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Mhm. Yeah, well, good afternoon ladies and

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gentlemen, thank you for coming and welcome to the

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Lyric Theatre and our first ever distinguished lecture on regenerative

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medicine. Our talk today would not have been possible

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without the generous support of the College of Agriculture and

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Life Sciences College of Liberal Arts and Human Sciences in

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the Virginia Maryland College of Veterinary Medicine and the interdisciplinary

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graduate education program, or hijab in regenerative medicine.

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Regenerative medicine is a promising new medical paradigm that envisions

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the use of stem cells to repair or replace tissues

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that have been damaged by injury, disease or congenital

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defect. This approach has particular promise for treating irreversible

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tissue damage caused by strokes, heart attacks, traumatic

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injuries and even auto immune diseases like juvenile diabetes.

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Virginia tech side and regenerative medicine is designed to train

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future leaders in the promising and growing field In this

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uh using an in traditional culinary approach that involves 15

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faculty and 30 graduate students from the college of veterinary

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medicine, Engineering, liberal arts and Human Sciences and

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business. Our students research ranges from cellular reprogramming and

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the engineering of bio materials based cellular scaffolds to bioethics

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and entrepreneurship, basically what it takes to generate stem

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cell based therapies in the lab and bring them through

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the market to the patient's bedside. That said the

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field of regenerative medicine and all of its potential and

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promise and indeed our own graduate program would not likely

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exist today, but for our guests insight, hard

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work and leadership that ultimately led to the birth of

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Dolly the sheep. Some 20 years ago. Ian

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Wilmut was born and raised near Coventry in England.

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As a boy. He worked weekends as a farmhand

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, which influenced his decision to major in animal agriculture

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at the University of Nottingham and to pursue graduate studies

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at Cambridge, where he earned a PhD for his

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work on the deep freezing of pig sperm no stranger

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to first in biology. Right out of the chute

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, as we might say in animal science, Dr

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Wilmot is the first to freeze bovine embryo for an

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extended period of time, then thought out transfer it

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to a surrogate cow and produced the first calf from

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a frozen embryo, whom he appropriately named Frosty That

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was in 1974. And the freezing technique pioneered by

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Dr Wilma is now a mainstay in the cattle industry

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and has contributed greatly to the genetic improvement of cattle

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worldwide. That same year, Dr Wilmot moved from

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Cambridge to the animal breeding research organization at Rosslyn in

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Scotland to study reproductive efficiency in livestock, in particular

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things affecting growth development and the survival of embryos during

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early pregnancy. Then in the mid 1980s, as

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it so often happens in science, a new technology

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burst onto the scene that board great promise for the

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benefit of livestock and human health alike. This was

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the technique technique of trans genesis, which enabled the

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production of novel genes or introduction of novel genes into

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animals. In particular, the scientists at Rosslyn,

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including dr Wilmot, were interested in the production of

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human pharmaceutical proteins in the milk of transgenic livestock.

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With this, doctor Willmott and his team produced another

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first Tracy, the first transgenic farm animal, a

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sheep to express a human protein in her milk.

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The prospect of harnessing the mammary gland is a bioreactor

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for making human medicines. Also captured the imagination of

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entrepreneurs as well. In 1987 Rosalind spun out a

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company, pharmaceutical proteins limited, or PPL for short

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, to develop and commercialize the technology. Other companies

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quickly followed suit, including Genzyme Transgenics in boston gen

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farm in the Netherlands and PPL inc or incorporated the

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american arm of PPL in Scotland. Located right here

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in the corporate research park at Virginia Tech introducing new

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jeans uh into sheep and other livestock was a tricky

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, unpredictable and inefficient business ever on the lookout.

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For better ways to do things. Dr Wilmott said

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about to find a better way to make transgenic sheep

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. And it was in this pursuit that ultimately led

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to dolly. Now with dolly in mind here's a

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quick visual on how dolly was made basically just run

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through this quickly up here on the upper left.

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Yeah. Yeah parking lot and a great machine seeing

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the green. Yes it is a nucleus. Mhm

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. Yeah. All right family. Your okay.

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Yeah. People hide right. Yeah. Yes.

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Yes. What? All very favorite. Something awesome

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. Mhm. Laboratory and then yeah. Okay so

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okay this case use the way oh you are do

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it behind the generation of dollars. Was that this

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is a doctor. Hey? Yeah. The way

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well being raised. Yeah. Yeah. You ready

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? Mm. You indicated so. Oh, very

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few single achievements in science have touched the public imagination

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and consciousness in the way that dolly has. Many

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of us remember and most of us know that dolly

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quickly jumped from the realm of science into the public's

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imagination around the world where she created wonder, amazement

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and to be sure some concerns and dolly has a

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very special connection. Even today, right here in

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Blacksburg 1997 PPL, incorporated up in the corporate research

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park, adapted the dalai technology very quickly to produce

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mr jefferson, one of the world's first cloned bulls

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in 2000 PPL was produced the world's first litter of

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cloned pigs. And today even today, this very

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day today revival core, also located up in the

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corporate research park in Blacksburg, is routinely cloning very

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special pigs for human compatible organs to alleviate the vast

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shortage of life saving human organs for transplant patients.

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For his outstanding accomplishments and influential achievements, Professor Willman

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has received numerous awards, accolades and honors among them

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fellowship in the Royal Society, share in the prestigious

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shaw prize with his fellow laureate and dolly collaborator,

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keith Campbell, Fellowship in the Academy of Medical Sciences

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and the european Molecular Biology Organization. And last but

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not least, Professor Wilmot was knighted by Queen Elizabeth

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in 2008 and now without further ado it is my

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great honor and pleasure to present to you, Professor

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Sir Ian Wilmott. Yeah, thank you will for

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that. Very generous introduction and you for your very

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well and welcome. Indeed. I'd like to take

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this opportunity to thank my host during this visit.

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It's been a great pleasure and you've been very kind

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to me. I am deeply grateful. Before I

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get into the biology, there are a couple of

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points that I want to make in background. First

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of all, we are as well as said,

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approaching a time with fantastic new opportunities in biology and

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medicine and I want to give the background too many

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of these in illustrate the way in which things may

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develop in the future. Secondly, to indicate that

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a huge number of people are actually involved in this

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sort of research, including this project. There were

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30 names on the slide that I used to list

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all of the people who had been involved in the

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project at Rosslyn. On the first occasion when I

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talked about the project, 30 people ranging at the

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top from secretaries, all the way through to the

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people who did the micro manipulation and looked after the

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stock. Unless you know, otherwise, you might

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very well think that cloning was something which developed perhaps

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50 years ago That in fact, it emerged from

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some science in the 19th century, not because people

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were actually doing cloning, but because they were thinking

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about the biology, um they knew about cells,

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they knew about eggs. The microscopes were good enough

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to see eggs and they were good enough to reveal

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the nucleus and the fact that it went through changes

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. But they had no idea, of course,

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as to how it control development. Recognize that chromosomes

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were only poorly understood and there was no knowledge at

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all of DNA and the knowledge that we have of

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chromosomal replication and so on. What they didn't know

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that was that there were cyclical changes in the nucleus

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and of course that the offspring very close resemblance to

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their parents. So there must be some sort of

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genetically mechanism of inheritance. What they were. Was

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not understood at all in that sort of background.

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It seems remarkable when you look at it, the

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sort of ideas that they emerged that emerged as they

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thought about this issue. How did the single cell

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of an embryo give rise to all of the different

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tissues of an adult? There there is in size

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a little bit from one mammal to another. But

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roughly speaking, there are 10th of a millim in

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diameter. That's roughly 201 200th of an inch.

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And that my new body gives rise to all of

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the different tissues of another. Just think, I

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mean, I'm not putting myself forward particularly finds.

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Yeah, just think just to start. Thanks.

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You know, that if it's do they form?

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And I'm going to read you two paragraphs written by

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august look Iceman In 1885. It must follow that

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during segmentation and subsequent cell division, that the nuclear

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plasm will enter upon definite and varied changes which must

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cause the differences in the cells that are produced.

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It's clear thinking, but not telling us very much

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just yet. He went on. The simplest hypothesis

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would be to suppose that it's each division of the

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nucleus. The specific substance divides into 2/2 of unequal

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quality so that the cell bodies would also be transferred

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. So, in other words, that, as

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we were put it in modern molecular biology, the

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two nuclei of the daughter cells after cell division have

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a tendency to do different things, perhaps the fall

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muscle, the phone skin, and that must depend

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upon the nucleus change. And that was taken in

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some further thinking to reflect loss of particular things that

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if the cell was going to form muscle, it

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lost the instructions for forming nerves, vice versa,

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It was going to form nerves. It lost the

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instructions performing muscle and that fairly quickly led to an

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experimental approach to understand this or to test it.

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If this was the case and you took a cell

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from an adult and put it into an unfertilized egg

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way that will describe it for you, it would

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not be able to support development to turn because it

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wouldn't have all of the instructions. So this was

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a not a biotechnology which was emerging. It was

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a biological question that was to be answered. Could

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the genetic information from an adult cell support development to

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turn or not now? Of course, particularly with

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the limited equipment that they had in those days.

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The sort of experiment that they came up with was

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very different from the ones that are done today.

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one very well known, which is brilliantly elegant,

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was carried out by an spiderman working with salamander.

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He took a very fine hair from his baby daughters

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head and tied it around the egg so that he

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could pull it tight And restrict the nucleus to 1/2

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. So he's got an N. You created half

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and half which had in its nucleus. And he

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let the nucleus divide until they were 16 nuclear in

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that half before he loosened the hair and let one

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nucleus go across the bridge and then re tighten the

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hair again. So that he had restricted one nucleus

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alone to the one half. And there were 15

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cells in the other. And the question was even

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at this very early stage, did that nuclear still

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have the instructions to control development to turn? And

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the answer is yes, because what he got was

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two salamanders and his notebooks copies of his notebooks are

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00:14:56.059 --> 00:14:58.549 A:middle L:90%
available in which you can see this really quite clearly

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. So what this was indicating was that at this

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stage at least both halves or fragments had still got

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all of the instructions for development. So this illustrates

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very neatly what people were expecting of cloning experiments.

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It was he in 1928 who first described what we

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would recognize as nuclear transfer. But it was not

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until 1938 or beyond that people first did nuclear transferring

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in amphibians. Working in amphibians because of the fact

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that their eggs are larger, relative robust and would

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tolerate the pressures and pushing and shoving and cutting and

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so on. That's involved in nuclear transfer, Briggs

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and King actually working in philadelphia were the first to

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describe experiments in which nuclear were transferred from early stages

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in a species of for our ground olympians. And

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some of them did develop. Yeah, part way

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through to turn but not to turn. They produced

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. And polls a little later Jon Gordon? Working

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00:16:03.549 --> 00:16:10.100 A:middle L:90%
in England used two different species Zeneca's and modified the

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procedure slightly. And this time when he transferred nuclei

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00:16:12.639 --> 00:16:15.519 A:middle L:90%
, he got, if he took the nucleus from

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an adult frog, he got tadpoles. If he

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took nuclei from temples, he got adults. But

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00:16:22.269 --> 00:16:26.690 A:middle L:90%
he never and neither has anybody else since got adult

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00:16:26.700 --> 00:16:30.299 A:middle L:90%
frogs following the transfer of nuclei from adult. So

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00:16:30.299 --> 00:16:33.240 A:middle L:90%
there seems to have been a barrier there of some

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00:16:33.240 --> 00:16:40.820 A:middle L:90%
kind. So the way in which this was interpreted

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00:16:40.820 --> 00:16:44.370 A:middle L:90%
was not to suggest that DNA had been lost from

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00:16:44.370 --> 00:16:47.039 A:middle L:90%
the cell, but rather it was speculated that it

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00:16:47.039 --> 00:16:51.059 A:middle L:90%
might reflect change against the functioning of the nucleus that

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development as Iceman had written dependent upon changes in the

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organization and function of the nucleus and that as time

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00:16:57.700 --> 00:17:00.679 A:middle L:90%
went by perhaps they became so complex and so rigidly

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00:17:00.690 --> 00:17:03.650 A:middle L:90%
fixed that they couldn't be reversed. That was an

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00:17:03.650 --> 00:17:11.420 A:middle L:90%
alternative explanation. The first mammalian nuclear transfer was carried

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00:17:11.420 --> 00:17:14.210 A:middle L:90%
out in sheep by steen Willadsen, working in Cambridge

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00:17:14.210 --> 00:17:18.059 A:middle L:90%
in England when he produced lambs following nuclear transfer from

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early cleavage stages. As far as I know at

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that stage, he didn't attend to carry out nuclear

257
00:17:22.099 --> 00:17:25.329 A:middle L:90%
transfer from later stages. So you can't draw any

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00:17:25.329 --> 00:17:29.269 A:middle L:90%
conclusions about the limits of the technique in cheap,

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00:17:29.640 --> 00:17:32.039 A:middle L:90%
really comment upon the fact that he's got the physical

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00:17:32.039 --> 00:17:40.509 A:middle L:90%
techniques sorted. What these experiments are all trying to

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investigate is how does this adult derived from the single

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cell of an adult of an embryo? Excuse me

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00:17:51.339 --> 00:17:52.240 A:middle L:90%
? The process which is involved, we would also

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know as differentiation because the single cell and its successes

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have the ability to differentiate to change to become all

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of the different tissues. And there was another way

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which was used to study differentiation and also the mechanisms

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that are involved. People were beginning to realize that

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DNA in the chromosomes must be controlling this, but

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we had absolutely no idea which fragments and how one

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way which is used to investigate this was to take

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fragments of DNA and inject them into cells and to

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see if they affected the functioning of that cell.

