Biochemist Melanie McConnell encounters unexpected resistance when she tests an experimental cancer treatment.

Melanie McConnell has a life-long interest in cancer cell biology. She has studied pediatric, brain, breast, and skin cancers, all to better understand the intricate process of gene regulation. After establishing the Cancer Stem Cell programme at the Malaghan Institute of Medical Research, she joined the School of Biological Sciences at Victoria University of Wellington. Her research is aimed at reducing relapse and improving to life-saving cancer therapies by understanding how cancer cells survive chemotherapy, immunotherapy, and radiation treatment. She’s currently focused on the role of mitochondria in therapy resistance. In her real life, she is married to Richard, is mum to two girls, and spends her time with them and the dog, making compost and tending to the weeds in her vege garden.

This story originally aired on February 2nd, 2018 on an episode called “Recovery”.

Story Transcript

So I’m at a cancer research conference.  It’s a pretty standard conference.  It’s a hotel room.  The curtains are pulled so that you can’t see the beautiful day outside. 

We’re all sitting on uncomfortable chairs.  We've been out to get our coffee and we’re coming back with our coffees, and I notice that the room is filling up.  There's a lot more people at this session than had been at the previous session, and that’s great because my research is being presented in this session.  I must be famous because people are coming to hear what my team is saying. 

I notice that the people coming into the room are wearing suits.  They're mostly middle-aged and older men and they're all wearing suits, so they're not scientists.  I thought, Oh, the doctors are here. 

We sit down and my team member she stands up and she says, “I'd really like to thank the organizers for the opportunity to talk to you today.  We’re going to talk about the work we've been doing on the role that high-dose Vitamin C might affect cancer therapy.” 

At this stage, I kind of turned and I glanced at the doctors and there was this row of grim, stony-faced, antagonistic people just bristling at her, and my heart just sank.  What an audience is that if you want to be famous? 

But I guess, to be honest, I wasn’t surprised at that reaction.  So if we go back a couple of years, my research group has been focused for a number of years now on trying to understand why cancer cells, especially brain cancer cells, don’t die when you hurt them.  You can give them chemo, you can give them radiation, they do not fall over.  If we could understand why that happened then we can design some tricks to pull the rug out from under them and then we can make life better for people with cancer and for their families. 

So I was in my office one day and my colleague, I’m going to call her Dr. P.  Some of you might know her.  She came in and she said to me, “What do you know about Vitamin C?” 

And I said, “Oh, scurvy,” because I’m kind of a smart aleck. 

She said, “No.  Vitamin C for cancer.” 

And I said, “For cancer?  Huh?” 

It turns out a really good friend of hers had been diagnosed with a really nasty cancer and conventional medicine couldn’t offer him anything.  So he had decided he was going to investigate some of the alternative therapies and he wanted to use an infusion of high-dose Vitamin C.  So we decided to figure out would that be any good. 

Now, I’m an open-minded person.  I’m happy with the idea that some of these alternative and these complementary therapies may have some mechanistic basis through which they might actually work.  That’s an entirely possible thing in my universe. 

Acupuncture is a really good example.  Acupuncture has been tested for a whole bunch of things and sometimes it works.  And we’re building a body of evidence that looks at the biomechanical effect of sticking a needle in and twisting it and we can see that that changes the way the cells and the tissues react and interact with each other so we can start to see how acupuncture is working. 

Then there's things like Rescue Remedy.  I love Rescue Remedy.  I don't know if it’s the flower essences or it’s the brandy that you infuse the flowers in, or maybe it’s just the placebo effect.  But I really like Rescue Remedy.  I should probably have had some.  I’m kind of whooh. 

I know that that puts me at odds with very many of my medical and my biomedical colleagues who would call acupuncture quackery and we’re not even going to go with the flower essences with many of my colleagues. 

So we start to find out about high-dose Vitamin C and cancer.  And so where do you start?  You ask Google. 

Google is great.  So what Google told us was that Vitamin C can cure cancer and it can cure influenza and it can cure Ebola.  And the only reason that we have disease in our society is that conventional medicine refuses to believe in Vitamin C.  And there's no intellectual property, so no big drug company will make money from Vitamin C.  If it wasn’t for those two things, the whole world would be a beautiful place. We also learnt that you pay about a hundred and fifty to three hundred dollars for every infusion of Vitamin C, that the doses and the timing seem completely arbitrary, and it seems to work really well when you combine it with a caffeine enema or maybe ozone therapy.  And if Gwyneth Paltrow had been a GOOPist then, maybe jade eggs.  I mean, we just don’t know.  I’m open-minded, but I’m not that open-minded. 

So we combed through the scientific literature and we found a little bit of evidence out there.  and we talked to Dr. P’s friend and he made the decision that was right for him.  He decided to spend the money and try this high-dose Vitamin C. 

