livestock and human health alike. This was
the technique technique of trans genesis, which enabled the
production of novel genes or introduction of novel genes into
animals. In particular, the scientists at Rosslyn,
including dr Wilmot, were interested in the production of
human pharmaceutical proteins in the milk of transgenic livestock.
With this, doctor Willmott and his team produced another
first Tracy, the first transgenic farm animal, a
sheep to express a human protein in her milk.
The prospect of harnessing the mammary gland is a bioreactor
for making human medicines. Also captured the imagination of
entrepreneurs as well. In 1987 Rosalind spun out a
company, pharmaceutical proteins limited, or PPL for short
, to develop and commercialize the technology. Other companies
quickly followed suit, including Genzyme Transgenics in boston gen
farm in the Netherlands and PPL inc or incorporated the
american arm of PPL in Scotland. Located right here
in the corporate research park at Virginia Tech introducing new
jeans uh into sheep and other livestock was a tricky
, unpredictable and inefficient business ever on the lookout.
For better ways to do things. Dr Wilmott said
about to find a better way to make transgenic sheep
. And it was in this pursuit that ultimately led
to dolly. Now with dolly in mind here's a
quick visual on how dolly was made basically just run
through this quickly up here on the upper left.
Yeah. Yeah parking lot and a great machine seeing
the green. Yes it is a nucleus. Mhm
. Yeah. All right family. Your okay.
Yeah. People hide right. Yeah. Yes.
Yes. What? All very favorite. Something awesome
. Mhm. Laboratory and then yeah. Okay so
okay this case use the way oh you are do
it behind the generation of dollars. Was that this
is a doctor. Hey? Yeah. The way
well being raised. Yeah. Yeah. You ready
? Mm. You indicated so. Oh, very
few single achievements in science have touched the public imagination
and consciousness in the way that dolly has. Many
of us remember and most of us know that dolly
quickly jumped from the realm of science into the public's
imagination around the world where she created wonder, amazement
and to be sure some concerns and dolly has a
very special connection. Even today, right here in
Blacksburg 1997 PPL, incorporated up in the corporate research
park, adapted the dalai technology very quickly to produce
mr jefferson, one of the world's first cloned bulls
in 2000 PPL was produced the world's first litter of
cloned pigs. And today even today, this very
day today revival core, also located up in the
corporate research park in Blacksburg, is routinely cloning very
special pigs for human compatible organs to alleviate the vast
shortage of life saving human organs for transplant patients.
For his outstanding accomplishments and influential achievements, Professor Willman
has received numerous awards, accolades and honors among them
fellowship in the Royal Society, share in the prestigious
shaw prize with his fellow laureate and dolly collaborator,
keith Campbell, Fellowship in the Academy of Medical Sciences
and the european Molecular Biology Organization. And last but
not least, Professor Wilmot was knighted by Queen Elizabeth
in 2008 and now without further ado it is my
great honor and pleasure to present to you, Professor
Sir Ian Wilmott. Yeah, thank you will for
that. Very generous introduction and you for your very
well and welcome. Indeed. I'd like to take
this opportunity to thank my host during this visit.
It's been a great pleasure and you've been very kind
to me. I am deeply grateful. Before I
get into the biology, there are a couple of
points that I want to make in background. First
of all, we are as well as said,
approaching a time with fantastic new opportunities in biology and
medicine and I want to give the background too many
of these in illustrate the way in which things may
develop in the future. Secondly, to indicate that
a huge number of people are actually involved in this
sort of research, including this project. There were
30 names on the slide that I used to list
all of the people who had been involved in the
project at Rosslyn. On the first occasion when I
talked about the project, 30 people ranging at the
top from secretaries, all the way through to the
people who did the micro manipulation and looked after the
stock. Unless you know, otherwise, you might
very well think that cloning was something which developed perhaps
50 years ago That in fact, it emerged from
some science in the 19th century, not because people
were actually doing cloning, but because they were thinking
about the biology, um they knew about cells,
they knew about eggs. The microscopes were good enough
to see eggs and they were good enough to reveal
the nucleus and the fact that it went through changes
. But they had no idea, of course,
as to how it control development. Recognize that chromosomes
were only poorly understood and there was no knowledge at
all of DNA and the knowledge that we have of
chromosomal replication and so on. What they didn't know
that was that there were cyclical changes in the nucleus
and of course that the offspring very close resemblance to
their parents. So there must be some sort of
genetically mechanism of inheritance. What they were. Was
not understood at all in that sort of background.
It seems remarkable when you look at it, the
sort of ideas that they emerged that emerged as they
thought about this issue. How did the single cell
of an embryo give rise to all of the different
tissues of an adult? There there is in size
a little bit from one mammal to another. But
roughly speaking, there are 10th of a millim in
diameter. That's roughly 201 200th of an inch.
And that my new body gives rise to all of
the different tissues of another. Just think, I
mean, I'm not putting myself forward particularly finds.
