[Speaker 1] The next generation of biological therapists,
they hope will do the same somehow.
Not radiotherapy, but instead of chemotherapy,
we just deliver these drugs
systemically to everywhere that you can somehow.
Can you get them to the tumor itself?
That same notion.
[Peter Almond] Yeah. But the interesting thing
is now with radiation therapy,
if you've got a tumor that's close
or wrapping around the spinal cord,
there was no way in
the past to treat that because you'd go through,
spinal cord is fairly sensitive,
you're limited by a dose,
otherwise you're going to cause paralysis.
[Speaker 1] Right.
[Peter Almond] But now you can get the radiation
to just wrap around the spinal cord and spare it.
It's quite amazing what they can do.
Because these are high-energy
X-rays that are being used,
skin dose is low,
there's no problem with
high skin doses and radiation burns of the skin.
I might be reveling I suppose,
but generally even that's going on today.
I think things have changed a lot.
That's why we went through the Betatron
and into the linear accelerators.
The Betatrons came along first.
They were easier to build and it
wasn't sure right at the beginning whether
Betatrons or linear accelerators were the way to go.
Most people started out with
Betatrons and went over to linear accelerators.
The Cobalt-60, again,
just got (noise) replaced by
very efficient and reliable linear accelerators.
When you turn a linear accelerator off, it's off,
but when you've got a Cobalt unit,
(laughing) it's never off.
While you're submitting, then you've
got to have the right kind
of shielding and protection and all kinds of things,
and regulatory people don't like those types of things.
They've almost disappeared completely.
There are a few around,
but not in this country, I don't think.
[Speaker 1] That Cobalt-60, why did
it bring such fame to (inaudible)? (crosstalk).
[Peter Almond] Well, first of all,
they were amongst the first people
to first have the idea
and then produce a working machine.
As you know, the big competition
was whether we were first or
whether Harold Jones and the people in Canada were first.
In fact it was simultaneous.
I don't think there's any doubt that
Harold Jones had this idea.
I knew Howard very well.
He developed Betatrons also.
He was a visionary and he saw
the use of both of these and he saw
Cobalt-60 and desired units
and the Canadians were
producing more Cobalt-60 than we were,
so he had that advantage.
That's where we got slowed up.
But Grommet and Fletcher both, I think,
saw that Cobalt-60 was
an ideal isotope to put into a treatment machine.
There wasn't anything else at that time.
This is really before Betatrons.
The idea was there but they hadn't really been developed.
Linear accelerators were just slower getting along.
Grommet, if you read his paper that he published here,
his idea was he saw this as
a low-cost device that could be
put anywhere and be
available to anybody throughout the world.
This was something that wasn't
a lot of technology involved.
Once it was built,
it was simple to run,
simple to operate, inexpensive in many ways.
He saw this as radiation oncology to a lot of people.
[Speaker 1] Did it?
[Peter Almond] Yeah, it did. It really did.
The race that was on to build one,
and Fletch and Grommet's design
was a very, very good design.
It's just that we couldn't get the Cobalt-60 for it soon
enough because of politics between
Canada and the United States and other things.
It wasn't there, but certainly
Grommet published the first design
for a cobalt unit before
anybody else and just
didn't get it loaded with cobalt soon enough.
But it was built here,
went into operation here,
and was used here and proved the concept.
It was then mainly the Canadian's
Atomic Energy of Canada Limited.
We had an arrangement with GE to
build the first unit here and GE then went
into an arrangement with
Canadians to build units and that didn't
last very long and GE got out of the business
and the Canadians relentlessly took over.
A company called the Atomic Energy of Canada Limited,
which was a crown company eventually
was the one that ended up building them.
Then the next-generation of the cobalt unit
was the cobalt unit F,
people used to say the F stood for Fletcher.
Whether it did (laughing), I don't know,
that's the next generation;
which rotated around the patient,
which was all the way around the patient,
which allowed you to, setups were easier
and you could do rotational treatments
and things like that.
Fletcher had a lot to do with that unit
and it was in use here for a long time.
But it really made
fairly inexpensive treatments available for anyone.
Certainly what happened was then they
built hundreds of these units
and they went in all over the place.
Treatments were far superior
to the other voltage machines because there was
no skin reaction or very little skin reaction.
It opened up radiation oncology
in lots and lots of places.
Eventually of course where it's gone to
is into developing countries.
You go to Central America, South America, India,
places like that,
who could afford a cobalt to
do what they couldn't afford anything else.
That made that available.
Certainly it was known
that part of the development was done here.
I think in terms of the treatment with cobalt units,
certainly Fletcher developed a lot
of those and got known for them.
[Speaker 1] Do those regimens spread with the machine?
