Good evening. I'm Tim O'Shea, I'm Principal and the vice chancellor of The
University of Edinburgh. A warm welcome to
this year's lecture. It's part of a very successful
series of public lectures on Our Changing
World which is a major public engagement exercising
at the university. We're now in the fourth
year of that.
That series has seen distinguished academics
within the university discussing many of the
global challenges that face society including atmospheric carbon and climate change, renewable energy and sustainable technologies,
the challenges and opportunities for medicine from understanding the human genome and advancement in stem cell research.
In that regard, it's very nice to see Sir Ian Wilmut sitting in the front row tonight.
The lectures have highlighted the importance
of interdisciplinary research and scholarship
in meeting these global challenges and the
excellent world leading research in these
areas taking place here. So for the regular
lectures, we have had about 250 to 300 members
of the public. Over 30 of these lectures 
are available to view online.
One of the key things about the Our Changing
World lectures are the basis of an interdisciplinary
course for first year undergraduates which
introduces them to global challenges in the
local context. This new course is part of
the university's strategic aim to introduce
sustainability and awareness into all of our
teaching. The course itself has been very
successful. It has various spin offs, one
of which is a MOOC, a Massive Open Online
Course on global health and critical thinking
to reach an audience of 75,000 online.
We are indebted to Professors Gareth Leng
and Mayank Dutia, in the school of Biomedical
Sciences, who have shown extraordinary leadership
in getting this important series off the ground.
Tonight we're really privileged. We'll be
addressed on the enlightenment lecture of
the Our Changing World series. Lord Winston,
who is Professor of science and society and
emeritus professor of studies at Imperial
College is going to be talking. He's a world
renowned and widely respected expert in human
fertility. The author of many popular science
books and for his series of award winning
BBC programmes which include The Human Body,
The Secret Life of Twins, and Superhuman.
He's a wonderful person. He's a nationally
successful scientist and a jolly good person.
Extensive contributions include microsurgery
and the development of gynaecological and
microsurgery, in-vitro fertilisation techniques
and ground breaking research which pioneered
techniques in the transfer of germ cells between
males. He's also the chairman of the research
council which does important research into
women's health and fertility.
So as I said we normally have an audience
of about 300. I'm delighted that we've got
1,000 people tonight. Entirely appropriate.
So please join me in welcoming Lord Winston.
(Clapping)
>> I once shared my CV to my austere Scottish
professor. He went through my CV before I
was applying for a job. He went down with
his pencil, bit by bit. Finally, he looked
up at me and said over his half-moon glasses
"Well, Winston, when I read my CV, I don't
recognize myself either."
(Laughter)
This woodcut by Nicolas Hartsoeker was published
around about the late end of the 17th century.
In it it's a very interesting woodcut to biologists
because it shows what Nicholas thought he
could see down the microscope. You'll remember
of course that the person who was pioneering
in Holland at the time was Van Leeuwenhoek.
The story that goes that he went to visit
Van Leeuwenhoek with his single lens objective
and was fascinated by these small moving animals
in ponds of water.
So Hartsoeker was really interested to think
what there might be in seminal fluid. Had
said to Van Leeuwenhoek, had he ever examined
seminal fluid but apparently was outraged.
So Hartsoeker went home. He was only about
19 at the time. As soon as he could, he examined
a specimen of his own seminal fluid down his
own microscope.
(Laughter)
What he saw were these wriggling creatures
that made him so frightened he assumed he
had some kind of disease. It is said that
he didn't look at the microscope for the next
two years. Whether that's true or not, when
he finally published his great book on microscopy,
which was certainly respected by the members
of the Royal Society - indeed von Leibniz
wrote to London about it - he showed this
woodcut in the front of the volume which is
a specimen of a human sperm with a homunculus
in the centre of the sperm. The interesting
thing about the homunculus is that it's complete
with its feet, its toes. Indeed, so much so
that there was an interesting discussion that
von Leibniz had with the Royal Society. He
said we can now see the sperm contains a little
man inside it which is so perfect, that if
it's a male, it will have little testicles.
That's interesting he said, inside the testes
will be sperm and half will be males. So,
inside them there will be little males, and
so it goes right back to creation. Von Leibniz,
though a mathematician, was deeply religious
and believed in creation.
Why I'm interested in this woodcut is because
of the ethical issues that it produces. Indeed
one of the fundamental questions, if there
is a little man inside the sperm, then the
destruction of the seed, by masturbation for
example, is clearly something which is reprehensible
indeed rather wrong and indeed a rabbi, writing
some 80 years after he read the volume wrote
this. I translated it from Mishnaic Hebrew
so forgive me if some of the words don't quite
make sense. He says, now it has been seen
through a viewing instrument, which was called
a microscope, that a drop of a man's sperm
- he means seminal fluid - whilst yet in its
original temperature - he means environment
- contains small creatures in man's image.
And therefore, he goes on to say that the
Talmudic idea of hash-hatat zera - which I
haven't translated, hash-hatat zera means
destruction of the seed, zera is seed in Mishnaic
Hebrew - is like murder.