Yeah, just think just to start. Thanks.
You know, that if it's do they form?
And I'm going to read you two paragraphs written by
august look Iceman In 1885. It must follow that
during segmentation and subsequent cell division, that the nuclear
plasm will enter upon definite and varied changes which must
cause the differences in the cells that are produced.
It's clear thinking, but not telling us very much
just yet. He went on. The simplest hypothesis
would be to suppose that it's each division of the
nucleus. The specific substance divides into 2/2 of unequal
quality so that the cell bodies would also be transferred
. So, in other words, that, as
we were put it in modern molecular biology, the
two nuclei of the daughter cells after cell division have
a tendency to do different things, perhaps the fall
muscle, the phone skin, and that must depend
upon the nucleus change. And that was taken in
some further thinking to reflect loss of particular things that
if the cell was going to form muscle, it
lost the instructions for forming nerves, vice versa,
It was going to form nerves. It lost the
instructions performing muscle and that fairly quickly led to an
experimental approach to understand this or to test it.
If this was the case and you took a cell
from an adult and put it into an unfertilized egg
way that will describe it for you, it would
not be able to support development to turn because it
wouldn't have all of the instructions. So this was
a not a biotechnology which was emerging. It was
a biological question that was to be answered. Could
the genetic information from an adult cell support development to
turn or not now? Of course, particularly with
the limited equipment that they had in those days.
The sort of experiment that they came up with was
very different from the ones that are done today.
one very well known, which is brilliantly elegant,
was carried out by an spiderman working with salamander.
He took a very fine hair from his baby daughters
head and tied it around the egg so that he
could pull it tight And restrict the nucleus to 1/2
. So he's got an N. You created half
and half which had in its nucleus. And he
let the nucleus divide until they were 16 nuclear in
that half before he loosened the hair and let one
nucleus go across the bridge and then re tighten the
hair again. So that he had restricted one nucleus
alone to the one half. And there were 15
cells in the other. And the question was even
at this very early stage, did that nuclear still
have the instructions to control development to turn? And
the answer is yes, because what he got was
two salamanders and his notebooks copies of his notebooks are
available in which you can see this really quite clearly
. So what this was indicating was that at this
stage at least both halves or fragments had still got
all of the instructions for development. So this illustrates
very neatly what people were expecting of cloning experiments.
It was he in 1928 who first described what we
would recognize as nuclear transfer. But it was not
until 1938 or beyond that people first did nuclear transferring
in amphibians. Working in amphibians because of the fact
that their eggs are larger, relative robust and would
tolerate the pressures and pushing and shoving and cutting and
so on. That's involved in nuclear transfer, Briggs
and King actually working in philadelphia were the first to
describe experiments in which nuclear were transferred from early stages
in a species of for our ground olympians. And
some of them did develop. Yeah, part way
through to turn but not to turn. They produced
. And polls a little later Jon Gordon? Working
in England used two different species Zeneca's and modified the
procedure slightly. And this time when he transferred nuclei
, he got, if he took the nucleus from
an adult frog, he got tadpoles. If he
took nuclei from temples, he got adults. But
he never and neither has anybody else since got adult
frogs following the transfer of nuclei from adult. So
there seems to have been a barrier there of some
kind. So the way in which this was interpreted
was not to suggest that DNA had been lost from
the cell, but rather it was speculated that it
might reflect change against the functioning of the nucleus that
development as Iceman had written dependent upon changes in the
organization and function of the nucleus and that as time
went by perhaps they became so complex and so rigidly
fixed that they couldn't be reversed. That was an
alternative explanation. The first mammalian nuclear transfer was carried
out in sheep by steen Willadsen, working in Cambridge
in England when he produced lambs following nuclear transfer from
early cleavage stages. As far as I know at
that stage, he didn't attend to carry out nuclear
transfer from later stages. So you can't draw any
conclusions about the limits of the technique in cheap,
really comment upon the fact that he's got the physical
techniques sorted. What these experiments are all trying to
investigate is how does this adult derived from the single
cell of an adult of an embryo? Excuse me
? The process which is involved, we would also
know as differentiation because the single cell and its successes
have the ability to differentiate to change to become all
of the different tissues. And there was another way
which was used to study differentiation and also the mechanisms
that are involved. People were beginning to realize that
DNA in the chromosomes must be controlling this, but
we had absolutely no idea which fragments and how one
way which is used to investigate this was to take
fragments of DNA and inject them into cells and to
see if they affected the functioning of that cell.
And in this way identified segments which had the power
to change cells. The likely conclusion that this included
the jeanne with that role during development and they found
a fragment which was given the name My OD.
They were studying the function of muscle. Thanks my
Oh my OD. Which if they injected it into
the predecessors, the precursors of muscle fibers promoted their
complete differentiation into muscle fiber. So they clearly had
identified one of the factors involved in the formation of
russell. However, when they put that factor into
cells that were destined to become deputy sites, liver
cells or special skin cells karate insights. They didn't
have the ability to promote the formation of Mosul.
