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For the Holy Grail - Transcript

PROGRAM TRANSCRIPT: Monday, 3 October , 2011

CAROLINE JONES, PRESENTER: Hello I'm Caroline Jones. Tonight we revisit the story of two Australian
scientists and their quest for one of the holy grails of medicine - how to treat cancer without any
of the dreaded side effects. Four years ago Dr Jennifer MacDiarmid and Dr Himanshu Brahmbhatt
sparked intense worldwide interest with a revolutionary technique to deliver chemotherapy. Animal
trials have produced spectacular results and now the two scientists are ready to move onto human
trials. This is their story.

DR HIMANSHU BRAHMBHATT: It was very clear right from the beginning that nature has most of the
answers that we seek and many times you will find that the answer is so right in front of our nose
tips. In terms of cancer treatment, there must be a key that will fit into the lock which is cancer
cell, specifically into that lock. The important thing is to try and find it.

DR JENNIFER MACDIARMID: We realised that in nature, bacteria sometimes spontaneously make little
particles, and that if we could make bacteria do that all the time so that you could harvest those
particles, here was a natural delivery system. It was already there. Nature had done it. So this
was the basis of the technology and we realised that this could revolutionise delivery of drugs to
cancer cells. The trouble with chemotherapy or the way we treat cancer now is that we flood the
body with poisonous chemicals and we all know people who've lost their hair, they're nauseated. We
are hoping to develop targeted therapies that take the drug straight into the cancer cell and
thereby reduces those terrible side effects.

PROFESSOR BOB SEAMARK, FLINDERS UNIVERSITY: They've done the research now to justify their claims
and I totally believe this is one of the most important breakthroughs in the cancer research area
for as long as I've been associated with cancer research, which is now over 20 years. What Himanshu
and Jennifer have done I think is unique, you know as I got to know them I began to appreciate how
important a team they were. In fact they seemed to spark each other off, and I used to call them
the dynamic duo.

IAN MACDIARMID, DR JENNIFER MACDIARMID'S HUSBAND: I see the connection with Jennifer and Himanshu,
the association there, as a bit like good cop, bad cop. It's quite an interesting relationship.
They put up with each other in a very close environment and they seem to do it very well.

DR DORIS MARIS, DR HIMANSHU BRAHMBHATT 'S PARTNER: They obviously share an office, they have
similar long working hours, and yes they probably spend more awake time together than Himanshu and
I do or that Jennifer and Ian do.

DR JENNIFER MACDIARMID: You know we have an odd blue but it's not very sustainable.

DR HIMANSHU BRAHMBHATT: Yeah, because you called me names or something.

DR JENNIFER MACDIARMID: In the late 80s and 90s I was working with CSIRO at the Division of Animal
Health and I was initially working on bacterial diseases in skin of sheep. It was very interesting,
however the CSIRO was going through a state of flux and so a lot of people including myself were
becoming disenchanted and I was beginning to get jaded and think about even stepping out of
science, frankly. In the early 90s Himanshu came to McMaster Laboratory. He really sparked my
scientific interest off again. He's like a child. He's like a sponge. Everything goes in, he
absorbs it and he assesses it, and then he can come up with a thousand ideas. He has a fantastic
imagination and he is creative, all the things that scientists really need but rarely have I think.

DR HIMANSHU BRAHMBHATT: At CSIRO there was a technician in my lab. He was a Hong Kong Chinese, and
he was a remarkably nice person, but unfortunately at the age of 40 he developed lung cancer and
very quickly he was in hospital and soon the doctors decided that there was nothing much that could
be done for him. We would go over and sit by his bedside, hold his hand, try and comfort him as
much as possible. But he was going very, very quickly and it started to really knock me around very
seriously. I began to feel that if I had been working in this science for so long, and if I am
going to tinker around with all these test tubes and not be able to save somebody or help somebody
in such an intense situation, this science is no good for me. I've got to shift.

DR JENNIFER MACDIARMID: Kin San Lee was lying in bed, he was clearly suffering immensely, you know
you could see that he was going to pass away in the not too distant future. It was awful.