If you think about it, the ethics of that
statement are impeccable. If there are little
men, in a sense it is like destroying human
beings. The problem of course is the ethics
of that statement are only as good as the
underlying science. As we learn about the
natural world around us, my point of course
is that our ethics have to change to take
in that learning. No rabbi now I think would
regard the seed potentially like the chair
itself for example. No non Jewish scholar
studying Jewish law would argue that was really
an issue.
That's important because when I was first
doing in-vitro fertilisation, I came under
huge pressure from people who felt that what
I was doing with embryos was so seriously
wrong, it was really like murder. And indeed
I was accused of that repeatedly in the media
and face-to-face on television. Because of
course, it was said that life began at fertilisation,
which religious authorities still believe.
That's a philosophical problem because of
course this wonderful experiment, by Kono
in Japan, shows that it is possible to get
fertilisation in a mouse - This is the mouse's
mother, and these are her offspring - without
ever being fertilized by a sperm. These have
been activated either by simply immersing
them in the wrong pH, the wrong acidity, or
more probably by pricking an egg with a pin.
So the interesting thing is although of course
the offspring, one of the foetuses survived
despite the misprinting of the imprinted of
the genes. This foetus which survived obviously
has to be female, because it has not come
in contact with a sperm it cannot be a male,
because the Y-chromosome is carried by the
sperm. But it can have, after fertilization
normally, these pups which may be either male
or female. The question really is, does this
mouse really exist, is it a figment of Kono's
imagination, or is it really a mouse? I think
most of us would argue that this is a mouse,
and actually this is an example of life beginning
without fertilisation.
However, that was not an easy argument to
be accepted. I wanted to set the scene before
moving on to what I think are the basics of
ethics. I don't intend to give a lecture on
conventional medical ethics to you. Other
people can do that very much better than I.
This paper by Beauchamps and Childress is
very well known. It argues essentially, there
are four key points looking at our ethical
attitudes when we treat patients.
The first is respect for the patient's autonomy.
The second is to try not to do harm. The third
is to try to do good. And the last is to attempt
to find a just solution to the problem that
the patient and society is faced with. Those
are which in fact come through this talk,
throughout.
So autonomy sounds wonderful. We respect the
patient's autonomy which means obviously informed
consent, adequate communication, proper deliberation
for the patient about their condition and
their treatment, no deception, telling the
patient of the truth, which I think is an
interesting issue in medicine, and of course
respecting the patient as a person.
Beneficence and non-maleficence are obviously
to all of you in this audience, but they include
weighing up the risks of the treatment against
the benefit and trying to provide something
which on the whole provides benefit rather
than harm. Trying to ensure when we promise
a benefit, it really isn't a paper promise,
and of course recognizing that sometimes beneficence
isn't always clear cut. For example, one of
the clear cases in which this might be true
is the issue of a mastectomy, maybe in somebody
who's got a gene which may give them a very
high risk of breast cancer but no guarantee
of breast cancer.
What comes into that is effective medical
research, which some of us might regard as
an obligation. It's actually beset with problems
in an ethical framework. How we may or may
not actually do our research with clinical
patients, whether or not randomized control
trials can be done without risk to patients
and so on.
With regards to justice, that's something
I want to increasingly focus on in this lecture.
It seems to me that's a real issue for health
services around the world today. One of the
things I wanted to discuss with you, but I
can't come to any clear cut conclusions, is
that worldwide we face healthcare which is
more and more expensive and more and more
less under control of governments and less
and less well controlled by governments. I
think that's one of the issues which is a
very real ethical issue in practical terms.
Raanan Gillon, who was an academic in ethics
at Imperial College London, where I come from,
added a fifth category. The category of scope,
which is really what are normative values,
who has the right to life. Actually we might
add, who has a right to death in current discussions.
Is there a right to a child, for example,
with in vitro fertilization. Clearly, I think
most of us would argue there's no right to
have a child right, you cannot have a right
where it can't be enforced. Clearly the right
to have a child is not within the scope of
medical care.
It's amusing perhaps to look at medical attitudes
towards concerns of research. So, for example,
this poll which was done by MORI some years
ago, seems to conclude that 80% of the population
from questionnaires regarded it acceptable
to do research on human volunteers, but only
one third thought it suitable on rates and
less than one third on bacteria. I have no
idea how he came to that conclusion. It might
be the idea of genetic modification of bacteria.
But I have to say, that this poll was taken
before synthetic biology was really very firmly
established as a key scientific endeavour.
The history of course of seriously adverse
research on humans and worse, the lack of
treatment of their autonomy goes way back.
It certainly does not start in Nazi Germany.
In fact probably the eugenic movement starts
in this country with Francis Galton. Francis
Galton believed in the survival of fittest,
and as a cousin of Darwin, that we should
be trying to preserve that, to make sure that
our society should be better as a consequence.
I don't intend to talk about the eugenic movement
in any detail.
What I want to argue with you is that eugenics
is a serious argument now as it ever has been.
This poster, of course, was taken from around
1936. It costs 60,000 reichsmarks to keep
this person with hereditary disease alive,
"auf Lebenszeit". And it's arguing people
should read Sie Neues Volk to see what the
truth of the argument is. Now 60,000 reichsmarks,
I looked up how much it's worth in contemporary
money. At the time it was about $140,000.