So what this was showing was that in the appropriate
circumstance this fragment can control development along a particular line
. But if the fragment was being put into cells
which were on a different lineage, they didn't have
the influence. And so there was a limit which
was critical for the orderly development of muscle and other
cell types. So it all seems to be fitting
into the idea that there are limits limits to nuclear
transfer, that something's maybe so rigidly fixed that cloning
won't work and that the regulatory factors, the transcription
factors also have a limited role which is appropriate in
the circumstances, some circumstances that is not effective in
others. So we then need to jump forward 10
or 15 years to the work that was done at
rustling, which was between 93 and 96 with sheep
nuclear transfer. And to consider giving this previous history
, Why were we successful in producing a clone from
an adult? And I think the key point is
that we understood in particular keith Campbell understood the importance
of cell cycle in regulating what happened when you fuse
two cells together, keith gained his PhD from work
done at the University of Sussex. Looking for one
of the key molecules in the regulation of cell cycle
, unfortunately failed to find it. But at least
this meant that he understood a lot about it and
he understood how to asset for its presence and therefore
look for it in eggs and early embryos and follow
its it's likely role during this very early stage of
development. So what do we mean by this little
jargon phrase of cell cycle? Well many cells in
the body will be growing and dividing as a way
of replacing tissues which have aged and no longer functioning
properly or as a way of growing. But this
only takes place in very carefully controlled circumstances so that
the cell will grow. It will take the time
to replicate all of the DNA and it's absolutely essential
that it replicates all of it. But only once
if it fails to replicate any or if it replicates
some of it more than once, then you'll have
an abnormal cell which may well either become conscious or
die. So you understand that there are very tight
and effective mechanisms ensuring that this happens usually. And
what a number of people had already argued in keith
emphasised this point was that it would be critical when
you took two cells and put them together to think
about the cell cycle stage that they were at.
If you remember wills diagram nuclear transfer involves an egg
recovered from animal. When usual issue would be mated
, the chromosomes are removed the donor cell, which
in this case came from mammary tissue when out of
you, no eggs as they are regulated the exits
there are violated our particular stage of the cycle and
relatively stable unusually to sell in the mammary tissue would
be growing through the cells cell cycle. So you
could predict reasonably accurately, but they egg would be
at a particular stage, but you could not know
exactly the stage of the donor cell. So unless
you took further steps to see that it's an appropriate
stage, you would be likely to end up with
an inappropriate combination, which will fail to develop.
The thing about the exits populate is is that it
is poised to begin development two as it is stimulated
either by our electric current or by the arrival of
a spur. There are profound changes in the functioning
of that cell as it unpacks the chromosomes as it
stimulates replication of chromosomes Ready to divide into the 1st
2 selves. So we know that that's what would
happen when we put a nucleus into it. And
what keith predicted was and his experiments confirmed this was
that if you put in a nucleus which was also
awaiting DNA replication, it would welcome the environment it
would find in the egg because that would simulate the
nucleus to to start development and to replicate DNA and
you'll be likely to end up with a normal chromosomes
such and the health yourself. By contrast, if
you took a nucleus at almost any other stage of
the cell site, if you put it into another
site, it will be stimulated to replicate DNA when
it might have already replicated all of the DNA wants
itself or alternatively be part way through the process of
replication. In which case in neither case would the
chromosome complement be normal? It would either be double
or somewhere between one and twice. You know?
And so from this, we predicted that there were
two ways in which we might hope to get a
normal chromosome complement. One was to take the other
side as it was populated and to put in a
nucleus awaiting DNA replication. Not indeed proved to be
probably the best what the combination that you could have
. The alternative was to stimulate the egg to begin
development. So this this activity known as NPF,
would decrease in the U. S. Site would
not trigger DNA replication. You could then fuse a
nucleus to it and it would replicate. So excuse
me, it would regulate whether or not replication took
place. We turn this universal recipient because under these
circumstances you'd expect to get a normal chromosome complement regardless
of the stage of the cell cycle of the donor
sound. And this proved to be the gate.
There was one more little trick which he introduced,
which depends upon us sell it. Don't sell that
stage, which I haven't yet mentioned, which is
called quiescence meaning resting. This is a cell which
has exited the cell cycle and paused cells are really
smart. If we're driving along in a car and
we forget to put gas in, it will stop
just where it runs out of fuel cell going through
the cell cycle will recognize that there's a problem coming
. And if it isn't going to be able to
complete the cell cycle, it will pause and exit
and park itself in this quiescent state, which is
stable. So it gives us a population to do
this with a group of egg, a group of
cells gives us a population of nuclear, which we
can leave on the bench to use over a period
of ours. And this is probably a procedure which
is used universally in the cloning process. So when
we did this with the memory nucleus that was used
for the production of dollies will show it earlier.