DR HIMANSHU BRAHMBHATT: And he lifted his hand and he pointed at us, said: "If somebody is going to
cure cancer, you can do it. Go and do it." Then I held his hand, "Yep, we will do it."

DR JENNIFER MACDIARMID: Himanshu looked at him and said, "I will, I will do that. We must do it, I
promise you."

DR HIMANSHU BRAHMBHATT: He knew he had affected me. He knew that that was a promise.

DR JENNIFER MACDIARMID: And you felt, you actually felt that Himanshu would do something about it,
that we had the capacity if we put our minds to it.

DR HIMANSHU BRAHMBHATT: I actually went straight back to Sydney University that night and I pulled
out all the journals. I just started reading. I had to read something about cancer and for the next
four months, I just kept on reading, anything and everything.

DR JENNIFER MACDIARMID: Our hours were quite long because we had to do the study on our cancer work
after hours.

DR HIMANSHU BRAHMBHATT: We had no idea what we are looking for. Absolutely no idea where are we
going to find these answers? There are no answers. There must be an answer in nature.

DR JENNIFER MACDIARMID: Clearly there was a lot of natural products out there that could help. We
came up with a lot of potential plant extracts that had clearly shown some advantages as far as
immune boosting or actual direct killing of cancer cells.

DR HIMANSHU BRAHMBHATT: While we were at CSIRO, a second event occurred. The CEO was Sir Malcolm
Macintosh, and he had developed kidney cancer. He had actually sent out an email to all staff
saying that unfortunately his days were numbered.

DR JENNIFER MACDIARMID: So we contacted him and we suggested that there may be things that we could
do due to our reading and we laid out in a document some of the findings we had that were clearly
not proven, that were just our ideas put together.

DR HIMANSHU BRAHMBHATT: We were asking him to be the first human guinea pig. He stood up and he
said I have a four-year-old son, I'd like to see more of him. I'm willing to do anything if it
might just prolong this thing.

DR JENNIFER MACDIARMID: He had nothing to lose. He'd been through every form of chemo known to man
and radiation. We ground up the plant material and did a crude extract, put it into capsules and
gave it to him in that way because it's very noxious to taste. His oncologist at the time said,
"You can do what you like but I don't think there's any value." And he did very well. He reported
that he felt very well. His scans showed no growth of the tumours and he went back to work.

DR HIMANSHU BRAHMBHATT: There was clear evidence of tumour regression and very interestingly he
survived almost a year after that.

DR JENNIFER MACDIARMID: He was so well that they decided to do some further treatment in hospital
and unfortunately he got a hospital infection and passed away. We were absolutely devastated
because he was, he'd become a friend and we'd seen him, you know he felt well. And to have some bug
take him out was just awful, absolutely awful.

DR HIMANSHU BRAHMBHATT: We knew that at least our thinking was correct. We were on the right track
so at that point Jennifer and I decided that we'd have to leave CSIRO and start something on our
own.

PROFESSOR BOB SEAMARK, FLINDERS UNIVERSITY: This is a very, very unusual thing for scientists to
do. It was a struggle for them. It was a hugely risky proposition. They followed their dream is the
best way to understand it, and eventually got to a point when the dream became the only real thing
they could ever do.

DR DORIS MARIS, DR HIMANSHU BRAHMBHATT 'S PARTNER: I said, if you really, really want to do it, go
ahead, give it your best shot. And you know, worst comes to worse it fails and so what? But you
know, if it works, imagine what would happen if it works. You could actually help so many people.
You could maybe even prevent cancer in some people.

DR JENNIFER MACDIARMID: So the first thing we had to do was raise a lot of money. My husband is a
sail maker and strangely enough it was connections with the sailing fraternity that opened doors
for us to wealthy people who were open to the suggestion of investing in a new start biotech
company.

DR HIMANSHU BRAHMBHATT: Our success with the plant extracts made us wonder: Wouldn't it be better
to have something that would rapidly kill off these cancer cells? That lead us to a new idea - to
create tiny little nano cells, much smaller than a normal cell, that could directly attack the
cancer cells but not hurt the normal cells.