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And in this way identified segments which had the power

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to change cells. The likely conclusion that this included

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the jeanne with that role during development and they found

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00:18:45.940 --> 00:18:48.839 A:middle L:90%
a fragment which was given the name My OD.

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They were studying the function of muscle. Thanks my

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00:18:51.289 --> 00:18:53.390 A:middle L:90%
Oh my OD. Which if they injected it into

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the predecessors, the precursors of muscle fibers promoted their

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00:18:57.579 --> 00:19:03.430 A:middle L:90%
complete differentiation into muscle fiber. So they clearly had

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00:19:03.430 --> 00:19:06.559 A:middle L:90%
identified one of the factors involved in the formation of

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russell. However, when they put that factor into

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cells that were destined to become deputy sites, liver

285
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cells or special skin cells karate insights. They didn't

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00:19:18.829 --> 00:19:22.269 A:middle L:90%
have the ability to promote the formation of Mosul.

287
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So what this was showing was that in the appropriate

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00:19:26.640 --> 00:19:30.960 A:middle L:90%
circumstance this fragment can control development along a particular line

289
00:19:30.839 --> 00:19:33.190 A:middle L:90%
. But if the fragment was being put into cells

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00:19:33.190 --> 00:19:36.720 A:middle L:90%
which were on a different lineage, they didn't have

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00:19:36.720 --> 00:19:38.430 A:middle L:90%
the influence. And so there was a limit which

292
00:19:38.430 --> 00:19:41.910 A:middle L:90%
was critical for the orderly development of muscle and other

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cell types. So it all seems to be fitting

294
00:19:48.029 --> 00:19:52.119 A:middle L:90%
into the idea that there are limits limits to nuclear

295
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transfer, that something's maybe so rigidly fixed that cloning

296
00:19:55.329 --> 00:19:59.880 A:middle L:90%
won't work and that the regulatory factors, the transcription

297
00:19:59.880 --> 00:20:03.420 A:middle L:90%
factors also have a limited role which is appropriate in

298
00:20:03.420 --> 00:20:07.410 A:middle L:90%
the circumstances, some circumstances that is not effective in

299
00:20:07.410 --> 00:20:18.150 A:middle L:90%
others. So we then need to jump forward 10

300
00:20:18.150 --> 00:20:19.369 A:middle L:90%
or 15 years to the work that was done at

301
00:20:19.369 --> 00:20:25.470 A:middle L:90%
rustling, which was between 93 and 96 with sheep

302
00:20:25.470 --> 00:20:29.849 A:middle L:90%
nuclear transfer. And to consider giving this previous history

303
00:20:30.240 --> 00:20:33.390 A:middle L:90%
, Why were we successful in producing a clone from

304
00:20:33.390 --> 00:20:37.390 A:middle L:90%
an adult? And I think the key point is

305
00:20:37.390 --> 00:20:41.500 A:middle L:90%
that we understood in particular keith Campbell understood the importance

306
00:20:41.500 --> 00:20:45.740 A:middle L:90%
of cell cycle in regulating what happened when you fuse

307
00:20:45.740 --> 00:20:49.640 A:middle L:90%
two cells together, keith gained his PhD from work

308
00:20:49.640 --> 00:20:52.170 A:middle L:90%
done at the University of Sussex. Looking for one

309
00:20:52.170 --> 00:20:56.269 A:middle L:90%
of the key molecules in the regulation of cell cycle

310
00:20:56.839 --> 00:20:59.279 A:middle L:90%
, unfortunately failed to find it. But at least

311
00:20:59.279 --> 00:21:00.920 A:middle L:90%
this meant that he understood a lot about it and

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00:21:00.920 --> 00:21:03.579 A:middle L:90%
he understood how to asset for its presence and therefore

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look for it in eggs and early embryos and follow

314
00:21:07.789 --> 00:21:11.049 A:middle L:90%
its it's likely role during this very early stage of

315
00:21:11.059 --> 00:21:17.819 A:middle L:90%
development. So what do we mean by this little

316
00:21:17.819 --> 00:21:21.869 A:middle L:90%
jargon phrase of cell cycle? Well many cells in

317
00:21:21.869 --> 00:21:25.670 A:middle L:90%
the body will be growing and dividing as a way

318
00:21:25.670 --> 00:21:29.130 A:middle L:90%
of replacing tissues which have aged and no longer functioning

319
00:21:29.130 --> 00:21:32.460 A:middle L:90%
properly or as a way of growing. But this

320
00:21:33.039 --> 00:21:37.250 A:middle L:90%
only takes place in very carefully controlled circumstances so that

321
00:21:37.250 --> 00:21:41.099 A:middle L:90%
the cell will grow. It will take the time

322
00:21:41.109 --> 00:21:44.779 A:middle L:90%
to replicate all of the DNA and it's absolutely essential

323
00:21:44.779 --> 00:21:47.759 A:middle L:90%
that it replicates all of it. But only once

324
00:21:48.539 --> 00:21:51.059 A:middle L:90%
if it fails to replicate any or if it replicates

325
00:21:51.059 --> 00:21:52.579 A:middle L:90%
some of it more than once, then you'll have

326
00:21:52.579 --> 00:21:55.829 A:middle L:90%
an abnormal cell which may well either become conscious or

327
00:21:55.839 --> 00:21:59.750 A:middle L:90%
die. So you understand that there are very tight

328
00:21:59.950 --> 00:22:04.019 A:middle L:90%
and effective mechanisms ensuring that this happens usually. And

329
00:22:04.019 --> 00:22:07.759 A:middle L:90%
what a number of people had already argued in keith

330
00:22:07.869 --> 00:22:10.930 A:middle L:90%
emphasised this point was that it would be critical when

331
00:22:10.930 --> 00:22:12.859 A:middle L:90%
you took two cells and put them together to think

332
00:22:12.859 --> 00:22:15.359 A:middle L:90%
about the cell cycle stage that they were at.

333
00:22:17.440 --> 00:22:21.099 A:middle L:90%
If you remember wills diagram nuclear transfer involves an egg

334
00:22:21.109 --> 00:22:22.670 A:middle L:90%
recovered from animal. When usual issue would be mated

335
00:22:23.140 --> 00:22:26.299 A:middle L:90%
, the chromosomes are removed the donor cell, which

336
00:22:26.299 --> 00:22:29.720 A:middle L:90%
in this case came from mammary tissue when out of

337
00:22:29.730 --> 00:22:34.240 A:middle L:90%
you, no eggs as they are regulated the exits

338
00:22:34.240 --> 00:22:37.759 A:middle L:90%
there are violated our particular stage of the cycle and

339
00:22:37.759 --> 00:22:41.710 A:middle L:90%
relatively stable unusually to sell in the mammary tissue would

340
00:22:41.720 --> 00:22:48.349 A:middle L:90%
be growing through the cells cell cycle. So you

341
00:22:48.349 --> 00:22:52.660 A:middle L:90%
could predict reasonably accurately, but they egg would be

342
00:22:52.660 --> 00:22:55.599 A:middle L:90%
at a particular stage, but you could not know

343
00:22:55.599 --> 00:22:57.700 A:middle L:90%
exactly the stage of the donor cell. So unless

344
00:22:57.700 --> 00:23:02.289 A:middle L:90%
you took further steps to see that it's an appropriate

345
00:23:02.289 --> 00:23:04.009 A:middle L:90%
stage, you would be likely to end up with

346
00:23:04.009 --> 00:23:07.170 A:middle L:90%
an inappropriate combination, which will fail to develop.

347
00:23:10.640 --> 00:23:12.029 A:middle L:90%
The thing about the exits populate is is that it

348
00:23:12.029 --> 00:23:15.980 A:middle L:90%
is poised to begin development two as it is stimulated

349
00:23:15.980 --> 00:23:18.230 A:middle L:90%
either by our electric current or by the arrival of

350
00:23:18.230 --> 00:23:22.470 A:middle L:90%
a spur. There are profound changes in the functioning

351
00:23:22.470 --> 00:23:26.559 A:middle L:90%
of that cell as it unpacks the chromosomes as it

352
00:23:27.420 --> 00:23:32.990 A:middle L:90%
stimulates replication of chromosomes Ready to divide into the 1st

353
00:23:32.990 --> 00:23:34.910 A:middle L:90%
2 selves. So we know that that's what would

354
00:23:34.910 --> 00:23:37.400 A:middle L:90%
happen when we put a nucleus into it. And

355
00:23:37.400 --> 00:23:41.200 A:middle L:90%
what keith predicted was and his experiments confirmed this was

356
00:23:41.200 --> 00:23:44.559 A:middle L:90%
that if you put in a nucleus which was also

357
00:23:44.569 --> 00:23:48.690 A:middle L:90%
awaiting DNA replication, it would welcome the environment it

358
00:23:48.690 --> 00:23:52.349 A:middle L:90%
would find in the egg because that would simulate the

359
00:23:52.359 --> 00:23:57.319 A:middle L:90%
nucleus to to start development and to replicate DNA and

360
00:23:57.319 --> 00:24:00.509 A:middle L:90%
you'll be likely to end up with a normal chromosomes

361
00:24:00.509 --> 00:24:03.619 A:middle L:90%
such and the health yourself. By contrast, if

362
00:24:03.619 --> 00:24:06.019 A:middle L:90%
you took a nucleus at almost any other stage of

363
00:24:06.019 --> 00:24:08.109 A:middle L:90%
the cell site, if you put it into another

364
00:24:08.109 --> 00:24:11.049 A:middle L:90%
site, it will be stimulated to replicate DNA when

365
00:24:11.049 --> 00:24:14.789 A:middle L:90%
it might have already replicated all of the DNA wants

366
00:24:14.789 --> 00:24:18.089 A:middle L:90%
itself or alternatively be part way through the process of

367
00:24:18.089 --> 00:24:21.500 A:middle L:90%
replication. In which case in neither case would the

368
00:24:21.500 --> 00:24:23.349 A:middle L:90%
chromosome complement be normal? It would either be double

369
00:24:23.740 --> 00:24:27.269 A:middle L:90%
or somewhere between one and twice. You know?