We were able to see development of embryos not only
with early stage nuclear of fetal nuclear, but also
for the first time from an adult. And this
undoubtedly this regulation of the cell cycle was one of
the major reasons for our success. Now. During
the years after that, we'll mention one case in
his introduction. A variety of other species have been
closed, including cattle and pigs, cuts and dogs
, horses. Mm hmm. And some less common
animals strikingly at that time, there were no primates
, no clutch successful cloning of primates. In recent
observations in two labs to different labs in the States
here demonstrated that's because the eggs of primates are particularly
sensitive so that if you handle them, what we
can now see is carelessly. They they begin to
develop prematurely. I'm not able to to reprogram the
nucleus to use the image that were used, however
, by modifying their protocols and treating the eggs mob
sensitively. This disadvantage appears to be overcome and it
may now be possible to clone primates successfully. We
don't know that it seems likely to be the case
, so then to pose for a minute and our
squat has been the significance of the Dalai experiment.
Well, first of all, it did formally confirmed
that there has been no irreversible change in the DNA
in mammalian cells or other species, either in cells
after they developed. There are regulatory mechanisms that control
development, but these can be reversed. Secondly,
extensive use has been used of this technique with livestock
for breed improvement, particularly here in North America.
Thirdly, well mentioned vivica here in Blacksburg, which
is doing fantastic, were genetically modifying pinks so that
one day their organs may be suitable for transfer into
patients. And some of that is being done through
cloning. Above all, though the most profound and
most important thing to come from the Dalai experiment was
that biologists were made to think differently. If you
remember early in the talk I emphasized there was a
thought that the DNA and the regulatory mechanisms were so
complex and so rigidly fixed that it would not be
possible to reverse the changes that take place during development
. At one point there was a very distinguished developmental
biologist who predicted it would never be possible to clone
an adult. Well, this is clearly not the
case. Not only is all of the DNA still
present, but it is possible or was possible for
unknown factors in the two reverse all the changes that
have been made in that cell and take the genetic
information back to the very beginning of developed. So
what lots of people were made to think was,
well, if the aid can do it, what
other ways are the of changing this, taking the
function of that nucleus back to the beginning? And
two groups working independently were the first to come forward
with protocols which were repeatable and effective. one The
best known in Japan. Led by Shinya Yamanaka Who
used a group of just four proteins and found that
they were able to reverse adult skin cells from mouse
and human back to the beginning of development to become
cells which were very similar indeed to embryo stem cells
. But remember they did not come from the embryo
, they came from skin and then were treated with
critical proteins. Jamie Thompson working in Madison Wisconsin,
he was a combination of I think five or six
proteins. Some overlap with those of chile Yamanaka to
achieve exactly the same thing. So what this means
is that in principle simply by introducing selected factors into
cells we can produce what are called pluripotent cells Glory
potent because they have the ability to form all of
the different tissues of an adult. Not only that
, but if you treat them right, they will
grow for a long period and produce very large numbers
of cells which can be used either in research or
in therapy. And it's those two things which I
want to move on to discuss. There are a
large number of diseases which reflect the fact that cells
in a particular tissue either died are failing to function
normally. We have we only have effective treatments for
a very small number of them and there are many
more for which we don't treatments. And it was
recognized that if this was an inherited case we could
take cells from the skin perhaps of a person with
such a disease, treat them with the special factors
and produced stem cells induced pluripotent stem cells. So
the jargon is IPs cells from that person which would
be expected to have the characteristics of the disease very
early in the life of the patient. And if
we did that with cells from a healthy person,
excuse me, a healthy person, ideally a fairly
close relative, then we will be able to compare
The healthy cells with the six cells and look for
the difference associated with the disease. If as is
the case with motor neuron disease or Lou Gehrig's disease
, the disease is in the spinal cord and the
nerves running out from it. This is the first
time that that's been possible because you simply can't take
bits of the central nervous system. Same thing goes
for the heart or nerves in the brain. Many
bits of tissue. This is a unique new opportunity
to study the disease and it's only by studying the
disease that you can begin to understand it and look
systematically for treatments which may either prevent the disease or
reduce its harmful effects. And in a group in
Edinburgh, we've done this with one particular mutation in
associated with ALS, and compared the disease cells with
healthy, healthy cells. And the expectation is that
the disease cells would not survive as long in culture
and indeed, that proves to be the case.