MARK BETHWAITE, FIRST INVESTOR: I thought it was fantastic. I just thought that was such an elegant
and far-reaching technology that I just had to come on board. I helped them with a business plan to
make it credible, to make it attractive to potential investors and then we started going around
town.

DR JENNIFER MACDIARMID: We wore out a lot of shoe leather and we were basically nobodies because
we'd come from CSIRO in the vaccine area, and here we were saying that we could potentially do
something about cancer. We had no evidence, we had no proof.

DR HIMANSHU BRAHMBHATT: Because all we had was an idea, we had nothing else with us. A lot of
people told us, you know, sorry, what have you got? Oh nothing, just an idea. Okay, goodbye.

DR JENNIFER MACDIARMID: We needed about $5 million, we thought and it took us 12 months to raise $4
million, so we said that's it, that's enough, we will get going.

PROFESSOR BOB SEAMARK, FLINDERS UNIVERSITY: This was a remarkable thing, that Himanshu and Jennifer
were able to find investors who would support them. It's very unusual for this to happen in
Australia because we just don't have a culture, say like they do in the States, where they're
prepared to take this risk.

DR JENNIFER MACDIARMID: And so we within a week had the premises and we started working furiously.
My brother-in-law made the benches, Himanshu and my husband and I pulled up carpets and cleaned the
floors, and we were up and running within a couple of weeks. And Himanshu and I even have got our
mums helping in a big way. Himanshu's mum comes in a couple of times a week and she processes the
mouse cages for us and autoclaves material for us, sterilises things for the laboratories. So she
cuts a dashing figure, resplendent in her sari with the lab coat over the top. And my mother does
boardroom lunches and so she makes an array of food for the board and for any visitors we have.

DR HIMANSHU BRAHMBHATT: The key question in the early days was whether our idea would work - to
create a nano cell that would target cancer cells, but leave the rest of the body unharmed.

DR JENNIFER MACDIARMID: Our first breakthrough came when we found that we could actually
genetically alter bacteria to create these little nano cells. And we called this little nano cell
or particle, the EDV, standing for engeneic delivery vehicle.

DR HIMANSHU BRAHMBHATT: Then we found that we could actually insert an anti-cancer drug directly
into the EDV particle. The next step was to coat the EDV with an anti-body that would recognise
only cancer cells. What we hoped was that the EDV would lock onto the cancer cell and be swallowed
by the cancer cell, then releasing the drug inside which would rush out and kill the cancer - much
like a trojan horse.

DR JENNIFER MACDIARMID: The first time we saw it working, it was very exciting. It was a truly
Eureka moment, and so, you know, we knew we were on our way then.

DR HIMANSHU BRAHMBHATT: When we saw these results we were just, not just blown away, but we felt
those eyes that had looked at us before with hope that we will some day do something for cancer, it
was almost like those people returned to us. Yes, it's happening. In future people might live
because of this.

PROFESSOR BOB SEAMARK, FLINDERS UNIVERSITY: We call it the magic bullet. Wouldn't it be wonderful
if we had a magic bullet that you could fire at cancers? This is something that so many of us have
tried to develop in the past, a magic bullet, but they seem to have done it.

DR JENNIFER MACDIARMID: And it was interesting that this idea came from nature. We were observing
natural systems and harnessing what nature had already taught us. The amazing thing about this
little particle, the EDV, is that we found that we could load up any drug, and you could change
these depending on what cancer you were going after. So for solid tumours, liver, colorectal,
breast cancer, prostate cancer, we have demonstrated in mouse models of all these types of cancer,
it stabilises tumours and it causes regression. The real advantage is that the amount of drug you
require is thousands of times less because it's a concentrated dose inside a little particle so you
don't get side effects. Your hair won't fall out, you won't be throwing up and have diarrhoea and
skin inflammation because we're delivering the drugs straight inside the target cell. It's not
flooding the body.

DR HIMANSHU BRAHMBHATT: We wrote up our scientific paper, our first paper and we submitted to a
leading journal in United States. Many of the researchers felt that this is too good to be true.
Can't be. How can this be true?