[Peter Almond] Yes. You used to be able to tell
an Anderson-trained radiation oncologist
by how they treated patients because it was
the way (laughing) Fletcher
would treat and there would be
the people from Stanford
and there was the Stanford treatment,
and Stanford never went with cobalt units.
They always start with linear accelerator.
They had one form of
treatment and there was the memorial treatment.
So people, very
much the approach to treatment became- (crosstalk)
[Speaker 1] What was the Memorial treatment?
[Peter Almond] Oh, I don't know. (crosstalk) It
was certainly probably different fractionations,
different dose levels,
and that type of thing that got developed.
But certainly I thank the development
of the Cobalt-60 to Fletcher,
but at the same time because by the time we
got the cobalt here was when this building opened.
This building, the original building
of course was opened.
They moved the cobalt unit in
shortly thereafter and the Betatron.
Fletcher was doing both at the same time.
[Speaker 1] This is in '54?
[Peter Almond] This is in the late '50s.
[Speaker 1] Okay.
[Peter Almond] It started in '54.
I think he developed both treatments and in many ways,
his treatment with the high-energy
x-rays I think got him a lot of notoriety.
Because not many people had
that energy and he was rarely advocating it.
When we got the first linear accelerator,
his instructions to (laughing) many people to produce
the beam from that Betatron
on the new linear accelerator.
That's essentially what he said.
He said, I've got this beam out of the Betatron and I
want the same beam out of
the linear accelerator. Make sure I get it.
That's what we had to do with the manufacturer.
We matched the beams for him. That's what he wanted.
Again, then in the '70s,
there became a fairly well-publicized controversy
between Anderson and a lot of other places because
Fletcher was saying you got to have
at least 20 million electron volt x-rays
and there were a lot of people using 10 to 15 MeV,
and he just said that's not high enough.
He got into some pretty good arguments with
manufacturers and other people
about what was the right energy to use.
That's disappeared today because of
this intensity-modulated radiation therapy.
You didn't do those with 6 MeV X-rays.
You don't need the high-energy X-rays anymore.
We've passed through the cobalt area into
linear accelerators and Betatrons and very high energies.
That era has just about disappeared because of
the techniques made them
obsolete and now you can use
lower energy machines to do it.
There are certain advantages
of using lower-energy X-rays.
When you produce very high energies above 15 MeV X-rays,
and the old Betatron and
the linear accelerators were above that energy,
you produce neutrons,
and they're not particularly nice to have around.
Take a lot of shielding and
also some danger for
patients to get whole-body neutron doses.
We've always worried about that here.
Now, you wanted to know about neutrons?
[Speaker 1] Yes.
[Peter Almond] And cyclotrons?
[Speaker 1] Right.
[Peter Almond] Okay. Well, this
goes back to home and suit and hyperbaric oxygen.
[James Stuart Olson] Trying to think of the timescale for this any house,
certainly by the '60s,
it was known later cells that were anoxic, that is,
they were not in oxygen atmosphere,
were about three times more radio resistant than
cells that were in oxygen or had oxygen supply to them.
I mean, you could say that
the other way if you have oxygen there,
the cells are more sensitive to radiation.
No oxygen, they're resistant to radiation.
It's well-known and was documented during
that period that in the center of solid tumors,
where the blood vessels have been pushed out,
the cells right in the middle will
die due to lack of oxygen.
There's a necrotic center to tumors.
They're unviable.
But right around the edge of that anoxic necrotic center,
if you have one, there are
cells which are starved from oxygen,
but they're still viable.
You try and treat those with radiation,
you may kill all of
the tumor cells on
the outside which have a good oxygen supply,
but you may not kill
the cells right in the center that have no oxygen.
That's called the oxygen effect,
is a factor of about three amount of radiation.
People started to think how can
we get over the oxygen effect.
That's why they put them in a hyperbaric oxygen chamber,
pump them up, hope
the oxygen would get there and diffuse in.
There were reasons to think that it could work,
but there were a lot of reasons
to think why it shouldn't work,
but it was tried and it didn't work.
Well. The number of people found out that in fact,
if you were radiated with neutrons
rather than electrons or X-rays,
the oxygen effect disappeared.
The killing mechanism is a little differently.
With neutrons, instead of being a factor of three,
it's a factor of 1.3.
It's a slight difference,
but not nearly as much of a difference.
The argument went,
if we could use neutrons,
we could kill all of the cancer cells and
maybe we could improve (inaudible) rates.
It was tried in the 1940s,
in California by the name of Stone.
It was tried in England in Hammersmith Hospital.
One of the difficulties is
that neutrons are very damaging to tissue.
Especially if there's any fat content
there because they interact with the protons in the fat,
and you get a lot of solid fibrosis with neutrons.
A lot of normal tissue damage that you don't want.
The initial trial add in Berkeley had come to
a screeching halt because the complications are too high.
There's too much fibrosis in normal tissues.