However kindly we treat these cells, the cells from
the patient with the disease last less long. That's
less well, So that if you examine them over
a 10 day period, there is a significant difference
. The technique was developed for having proteins inside the
cells which would escape if the cell died. So
this means this meant that a robotic system set up
by steve I think china in SAn Francisco could be
followed by robots. There's no need for students to
sit there night and day for a week. The
robots can do this and look and see how many
cells are there and how many have disappeared over a
period of time. And then to plot out death
plots the speed with which cells die differences were apparent
. And as you would expect, my colleagues now
have an opportunity to look for medicines, potential medicines
which would have, which would reduce the harmful effects
of the mutation in the cell line and promote their
life in culture. Now there are literally hundreds of
inherited diseases like this. We all know about one
or two of them, like Parkinson's disease, some
causes of stroke of heart and heart failure, some
skin conditions. But if you look in great detail
into the textbook, you'll find that there are hundreds
of them and provided that the technique is available to
produce the cells in culture of the tissue which is
damaged in that disease. Then we're now able to
study it and look for protective molecules for a relatively
small amount. The current procedure would depend upon identifying
the genetic error and then using molecular biology to introduce
that into small animals, perhaps mice, and then
to look for drugs which were able to overcome the
harmful effect of the new mutation in those animals,
an extremely expensive process and time consuming. So it's
to be expected, expected that over the next decade
or two, many other diseases will be studied in
this way too many of us in our center in
Edinburgh. It's this use to study disease and look
for drugs which will be the most important use of
the cells for for the foreseeable future. But in
the popular imagination, the application, which is considered
more frequently is for self therapy. The idea being
that if you've identified the cells which are damaged in
the disease, if you can produce healthy examples of
the same kind from an IPs cell which was produced
from the patient, then you would be able to
put those healthy cells back into the right place.
They would replace the dead cells, damaged cells and
and treat the disease in just two or three sentences
that I covered enormous range of technical objectives. You
have to produce exactly the right kind of cell and
have a culture which is not contaminated by any cells
of any other type, you have to know where
to put them in to be able to put them
and sometimes that will be deep in the brain or
in the spinal cord or in the heart. Um
, physically challenging, you have to put the right
number in and create an environment which will be appropriate
in supporting for ourselves a huge challenge. These are
sort of reasons why we think that's using the approach
to study the diseases and develop drugs is much more
likely to be productive in the foreseeable future. Having
said that the lots of groups, including our own
that are working towards self therapy, if we're going
to put cells into patients, there are several requirements
which I just skimmed through most of them, ideally
they should be ideologically matched to the patient. And
this is one of the apparent advantages of these IPs
cells. You take skin cells, you make the
pluripotent cells and then use them for whatever purpose and
they are genetically identical to the patients. And so
you can put the cells into them without without problem
. It isn't quite as simple as that. Some
of the diseases we're treating our auto immune, in
other words, there's an immune response against the person
him or herself, Type one diabetes, for example
. So it's known that in that circumstance, if
you put more pancreatic tissue of that genotype into the
patient, they will be destroyed because there are antibodies
there already. So there are some exceptions to this
. That's the sort of basic approach. And one
of the summary descriptions of this approach for cell therapy
was that you could have patient specific cells. That's
what I've just described. Cells that would be genetically
identical to the patient would be used. But that
would mean that we were producing a huge number of
cell lines, millions and too many of us myself
included. It's simply impracticable. Some fortunate people might
have that privilege, but we really need to come
up with an alternative strategy. And for many years
now people have been looking for ways that damping down
the immune response or making cells less mediagenic as a
way of avoiding the need for patient specific cells.
And this warning approach to that which may prove to
the successful. There are major proteins on the surface
of cells which promote the immune rejection. We each
have two copies of the the the protein product of
the gene and usually they're different. So there's great
diversity. This is why when you see people looking
for bone marrow transplants, they're looking among one in
tens of thousands and they're putting out calls for help
all around the world to identify the rare individuals was
genetically identical. It's impractical to think of doing that
for large numbers of people but it's not actually necessary
for it should be identical now. Rather doubted by
can illustrate Those that these are the two just posted
on the cell surface has these two do so much
look for another person with these, suppose in fact
, instead, different person two, two terms of
display that would also be active because the person right
, wouldn't be in mind this Now. People with
two copies that are identical are rare, so it
takes a lot of effort to find them. But
the converse point is that they are incredibly useful.
An immunologist working in Cambridge, England has estimated that
the library of 150 cell lines would provide this sort
of match For more than 90 of the UK population
. So you might be talking about producing Say 200
cell lines that seems manager. It seems realistic to
think that we could produce a library of that scale
. The population in the United States is rather more
varied. So you probably would need and across it's
much bigger that you would probably need rather more than
150 lines. But that sort of ratio would still
apply Japan, by contrast, is rather inbred country
. They're more uniform because of the time when they
were a closed country. So rather less than 150
lines would be necessary. This is only a partial
match. It's not a perfect match. So nobody
knows how much rejection there would be against these cells
. The only way to find out will be one
day to put cells into people to look and see
what happens. But the returns, the benefits from
having a system like this that worked will be so
large that it seems appropriate to invest now in producing
libraries of this sort of scale and then beginning to
do tests to see how acceptable cells of that kind
are. And an organization was formed last year made
up of countries, excuse me, laboratories from countries
around the world with a view of setting up such
a library. Um, and then going on with
the research after that. It is of course extremely
important that that organization should carry out tests to establish
routines which are consistent self routines for producing themselves that
are consistent all around the world. It's essential that
there would be effective monitoring of the cells to ensure
that they were safe and effective. And that is
what the organization organization, excuse me, is dedicated
to carry. So there's one other potential use of
this technique haven't managed to mention so before I finally
summarized. And that is that what you are preparing
cells to put into a person would be an opportunity
to make genetic change. If you're trying to treat
a person who had thalassemia, which needs to be
want to no websites, which are less effective,
but also across pains that cuts through this. One
way to approach this. One new way to approach
this is to take tissue first to make the jury
problem steps probably at that stage to correct you could
then induce the formation reporting stem cells. These are
the stems. So it seems likely that this approach
could be used to produce treatment fully affected Children.