But what I saw really intrigued me because I’m really interested in radiation.  The reason I like radiation is that when you treat someone with radiation you can direct a beam of radiation just exactly at the tumor and you limit the damage to the surrounding cells.  That makes it a really powerful technique because you can avoid a lot of that damage that you get with things like chemotherapy. 

And what we saw is that, sometimes, high-dose Vitamin C can be converted in the body to hydrogen peroxide.  Now, anyone who’s tried to bleach their own hair with hydrogen peroxide can tell you… it was the ‘80s.  We all tried it.  It’s a biologically active molecule.  If you can get --and this is a big “if” -- If you can get that hydrogen peroxide into the cancer cells and then you hit them with radiation, the damage of those two combined could completely obliterate those cancer cells – in theory. 

Now, this was really cool because this was potentially… and that’s a big potential, but it was potentially a way that we could cheaply and easily sensitize someone’s tumor to radiation.  That would be amazing if that was the case.  So we decided to do the experiments and find out. 

Now, it takes a while to build up the evidence base and we persevered away for months.  Finally, we had some data and the data backed up this idea that, yes, we could take brain cancer cells in a dish, we could give them high-dose Vitamin C, turn it into peroxide, hit them with radiation, kaboom.  We really killed these brain cancer cells. 

We were pretty excited. We thought the science was good.  We wrote up the paper.  We sent it off for publication.  Our institutions made a press release.  That press release must have landed in a very slow news cycle because it got picked up all over the world and they overstated what we had said.  This is where things got really, really complicated for us. 

At this stage, I should say that some people have been very supportive and some funders have been supportive and we’re really grateful to them for that, but not everybody has supported this research.  So the quack-busting science bloggers got involved. 

So we were adding to the hysteria around Vitamin C and cancer while, at the same time, inducing a collective yawn in the scientific community.  I’m not going to Google my own work again.  That was really traumatic. 

Our interactions with our oncology colleagues changed. They thought we’d gone completely mad.  We joined this lunatic fringe of the Vitamin C purveyors.  They could see no reason why this should work and they just hated what we were doing.  They wanted nothing to do with it. 

We talked to the alternative medicine community and they hated what we were doing.  We tried to find out their data.  I’m data-driven.  We tried to find out about the doses and the timing and how they were using it and what the outcomes were for their patients.  They wanted nothing to do with us.  As far as they were concerned, we were science establishment anti-Vitamin C and we were just out there to take them down.  They refused to have anything to do with us. 

So that’s three hits: science, medicine, alternative medicine. 

The public loved it. I would regularly get phone calls from someone with cancer or from a family member and they would say to me, “I've got this cancer and I've got this diagnosis and I’m having these drugs and I want to take Vitamin C.  What do you think I should do?” 

And then they would say, “My oncologist thinks it’s a really terrible idea.  What do you think?” 

I would really patiently explain that we don’t have the data for me to make any kind of decision and I’m not going to second-guess their oncologist.  Anyway, I think the reaction of those doctors at that conference was starting to make a lot of sense. 

So it was really, really hard, though, when a friend called me, a friend I hadn’t spoken to for years.  A phone call out of the blue from an old friend, that should be a time of joy.  You should have some moment of excitement in talking to them.  But when they're reaching out to you because they have no hope and they just want something, they just want anything, and you have nothing that you can give them, that’s not joyful.  That was just heart wrenching. 

So it was the saddest, most frustrating, most infuriating experience of my life.  All we wanted to do was test and see does this therapy do anything.  It’s very expensive.  It could be good.  It could be bad.  It might be completely useless.  We don’t know.  And we were being blocked by all these people who had this bias and they couldn’t see past their bias to that really obvious question. 

I kind of felt like we were standing there in the middle of this battlefield, kind of a no-man’s land and we’re taking these hits from all sides.  I thought of Wonder Woman in that latest movie, which was cool, but I’m not Wonder Woman.  I don't have super powers.  I can’t bound through and fight off these bullets. 

So we went back to the lab.  We hunkered down and we did some more experiments.  And we learnt a whole lot more about how radiation and Vitamin C would go together.  Then we made a strategic retreat. 

We said, “Enough.  We don’t have an answer.  There is going to be no simple answer for this problem.” 

Dr. P’s friend did really, really well.  He lived much longer than we anticipated, than anyone expected.  Was that the Vitamin C?  I don't know.  We don’t have the evidence to do that. 

So I know in my brain, I know that being glared at by a row of doctors is not the worst thing in the world.  I can see that.  But it really hurts.  It hurts to have your reputation and your work laughed at. 

We had one person in New Zealand who told everyone our work was a complete load of rubbish while my colleague was sitting in the room at the same time.  It’s a difficult place to be. 

But we hit this bias and that bias is a really fundamental part of human nature.  I think what I've learnt is that while it would be great to be Wonder Woman, that Lasso of Truth could be really useful to get people to confront their biases, I think the only tool that we have is that of science.  So while I would love the wrist bands and that lasso, I think I’m stuck with good science.  We need evidence, we need an open mind, and you need a really, really thick skin. 

Thank you.