But they were using low energy neutrons.
One thought that maybe one should try it now and see.
This was in the late 1960s.
Then Texas A&M build
a great big cyclotron in the late 1960s.
We approached Texas A&M,
and said would they be interested in the joint project
if we could take a beam line off of their cyclotron,
very high energies and make neutrons with it,
we would get high-energy neutrons
much higher than the people at Berkeley had had.
We would like to see whether we
could try neutrons therapy.
We had a joint agreement with Texas A&M,
developed the program out there,
built one research area there which
we turned into a treatment area and
then bust the patients up, twice a week.
Turns out with neutrons, the fractionation,
how many times you give treatments,
is not as critical as it is with X-rays.
You could go twice a week.
[Peter Almond] Instead of every day?
[James Stuart Olson] Instead of every day.
Eventually what we did,
we mixed the neutrons with X-rays,
which seemed to work very well.
Anyhow that program seemed to work.
We could certainly get rid of the tubules,
the long term complications seemed to be less.
It was decided, well,
we can't continue to take
patients up there and staff up there,
run these two limousines.
There was the day the wheel came off the limousine.
The wheel took off down the road.
He never knew what was going
to happen. That was a fairly.
[Peter Almond] Who was in the limousine
when that happened? Which one of you?
[James Stuart Olson] I wasn't there, Dave (inaudible),
I forget who was the physicists at that time.
That wasn't my day.
(inaudible) Limousine.
[Peter Almond] With the patient?
[Lesley Williams Brunet] The patients went up in the limousine.
[James Stuart Olson] Yeah, and so did the (inaudible).
[Peter Almond] And so the physicist?
[James Stuart Olson] Physicist and radio, I
mean we would cram into this limousine,
we'd have a drive and drive up.
We eventually ended up with an apartment or
two a day in MMC, and we stayed up there.
Anyhow, that pilot project seemed to work.
We decided we would see whether we
would get a cyclotron there at Anderson,
and went to NCI and got funding for one.
A cyclotron, instead of accelerating electrons,
which all the other devices
do, accelerates charged particles.
We ended up accelerating deutrons,
which is a proton and a neutron together.
That's the nucleus of a deuterium,
would take the electron on.
Because if deuterium at
high energies hits a beryllium target,
it will produce neutrons.
These are fairly high energy neutrons,
it gives a nice distribution,
like the distribution out
of a linear accelerator for high-energy X-rays.
It was probably better than cobalt
60 in terms of the distribution and depth of penetration.
We went to the cyclotron cooperation in Berkeley
that have built one or two cyclotrons.
They were willing to build us
a cyclotron to be housed in the hospital.
Memorial had a cyclotron up
in New York for production of isotope,
but not for it.
The only other hospital-based cyclotron
was at Hammersmith Hospital in
England where they were doing neutron therapy.
They claimed a lot of success.
[Peter Almond] There's so much hoopla about it when it happens.
It seems to die off to me.
[James Stuart Olson] Well, it did. We eventually got the cyclotron,
we got it operational,
we put it in the basement here
and got it and treated a lot of patients with it.
What we found out,
I think in the long run was the initial study had found
out although we could cure patients,
the long-term complications were just too high.
[Peter Almond] Tissue damage?
[James Stuart Olson] Tissue damage. It just was not acceptable.
Say if we try regimen a part neutrons and part X-rays,
which seemed to help,
some people continued a little longer than we did.
There may have been one or two sites
that might have been useful.
It could have been treated by neutrons,
but you really couldn't justify the expense.
Fairly expensive product,
machine was expensive,
keeping operational was expensive.
Produces a lot of unwanted radio activities
or health physics wise.
It was a project that needed to be tried.
The pilot study it seemed to work we got the cyclotron
here and they had treated a lot of patients on it.
But as those were followed out just proved.
I think also what's
happened the other technologies and the other forms of
radiation therapy have really
improved so that you can get
the dose to the tumors that you want.
In some cases with intensity modulated radiation therapy,
you can go up to doses
half as high again as you used to be able to go.
That's a significant increase and hopefully the two were.
Now the big arguments you always get
is (laughing) are you sure you're doing any good.
(laughing) (crosstalk)
[Peter Almond] The bottom line question again.
[James Stuart Olson] No one has ever shown that you've
improved survival rates and all of that.
I always say to those people,
you're questioning whether should we pour
all these money and all these funds in
new treatments and whether it's worth and whether we're
going to improve survival rates.
If you are unfortunate enough to ever need
the services of a radiation oncologist,
I'll give you a choice.
Do you want to be treated how they were treating
40 years ago (laughing)
or how they're trading today? (laughing)
[Peter Almond] In deed.
[James Stuart Olson] Then the argument is over you see.
In fact, survival rates are better it's very hard,
but it's the incremental so the small ones.