This is similar approach was used with in an experimental
demonstration in Nice a few years ago and I've no
doubt that various labs around the world now working on
this, it seems quite inappropriate and safe way to
use genetic modification because at the time when the changes
made, the cells are out in a dish and
you'd only put them back into the patient If you're
absolutely convinced. Excuse me. If you're absolutely convinced
now the change has been made accurately and that there
had been no other unintentional jane. If you were
contemplating changing, let's say, a motor neuron,
there would be a different matter altogether. Because that
would have to be done in the body. You
would have no way of really knowing whether or not
it. Okay. Maybe I'm being in Judah,
customers take. Certainly in some cases, the ability
to produce i ps cells will create opportunities or is
creating opportunities to treat genetic diseases which can be treated
at the present. So, in concluding, if
we look back 100 or so years, maybe more
. If you go back to the iceman's time,
18 sixties when he made his analysis, an enormous
amount has been achieved in the control and elimination of
effective infectious diseases during that period. Not only that
, but we feed the population. We feed ourselves
rather better. Virtually all of the water that we
drink is clean and stuff. We've learned an awful
lot about infectious agents. But if you think about
it, by contrast, very little has been achieved
in the treatment or even the understanding of the degenerative
diseases which reflect loss or death of cells throughout the
project. What seems likely is that during the next
100 years there will be an opportunity of several opportunities
to study the men treat these diseases and transform our
ability to treat treatment. And if you think many
of them are associated with people in old age,
so it may well be that we can give our
family members healthier whole age if we can eliminate or
treat degenerative diseases like this, it seems to me
this is incredibly exciting. We should be excited by
this and not afraid of. We should be cautious
about the way in which we use them. Except
this is really, really let's see that and spend
the necessary money developing these procedures and make dr just
put it down what then you time himself. That
in principle should not the satellite. I think it's
important to realize that it will take quite a long
time to achieve these different goals. I've said several
times today in conversation. This is the disappointing,
particularly you or your the husband. It's important to
be careful with the local trials to say for drugs
. I was going that's think unexpectedly arising from Some
thinking in the 1860s, Early developments through the 20th
century. Then the Dalai experiment towards the there's a
very strong chance that we can revolutionize action, particularly
the treatment of the judge. Thank you in that
excellent and exciting presentation. We do have a few
more minutes for questions. We have a couple of
microphones at the forward end of each. I'll,
if you'd like to ask a question, uh,
police approach the microphones and even will do his best
to answer. I'm sure. Yeah, I can't
really. Well if you don't mind, I might
ask the question. Should um, you meant you
very eloquently presented a very optimistic picture for how and
technology that you develop with dolly and that has been
carried on by others into the human medical field.
How do you see the Dalai technology which after all
, was developed in a sheep and a species of
livestock perhaps affecting the the livestock industry and our ability
to feed the world? Thank you. I think
that the impact of cloning as such, I personally
think will be relatively limited. Animal breeders worked out
decades ago that the most effective thing to speed breed
improvement is to collect semen and disseminate it because you
can do really accurate and effective performance test on the
males before you do that. On the other hand
, um, cloning can be used as a way
of introducing genetic change. There's research at all sorts
of different universities, including attack here, showing identifying
some factors which are critical for growth and production of
lean meat, for example, factors which are waiting
now to be introduced into livestock to speed the production
of high quality lean meat in livestock. There are
ideas being developed for conferring resistance to infectious disease on
livestock species by making genetic change. Um, it
seems to me that it's shameful, wasteful to not
take these opportunities. Of course it's essential to consider
animal welfare cloning how Scottish disadvantages we should be careful
to minimize the stress that's involved. But careful use
of this technique could introduced profound genetic changes into lifestyle
with benefit to them sometimes and to us. So
since it's been 20 years since dolly and there are
many people in this room who weren't even alive,
they're younger than dolly. I wondered if you could
take us back to that time in 1996-97 and talk
a little bit about um what the atmosphere was like
because I remember people were frightened. And it's hard
when you look at that adorable sheep up on the
screen that we saw earlier to think that people were
really, really scared of this technology. What was
that like for you? And what do you think
the reasons were for that? And how do you
think it's now been so absorbed into society that people
no longer have that visceral reaction to cloning? Can
I just quickly check before you go, mm.