So in present time that's something like about
a third of a million to keep this individual
alive. The argument is very clear to us with
hindsight of our perfect society.
I would argue to you that it's not so far-fetched
to consider that in a world which is beset
with climate change, conflict, with water
shortages, with food shortages, with lack
of education, with fundamentalism that we
could see easily that the eugenic argument
could again strike a chord. It's never, in
my view, gone away. And, I think it is remarkable
to consider that after the holocaust in Germany
we in this country and by that I mean the
United Kingdom, including Scotland, were sterilising
people without consent as they were in California
and in probably the most liberal democracy
in Europe, Sweden. In fact, 40,000 women were
sterilised without consent.
In the Carnegie institute we see this rather
revealing 
microscopic carrier type, done by a scientist
in the lab. You can count the number of chromosomes,
24 pairs which is more than there are in the
human genome. So we can date this as being
about 1952, when I was first learning biology
at school. And the supposition is that the
microscopist can tell the difference by looking
down the microscope between a Negro and a
white. It's worth bearing in mind that at
that time in the United States there was still
criminal laws for miscegenation. For instance,
it was considered a criminal offence for a
black to sleep with a white in 3 states of
the United States of America. In fact, in
Virginia, that law was only repealed in the
late 1960s.
That racism is something which of course is
not founded in any real evidence. But it also
tells us something about scientists. It's
my contention that all of us as scientists
will see down the microscope, or on the gel,
what we want to see. We are objective as non-scientists,
we are subjective as non-scientists, and we're
likely to be persuaded, increasingly by our
urge to be right and our urge to see the truth,
which I think is actually something which
we are inclined to forget when we like to
believe we're above this kind of bias. I don't
think that's true.
When I was a young medic this is published
in 1977 - so I would have then been a Senior
Lecturer, which in England carries consultant
status. I was a consultant when I published
this little paper in the British Medical Journal.
I don't rate it as a great paper. It's not.
At that time I was doing a lot of corrective
surgery. These women requesting reversal of
sterilisation. These women had come to my
clinic because of the techniques we were using.
Actually, the paper only describes the first
103 but I saw nearly 300 in a short period
of time.
Pretty well, ladies and gentlemen, all these
women had been sterilized because they had
requested a termination of a pregnancy. The
pregnancy was terminated on condition that
they were prepared to be sterilized. Some
of these women were teenagers. Some of them
were 19. One or two were 18.
Of course not surprisingly, this damage to
their whole being as women was monstrous.
In fact, very few of those women were actually
in later years and not many of them had more
than one child. Some had two. One or two had
more. It struck me when I looked at this paper
again recently, and I suddenly remembered
again, when I was a surgeon in training doing
Caesarean sections for women having perhaps
a fourth baby, it was not uncommon for my
consultant to jokingly say, "If you take the
Spencer Wells forceps and crush the fallopian
tubes by mistake, she's had four children
already. She can't really afford anymore anyway.
This is not such a bad thing to do." It was
that kind of notion which is close to eugenics
in a very democratic society.
I don't think that has ever gone away. I think
it remains a real risk and might be an increasing
risk given certain pertivations in society
and with the increase of certain technologies.
This was published in, I forget which newspaper,
this July. It's the governor of this prison
in California saying it's costs us $147,000
for the sterilization programme for these
inmates. But, when you consider how much it
costs these people to bring up a child, this
is nothing to the public purse, it's worth
doing. There's no suggestion, of course, that
these women were sterilized with any form
of consent, as indeed we know they weren't.
So this is happening even in that great democracy
across the Atlantic.
I can't but not avoid talking about my own
field one of the things that really concerns
me increasingly how that I've retired from
active clinical reproductive medicine is the
massive cost that is used for the treatments.
Not only in England but also in America and
most parts of the continent and many other
parts of the world indeed. For example, a
typical charge - and these are two private
clinics in London - for in vitro fertilisation,
£2,500 and £3,500 pounds.
Notice that to store embryo in liquid nitrogen
is charged at £250 to £350 per year. The
cost of liquid nitrogen is a few pence per
litre. You might replace that flagon of liquid
nitrogen every two months. So the cost of
that treatment is hideously exploitative.
I looked at what it might cost to take a basic
unit, where the most expensive thing is undoubtedly
the salaries, you can see that to deliver
the basic cost of in vitro fertilization are
probably under £700 providing you have enough
patients.
Why does this matter? It matters increasingly
because we're facing more and more privatization
of medicine. I know it's not happened in Scotland
yet but it's certainly happening in England.
It's happening particularly in our National
Health Service. The National Health Service
has never costed out what it costs to deal
with the infertile patient, I know that from
running a unit. So many NHS hospitals are
charging far more than that sum in their costs
because of course they make a handsome profit
from the treatment. My own unit was making
millions for Hammersmith Hospital by the time
I returned.
That is regrettable, because as we pass on
that treatment to private providers we will
increasingly be expecting the public purse
to be paying for what the market will bear
and not the cost of the treatment. To my mind
that is a massive ethical issue. It's a massive
ethical issue which is compounded by this
horror. This is regular advertisement in the
London Underground. It costs £35,000 every
two week to advertise on the London transport.