But what's better is the complication rates
are much lower.
Treatments are much more safe and
much more precise, much better given.
It's just better overall
and hopefully as you follow this then through.
[Peter Almond] That to me seems true of surgery,
of chemotherapy, some of the major gains have
been in preserving their survival rate with less damage.
[Speaker 2] That's right.
[James Stuart Olson] That's a good deal as
I see it for cancer treatment is that.
As I said, Fletcher was known
for being really aggressive.
You got to be aggressive with cancer.
Of course it was the patient that paid the price.
He was willing to say I'm going to be aggressive.
I think he told the patients
we're going to be aggressive there's going to
be a certain probability
that you will have some complications.
But he always felt that trade-off was worth it.
If you have that attitude you can get
pretty good cancer control and then you can
slowly make sure the complications
get right. You're much better off.
You start off if not accepting the complications.
I don't think you ever move forward
because you don't have the complications
and very often you
hear people say they
get treated for cancer with radiation.
If they were the radiation oncologist
that is not aggressive,
so they make sure
the patients doesn't get a complication.
It used to be a lot of
private radiation oncology and
I think it's less and less.
Well, what happen is the patient would get treatment.
They wouldn't get any complications,
wouldn't get any skin reaction.
They got treated and maybe
felt better for a little while then
the cancer would come back.
Well, that's just the nature of cancer.
Well, that's an act of God.
Same patient had they gone to
an aggressive radiation oncologist,
where patient gets some complications
and the skin reactions,
patient will come and say,
but I got burned up by that radiation oncologist and so
the radiation oncologist (inaudible)
even though they may be cured of that cancer.
You have those two extremes and
Fletcher pushed the envelope
in aggressives of treatment
even though he had the complications.
[Peter Almond] Today I just hear a story in the news
about a survey of oncologists
who don't give enough of the dose
because they want to reduce the side effects.
[James Stuart Olson] That's always there.
It has been around for a long time and it's still
there and it's a profitable for chemotherapies,
it is for radiation oncology.
Certainly if you get out into
the small community radiation
oncologist and if you get in then of
course trouble is medical liability
and loss to the problem and that's always there.
We've always been very fortunate here because
I think one documentation and
radiation and then quality
and control and assurance have always been very
careful and I think
from small independent people it's difficult to do.
Anyhow, it looks to me now so this question
of the oxygen effect to neutrons that's gone away.
Some people would try to alter
that ratio with sensitizers.
Chemical sensitizers were tried,
chemical protectors were tried,
hyperbaric oxygen was tried,
and then suits technique
for anoxic treatments were tried.
But eventually I suppose it will eventually come down
to some molecular treatment radiation.
Although I'm not involved but I think there's
some interaction between people who work on
the molecular level and radiation to see
whether those can converge a little bit.
Which I probably will at some point.
[Peter Almond] What about all the hoopla about proton therapy?
I think I just heard of add from
Loma Linda University the other day. (crosstalk)
[James Stuart Olson] Proton therapy takes advantage
only of the physical distribution of the radiation.
There's no trying to manipulate
the radiobiology of the tumor cells or anything.
Protons, again, are
charged particles and they tend to go into
the body and at the end of their range
create a lot of ionization so the dose suddenly goes up.
They go in and
the dose increases at the end and then stops.
The protons stop.
If you can send
in a number of protons with different energies,
they will go in and radiation give
off their energy and stop and you can build
up so they go in and you could cover the tumor with dose
because you've chosen the energies to go in
and some to stop at
the front of the tumor some at the end of the tumor.
Used to think there was some biological advantage
of protons but they're not.
But they are and you can very
precisely now choose these energies.
You can again choose
the dose to go very precisely around the tumor.
No dose behind, no dose to the side.
You gave it and can
give very high doses just to the tumor.
In fact, Loma Linda was one of the first.
Then they were not the first the Russians have been
doing it for a long time the Swedish have tried it.
But on a full scale thing on their own,
Loma Linda did this,
they got their funding and build the device.
Then Mass General Herman Suit,
one of his big contributions was he always
thought protons should be tried, so Mass General.
Then of course, Indians have decided to get in.
I will have to say this that I'm not
sure what the clinical results are today.
Loma Linda should have results they've been treating long
enough certainly for things like
prostate and things I think they should do very well.
Mass General has pre-treated
semi tumors but she could send them into the front of
the eye and deposit the dose right on
the right and nothing else and they do that.
The travel with protons how the machines
accelerate the protons are very expensive.
Protons are difficult to bend.
They come out of the machine in a straight line
but to use them you've got a bend them
onto the patient and then move them around.
The devices to do that become very big because they take
very high magnetic fields to do that and
so the gantries that move around the patients are huge.
You need to go over to
our proton facility sometime and see them.
It's a very big engineering project to do that.