Do you think it has been absorbed? Do you
think it isn't? I'm asking you I'm asking you
, you made the assertion. Uh huh. Yeah
. It was it was really quite a difficult time
mostly because of the enormous interest in scale of work
that's required when the announcement was made. I've long
ago forgotten the number of inquiries which we receive but
ran into hundreds within a few days. Um,
so there was enormous pressure for newspaper reporters for TVs
for radios and so on. Um I think we'd
those of us in the group had thought through the
whole business for ourselves long before. I mean the
image in the in the communities experiment is he sat
in his bath, had an idea, jumped out
and said Eureka. As many of you will know
pregnancy and sheep last 150 days. That's a hell
of a long eureka. Yeah. So we've had
time and had our own conversations within the group to
consider our views to the use of technologies to increase
efficiency food production. So on. Mostly even then
we focused on its using in human reproduction where we
in favor of cloning people and the answer universally was
no. So we had no difficulty consistently saying that
the acid test that we use and I used it
earlier on today in a class is to ask particularly
the young people in this audience, would you like
to be a genetically identical twin of your father or
mother? The same parent of the same gender?
It was a majority said no as a father.
I can't understand that. I think if you are
being blunt mindy, what you might say is that
I'm being naive and optimistic and you know, that's
a fairly universal, fairly general partner of my behavior
. Um, because I wanted to get over the
point that there are real opportunities here. Um but
they will only be developed to the full if those
of us who have the opportunity to make the case
for them to be applied in our own community.
Yeah. Is there something that led to dali's passing
or was it simply natural death? No, I'm
afraid it wasn't. So, I hope you can
hear the question, could you at the back?
Maybe not? Yes. Okay. Right. Um
sadly dolly had a virus, virally induced cancer.
Um It's not terribly common but it does occur around
the southeast of Scotland where we work and live.
Um There is no test for it. There is
no treatment for it. And in order to do
the work, we used hundreds of sheep each year
. This sort of research we couldn't possibly produce from
our own produce them from our own flock. We
had to buy in Ge. And obviously what happened
to us at least once we introduced an animal with
the um, the disease, had there been a
test, we would have tested them all on the
way into the, to the farm, but there
wasn't, there isn't. So that was an option
open to us. So when one of the sheep
went down with the symptoms, we realized that it
was likely she'd already passed it on to dolly.
And that's indeed proved to be the the case.
Unfortunately, because there's no treatment, there was nothing
we could do. Um, the effect is when
the tumor grows in the animals along is to not
quite suffocated but make breathing difficult. What you begin
to see is fluid running out of the mouth.
So she was taken across to the nearby vet school
and scanned and my colleagues were shocked at the size
of the tumor. She also had difficulty recovering from
the anesthetic which we use to make a restful what
she was scanned. And so we decided it was
kind of to enter life rather than subject to this
over a period of time. There's no reason to
think that infection with this agent has anything to do
with cloning itself. She did, on the other
hand, have arthritis. We've seen the evidence of
this in one of her back legs for many months
and that had been treated. But it was only
when a full history pathology was carried out that it
was realized that there was arthritis all along. Maybe
not all, but large segments of her backbone.
Um really quite serious arthritis, I guess, as
I say, it was really only really visible once
you've been dissected and was being prepared for preservation.
To my knowledge, she's the only one of our
animals who had this. Um and certainly groups of
animals or clone subsequently, none of them showed any
sign of arthritis, so I don't think it's a
general side effects of being actually that my question was
going off of that. Um So once you've called
them, you obviously use like an older animal to
clone the the animals. Do you, do they
require special care when you, after you've clone them
? Um Do they require like special, do they
require um like do not, they do they look
after them with, so they don't have like those
issues later on in life because I know that in
Argentina they do um do the same thing with their
polo ponies and their polo ponies do play in like
the Argentine Open and things like that, and um
do they have to take care of them in a
special way so that they don't so they don't have
these issues as frequently later on in life? Um
I'm so far away from animal cloning these days and
I'm really not the right person to answer that question
, but probably people in this audience who I'll give
it a good answer, which is certainly known that
there is a um a likelihood that the animal will
have more mutations, both in the chromosome of DNA
and in the mitochondria. Mhm. But other than
that, and they're really not aware of things associated
with age. Mhm. As we've seen more rapid
advancements in not only technology, but also genetic.
The theory of genetics. Do you the media often
says that there could be designer babies in the future
of people being able to dictate different traits, be
it genetic or personality wise? Now, I know
some people scoff at that idea and that that's a
ridiculous idea. But we've seen ridiculous ideas become reality
and common practice. Do you foresee in the next
100 years or so of that? Human genetic modification
can become common practice and what positive, positive and
negative after effects do you see of that? Okay
, very interesting question. I think whereas cloning,
please don't go away for a minute. Yeah.