Here we see a clinic offering fertility for
over-40s, that is freezing eggs, a very poor
technology which has all sorts of risks and
very few advantages - it is not likely to
work, without going into the mathematics of
it.
And of course we know this is deeply exploitative
of the women being treated. This I think is
extremely worrying indeed. The consequence
of the high fees in this particular area of
medicine means a lack of equity in healthcare,
extra cost to the health service, a recognition
that IVF is so suitable for treatment that
you don't make a diagnosis anymore. We treat
the symptom rather than the underlying cause,
so success rates are limited. We have unproven
treatments and research treatments being charged
for increasingly such as pre-implantation
genetic screening. We have patients being
sent by British clinics overseas where that
clinic is offering something that would be
illegal in British law. And of course, most
importantly, there's therefore a pressure
for multiple embryo transfer, with the extra
cost of twins or triplets on the health service
and very importantly failure to recruit good
people into academic medicine because frankly
it's easier to earn a very good living in
the private sector.
What I think is rather shocking is that organisations
like the human fertilization and embryology
authority sign up for this kind of misinformation
for patients. That's also an ethical problem.
They are there to police ethics, but here
they say, for example, the biggest risk of
fertility treatment is a multiple pregnancy.
Ladies and gentlemen, the biggest risks of
a fertility treatment is failure of the treatment.
That's is something which we have to recognize,
that two thirds of patients going through
this treatment don't succeed.
Enoch Powell, my old adversary, during the
embryology bill he introduced in 1985 argued
that any research on the embryo was repugnant.
I was surprised that somebody of his undoubted
integrity and huge intellect would feel that
strongly. But it was because he switched out
of the Tory party in London and had gone to
represent a Catholic community in Northern
Ireland. I don't know.
But it was really shocking to see how he could
produce a bill which was the protection of
the unborn child. The unborn child of course
is the embryo which as we know has a success
rate of implantation per embryo of around
about 18, 22 per cent. Most human embryos
do not implant in the uterus under ideal conditions
at the pre-implantation stage.
One of the things that fortunately got more
lax legislation through was unquestionably
Nature's coverage of this paper of ours in
the week of that debate and finally the HFEA
bill came up before the House of Commons.
This photograph of a human embryo, is taken
with time lapse photography. What you can
see here is a technique for looking at the
individual DNA in individual cells which we
did by removing a single cell from the embryo.
The week this was published with the first
pregnancies was actually the week that Nature
rather surprisingly the data was published.
Here you can see a hole being made in the
embryo which becomes transfixed. This embryo
is invisibility to the naked eye. This sucker
is too small to be seen by the naked eye as
well, these glass pipettes.
This technology which was used to do single
cell polymerase chain reaction by hand by
Alan Handyside and myself at Hammersmith led
a diagnosis of genetic defects and our ability
to decide whether an embryo had a specific
defect which might be screened, given a clutch
of embryos from the same patient.
That injury is in fact not serious. Although
we lost a cell, all these cells in the embryo
are totipotential so the removal of one single
cell at this stage of development is not an
adverse event. The first two babies who are
now 23 and a half, Lisa and Harriet. The press
called them perfect babies, which they certainly
are not. They have one base pair difference
from the deletion, the single pair deletion,
which killed their elder brother, aged 3 and
a half. The other three billion are not screened
for in this technique.
Lisa of course - actually Harriet I should
say - is not free of blemish, she's got this
thing on her chin, which isn't because she
lost a cell at biopsy stage, it's because
she fell over just before the photograph was
taken.
(Laughter)
At that time almost coterminous with the publication
in Nature just about two weeks beforehand,
Paul Johnson in a rather right wing newspaper
published this about the work he was doing.
He didn't know we would be able to treat patients
who watch a baby or young child die of a hideous
disease. It's worth looking at the language,
because we need to be aware of language at
all times as members of the public, as non-scientists,
and as scientists. I've highlighted in white
the relevant words.
So, the idea that the embryo is a child in
the womb is nonsense; it's not literally at
our mercy; it is never 14 days old because
the technology is really only for the first
few days; it's not on a colossal scale; the
benefits are not uncertain because two weeks
later we were able to announce not only that
pregnancy but two others in the paper in Nature;
we have "reinvented human sacrifice" is a
slur, but it's very difficult for a scientist
to actually tolerate that kind of slur when
it's so widespread in the public arena.
"Does it shock you...as high priests of progress,
we've consigned all our opponents to reactionary
perdition...betraying the moral laws of our
civilisations."
It's hard to take that kind of criticism - which
it seems bizarre now only 13 years later - was
so, so, so prevalent. It's extraordinary how
that has changed.
Worse still, is this: this is published in
one of the greatest journals in the world,
Science, by Humphrey Lodish, a very distinguished
molecular biologist. He says of our work a
few years later, that it's now possible to
take a single cell from the embryo, characterise
the DNA, work out what proteins may be expressed
or not expressed. Once we've got proper supercomputing
we'll be able to transfer the information
about that together with information about
the environment and we will be able, he says,
after computing, to make a colour movie, in
which the embryo develops in to a foetus,
before the embryo is implanted, and show the
mother, while the embryo is being transferred
to her uterus, a movie in which the baby grows
up into an adult and speaks or sings.