370
00:24:30.539 --> 00:24:32.970 A:middle L:90%
And so from this, we predicted that there were

371
00:24:32.970 --> 00:24:33.759 A:middle L:90%
two ways in which we might hope to get a

372
00:24:33.759 --> 00:24:37.160 A:middle L:90%
normal chromosome complement. One was to take the other

373
00:24:37.160 --> 00:24:40.589 A:middle L:90%
side as it was populated and to put in a

374
00:24:40.589 --> 00:24:45.059 A:middle L:90%
nucleus awaiting DNA replication. Not indeed proved to be

375
00:24:45.279 --> 00:24:48.359 A:middle L:90%
probably the best what the combination that you could have

376
00:24:48.740 --> 00:24:52.630 A:middle L:90%
. The alternative was to stimulate the egg to begin

377
00:24:52.630 --> 00:24:56.150 A:middle L:90%
development. So this this activity known as NPF,

378
00:24:56.160 --> 00:24:57.400 A:middle L:90%
would decrease in the U. S. Site would

379
00:24:57.400 --> 00:25:00.529 A:middle L:90%
not trigger DNA replication. You could then fuse a

380
00:25:00.529 --> 00:25:04.009 A:middle L:90%
nucleus to it and it would replicate. So excuse

381
00:25:04.009 --> 00:25:07.970 A:middle L:90%
me, it would regulate whether or not replication took

382
00:25:07.970 --> 00:25:14.049 A:middle L:90%
place. We turn this universal recipient because under these

383
00:25:14.049 --> 00:25:17.869 A:middle L:90%
circumstances you'd expect to get a normal chromosome complement regardless

384
00:25:18.019 --> 00:25:19.000 A:middle L:90%
of the stage of the cell cycle of the donor

385
00:25:19.000 --> 00:25:22.670 A:middle L:90%
sound. And this proved to be the gate.

386
00:25:26.740 --> 00:25:30.089 A:middle L:90%
There was one more little trick which he introduced,

387
00:25:30.359 --> 00:25:33.029 A:middle L:90%
which depends upon us sell it. Don't sell that

388
00:25:33.029 --> 00:25:34.359 A:middle L:90%
stage, which I haven't yet mentioned, which is

389
00:25:34.359 --> 00:25:38.759 A:middle L:90%
called quiescence meaning resting. This is a cell which

390
00:25:38.759 --> 00:25:44.519 A:middle L:90%
has exited the cell cycle and paused cells are really

391
00:25:44.519 --> 00:25:47.400 A:middle L:90%
smart. If we're driving along in a car and

392
00:25:47.400 --> 00:25:48.670 A:middle L:90%
we forget to put gas in, it will stop

393
00:25:49.140 --> 00:25:53.069 A:middle L:90%
just where it runs out of fuel cell going through

394
00:25:53.069 --> 00:25:56.150 A:middle L:90%
the cell cycle will recognize that there's a problem coming

395
00:25:56.150 --> 00:25:57.319 A:middle L:90%
. And if it isn't going to be able to

396
00:25:57.319 --> 00:26:00.529 A:middle L:90%
complete the cell cycle, it will pause and exit

397
00:26:00.630 --> 00:26:03.680 A:middle L:90%
and park itself in this quiescent state, which is

398
00:26:03.680 --> 00:26:07.599 A:middle L:90%
stable. So it gives us a population to do

399
00:26:07.599 --> 00:26:08.099 A:middle L:90%
this with a group of egg, a group of

400
00:26:08.099 --> 00:26:11.880 A:middle L:90%
cells gives us a population of nuclear, which we

401
00:26:11.880 --> 00:26:12.849 A:middle L:90%
can leave on the bench to use over a period

402
00:26:12.849 --> 00:26:15.549 A:middle L:90%
of ours. And this is probably a procedure which

403
00:26:15.549 --> 00:26:25.259 A:middle L:90%
is used universally in the cloning process. So when

404
00:26:25.259 --> 00:26:29.559 A:middle L:90%
we did this with the memory nucleus that was used

405
00:26:29.569 --> 00:26:33.160 A:middle L:90%
for the production of dollies will show it earlier.

406
00:26:33.039 --> 00:26:37.180 A:middle L:90%
We were able to see development of embryos not only

407
00:26:37.180 --> 00:26:40.450 A:middle L:90%
with early stage nuclear of fetal nuclear, but also

408
00:26:40.450 --> 00:26:42.279 A:middle L:90%
for the first time from an adult. And this

409
00:26:42.279 --> 00:26:45.640 A:middle L:90%
undoubtedly this regulation of the cell cycle was one of

410
00:26:45.640 --> 00:26:53.420 A:middle L:90%
the major reasons for our success. Now. During

411
00:26:53.420 --> 00:26:56.980 A:middle L:90%
the years after that, we'll mention one case in

412
00:26:56.980 --> 00:26:59.880 A:middle L:90%
his introduction. A variety of other species have been

413
00:26:59.880 --> 00:27:03.390 A:middle L:90%
closed, including cattle and pigs, cuts and dogs

414
00:27:03.539 --> 00:27:07.910 A:middle L:90%
, horses. Mm hmm. And some less common

415
00:27:07.910 --> 00:27:15.259 A:middle L:90%
animals strikingly at that time, there were no primates

416
00:27:15.359 --> 00:27:18.990 A:middle L:90%
, no clutch successful cloning of primates. In recent

417
00:27:18.000 --> 00:27:22.259 A:middle L:90%
observations in two labs to different labs in the States

418
00:27:22.259 --> 00:27:26.420 A:middle L:90%
here demonstrated that's because the eggs of primates are particularly

419
00:27:26.420 --> 00:27:30.410 A:middle L:90%
sensitive so that if you handle them, what we

420
00:27:30.410 --> 00:27:33.109 A:middle L:90%
can now see is carelessly. They they begin to

421
00:27:33.109 --> 00:27:38.420 A:middle L:90%
develop prematurely. I'm not able to to reprogram the

422
00:27:38.420 --> 00:27:42.849 A:middle L:90%
nucleus to use the image that were used, however

423
00:27:42.859 --> 00:27:47.369 A:middle L:90%
, by modifying their protocols and treating the eggs mob

424
00:27:47.380 --> 00:27:51.700 A:middle L:90%
sensitively. This disadvantage appears to be overcome and it

425
00:27:51.700 --> 00:27:55.039 A:middle L:90%
may now be possible to clone primates successfully. We

426
00:27:55.039 --> 00:27:56.950 A:middle L:90%
don't know that it seems likely to be the case

427
00:28:02.240 --> 00:28:03.670 A:middle L:90%
, so then to pose for a minute and our

428
00:28:03.670 --> 00:28:07.759 A:middle L:90%
squat has been the significance of the Dalai experiment.

429
00:28:07.539 --> 00:28:11.450 A:middle L:90%
Well, first of all, it did formally confirmed

430
00:28:11.009 --> 00:28:14.970 A:middle L:90%
that there has been no irreversible change in the DNA

431
00:28:14.980 --> 00:28:18.559 A:middle L:90%
in mammalian cells or other species, either in cells

432
00:28:18.140 --> 00:28:25.279 A:middle L:90%
after they developed. There are regulatory mechanisms that control

433
00:28:25.279 --> 00:28:30.849 A:middle L:90%
development, but these can be reversed. Secondly,

434
00:28:32.359 --> 00:28:34.559 A:middle L:90%
extensive use has been used of this technique with livestock

435
00:28:36.099 --> 00:28:38.460 A:middle L:90%
for breed improvement, particularly here in North America.

436
00:28:41.940 --> 00:28:47.349 A:middle L:90%
Thirdly, well mentioned vivica here in Blacksburg, which

437
00:28:47.349 --> 00:28:51.789 A:middle L:90%
is doing fantastic, were genetically modifying pinks so that

438
00:28:51.789 --> 00:28:53.970 A:middle L:90%
one day their organs may be suitable for transfer into

439
00:28:53.970 --> 00:28:57.000 A:middle L:90%
patients. And some of that is being done through

440
00:28:57.009 --> 00:29:03.519 A:middle L:90%
cloning. Above all, though the most profound and

441
00:29:03.519 --> 00:29:07.579 A:middle L:90%
most important thing to come from the Dalai experiment was

442
00:29:07.579 --> 00:29:11.660 A:middle L:90%
that biologists were made to think differently. If you

443
00:29:11.660 --> 00:29:15.059 A:middle L:90%
remember early in the talk I emphasized there was a

444
00:29:15.059 --> 00:29:21.309 A:middle L:90%
thought that the DNA and the regulatory mechanisms were so

445
00:29:21.309 --> 00:29:23.319 A:middle L:90%
complex and so rigidly fixed that it would not be

446
00:29:23.319 --> 00:29:26.859 A:middle L:90%
possible to reverse the changes that take place during development

447
00:29:27.920 --> 00:29:30.500 A:middle L:90%
. At one point there was a very distinguished developmental

448
00:29:30.500 --> 00:29:33.849 A:middle L:90%
biologist who predicted it would never be possible to clone

449
00:29:33.849 --> 00:29:37.470 A:middle L:90%
an adult. Well, this is clearly not the

450
00:29:37.470 --> 00:29:38.400 A:middle L:90%
case. Not only is all of the DNA still

451
00:29:38.400 --> 00:29:41.900 A:middle L:90%
present, but it is possible or was possible for

452
00:29:41.910 --> 00:29:47.460 A:middle L:90%
unknown factors in the two reverse all the changes that

453
00:29:47.460 --> 00:29:49.779 A:middle L:90%
have been made in that cell and take the genetic

454
00:29:49.789 --> 00:29:55.400 A:middle L:90%
information back to the very beginning of developed. So

455
00:29:55.400 --> 00:29:56.309 A:middle L:90%
what lots of people were made to think was,

456
00:29:56.309 --> 00:29:59.640 A:middle L:90%
well, if the aid can do it, what

457
00:29:59.640 --> 00:30:02.880 A:middle L:90%
other ways are the of changing this, taking the

458
00:30:02.890 --> 00:30:07.460 A:middle L:90%
function of that nucleus back to the beginning? And

459
00:30:07.460 --> 00:30:10.210 A:middle L:90%
two groups working independently were the first to come forward

460
00:30:10.210 --> 00:30:12.779 A:middle L:90%
with protocols which were repeatable and effective. one The

461
00:30:12.779 --> 00:30:18.200 A:middle L:90%
best known in Japan. Led by Shinya Yamanaka Who

462
00:30:18.210 --> 00:30:22.029 A:middle L:90%
used a group of just four proteins and found that

463
00:30:22.039 --> 00:30:25.210 A:middle L:90%
they were able to reverse adult skin cells from mouse

464
00:30:25.210 --> 00:30:27.460 A:middle L:90%
and human back to the beginning of development to become

465
00:30:29.599 --> 00:30:33.460 A:middle L:90%
cells which were very similar indeed to embryo stem cells

466
00:30:33.140 --> 00:30:36.369 A:middle L:90%
. But remember they did not come from the embryo

467
00:30:36.380 --> 00:30:38.130 A:middle L:90%
, they came from skin and then were treated with

468
00:30:38.130 --> 00:30:42.960 A:middle L:90%
critical proteins. Jamie Thompson working in Madison Wisconsin,

469
00:30:44.539 --> 00:30:45.460 A:middle L:90%
he was a combination of I think five or six

470
00:30:45.460 --> 00:30:49.329 A:middle L:90%
proteins. Some overlap with those of chile Yamanaka to

471
00:30:49.329 --> 00:31:02.400 A:middle L:90%
achieve exactly the same thing. So what this means

472
00:31:02.400 --> 00:31:06.400 A:middle L:90%
is that in principle simply by introducing selected factors into

473
00:31:06.400 --> 00:31:11.640 A:middle L:90%
cells we can produce what are called pluripotent cells Glory

474
00:31:11.640 --> 00:31:12.869 A:middle L:90%
potent because they have the ability to form all of

475
00:31:12.869 --> 00:31:15.789 A:middle L:90%
the different tissues of an adult. Not only that

476
00:31:15.799 --> 00:31:18.599 A:middle L:90%
, but if you treat them right, they will

477
00:31:18.599 --> 00:31:19.819 A:middle L:90%
grow for a long period and produce very large numbers

478
00:31:19.819 --> 00:31:23.039 A:middle L:90%
of cells which can be used either in research or

479
00:31:23.039 --> 00:31:26.390 A:middle L:90%
in therapy. And it's those two things which I

480
00:31:26.390 --> 00:31:38.279 A:middle L:90%
want to move on to discuss. There are a

481
00:31:38.279 --> 00:31:42.480 A:middle L:90%
large number of diseases which reflect the fact that cells