DR JENNIFER MACDIARMID: Eventually we did get our article published in 'Cancer Cell' which is a
very prestigious journal and we are amazed actually at the amount of publicity we've generated
around the world. We went from 200 mentions on the web to 23,000.

PROFESSOR BOB SEAMARK, FLINDERS UNIVERSITY: It attracted a huge amount of attention amongst the
scientists in these institutes overseas. I'm hoping that programs like this will give Jennifer and
Himanshu the recognition in Australia that they deserve. These are some of our special heroes.

MARK BETHWAITE, FIRST INVESTOR: They're the sort of people that Australians I think should put on a
pedestal like our gold medal swimmers and our cricketers. These are people who really are world
class in their own field.

PROFESSOR IAN OLVER, CANCER COUNCIL OF AUSTRALIA: Part of my job with the Cancer Council is
interpreting some of the new advances for the general public and I often get called up to read
through scientific papers and extract the meaning from them. My reaction to this is that so far
it's looking very promising. My caution is that I've seen a lot of new treatments look promising in
the laboratory and in small animal studies, but they haven't translated into the human situation.
So my caution is I am waiting for the first human studies.

DR JENNIFER MACDIARMID: We have done some pilot studies with dogs suffering from non-Hodgkin's
lymphoma and these are very important because they're much closer to human studies than studies in
mice. But we found that if we gave them our EDV treatment we were able to regress their tumours,
and one dog actually suffered a thing called tumour licus syndrome which means the tumours collapse
completely. We hope to get into smaller scale trials in humans by the end of the year.

DR HIMANSHU BRAHMBHATT: If the therapeutic effect is as what we predict then we see no reason why
regulators would not give us fast track status, to be able to get it out onto the market as quickly
as possible. But that still would take about three to four years. This research is all consuming. I
usually start work at five in the morning and finish around ten at night. This is seven days of the
week, 365 days of the year. If I pursue any other hobby, like I've got guitars sitting everywhere
at home, but if I touch the guitar I feel I am wasting my time, because somebody is dying out there
and so I can't seem to be able to do anything else now. I have had good fortune to meet Doris and
we've been together now for almost 20 years and we barely meet. I have often thought that some day
if I have some time, maybe on a Sunday, maybe we can find half an hour and maybe even get married.

DR DORIS MARIS, DR HIMANSHU BRAHMBHATT 'S PARTNER: I know what's driving him, I know that he's
genuinely interested in trying to solve this problem of cancer, and I know it won't be forever. So
I'm very hopeful that once this technology is out there and is being used, that things will go back
to normal.

PROFESSOR BOB SEAMARK, FLINDERS UNIVERSITY: There's every prospect this is going to be one of the
biggest selling products for any drug company. I know one of the overseas companies was chasing
their development was just overwhelmed by the fact that a small company like Himanshu and
Jennifer's could achieve what they did. Their estimate was they required a team of anything between
60 and 600 people to do the same thing.

DR HIMANSHU BRAHMBHATT: Finding a cure for cancer is the holy grail for pharmaceutical companies
involved in it as well as all the researchers. It would be foolish to say that money is not an
interest. Currently the company is a privately held company by the various shareholders. For me the
prime motivating factor is to see the cancer patient walk out of hospital, to see the smile on a
cancer patient, that would be a spectacular prize. No money can buy that. That smile is worth, is
priceless.

DR JENNIFER MACDIARMID: At EnGeneIC we have a cupboard where we've got some records and some
intellectual property stored. It's a precious cupboard. Also in that cupboard is a shelf on which
we have champagne bottles. Our investors have given us various sizes of champagne every time we've
had a breakthrough. The first bottle will be opened when we have a patient who goes into remission
from being treated with EDV therapy, and that is well worth celebrating. That is when we'll pop a
cork on the champagne.

END CAPTIONS:

Safety trials of the EDV treatment have been completed successfully on more than 20 patients
according to EnGeneIC.

In animal trials, brain tumours were slowed or eliminated in 10 out of 10 dogs tested.

The next phase, human brain cancer clinical trials will begin soon.

But Drs MacDiarmid and Brahmbhatt say further work is dependent of continued funding and there are
no guarantees.