Now, I must say to you that it takes a little
realisation, at least 6 minutes, before you
realise that actually this praise is complete
and utter trash. It's the Science Delusion.
Many of you will have heard of the God Delusion,
which I think is odious in my view, I don't
think the God Delusion is a helpful title
for a book from a scientist, nor do I think
the Science Delusion is helpful for us to
be so determinate either. I think we need
to be much more reflective of what we're saying.
But it's easy to see how one could be transported
by one's own sense of power or influence.
I now regard pre-implantation genetic diagnosis
as a relatively trivial issue, which has helped
a few families around the world but it's not
particularly important.
>> (Music playing) Ladies and gentlemen, the
president of the United States accompanied
by Dr Francis Collins and Dr J Craig Venter.
(Clapping)
Here comes Francis Collins, who's looking
very pleased with himself and Craig Venter,
who I rather like, looking very embarrassed
to be in the company.
Interestingly, we often forget the private
sequence of the human genome costs about one
quarter of what the public one did. I won't
trouble you with what President Clinton said
at this announcement of the first milestone
in June 2000. Tony Blair was on the line at
the other end when it was broadcast. Tony
Blair said this tells us more about humanity
than any previous human achievement. I would
argue that perhaps in 1599 when Shakespeare
wrote Hamlet that tells us rather more about
our humanity, but that's arguable.
President Clinton said that this is a map,
which is more important than any map ever
drawn by humans. I would argue that actually
the map of Washington DC is a good deal more
reliable. Of course it's now fair to say that
we begin to recognize that the human genome
is actually only a part of the story, and
the amount of benefit we have had from the
sequencing of the human genome is still receding.
I'm not saying it was a useless exercise;
I'm glad it was done, but a huge proportion
of human genetics actually could have been
done without it, including our work on pre-implantation
diagnosis and many other examples of diagnosis.
The cost of the genome sequencing is decreasing
faster than Moore's Law. It will soon be a
matter of time before we have the cost of
a genome down to perhaps £1,000.
What is interesting is to consider what the
public perception of that hype is. This journalist
writing in the Observer this year in June,
Carol Cadwalladr, said she had a genome sequenced.
I suppose the Observer must have paid for
it. And she says look what it's told me. First
of all, she has the gene for male pattern
baldness. Well, that's interesting, but she
could have looked at her father and her two
brothers.
(Laughter)
She's got the sprinter's power gene, apparently.
I notice that she doesn't run herself, so
it's probably not a great deal of use to her,
but she has that gene, which is in common
with a large number of athletes. The "gene",
I think, should be in inverted commas.
She has no knowledge of whether she has the
genetics, which might encourage late onset
Alzheimer's, because she decided not to find
out. So, although they looked for that area
of genetics, she didn't ask the people whether
or not she was more likely to have Alzheimer's
or not. Very interesting.
She has a mutation for galactosaemia. Well,
that's interesting too, but almost entirely
irrelevant, given that galactosaemia affects
1 in 16,000 of the population. Presumably
she's married already, so if her husband hasn't
got that gene as well as a recessive, it's
not likely to affect her children.
She has no BRACA 1, so she's under the impression
she's not likely to get breast cancer. A rather
foolish assumption, in spite of what she says
in the article, it actually reduces the chances
of breast cancer slightly but her chance overall
as a member of the British population is still
a very serious risk.
She has a gene in common with quite a lot
of us in the audience, myself included, for
increased waste circumference.
And lastly she has no gene of conscientiousness.
So, I emailed her saying I was interested
to see that you have no gene for conscientiousness,
do you think that affects your journalism.
(Laughter)
She didn't respond to my email.
(Laughter)
That issue of course is a very real issue
as an ethical issue in medicine today. Just
two weeks ago, some of you will be aware,
researchers in Leicester described an experiment
that argued that they could change apoptosis
in the brain using a model. They didn't say
what the model was on the Today programme;
they were studious in explaining the science
rather well, I thought, but refused to say
that the model was an animal model. Now, in
my view, not to say it was an animal model,
is a dereliction of duty as a scientist.
It's very important to be up front in saying
we are doing animal research, because it's
essential for our medical development. More
importantly they gave the impression that
a cure for Alzheimer's might be pretty soon,
in the next few years. Here we see Professor
Markram, just two weeks later, in fact this
weekend, saying that actually the search for
dementia cures is fading rather than increasing.
So, given that this is a massive gene that
most of us my age group and most people in
the audience are seriously worried about,
does this present our medical progress in
the most responsible and best way? There is,
ladies and gentlemen, I would argue, a real
risk to this sense of spurious achievement.
In the field of cancer, you can see from this
paper, that there is a growing amazing development
of anti-cancer drugs. In fact we're looking
at the last few years of around 900 compounds,
some of them single molecules, some more biological.
But unlike almost any other drug development.
Certainly, it really does look as if the genome
is helping us to understand cancer treatment.
There's intense competition for cancer drugs.
You'll notice that, for example, most of these
drugs are competing with other drugs with
a similar target in the genome and this classification
based on the primary molecular target means
there are around 397 compounds which have
been looked at by Bergen in his review in
Nature Reviews.