482
00:31:42.480 --> 00:31:47.289 A:middle L:90%
in a particular tissue either died are failing to function

483
00:31:47.289 --> 00:31:52.990 A:middle L:90%
normally. We have we only have effective treatments for

484
00:31:52.990 --> 00:31:53.630 A:middle L:90%
a very small number of them and there are many

485
00:31:53.630 --> 00:31:57.400 A:middle L:90%
more for which we don't treatments. And it was

486
00:31:57.400 --> 00:32:01.329 A:middle L:90%
recognized that if this was an inherited case we could

487
00:32:01.329 --> 00:32:05.420 A:middle L:90%
take cells from the skin perhaps of a person with

488
00:32:05.430 --> 00:32:08.210 A:middle L:90%
such a disease, treat them with the special factors

489
00:32:08.440 --> 00:32:14.900 A:middle L:90%
and produced stem cells induced pluripotent stem cells. So

490
00:32:14.900 --> 00:32:20.269 A:middle L:90%
the jargon is IPs cells from that person which would

491
00:32:20.279 --> 00:32:22.960 A:middle L:90%
be expected to have the characteristics of the disease very

492
00:32:22.960 --> 00:32:25.700 A:middle L:90%
early in the life of the patient. And if

493
00:32:25.700 --> 00:32:29.970 A:middle L:90%
we did that with cells from a healthy person,

494
00:32:29.970 --> 00:32:31.329 A:middle L:90%
excuse me, a healthy person, ideally a fairly

495
00:32:31.329 --> 00:32:35.559 A:middle L:90%
close relative, then we will be able to compare

496
00:32:36.140 --> 00:32:37.970 A:middle L:90%
The healthy cells with the six cells and look for

497
00:32:37.980 --> 00:32:44.829 A:middle L:90%
the difference associated with the disease. If as is

498
00:32:44.829 --> 00:32:47.730 A:middle L:90%
the case with motor neuron disease or Lou Gehrig's disease

499
00:32:47.740 --> 00:32:50.529 A:middle L:90%
, the disease is in the spinal cord and the

500
00:32:50.529 --> 00:32:52.250 A:middle L:90%
nerves running out from it. This is the first

501
00:32:52.250 --> 00:32:54.710 A:middle L:90%
time that that's been possible because you simply can't take

502
00:32:54.720 --> 00:32:59.059 A:middle L:90%
bits of the central nervous system. Same thing goes

503
00:32:59.059 --> 00:33:00.519 A:middle L:90%
for the heart or nerves in the brain. Many

504
00:33:00.519 --> 00:33:04.759 A:middle L:90%
bits of tissue. This is a unique new opportunity

505
00:33:04.769 --> 00:33:07.099 A:middle L:90%
to study the disease and it's only by studying the

506
00:33:07.099 --> 00:33:12.880 A:middle L:90%
disease that you can begin to understand it and look

507
00:33:12.880 --> 00:33:16.490 A:middle L:90%
systematically for treatments which may either prevent the disease or

508
00:33:16.490 --> 00:33:21.769 A:middle L:90%
reduce its harmful effects. And in a group in

509
00:33:21.769 --> 00:33:24.769 A:middle L:90%
Edinburgh, we've done this with one particular mutation in

510
00:33:25.240 --> 00:33:30.289 A:middle L:90%
associated with ALS, and compared the disease cells with

511
00:33:30.299 --> 00:33:35.329 A:middle L:90%
healthy, healthy cells. And the expectation is that

512
00:33:35.549 --> 00:33:37.170 A:middle L:90%
the disease cells would not survive as long in culture

513
00:33:37.720 --> 00:33:39.339 A:middle L:90%
and indeed, that proves to be the case.

514
00:33:39.339 --> 00:33:43.420 A:middle L:90%
However kindly we treat these cells, the cells from

515
00:33:43.420 --> 00:33:46.130 A:middle L:90%
the patient with the disease last less long. That's

516
00:33:46.130 --> 00:33:49.569 A:middle L:90%
less well, So that if you examine them over

517
00:33:49.569 --> 00:33:52.089 A:middle L:90%
a 10 day period, there is a significant difference

518
00:33:53.640 --> 00:33:58.079 A:middle L:90%
. The technique was developed for having proteins inside the

519
00:33:58.079 --> 00:34:01.990 A:middle L:90%
cells which would escape if the cell died. So

520
00:34:01.990 --> 00:34:05.950 A:middle L:90%
this means this meant that a robotic system set up

521
00:34:05.960 --> 00:34:09.780 A:middle L:90%
by steve I think china in SAn Francisco could be

522
00:34:09.780 --> 00:34:13.059 A:middle L:90%
followed by robots. There's no need for students to

523
00:34:13.059 --> 00:34:15.309 A:middle L:90%
sit there night and day for a week. The

524
00:34:15.320 --> 00:34:19.400 A:middle L:90%
robots can do this and look and see how many

525
00:34:19.400 --> 00:34:21.530 A:middle L:90%
cells are there and how many have disappeared over a

526
00:34:21.539 --> 00:34:23.809 A:middle L:90%
period of time. And then to plot out death

527
00:34:23.809 --> 00:34:30.159 A:middle L:90%
plots the speed with which cells die differences were apparent

528
00:34:30.539 --> 00:34:34.510 A:middle L:90%
. And as you would expect, my colleagues now

529
00:34:34.510 --> 00:34:38.090 A:middle L:90%
have an opportunity to look for medicines, potential medicines

530
00:34:38.099 --> 00:34:40.980 A:middle L:90%
which would have, which would reduce the harmful effects

531
00:34:40.989 --> 00:34:45.849 A:middle L:90%
of the mutation in the cell line and promote their

532
00:34:46.239 --> 00:34:52.289 A:middle L:90%
life in culture. Now there are literally hundreds of

533
00:34:52.289 --> 00:34:55.280 A:middle L:90%
inherited diseases like this. We all know about one

534
00:34:55.280 --> 00:34:59.900 A:middle L:90%
or two of them, like Parkinson's disease, some

535
00:34:59.900 --> 00:35:04.409 A:middle L:90%
causes of stroke of heart and heart failure, some

536
00:35:04.409 --> 00:35:07.179 A:middle L:90%
skin conditions. But if you look in great detail

537
00:35:07.179 --> 00:35:08.340 A:middle L:90%
into the textbook, you'll find that there are hundreds

538
00:35:08.349 --> 00:35:13.119 A:middle L:90%
of them and provided that the technique is available to

539
00:35:13.119 --> 00:35:15.460 A:middle L:90%
produce the cells in culture of the tissue which is

540
00:35:15.469 --> 00:35:19.300 A:middle L:90%
damaged in that disease. Then we're now able to

541
00:35:19.300 --> 00:35:22.239 A:middle L:90%
study it and look for protective molecules for a relatively

542
00:35:22.239 --> 00:35:27.760 A:middle L:90%
small amount. The current procedure would depend upon identifying

543
00:35:28.239 --> 00:35:30.780 A:middle L:90%
the genetic error and then using molecular biology to introduce

544
00:35:30.780 --> 00:35:35.090 A:middle L:90%
that into small animals, perhaps mice, and then

545
00:35:35.099 --> 00:35:37.699 A:middle L:90%
to look for drugs which were able to overcome the

546
00:35:37.699 --> 00:35:42.670 A:middle L:90%
harmful effect of the new mutation in those animals,

547
00:35:43.130 --> 00:35:49.269 A:middle L:90%
an extremely expensive process and time consuming. So it's

548
00:35:49.269 --> 00:35:52.059 A:middle L:90%
to be expected, expected that over the next decade

549
00:35:52.059 --> 00:35:55.519 A:middle L:90%
or two, many other diseases will be studied in

550
00:35:55.519 --> 00:36:06.179 A:middle L:90%
this way too many of us in our center in

551
00:36:06.179 --> 00:36:07.849 A:middle L:90%
Edinburgh. It's this use to study disease and look

552
00:36:07.849 --> 00:36:10.969 A:middle L:90%
for drugs which will be the most important use of

553
00:36:12.289 --> 00:36:16.190 A:middle L:90%
the cells for for the foreseeable future. But in

554
00:36:16.190 --> 00:36:20.489 A:middle L:90%
the popular imagination, the application, which is considered

555
00:36:20.500 --> 00:36:22.920 A:middle L:90%
more frequently is for self therapy. The idea being

556
00:36:22.920 --> 00:36:25.840 A:middle L:90%
that if you've identified the cells which are damaged in

557
00:36:25.840 --> 00:36:29.650 A:middle L:90%
the disease, if you can produce healthy examples of

558
00:36:29.659 --> 00:36:34.750 A:middle L:90%
the same kind from an IPs cell which was produced

559
00:36:34.750 --> 00:36:36.760 A:middle L:90%
from the patient, then you would be able to

560
00:36:36.760 --> 00:36:38.130 A:middle L:90%
put those healthy cells back into the right place.

561
00:36:38.559 --> 00:36:42.960 A:middle L:90%
They would replace the dead cells, damaged cells and

562
00:36:45.130 --> 00:36:47.739 A:middle L:90%
and treat the disease in just two or three sentences

563
00:36:47.739 --> 00:36:52.070 A:middle L:90%
that I covered enormous range of technical objectives. You

564
00:36:52.070 --> 00:36:54.820 A:middle L:90%
have to produce exactly the right kind of cell and

565
00:36:54.820 --> 00:36:58.300 A:middle L:90%
have a culture which is not contaminated by any cells

566
00:36:58.300 --> 00:37:00.639 A:middle L:90%
of any other type, you have to know where

567
00:37:00.639 --> 00:37:01.059 A:middle L:90%
to put them in to be able to put them

568
00:37:01.059 --> 00:37:04.010 A:middle L:90%
and sometimes that will be deep in the brain or

569
00:37:04.010 --> 00:37:07.659 A:middle L:90%
in the spinal cord or in the heart. Um

570
00:37:07.130 --> 00:37:09.639 A:middle L:90%
, physically challenging, you have to put the right

571
00:37:09.639 --> 00:37:15.179 A:middle L:90%
number in and create an environment which will be appropriate

572
00:37:15.179 --> 00:37:19.670 A:middle L:90%
in supporting for ourselves a huge challenge. These are

573
00:37:19.670 --> 00:37:23.380 A:middle L:90%
sort of reasons why we think that's using the approach

574
00:37:23.389 --> 00:37:27.670 A:middle L:90%
to study the diseases and develop drugs is much more

575
00:37:27.670 --> 00:37:32.500 A:middle L:90%
likely to be productive in the foreseeable future. Having

576
00:37:32.500 --> 00:37:36.550 A:middle L:90%
said that the lots of groups, including our own

577
00:37:37.039 --> 00:37:40.840 A:middle L:90%
that are working towards self therapy, if we're going

578
00:37:40.840 --> 00:37:45.880 A:middle L:90%
to put cells into patients, there are several requirements

579
00:37:45.880 --> 00:37:49.019 A:middle L:90%
which I just skimmed through most of them, ideally

580
00:37:49.019 --> 00:37:52.489 A:middle L:90%
they should be ideologically matched to the patient. And

581
00:37:52.489 --> 00:37:54.539 A:middle L:90%
this is one of the apparent advantages of these IPs

582
00:37:54.539 --> 00:37:58.820 A:middle L:90%
cells. You take skin cells, you make the

583
00:37:58.820 --> 00:38:00.789 A:middle L:90%
pluripotent cells and then use them for whatever purpose and

584
00:38:00.789 --> 00:38:04.570 A:middle L:90%
they are genetically identical to the patients. And so

585
00:38:04.570 --> 00:38:07.750 A:middle L:90%
you can put the cells into them without without problem

586
00:38:10.519 --> 00:38:13.260 A:middle L:90%
. It isn't quite as simple as that. Some

587
00:38:13.260 --> 00:38:15.340 A:middle L:90%
of the diseases we're treating our auto immune, in

588
00:38:15.340 --> 00:38:17.610 A:middle L:90%
other words, there's an immune response against the person

589
00:38:17.619 --> 00:38:21.650 A:middle L:90%
him or herself, Type one diabetes, for example