All right. Whereas cloning and gene transfer was the
subject of our debate 2030 years ago when we began
from I think genetic not education will become more and
more focus of interest and anxiety. I will answer
the question. You know what I do think is
that shouldn't be afraid. Mhm. Technology often has
an edge and important unfortunate disadvantage. If you think
way back the first time somebody stuck a sharp stone
a mistake and have the first house, it could
be used either to chop firewood or to feel animals
, which is considered to be good or to kill
the neighbors. Which is bigger scale. If you
think of the um two Atomic problems which destroyed two
Japanese cities, 60 regions, I guess that much
of the maths in the electronics which control to them
subsequently inspector involved in the production of our mobil's ipods
, ipads, laptops, modern digital cameras. And
so you just have to upset that there may well
be disadvantage. I think that there will be such
advantages from genetic modification that we mustn't northerners think about
them. So then you come to the question well
, how do you draw the line and said it's
going to? I think the further you can go
along track of being able to chest ideas in cells
in animals before you would interfere with using better,
obviously better you're able to have confirmed that the change
that you have made themselves and the animals is exactly
and only wanted to the best causing homes. Mhm
. Instead I also put in a point which I
picked up the something from Julian, several s screams
and philosopher dr lots of medic matters in Oxford.
Yes. That we discussed human beings as if they
were perfect. These are we are not magnificent.
Pieces of china, perfectly sculpt. Yes. Perfect
brains. We are perhaps shouldn't be quite so afraid
. True. In some circumstances you would. Mhm
. You're staying take a few minutes. The problem
is who makes the decision that to me many times
used as an image except to yourself, genetics potentially
made in one of your Children. Mhm. And
then discovering. Was it? Yeah. In effect
have conversations which 1? I'm terribly sorry this time
where you managed to draw that line? Do hope
you participate. Yes. And I use one example
of treating Palestinian. What's up to diseases of the
blood system would be a good start. No sir
, diseases. For the reason I mention which is
that you can do all of the outside the boat
, know that the cells are exactly what you want
in the end. I have to sure, anxiety
with upset that there has to be. Mm Let's
push it. Mhm. Thank you. We have
time for one more question. Thank you. Hello
, sir. Um why was it decided to clone
a sheep when your team tried it? Why did
you decide on a sheep and not any other animal
? Uh monkeys? I don't know. Yeah.
The reason we worked with sheep was that as I
think we both mentioned, one of our earlier project
was to produce proteins in milk. So ideally it
would be a species which was used to being milt
and which had routines and equipment that was suitable in
some ways you'd like to use cows because of the
greater volume that they would produce. But they are
more expensive and have a longer generation. So really
we thought of these sheep as being small, cheap
cows. Yeah, I do work in Scotland after
, I'll remember. Yeah. Uh huh drift.
Um we believed that anything we developed in sheet would
also work in count and that indeed is the case
. We'll mention the cloning which was done here shortly
after cattle shortly afterward. Mostly. Yeah, there
are some really interesting biological questions you could ask using
primates and that would be extremely tightly regulated in the
United Kingdom. I can't imagine how you would gain
permission. I could imagine some clinical trials, clinical
experiments you might want. It's thinking in terms of
put themselves into two people. The limitation of primates
is that there aren't any inbred lines. You could
create them in effect by cloning to make genetic.
But thinking in terms of testing out this idea of
having cell lines which are homes egress of the major
L. A. Antigens. Use the technical job
. It would be really interesting to do that in
primates but there just aren't any sort of new population
. Thank you. Got anything that particularly that you
suggest. Nothing. Thank you. Uh huh.
Okay. A year ago um an article was published
discussing how Tianjin china wanted to create the largest animal
cloning facility and their main reason was for beef cattle
production to meet market demand. Do you feel this
is a positive or negative use of regenerative medicine?
Yeah. And why? Yeah. Yeah. First
comment is you're allowing regenerative medicine claims and stop Mhm
. Lifestyle. So do I approve of. Mhm
. I think I've already said that. I don't
think that cloning is a particularly effective way of gaining
genetically improved or even disseminating. It's much much better
. And this isn't a sexist remark, it's much
much better to select the best bowls and then to
collect that semen and disseminate its right. So for
that sort of very practical reading. Mhm. I
don't approve of this I guess. I don't really
mind the music. That what do you think?
I mean if you're lacking in cattle already cloney isn't
really going to help you in the future. I
think that's a good point. Maybe you're ready blood
in that area. I think what the young lady
said was that if you're lacking in cows, cloning
doesn't really help you. You need cattle to produce
the others think is what? Thank you. Great
country you very much. Thank you all for coming
and have a safe trip home. Exactly. Right
now, he's a come here. All right.