This of course is important because you'll
be aware that each new drug that is licensed
is costing around $900million to produce.
Perhaps that can be decreased to around $600
million, but it's a very serious issue because
clearly one of the concerns is that as we
get older and older, as this paper from Mike
Stratton from the Sanger Institute shows,
every stage in our lifetime we develop more
mutations which give rise to more likelihood
of more tumours, so that by the time we're
in my age group, those mutations are literally
tens of thousands.
Let's just take one example. Let's just take
the BRAF gene with its interaction with KRAS.
You'll be aware, I think, that last year in
the New England Journal of Medicine, there
was a publication that showed that we can
now treat melanoma in advanced cases with
this remarkable magic drug by giving people
with advanced metastases, which actually made
the metastases rapidly disappear. It was heralded
as a fantastic success. Indeed in London,
Richard Marais said it was the biggest breakthrough
in melanoma treatment in more than 30 years.
But, actually, when you look at the papers
that are published, what you see is that the
survival time after the treatment is still
only just over five months. So the risk I
think to our reputation is a very real risk
indeed. The risk is, I think, the increased
hope through the hype we produce and the increase
cost we may be producing on the health service.
This recent publication by BUPA, admittedly
it's a private organisation, but it's looked
at the cost of cancer treatment in the NHS
by millions and the private sector. It is
suggesting that from 2010 when the cost was
£9 million for cancer treatment, it's now
up to over £15 million by the year 2020.
Of course one of the issues in our ethics
therefore comes back to that issue of scope.
How we decide with more and more drugs treating
fewer and fewer conditions we actually can
find an ethical solution for healthcare. I
fear that's going to be dominated by the market.
I don't know why I've got this slide, but
it shows two of my embryologists during an
IVF session in the days when we were doing
egg collection by laparoscopy, well before
ultrasound was possible. Steve Hillier, who
isn't here today but is at the University
of Edinburgh, was my senior embryologist.
We had an open tube which was sucking in fluid,
I handed it to Steve, but the problem was
it was a laparoscopy at the time of the LH
surge at about 3 o'clock in the morning, and
we were very concerned the patient was under
general anaesthetic. It had taken me an hour
and a half to find the follicles in spite
of the adhesions she had around the ovary,
and I turned to Steve, briefly as I was looking
down the telescope, "Steve, what's the time?"
He did this... (mimes looking at wristwatch).
(Laughter)
We lost the egg, which in fact the other Steve
here in this photo had found. We couldn't
really transfer that.
Luckily, we had one other follicle, we had
one other egg. Amazingly, in the early days
of IVF that fertilized. We transferred it.
The lady got pregnant. Extraordinary fluke.
Two years later I had an ethical problem because
I was going through the supermarket in Golders
Green and there, to my horror, was Mrs B with
a carrycot with a baby in it. I wanted to
say to her that it could have been twins,
but I couldn't.
I think one of the other issues which filters
in with the cost of healthcare is the issue
about how we harm ourselves. For example,
the UK has the third biggest epidemic of obesity
after America and New Zealand. The question
is do we continue to treat people who smoke
in Glasgow or drink in Edinburgh or are grossly
overweight. How do we actually handle that
in a healthcare system?
I've always wanted to give a lecture where
I could show a picture of Michael Jackson.
I've never done so before. But Michael Jackson
had a diagnosis appended to him, which he
finally admitted to, this curious white face
was due to vitiligo. And it raises a very
interesting point, that is easy to forget,
and what I think is one of our most difficult
ethical issues. Is it ethical, ladies and
gentlemen, for us to experiment on animals?
Here is a vitiligo mouse. You might argue
that for a serious genetic disease, that's
a real issue. May we make that mouse by modification
have vitiligo when vitiligo does not increase
the risk of a melanoma. As it turns out these
patients do not develop serious skin malignancies
in general with exposure to sunlight. They
have inconvenience, they have disfigurement,
but they have minor problems.
I think the whole issue of the mouse experimentation
- like any other animal experimentation - is
difficult. My own view is that the guiding
principal has to be to try to save human life.
But I think it's a very real and difficult
issue.
This coming Friday, I'm introducing a bill
into the House of Lords for its second reading,
which is the Medicinal Labelling Bill, which
will require all drug companies producing
drugs to label the packet very clearly that
this medical product has been produced as
a result of research on animals. You may disagree
with that, but it seems we need a much more
open debate about the use of research on animals
I this country. In my view, I don't believe
it will put people off having medicines. This
certainly still applies to vaccines. Of course
with reverse vaccinology that will change.
But virtually every single drug in the Pharmacopoeia
is produced as a result of mouse work.
Most of the scientists I've taken opinions
from before introducing this for its first
reading were very much in favour. It will
be interesting what the reaction of the pharmaceutical
companies is. I rather hope they approve of
it because they've been extraordinarily flaccid
in trying to defend the use of animals, preferring
to hide behind people like myself who are
prepared to say we do.
This video is taken from a neighbouring city,
which you'll be aware of in Scotland. This
is Calton in Glasgow. It's rather shocking
this environment results in one of the highest
losses of male life, for example, for anywhere
in the world. The death rate in Glasgow for
adult males is higher per age than it is,
for example, in Mali or Mozambique.