590
00:38:22.219 --> 00:38:23.150 A:middle L:90%
. So it's known that in that circumstance, if

591
00:38:23.150 --> 00:38:28.630 A:middle L:90%
you put more pancreatic tissue of that genotype into the

592
00:38:28.639 --> 00:38:30.409 A:middle L:90%
patient, they will be destroyed because there are antibodies

593
00:38:30.409 --> 00:38:32.860 A:middle L:90%
there already. So there are some exceptions to this

594
00:38:35.019 --> 00:38:43.940 A:middle L:90%
. That's the sort of basic approach. And one

595
00:38:43.940 --> 00:38:46.670 A:middle L:90%
of the summary descriptions of this approach for cell therapy

596
00:38:46.670 --> 00:38:50.389 A:middle L:90%
was that you could have patient specific cells. That's

597
00:38:50.389 --> 00:38:52.340 A:middle L:90%
what I've just described. Cells that would be genetically

598
00:38:52.340 --> 00:38:55.389 A:middle L:90%
identical to the patient would be used. But that

599
00:38:55.389 --> 00:38:59.050 A:middle L:90%
would mean that we were producing a huge number of

600
00:38:59.050 --> 00:39:02.329 A:middle L:90%
cell lines, millions and too many of us myself

601
00:39:02.329 --> 00:39:07.840 A:middle L:90%
included. It's simply impracticable. Some fortunate people might

602
00:39:07.840 --> 00:39:08.619 A:middle L:90%
have that privilege, but we really need to come

603
00:39:08.619 --> 00:39:13.760 A:middle L:90%
up with an alternative strategy. And for many years

604
00:39:13.760 --> 00:39:16.550 A:middle L:90%
now people have been looking for ways that damping down

605
00:39:16.550 --> 00:39:22.510 A:middle L:90%
the immune response or making cells less mediagenic as a

606
00:39:22.510 --> 00:39:25.840 A:middle L:90%
way of avoiding the need for patient specific cells.

607
00:39:27.869 --> 00:39:30.630 A:middle L:90%
And this warning approach to that which may prove to

608
00:39:30.630 --> 00:39:37.869 A:middle L:90%
the successful. There are major proteins on the surface

609
00:39:37.869 --> 00:39:43.659 A:middle L:90%
of cells which promote the immune rejection. We each

610
00:39:43.659 --> 00:39:47.510 A:middle L:90%
have two copies of the the the protein product of

611
00:39:47.510 --> 00:39:52.579 A:middle L:90%
the gene and usually they're different. So there's great

612
00:39:52.579 --> 00:39:54.920 A:middle L:90%
diversity. This is why when you see people looking

613
00:39:54.920 --> 00:39:59.809 A:middle L:90%
for bone marrow transplants, they're looking among one in

614
00:39:59.809 --> 00:40:01.760 A:middle L:90%
tens of thousands and they're putting out calls for help

615
00:40:01.760 --> 00:40:05.460 A:middle L:90%
all around the world to identify the rare individuals was

616
00:40:05.460 --> 00:40:09.119 A:middle L:90%
genetically identical. It's impractical to think of doing that

617
00:40:09.130 --> 00:40:15.289 A:middle L:90%
for large numbers of people but it's not actually necessary

618
00:40:15.360 --> 00:40:20.969 A:middle L:90%
for it should be identical now. Rather doubted by

619
00:40:20.969 --> 00:40:34.590 A:middle L:90%
can illustrate Those that these are the two just posted

620
00:40:34.599 --> 00:40:39.139 A:middle L:90%
on the cell surface has these two do so much

621
00:40:39.510 --> 00:40:45.300 A:middle L:90%
look for another person with these, suppose in fact

622
00:40:45.300 --> 00:40:52.460 A:middle L:90%
, instead, different person two, two terms of

623
00:40:52.460 --> 00:41:00.139 A:middle L:90%
display that would also be active because the person right

624
00:41:02.110 --> 00:41:12.630 A:middle L:90%
, wouldn't be in mind this Now. People with

625
00:41:12.639 --> 00:41:17.199 A:middle L:90%
two copies that are identical are rare, so it

626
00:41:17.199 --> 00:41:21.110 A:middle L:90%
takes a lot of effort to find them. But

627
00:41:21.119 --> 00:41:22.739 A:middle L:90%
the converse point is that they are incredibly useful.

628
00:41:23.809 --> 00:41:28.039 A:middle L:90%
An immunologist working in Cambridge, England has estimated that

629
00:41:28.039 --> 00:41:32.010 A:middle L:90%
the library of 150 cell lines would provide this sort

630
00:41:32.010 --> 00:41:37.139 A:middle L:90%
of match For more than 90 of the UK population

631
00:41:37.210 --> 00:41:39.820 A:middle L:90%
. So you might be talking about producing Say 200

632
00:41:39.820 --> 00:41:45.369 A:middle L:90%
cell lines that seems manager. It seems realistic to

633
00:41:45.369 --> 00:41:47.940 A:middle L:90%
think that we could produce a library of that scale

634
00:41:51.619 --> 00:41:52.760 A:middle L:90%
. The population in the United States is rather more

635
00:41:52.760 --> 00:41:55.400 A:middle L:90%
varied. So you probably would need and across it's

636
00:41:55.400 --> 00:41:59.139 A:middle L:90%
much bigger that you would probably need rather more than

637
00:41:59.610 --> 00:42:01.119 A:middle L:90%
150 lines. But that sort of ratio would still

638
00:42:01.119 --> 00:42:06.360 A:middle L:90%
apply Japan, by contrast, is rather inbred country

639
00:42:06.360 --> 00:42:07.239 A:middle L:90%
. They're more uniform because of the time when they

640
00:42:07.239 --> 00:42:12.150 A:middle L:90%
were a closed country. So rather less than 150

641
00:42:12.150 --> 00:42:16.739 A:middle L:90%
lines would be necessary. This is only a partial

642
00:42:16.909 --> 00:42:21.090 A:middle L:90%
match. It's not a perfect match. So nobody

643
00:42:21.090 --> 00:42:23.920 A:middle L:90%
knows how much rejection there would be against these cells

644
00:42:24.800 --> 00:42:27.630 A:middle L:90%
. The only way to find out will be one

645
00:42:27.630 --> 00:42:30.639 A:middle L:90%
day to put cells into people to look and see

646
00:42:30.650 --> 00:42:35.389 A:middle L:90%
what happens. But the returns, the benefits from

647
00:42:35.389 --> 00:42:37.239 A:middle L:90%
having a system like this that worked will be so

648
00:42:37.239 --> 00:42:43.309 A:middle L:90%
large that it seems appropriate to invest now in producing

649
00:42:43.309 --> 00:42:45.300 A:middle L:90%
libraries of this sort of scale and then beginning to

650
00:42:45.300 --> 00:42:51.000 A:middle L:90%
do tests to see how acceptable cells of that kind

651
00:42:51.000 --> 00:42:55.250 A:middle L:90%
are. And an organization was formed last year made

652
00:42:55.250 --> 00:42:59.989 A:middle L:90%
up of countries, excuse me, laboratories from countries

653
00:42:59.989 --> 00:43:02.110 A:middle L:90%
around the world with a view of setting up such

654
00:43:02.110 --> 00:43:07.409 A:middle L:90%
a library. Um, and then going on with

655
00:43:07.409 --> 00:43:12.739 A:middle L:90%
the research after that. It is of course extremely

656
00:43:12.739 --> 00:43:17.679 A:middle L:90%
important that that organization should carry out tests to establish

657
00:43:17.679 --> 00:43:22.570 A:middle L:90%
routines which are consistent self routines for producing themselves that

658
00:43:22.570 --> 00:43:25.320 A:middle L:90%
are consistent all around the world. It's essential that

659
00:43:25.320 --> 00:43:30.539 A:middle L:90%
there would be effective monitoring of the cells to ensure

660
00:43:30.539 --> 00:43:34.130 A:middle L:90%
that they were safe and effective. And that is

661
00:43:34.130 --> 00:43:37.420 A:middle L:90%
what the organization organization, excuse me, is dedicated

662
00:43:37.420 --> 00:43:49.179 A:middle L:90%
to carry. So there's one other potential use of

663
00:43:49.179 --> 00:43:52.230 A:middle L:90%
this technique haven't managed to mention so before I finally

664
00:43:52.230 --> 00:43:57.440 A:middle L:90%
summarized. And that is that what you are preparing

665
00:43:57.440 --> 00:44:00.989 A:middle L:90%
cells to put into a person would be an opportunity

666
00:44:00.989 --> 00:44:04.869 A:middle L:90%
to make genetic change. If you're trying to treat

667
00:44:04.869 --> 00:44:07.610 A:middle L:90%
a person who had thalassemia, which needs to be

668
00:44:08.090 --> 00:44:13.590 A:middle L:90%
want to no websites, which are less effective,

669
00:44:13.599 --> 00:44:17.719 A:middle L:90%
but also across pains that cuts through this. One

670
00:44:17.719 --> 00:44:20.829 A:middle L:90%
way to approach this. One new way to approach

671
00:44:20.829 --> 00:44:24.559 A:middle L:90%
this is to take tissue first to make the jury

672
00:44:24.559 --> 00:44:30.789 A:middle L:90%
problem steps probably at that stage to correct you could

673
00:44:30.789 --> 00:44:35.500 A:middle L:90%
then induce the formation reporting stem cells. These are

674
00:44:35.500 --> 00:44:42.980 A:middle L:90%
the stems. So it seems likely that this approach

675
00:44:42.980 --> 00:44:47.420 A:middle L:90%
could be used to produce treatment fully affected Children.

676
00:44:47.789 --> 00:44:53.579 A:middle L:90%
This is similar approach was used with in an experimental

677
00:44:53.579 --> 00:44:57.349 A:middle L:90%
demonstration in Nice a few years ago and I've no

678
00:44:57.349 --> 00:45:00.460 A:middle L:90%
doubt that various labs around the world now working on

679
00:45:00.460 --> 00:45:06.190 A:middle L:90%
this, it seems quite inappropriate and safe way to

680
00:45:06.199 --> 00:45:08.550 A:middle L:90%
use genetic modification because at the time when the changes

681
00:45:08.550 --> 00:45:12.369 A:middle L:90%
made, the cells are out in a dish and

682
00:45:12.369 --> 00:45:14.309 A:middle L:90%
you'd only put them back into the patient If you're

683
00:45:14.320 --> 00:45:19.739 A:middle L:90%
absolutely convinced. Excuse me. If you're absolutely convinced

684
00:45:19.750 --> 00:45:22.659 A:middle L:90%
now the change has been made accurately and that there

685
00:45:22.659 --> 00:45:25.280 A:middle L:90%
had been no other unintentional jane. If you were

686
00:45:25.280 --> 00:45:28.920 A:middle L:90%
contemplating changing, let's say, a motor neuron,

687
00:45:29.489 --> 00:45:31.230 A:middle L:90%
there would be a different matter altogether. Because that

688
00:45:31.230 --> 00:45:34.449 A:middle L:90%
would have to be done in the body. You

689
00:45:34.449 --> 00:45:36.769 A:middle L:90%
would have no way of really knowing whether or not

690
00:45:36.769 --> 00:45:39.469 A:middle L:90%
it. Okay. Maybe I'm being in Judah,

691
00:45:39.469 --> 00:45:44.380 A:middle L:90%
customers take. Certainly in some cases, the ability

692
00:45:44.380 --> 00:45:47.360 A:middle L:90%
to produce i ps cells will create opportunities or is

693
00:45:47.360 --> 00:45:52.800 A:middle L:90%
creating opportunities to treat genetic diseases which can be treated

694
00:45:52.800 --> 00:46:01.289 A:middle L:90%
at the present. So, in concluding, if

695
00:46:01.289 --> 00:46:07.730 A:middle L:90%
we look back 100 or so years, maybe more

696
00:46:07.849 --> 00:46:08.460 A:middle L:90%
. If you go back to the iceman's time,

697
00:46:08.469 --> 00:46:14.309 A:middle L:90%
18 sixties when he made his analysis, an enormous

698
00:46:14.309 --> 00:46:16.309 A:middle L:90%
amount has been achieved in the control and elimination of

699
00:46:16.309 --> 00:46:22.980 A:middle L:90%
effective infectious diseases during that period. Not only that

700
00:46:22.989 --> 00:46:27.230 A:middle L:90%
, but we feed the population. We feed ourselves

701
00:46:27.230 --> 00:46:30.900 A:middle L:90%
rather better. Virtually all of the water that we

702
00:46:30.900 --> 00:46:34.550 A:middle L:90%
drink is clean and stuff. We've learned an awful

703
00:46:34.550 --> 00:46:37.579 A:middle L:90%
lot about infectious agents. But if you think about

704
00:46:37.579 --> 00:46:40.349 A:middle L:90%
it, by contrast, very little has been achieved

705
00:46:40.349 --> 00:46:45.050 A:middle L:90%
in the treatment or even the understanding of the degenerative

706
00:46:45.050 --> 00:46:47.940 A:middle L:90%
diseases which reflect loss or death of cells throughout the

707
00:46:47.949 --> 00:46:54.099 A:middle L:90%
project. What seems likely is that during the next

708
00:46:54.099 --> 00:46:58.980 A:middle L:90%
100 years there will be an opportunity of several opportunities

709
00:46:59.090 --> 00:47:05.300 A:middle L:90%
to study the men treat these diseases and transform our

710
00:47:05.300 --> 00:47:09.110 A:middle L:90%
ability to treat treatment. And if you think many

711
00:47:09.110 --> 00:47:12.599 A:middle L:90%
of them are associated with people in old age,

712
00:47:14.679 --> 00:47:16.960 A:middle L:90%
so it may well be that we can give our

713
00:47:16.969 --> 00:47:23.610 A:middle L:90%
family members healthier whole age if we can eliminate or

714
00:47:23.610 --> 00:47:35.429 A:middle L:90%
treat degenerative diseases like this, it seems to me

715
00:47:35.429 --> 00:47:39.610 A:middle L:90%
this is incredibly exciting. We should be excited by

716
00:47:39.610 --> 00:47:44.190 A:middle L:90%
this and not afraid of. We should be cautious

717
00:47:44.190 --> 00:47:45.000 A:middle L:90%
about the way in which we use them. Except

718
00:47:46.380 --> 00:47:52.460 A:middle L:90%
this is really, really let's see that and spend

719
00:47:52.460 --> 00:48:00.170 A:middle L:90%
the necessary money developing these procedures and make dr just

720
00:48:00.170 --> 00:48:06.570 A:middle L:90%
put it down what then you time himself. That

721
00:48:06.570 --> 00:48:22.159 A:middle L:90%
in principle should not the satellite. I think it's

722
00:48:22.159 --> 00:48:23.150 A:middle L:90%
important to realize that it will take quite a long

723
00:48:23.150 --> 00:48:27.579 A:middle L:90%
time to achieve these different goals. I've said several

724
00:48:27.579 --> 00:48:30.389 A:middle L:90%
times today in conversation. This is the disappointing,

725
00:48:32.369 --> 00:48:37.530 A:middle L:90%
particularly you or your the husband. It's important to

726
00:48:37.539 --> 00:48:43.780 A:middle L:90%
be careful with the local trials to say for drugs

727
00:48:44.369 --> 00:48:52.389 A:middle L:90%
. I was going that's think unexpectedly arising from Some

728
00:48:52.389 --> 00:48:55.409 A:middle L:90%
thinking in the 1860s, Early developments through the 20th

729
00:48:55.409 --> 00:49:00.530 A:middle L:90%
century. Then the Dalai experiment towards the there's a

730
00:49:00.539 --> 00:49:06.199 A:middle L:90%
very strong chance that we can revolutionize action, particularly

731
00:49:06.199 --> 00:49:35.329 A:middle L:90%
the treatment of the judge. Thank you in that

732
00:49:35.340 --> 00:49:37.929 A:middle L:90%
excellent and exciting presentation. We do have a few

733
00:49:37.929 --> 00:49:40.010 A:middle L:90%
more minutes for questions. We have a couple of

734
00:49:40.010 --> 00:49:43.469 A:middle L:90%
microphones at the forward end of each. I'll,

735
00:49:43.480 --> 00:49:45.409 A:middle L:90%
if you'd like to ask a question, uh,

736
00:49:45.420 --> 00:49:49.130 A:middle L:90%
police approach the microphones and even will do his best

737
00:49:49.130 --> 00:49:51.110 A:middle L:90%
to answer. I'm sure. Yeah, I can't

738
00:49:51.110 --> 00:50:08.130 A:middle L:90%
really. Well if you don't mind, I might

739
00:50:08.130 --> 00:50:14.019 A:middle L:90%
ask the question. Should um, you meant you

740
00:50:14.030 --> 00:50:20.420 A:middle L:90%
very eloquently presented a very optimistic picture for how and

741
00:50:20.420 --> 00:50:22.400 A:middle L:90%
technology that you develop with dolly and that has been

742
00:50:22.409 --> 00:50:25.489 A:middle L:90%
carried on by others into the human medical field.

743
00:50:27.960 --> 00:50:30.360 A:middle L:90%
How do you see the Dalai technology which after all

744
00:50:30.360 --> 00:50:32.329 A:middle L:90%
, was developed in a sheep and a species of

745
00:50:32.329 --> 00:50:42.500 A:middle L:90%
livestock perhaps affecting the the livestock industry and our ability

746
00:50:42.510 --> 00:50:46.969 A:middle L:90%
to feed the world? Thank you. I think

747
00:50:46.969 --> 00:50:52.019 A:middle L:90%
that the impact of cloning as such, I personally

748
00:50:52.019 --> 00:50:57.300 A:middle L:90%
think will be relatively limited. Animal breeders worked out

749
00:50:57.309 --> 00:51:00.590 A:middle L:90%
decades ago that the most effective thing to speed breed

750
00:51:00.590 --> 00:51:05.449 A:middle L:90%
improvement is to collect semen and disseminate it because you

751
00:51:05.449 --> 00:51:08.250 A:middle L:90%
can do really accurate and effective performance test on the

752
00:51:08.250 --> 00:51:13.079 A:middle L:90%
males before you do that. On the other hand

753
00:51:13.659 --> 00:51:16.000 A:middle L:90%
, um, cloning can be used as a way

754
00:51:16.000 --> 00:51:21.449 A:middle L:90%
of introducing genetic change. There's research at all sorts

755
00:51:21.449 --> 00:51:25.769 A:middle L:90%
of different universities, including attack here, showing identifying

756
00:51:25.769 --> 00:51:29.829 A:middle L:90%
some factors which are critical for growth and production of

757
00:51:29.829 --> 00:51:32.730 A:middle L:90%
lean meat, for example, factors which are waiting

758
00:51:32.730 --> 00:51:36.969 A:middle L:90%
now to be introduced into livestock to speed the production

759
00:51:36.969 --> 00:51:42.480 A:middle L:90%
of high quality lean meat in livestock. There are

760
00:51:42.480 --> 00:51:49.849 A:middle L:90%
ideas being developed for conferring resistance to infectious disease on

761
00:51:49.849 --> 00:51:54.530 A:middle L:90%
livestock species by making genetic change. Um, it

762
00:51:54.530 --> 00:52:02.260 A:middle L:90%
seems to me that it's shameful, wasteful to not

763
00:52:02.269 --> 00:52:06.929 A:middle L:90%
take these opportunities. Of course it's essential to consider

764
00:52:06.929 --> 00:52:14.179 A:middle L:90%
animal welfare cloning how Scottish disadvantages we should be careful

765
00:52:14.179 --> 00:52:17.710 A:middle L:90%
to minimize the stress that's involved. But careful use

766
00:52:17.710 --> 00:52:22.670 A:middle L:90%
of this technique could introduced profound genetic changes into lifestyle

767
00:52:22.679 --> 00:52:30.780 A:middle L:90%
with benefit to them sometimes and to us. So

768
00:52:30.780 --> 00:52:34.420 A:middle L:90%
since it's been 20 years since dolly and there are

769
00:52:34.420 --> 00:52:36.559 A:middle L:90%
many people in this room who weren't even alive,

770
00:52:36.570 --> 00:52:38.429 A:middle L:90%
they're younger than dolly. I wondered if you could

771
00:52:38.429 --> 00:52:43.829 A:middle L:90%
take us back to that time in 1996-97 and talk

772
00:52:43.829 --> 00:52:46.260 A:middle L:90%
a little bit about um what the atmosphere was like

773
00:52:46.269 --> 00:52:50.320 A:middle L:90%
because I remember people were frightened. And it's hard

774
00:52:50.320 --> 00:52:52.039 A:middle L:90%
when you look at that adorable sheep up on the

775
00:52:52.039 --> 00:52:55.139 A:middle L:90%
screen that we saw earlier to think that people were

776
00:52:55.139 --> 00:52:59.059 A:middle L:90%
really, really scared of this technology. What was

777
00:52:59.059 --> 00:53:00.579 A:middle L:90%
that like for you? And what do you think

778
00:53:00.590 --> 00:53:01.409 A:middle L:90%
the reasons were for that? And how do you

779
00:53:01.409 --> 00:53:06.519 A:middle L:90%
think it's now been so absorbed into society that people

780
00:53:06.519 --> 00:53:09.559 A:middle L:90%
no longer have that visceral reaction to cloning? Can

781
00:53:09.559 --> 00:53:13.480 A:middle L:90%
I just quickly check before you go, mm.

782
00:53:13.849 --> 00:53:15.409 A:middle L:90%
Do you think it has been absorbed? Do you

783
00:53:15.409 --> 00:53:19.989 A:middle L:90%
think it isn't? I'm asking you I'm asking you

784
00:53:20.000 --> 00:53:23.460 A:middle L:90%
, you made the assertion. Uh huh. Yeah

785
00:53:27.250 --> 00:53:29.510 A:middle L:90%
. It was it was really quite a difficult time

786
00:53:29.510 --> 00:53:32.920 A:middle L:90%
mostly because of the enormous interest in scale of work

787
00:53:32.920 --> 00:53:36.969 A:middle L:90%
that's required when the announcement was made. I've long

788
00:53:36.969 --> 00:53:38.719 A:middle L:90%
ago forgotten the number of inquiries which we receive but

789
00:53:38.719 --> 00:53:43.179 A:middle L:90%
ran into hundreds within a few days. Um,

790
00:53:44.050 --> 00:53:46.510 A:middle L:90%
so there was enormous pressure for newspaper reporters for TVs

791
00:53:46.510 --> 00:53:52.880 A:middle L:90%
for radios and so on. Um I think we'd

792
00:53:53.349 --> 00:53:57.400 A:middle L:90%
those of us in the group had thought through the

793
00:53:57.400 --> 00:54:00.800 A:middle L:90%
whole business for ourselves long before. I mean the

794
00:54:00.800 --> 00:54:02.769 A:middle L:90%
image in the in the communities experiment is he sat

795
00:54:02.769 --> 00:54:06.150 A:middle L:90%
in his bath, had an idea, jumped out

796
00:54:06.150 --> 00:54:08.210 A:middle L:90%
and said Eureka. As many of you will know

797
00:54:08.210 --> 00:54:12.480 A:middle L:90%
pregnancy and sheep last 150 days. That's a hell

798
00:54:12.480 --> 00:54:19.559 A:middle L:90%
of a long eureka. Yeah. So we've had

799
00:54:19.570 --> 00:54:22.940 A:middle L:90%
time and had our own conversations within the group to

800
00:54:22.940 --> 00:54:28.320 A:middle L:90%
consider our views to the use of technologies to increase

801
00:54:28.329 --> 00:54:31.760 A:middle L:90%
efficiency food production. So on. Mostly even then

802
00:54:32.139 --> 00:54:37.530 A:middle L:90%
we focused on its using in human reproduction where we

803
00:54:37.530 --> 00:54:42.400 A:middle L:90%
in favor of cloning people and the answer universally was

804
00:54:42.409 --> 00:54:45.260 A:middle L:90%
no. So we had no difficulty consistently saying that

805
00:54:46.449 --> 00:54:49.309 A:middle L:90%
the acid test that we use and I used it

806
00:54:49.309 --> 00:54:52.530 A:middle L:90%
earlier on today in a class is to ask particularly

807
00:54:52.530 --> 00:54:53.730 A:middle L:90%
the young people in this audience, would you like

808
00:54:53.730 --> 00:54:57.820 A:middle L:90%
to be a genetically identical twin of your father or

809
00:54:57.820 --> 00:54:59.860 A:middle L:90%
mother? The same parent of the same gender?