Oddly, if you just cross over to Lenzie, you
have one of the highest longevity rates.
The reason I showed you this is because whilst
we in great universities like Edinburgh are
making massive advances in high technology
medicine - as I hope they're trying to do
at Imperial College as well, and Oxford and
Cambridge and University College London and
many other great institutions - we're shockingly
bad at implementing research in to public
health. This is a massive problem.
My niece, Rebecca Landy, who is a mathematician
working at Cambridge, has analysed the population
of Calton and shown that after you've corrected
for alcohol, smoking and obesity, this shortened
longevity of males is unexplained. In my view,
it's most likely to be due to epigenetic changes.
Another problem we have is shown in this slide
- one of Michael's Schneider's - of a cell
which has been dosed in a way to make it beat.
This is now a cardiac myocyte. It's very difficult
as a scientist not to be transfixed by the
wonder of that sight down a microscope. It's
easy to see how we seduce ourselves into being
more positive about what we're doing than
really is justified.
That wonder is, I think, a real problem for
us. But I don't believe that it's wise for
scientists, like my friend Richard Dawkins,
to make statements about people's beliefs
in the way that he does.
The notice on this bus says "There's probably
no god so stop worrying", it's not correct
anyway. There he is with Polly Toynbee. And
I wonder whether this is one of his PhD students,
I don't know. That's no slur on Richard, who
I know to be a very happily married man.
(Laughter)
But the fact is what little research is done
suggests that people who are religious are
less likely to be worrying than people who
are not religious. The problem is something
that is deeply disturbing: it's not a far
stretch from this type of campaign to actually
suggest this on a London bus or this on a
London bus [slides showing buses with anti-Islam
campaigns].
You must forgive me for singling out Islam.
But the reason to do so is entirely supported,
because it perverts something that is really
important.
This certainty of the truth is something that
is deeply disturbing. In my view in many ways
our search in science is about our uncertainty
about the natural world rather like how religion
is about uncertainty. Actually, science like
religion, is sometimes most dangerous when
we are convinced by our certainty. That to
my mind is something which is really important
in terms of our ethics.
Finally, I come to the end of this talk. I
want to describe briefly an experiment which
is not published but has been accepted for
publication, which I think is a very serious
issue.
These mice have been modified genetically;
the father has a dominant gene for a black
coat; the offspring have a brown coat because
Carol Readhead and I have modified the sperm
in the testes. Some time ago we realized that
we could get very reliable transgenic technology
by doing something much more simple than modifying
embryos.
For many years now she and I, with my team
at Hammersmith, and to some extent her team
at Caltech in California, have been looking
at ways to get transgenics much more efficiently
by modifying them using viral vectors. This
work will be published in due course. What's
astonishing is instead of the usual success
rate, which is 1-5%, depending on how we modify
the media and other things, we can get around
90% of our embryos actually producing the
gene that we're interested in; we think we
can get more than one gene construct simultaneously;
gene expression has now been shown up to the
third generation; and it seems to work in
large animals like pigs.
From a medical point of view it's interesting
because it opens the possibility again of
zeno transplantation, of being able to modify
pigs organs so that they're not seen by the
human immune system and we can modify the
rejection phenomenon, hopefully in time. But
it also argues something extraordinarily threatening
all of us, and how do you regulate that?
If we can really regulate the genome of a
large animal and we really want to use modern
eugenics then we can change cognition, we
can change strength, we can change all sorts
of things that we regard as desirable characteristics.
This film clip of Hakimi's work in Chicago
shows it rather well. The front mouse has
been modified so that it uses oxygen very
efficiently, and it runs much faster than
the wild type mouse, which gives up after
about 200 kilometres. The genetically modified
mouse will run and keeps on going. Can it
run for 2 hours? Yes, ladies and gentlemen,
it can run for 2 hours. Can it run for 3 hours
without stopping? Yes, it enjoys it so much
it can run for 3 hours. This mouse was filmed
for over 4 hours running on the treadmill.
Interestingly, it uses much more carbohydrate
than a normal mouse, and it is much more aggressive
than the normal mouse. It's not the sort of
mouse you'd want in your kitchen. It never
gets fat. It lives for about a third of its
life longer. That's the unpredictable effect
as a result of the genetic modification.
>> So, Lord Winston has kindly agreed to take
a few questions, so if you would like to ask
a questions please raise your hand.
>> Hi. My name is Morina Johnson. Regarding
the bill you want to put through the house
of lords: you say that most drugs are tested
on animals anyway, why do you feel it's so
important that this should be on the packaging?
>> I think it's important it should be on
the package because I think there's a need
for people to recognize how essential animal
research, and particularly research on mice,
is necessary for the progress of biology.
What is interesting is again and again there
have been moves, particularly in Europe, to
try and reduce the number of animals that
we're using. If you look at statistics published
by the home office in London, there's a rise
in genetically modified mice, which are being
made in laboratories, which are necessary
in my view essential for progress of much
pharmacogenetics and many other experiments
which are needed for human health.