810
00:55:00.239 --> 00:55:06.389 A:middle L:90%
It was a majority said no as a father.

811
00:55:06.389 --> 00:55:16.920 A:middle L:90%
I can't understand that. I think if you are

812
00:55:16.920 --> 00:55:19.699 A:middle L:90%
being blunt mindy, what you might say is that

813
00:55:19.699 --> 00:55:22.510 A:middle L:90%
I'm being naive and optimistic and you know, that's

814
00:55:22.510 --> 00:55:24.260 A:middle L:90%
a fairly universal, fairly general partner of my behavior

815
00:55:24.739 --> 00:55:28.280 A:middle L:90%
. Um, because I wanted to get over the

816
00:55:28.280 --> 00:55:32.650 A:middle L:90%
point that there are real opportunities here. Um but

817
00:55:32.659 --> 00:55:36.909 A:middle L:90%
they will only be developed to the full if those

818
00:55:36.909 --> 00:55:39.309 A:middle L:90%
of us who have the opportunity to make the case

819
00:55:39.309 --> 00:55:43.969 A:middle L:90%
for them to be applied in our own community.

820
00:55:44.340 --> 00:55:47.320 A:middle L:90%
Yeah. Is there something that led to dali's passing

821
00:55:47.320 --> 00:55:50.510 A:middle L:90%
or was it simply natural death? No, I'm

822
00:55:50.510 --> 00:55:52.909 A:middle L:90%
afraid it wasn't. So, I hope you can

823
00:55:52.909 --> 00:55:53.170 A:middle L:90%
hear the question, could you at the back?

824
00:55:55.539 --> 00:55:59.860 A:middle L:90%
Maybe not? Yes. Okay. Right. Um

825
00:56:00.699 --> 00:56:04.650 A:middle L:90%
sadly dolly had a virus, virally induced cancer.

826
00:56:05.230 --> 00:56:08.480 A:middle L:90%
Um It's not terribly common but it does occur around

827
00:56:08.480 --> 00:56:12.250 A:middle L:90%
the southeast of Scotland where we work and live.

828
00:56:12.829 --> 00:56:15.039 A:middle L:90%
Um There is no test for it. There is

829
00:56:15.039 --> 00:56:19.869 A:middle L:90%
no treatment for it. And in order to do

830
00:56:19.869 --> 00:56:22.380 A:middle L:90%
the work, we used hundreds of sheep each year

831
00:56:22.420 --> 00:56:25.599 A:middle L:90%
. This sort of research we couldn't possibly produce from

832
00:56:25.599 --> 00:56:28.400 A:middle L:90%
our own produce them from our own flock. We

833
00:56:28.400 --> 00:56:30.510 A:middle L:90%
had to buy in Ge. And obviously what happened

834
00:56:30.510 --> 00:56:32.800 A:middle L:90%
to us at least once we introduced an animal with

835
00:56:32.809 --> 00:56:37.480 A:middle L:90%
the um, the disease, had there been a

836
00:56:37.480 --> 00:56:38.130 A:middle L:90%
test, we would have tested them all on the

837
00:56:38.130 --> 00:56:40.119 A:middle L:90%
way into the, to the farm, but there

838
00:56:40.119 --> 00:56:43.530 A:middle L:90%
wasn't, there isn't. So that was an option

839
00:56:43.530 --> 00:56:45.849 A:middle L:90%
open to us. So when one of the sheep

840
00:56:45.849 --> 00:56:46.920 A:middle L:90%
went down with the symptoms, we realized that it

841
00:56:46.920 --> 00:56:50.289 A:middle L:90%
was likely she'd already passed it on to dolly.

842
00:56:50.289 --> 00:56:52.849 A:middle L:90%
And that's indeed proved to be the the case.

843
00:56:52.110 --> 00:56:54.480 A:middle L:90%
Unfortunately, because there's no treatment, there was nothing

844
00:56:54.480 --> 00:57:00.219 A:middle L:90%
we could do. Um, the effect is when

845
00:57:00.219 --> 00:57:06.559 A:middle L:90%
the tumor grows in the animals along is to not

846
00:57:06.559 --> 00:57:09.630 A:middle L:90%
quite suffocated but make breathing difficult. What you begin

847
00:57:09.630 --> 00:57:12.659 A:middle L:90%
to see is fluid running out of the mouth.

848
00:57:13.329 --> 00:57:15.579 A:middle L:90%
So she was taken across to the nearby vet school

849
00:57:15.579 --> 00:57:17.800 A:middle L:90%
and scanned and my colleagues were shocked at the size

850
00:57:17.800 --> 00:57:22.059 A:middle L:90%
of the tumor. She also had difficulty recovering from

851
00:57:22.059 --> 00:57:24.719 A:middle L:90%
the anesthetic which we use to make a restful what

852
00:57:24.719 --> 00:57:28.880 A:middle L:90%
she was scanned. And so we decided it was

853
00:57:28.880 --> 00:57:31.000 A:middle L:90%
kind of to enter life rather than subject to this

854
00:57:31.429 --> 00:57:36.679 A:middle L:90%
over a period of time. There's no reason to

855
00:57:36.679 --> 00:57:42.639 A:middle L:90%
think that infection with this agent has anything to do

856
00:57:42.639 --> 00:57:45.280 A:middle L:90%
with cloning itself. She did, on the other

857
00:57:45.280 --> 00:57:49.599 A:middle L:90%
hand, have arthritis. We've seen the evidence of

858
00:57:49.599 --> 00:57:52.050 A:middle L:90%
this in one of her back legs for many months

859
00:57:52.050 --> 00:57:53.329 A:middle L:90%
and that had been treated. But it was only

860
00:57:53.329 --> 00:57:57.090 A:middle L:90%
when a full history pathology was carried out that it

861
00:57:57.090 --> 00:58:00.420 A:middle L:90%
was realized that there was arthritis all along. Maybe

862
00:58:00.420 --> 00:58:02.840 A:middle L:90%
not all, but large segments of her backbone.

863
00:58:04.420 --> 00:58:08.030 A:middle L:90%
Um really quite serious arthritis, I guess, as

864
00:58:08.030 --> 00:58:10.739 A:middle L:90%
I say, it was really only really visible once

865
00:58:10.739 --> 00:58:15.150 A:middle L:90%
you've been dissected and was being prepared for preservation.

866
00:58:16.219 --> 00:58:19.650 A:middle L:90%
To my knowledge, she's the only one of our

867
00:58:19.659 --> 00:58:27.719 A:middle L:90%
animals who had this. Um and certainly groups of

868
00:58:27.719 --> 00:58:30.599 A:middle L:90%
animals or clone subsequently, none of them showed any

869
00:58:30.599 --> 00:58:32.070 A:middle L:90%
sign of arthritis, so I don't think it's a

870
00:58:32.079 --> 00:58:37.429 A:middle L:90%
general side effects of being actually that my question was

871
00:58:37.429 --> 00:58:39.929 A:middle L:90%
going off of that. Um So once you've called

872
00:58:39.929 --> 00:58:43.380 A:middle L:90%
them, you obviously use like an older animal to

873
00:58:43.389 --> 00:58:45.590 A:middle L:90%
clone the the animals. Do you, do they

874
00:58:45.599 --> 00:58:47.110 A:middle L:90%
require special care when you, after you've clone them

875
00:58:47.119 --> 00:58:51.280 A:middle L:90%
? Um Do they require like special, do they

876
00:58:51.289 --> 00:58:54.050 A:middle L:90%
require um like do not, they do they look

877
00:58:54.059 --> 00:58:57.570 A:middle L:90%
after them with, so they don't have like those

878
00:58:57.579 --> 00:59:00.210 A:middle L:90%
issues later on in life because I know that in

879
00:59:00.210 --> 00:59:02.320 A:middle L:90%
Argentina they do um do the same thing with their

880
00:59:02.320 --> 00:59:05.719 A:middle L:90%
polo ponies and their polo ponies do play in like

881
00:59:05.719 --> 00:59:07.760 A:middle L:90%
the Argentine Open and things like that, and um

882
00:59:07.769 --> 00:59:09.409 A:middle L:90%
do they have to take care of them in a

883
00:59:09.409 --> 00:59:13.130 A:middle L:90%
special way so that they don't so they don't have

884
00:59:13.130 --> 00:59:16.949 A:middle L:90%
these issues as frequently later on in life? Um

885
00:59:19.820 --> 00:59:22.079 A:middle L:90%
I'm so far away from animal cloning these days and

886
00:59:22.079 --> 00:59:23.110 A:middle L:90%
I'm really not the right person to answer that question

887
00:59:23.119 --> 00:59:25.340 A:middle L:90%
, but probably people in this audience who I'll give

888
00:59:25.340 --> 00:59:28.909 A:middle L:90%
it a good answer, which is certainly known that

889
00:59:28.920 --> 00:59:32.389 A:middle L:90%
there is a um a likelihood that the animal will

890
00:59:32.389 --> 00:59:37.280 A:middle L:90%
have more mutations, both in the chromosome of DNA

891
00:59:37.280 --> 00:59:43.760 A:middle L:90%
and in the mitochondria. Mhm. But other than

892
00:59:43.760 --> 00:59:47.789 A:middle L:90%
that, and they're really not aware of things associated

893
00:59:47.789 --> 00:59:54.219 A:middle L:90%
with age. Mhm. As we've seen more rapid

894
00:59:54.230 --> 00:59:58.840 A:middle L:90%
advancements in not only technology, but also genetic.

895
00:59:59.420 --> 01:00:02.690 A:middle L:90%
The theory of genetics. Do you the media often

896
01:00:02.699 --> 01:00:06.849 A:middle L:90%
says that there could be designer babies in the future

897
01:00:06.860 --> 01:00:10.960 A:middle L:90%
of people being able to dictate different traits, be

898
01:00:10.960 --> 01:00:16.750 A:middle L:90%
it genetic or personality wise? Now, I know

899
01:00:16.750 --> 01:00:21.300 A:middle L:90%
some people scoff at that idea and that that's a

900
01:00:21.300 --> 01:00:23.630 A:middle L:90%
ridiculous idea. But we've seen ridiculous ideas become reality

901
01:00:23.639 --> 01:00:29.010 A:middle L:90%
and common practice. Do you foresee in the next

902
01:00:29.010 --> 01:00:32.980 A:middle L:90%
100 years or so of that? Human genetic modification

903
01:00:32.980 --> 01:00:37.820 A:middle L:90%
can become common practice and what positive, positive and

904
01:00:37.820 --> 01:00:39.440 A:middle L:90%
negative after effects do you see of that? Okay

905
01:00:40.409 --> 01:00:44.530 A:middle L:90%
, very interesting question. I think whereas cloning,

906
01:00:44.539 --> 01:00:45.630 A:middle L:90%
please don't go away for a minute. Yeah.