I don't think that's likely to decrease because
although we talk about the 3 Rs, reduction,
refinement and replacement. Computer modelling,
cell culture and a whole range of other things
cannot do what research in the intact animal
can do. In my view it's important to show
we're using the mice wisely and humanly, not
excessively, but especially to protect humans
and indeed animal health as well.
>> You talk a lot about the public perception
of science. I'm curious as to what you feel
the scientist's responsibility is for the
life of their findings take on once they leave
their labs. I think personally the relationship
between science and media is dysfunctional.
I was wondering if you have any insight into
how to improve that process so we are ethically
presenting our findings to the public in a
way that's transparent and clear about uncertainty.
>> I'm not sure that the relationship between
the media and the scientist is quite as dysfunctional
as it has been in the past. I think there
are lots of signs it's improving. Even that
great organ of science, the leading scientific
journal in the popular press, The Daily Mail,
has been increasingly more responsible in
its reporting. The classic example, was the
reporting of the Fukushima example in Japan
with the nuclear reactors that were flooded.
What was extraordinary was that Mike Hanlon,
the science correspondent, produced a series
of really responsible arguments saying we
mustn't look at that as a way to negate the
need for nuclear power in the United Kingdom.
I thought it was an astonishing breakthrough
in journalism.
In general, I think the dysfunction mostly
comes from us as scientists. I think we're
very ready to give the impression that things
we've done are much closer to fruition than
they really are. I think that's dangerous.
Journalists, on the whole, want to be sensational
and attract headlines. But good journalists,
who I think are on the increase, are very
wary about hyperbole from our community. I
think, on the whole, they're printing what
they're told to print, rather than making
it up.
So I think the onus has to be on us. The fact
is as I said to a group of students this morning,
if you're a PhD student doing a PhD project...
Actually it wasn't students, it was to colleagues
here. If you can't explain in three sentences
what your PhD is about to a non-scientist,
it's possibly not worth doing. We are very
bad at explaining the science we do. That's
a real problem. We need to be much more concerned
about how we express that. If we express our
science properly, we'll actually do better
experiments, in my view.
>> Thank you. David Stevenson from Queen Margaret
University. I was really pleased to hear you
question the concept that truth is absolute
and to point out the danger of certainty.
I suppose with that, we're lucky in Scotland
that we don't have the same funding situation
they have at Universities in England. But
I wondered what fear you saw for science in
the removal of funding for the humanities
and to what degree should STEM subjects actually
be saying that language and work of humanities
and the work of critical language studies
are as important to our scientific research
as the science itself.
>> Well, I take the rap over the knuckles
which is implied by your question to heart,
but I do think that science is not necessarily
going to be the answer to many of the questions
with which we are plagued; the expanding Universe,
black holes and so on. There are many things
which we are not going to be able to explore,
increasingly, in biology. I think there's
a growing recognition that quantum is going
to be quite important in biology too, which
is quite mysterious.
I don't know how we get around that. There
needs to be, and that's why universities are
so important. The problem I have working at
Imperial College is that it's a science University,
very unusual in the British isles in that
respect, very good science but not great humanities.
I think that's a huge lack. It worries me
massively that in the budgets which have been
presented to research councils, the humanities
have come out much worse than they should
have done. Ultimately the humanities are of
key importance in how we deal with our science.
That, I think, is deeply troubling.
Of course we want to see more science research
being done properly. Of course it should be
properly funded; nobody argues with that.
I think the worry is that we have a scored
a hit at the cost of humanities is very, very
serious.
>> Thank you, that was a very interesting
talk. I was wondering, I have three questions,
maybe four, but I will stop at three.
>> I think you might get into trouble with
the Principal.
>> One question.
>> One question; you didn't say anything about
genetically modified food.
>> No, I didn't say anything about genetically
modified food because I think it's essential
technology which we need urgently. The evidence
that genetically modified view is in any way
harmful to humans is completely absent, in
my view. I know I'm talking in absolutes,
but I've not seen any good data to suggest
it's harmful. We're living on a planet where
cereals are threatened by pestilence and drought.
Many are killed when they've used most of
their water. And we have a duty to pursue
our technology. What is an affront to the
nationality, is that in England at least,
I don't know how it is in Scotland, but in
England researchers doing work on modified
crops get assaulted and their fields torn
up by protestors which I think is very shocking.
I would like to see more research. There are
some environmental issues. I suspect they're
much more trivial than some people are prepared
to believe. Certainly what's been published
in the leading journal Nature have shown several
occasions the list of genetically modified
crops are far less than has been stated by
its opponents.
>> I'd like to propose a thanks. Understanding
medicine and understanding these developments
in genetics is really quite demanding. Robert
has talked about these developments - and
he's been one of the key scientific leaders
in some of the very important developments
in medical genetics - he's talked about these
with tremendous clarity. Putting these developments
in a societal complex is also very demanding
but he has very successfully, in his very
clear lecture, put them in a societal context.
And for many of us, talking in a clear and
honest way about ethical issues is a tremendously
hard thing to do. I think he's a tremendous
credit to Lord Winston that he talks about
genetics and societal issues and interaction
with possible ethical views with such great
clarity, such obvious personal integrity.
So I now invite you to join me in applauding
him. Thank you very much.
(Clapping)
This production is brought to you by The University
of Edinburgh.