907
01:00:46.510 --> 01:00:52.519 A:middle L:90%
All right. Whereas cloning and gene transfer was the

908
01:00:52.519 --> 01:00:55.320 A:middle L:90%
subject of our debate 2030 years ago when we began

909
01:00:55.320 --> 01:01:00.690 A:middle L:90%
from I think genetic not education will become more and

910
01:01:00.690 --> 01:01:07.389 A:middle L:90%
more focus of interest and anxiety. I will answer

911
01:01:07.389 --> 01:01:09.170 A:middle L:90%
the question. You know what I do think is

912
01:01:09.170 --> 01:01:15.829 A:middle L:90%
that shouldn't be afraid. Mhm. Technology often has

913
01:01:17.010 --> 01:01:21.610 A:middle L:90%
an edge and important unfortunate disadvantage. If you think

914
01:01:21.619 --> 01:01:23.909 A:middle L:90%
way back the first time somebody stuck a sharp stone

915
01:01:23.909 --> 01:01:27.219 A:middle L:90%
a mistake and have the first house, it could

916
01:01:27.219 --> 01:01:29.699 A:middle L:90%
be used either to chop firewood or to feel animals

917
01:01:29.699 --> 01:01:30.699 A:middle L:90%
, which is considered to be good or to kill

918
01:01:30.699 --> 01:01:36.369 A:middle L:90%
the neighbors. Which is bigger scale. If you

919
01:01:36.369 --> 01:01:39.719 A:middle L:90%
think of the um two Atomic problems which destroyed two

920
01:01:39.719 --> 01:01:45.340 A:middle L:90%
Japanese cities, 60 regions, I guess that much

921
01:01:45.340 --> 01:01:49.639 A:middle L:90%
of the maths in the electronics which control to them

922
01:01:50.110 --> 01:01:54.030 A:middle L:90%
subsequently inspector involved in the production of our mobil's ipods

923
01:01:54.039 --> 01:01:58.769 A:middle L:90%
, ipads, laptops, modern digital cameras. And

924
01:01:58.769 --> 01:02:00.809 A:middle L:90%
so you just have to upset that there may well

925
01:02:00.809 --> 01:02:05.789 A:middle L:90%
be disadvantage. I think that there will be such

926
01:02:05.789 --> 01:02:09.210 A:middle L:90%
advantages from genetic modification that we mustn't northerners think about

927
01:02:09.210 --> 01:02:13.070 A:middle L:90%
them. So then you come to the question well

928
01:02:13.070 --> 01:02:15.619 A:middle L:90%
, how do you draw the line and said it's

929
01:02:15.619 --> 01:02:20.030 A:middle L:90%
going to? I think the further you can go

930
01:02:20.030 --> 01:02:24.460 A:middle L:90%
along track of being able to chest ideas in cells

931
01:02:24.469 --> 01:02:29.679 A:middle L:90%
in animals before you would interfere with using better,

932
01:02:29.690 --> 01:02:34.670 A:middle L:90%
obviously better you're able to have confirmed that the change

933
01:02:34.670 --> 01:02:38.050 A:middle L:90%
that you have made themselves and the animals is exactly

934
01:02:38.050 --> 01:02:46.429 A:middle L:90%
and only wanted to the best causing homes. Mhm

935
01:02:49.099 --> 01:02:54.059 A:middle L:90%
. Instead I also put in a point which I

936
01:02:54.059 --> 01:02:57.750 A:middle L:90%
picked up the something from Julian, several s screams

937
01:02:57.750 --> 01:03:00.320 A:middle L:90%
and philosopher dr lots of medic matters in Oxford.

938
01:03:00.800 --> 01:03:06.989 A:middle L:90%
Yes. That we discussed human beings as if they

939
01:03:06.989 --> 01:03:10.420 A:middle L:90%
were perfect. These are we are not magnificent.

940
01:03:10.429 --> 01:03:15.900 A:middle L:90%
Pieces of china, perfectly sculpt. Yes. Perfect

941
01:03:15.909 --> 01:03:21.230 A:middle L:90%
brains. We are perhaps shouldn't be quite so afraid

942
01:03:22.099 --> 01:03:25.429 A:middle L:90%
. True. In some circumstances you would. Mhm

943
01:03:29.099 --> 01:03:31.269 A:middle L:90%
. You're staying take a few minutes. The problem

944
01:03:31.269 --> 01:03:37.190 A:middle L:90%
is who makes the decision that to me many times

945
01:03:37.190 --> 01:03:42.449 A:middle L:90%
used as an image except to yourself, genetics potentially

946
01:03:42.449 --> 01:03:44.329 A:middle L:90%
made in one of your Children. Mhm. And

947
01:03:44.329 --> 01:03:46.309 A:middle L:90%
then discovering. Was it? Yeah. In effect

948
01:03:46.320 --> 01:03:52.519 A:middle L:90%
have conversations which 1? I'm terribly sorry this time

949
01:03:52.900 --> 01:03:55.789 A:middle L:90%
where you managed to draw that line? Do hope

950
01:03:55.800 --> 01:04:00.110 A:middle L:90%
you participate. Yes. And I use one example

951
01:04:00.110 --> 01:04:03.159 A:middle L:90%
of treating Palestinian. What's up to diseases of the

952
01:04:03.159 --> 01:04:10.710 A:middle L:90%
blood system would be a good start. No sir

953
01:04:11.690 --> 01:04:13.489 A:middle L:90%
, diseases. For the reason I mention which is

954
01:04:13.489 --> 01:04:15.710 A:middle L:90%
that you can do all of the outside the boat

955
01:04:16.489 --> 01:04:18.610 A:middle L:90%
, know that the cells are exactly what you want

956
01:04:21.360 --> 01:04:26.130 A:middle L:90%
in the end. I have to sure, anxiety

957
01:04:26.139 --> 01:04:30.980 A:middle L:90%
with upset that there has to be. Mm Let's

958
01:04:30.980 --> 01:04:40.119 A:middle L:90%
push it. Mhm. Thank you. We have

959
01:04:40.119 --> 01:04:43.920 A:middle L:90%
time for one more question. Thank you. Hello

960
01:04:43.920 --> 01:04:45.369 A:middle L:90%
, sir. Um why was it decided to clone

961
01:04:45.369 --> 01:04:48.119 A:middle L:90%
a sheep when your team tried it? Why did

962
01:04:48.119 --> 01:04:49.909 A:middle L:90%
you decide on a sheep and not any other animal

963
01:04:56.190 --> 01:05:00.989 A:middle L:90%
? Uh monkeys? I don't know. Yeah.

964
01:05:01.889 --> 01:05:05.880 A:middle L:90%
The reason we worked with sheep was that as I

965
01:05:05.889 --> 01:05:10.030 A:middle L:90%
think we both mentioned, one of our earlier project

966
01:05:10.030 --> 01:05:12.889 A:middle L:90%
was to produce proteins in milk. So ideally it

967
01:05:12.889 --> 01:05:15.400 A:middle L:90%
would be a species which was used to being milt

968
01:05:15.400 --> 01:05:20.139 A:middle L:90%
and which had routines and equipment that was suitable in

969
01:05:20.139 --> 01:05:23.050 A:middle L:90%
some ways you'd like to use cows because of the

970
01:05:23.050 --> 01:05:24.949 A:middle L:90%
greater volume that they would produce. But they are

971
01:05:24.949 --> 01:05:28.690 A:middle L:90%
more expensive and have a longer generation. So really

972
01:05:28.690 --> 01:05:30.739 A:middle L:90%
we thought of these sheep as being small, cheap

973
01:05:30.750 --> 01:05:36.519 A:middle L:90%
cows. Yeah, I do work in Scotland after

974
01:05:36.519 --> 01:05:41.730 A:middle L:90%
, I'll remember. Yeah. Uh huh drift.

975
01:05:42.789 --> 01:05:47.550 A:middle L:90%
Um we believed that anything we developed in sheet would

976
01:05:47.550 --> 01:05:50.469 A:middle L:90%
also work in count and that indeed is the case

977
01:05:50.610 --> 01:05:53.849 A:middle L:90%
. We'll mention the cloning which was done here shortly

978
01:05:53.849 --> 01:06:01.559 A:middle L:90%
after cattle shortly afterward. Mostly. Yeah, there

979
01:06:01.559 --> 01:06:04.849 A:middle L:90%
are some really interesting biological questions you could ask using

980
01:06:04.860 --> 01:06:12.440 A:middle L:90%
primates and that would be extremely tightly regulated in the

981
01:06:12.440 --> 01:06:16.139 A:middle L:90%
United Kingdom. I can't imagine how you would gain

982
01:06:16.150 --> 01:06:21.369 A:middle L:90%
permission. I could imagine some clinical trials, clinical

983
01:06:21.369 --> 01:06:26.570 A:middle L:90%
experiments you might want. It's thinking in terms of

984
01:06:26.570 --> 01:06:30.760 A:middle L:90%
put themselves into two people. The limitation of primates

985
01:06:30.760 --> 01:06:38.730 A:middle L:90%
is that there aren't any inbred lines. You could

986
01:06:38.730 --> 01:06:41.590 A:middle L:90%
create them in effect by cloning to make genetic.

987
01:06:44.880 --> 01:06:46.400 A:middle L:90%
But thinking in terms of testing out this idea of

988
01:06:46.400 --> 01:06:53.710 A:middle L:90%
having cell lines which are homes egress of the major

989
01:06:53.840 --> 01:06:56.400 A:middle L:90%
L. A. Antigens. Use the technical job

990
01:06:58.380 --> 01:07:00.019 A:middle L:90%
. It would be really interesting to do that in

991
01:07:00.019 --> 01:07:02.099 A:middle L:90%
primates but there just aren't any sort of new population

992
01:07:04.780 --> 01:07:06.860 A:middle L:90%
. Thank you. Got anything that particularly that you

993
01:07:06.860 --> 01:07:15.699 A:middle L:90%
suggest. Nothing. Thank you. Uh huh.

994
01:07:16.380 --> 01:07:19.440 A:middle L:90%
Okay. A year ago um an article was published

995
01:07:19.449 --> 01:07:24.099 A:middle L:90%
discussing how Tianjin china wanted to create the largest animal

996
01:07:24.099 --> 01:07:27.750 A:middle L:90%
cloning facility and their main reason was for beef cattle

997
01:07:27.750 --> 01:07:30.349 A:middle L:90%
production to meet market demand. Do you feel this

998
01:07:30.349 --> 01:07:32.599 A:middle L:90%
is a positive or negative use of regenerative medicine?

999
01:07:41.480 --> 01:07:57.710 A:middle L:90%
Yeah. And why? Yeah. Yeah. First

1000
01:07:57.710 --> 01:08:05.500 A:middle L:90%
comment is you're allowing regenerative medicine claims and stop Mhm

1001
01:08:05.969 --> 01:08:13.199 A:middle L:90%
. Lifestyle. So do I approve of. Mhm

1002
01:08:13.570 --> 01:08:15.380 A:middle L:90%
. I think I've already said that. I don't

1003
01:08:15.380 --> 01:08:17.010 A:middle L:90%
think that cloning is a particularly effective way of gaining

1004
01:08:17.010 --> 01:08:20.989 A:middle L:90%
genetically improved or even disseminating. It's much much better

1005
01:08:21.130 --> 01:08:24.800 A:middle L:90%
. And this isn't a sexist remark, it's much

1006
01:08:24.800 --> 01:08:27.619 A:middle L:90%
much better to select the best bowls and then to

1007
01:08:27.619 --> 01:08:31.319 A:middle L:90%
collect that semen and disseminate its right. So for

1008
01:08:31.319 --> 01:08:35.800 A:middle L:90%
that sort of very practical reading. Mhm. I

1009
01:08:35.810 --> 01:08:41.920 A:middle L:90%
don't approve of this I guess. I don't really

1010
01:08:41.930 --> 01:08:47.289 A:middle L:90%
mind the music. That what do you think?

1011
01:08:51.470 --> 01:08:55.869 A:middle L:90%
I mean if you're lacking in cattle already cloney isn't

1012
01:08:55.880 --> 01:08:57.789 A:middle L:90%
really going to help you in the future. I

1013
01:08:57.789 --> 01:09:00.199 A:middle L:90%
think that's a good point. Maybe you're ready blood

1014
01:09:00.199 --> 01:09:02.720 A:middle L:90%
in that area. I think what the young lady

1015
01:09:02.720 --> 01:09:05.409 A:middle L:90%
said was that if you're lacking in cows, cloning

1016
01:09:05.409 --> 01:09:10.359 A:middle L:90%
doesn't really help you. You need cattle to produce

1017
01:09:10.359 --> 01:09:15.649 A:middle L:90%
the others think is what? Thank you. Great

1018
01:09:15.649 --> 01:09:38.840 A:middle L:90%
country you very much. Thank you all for coming

1019
01:09:38.840 --> 01:09:43.760 A:middle L:90%
and have a safe trip home. Exactly. Right

1020
01:09:43.760 --> 01:09:47.289 A:middle L:90%
now, he's a come here. All right.