BLANCH : We begin with a breath test that will revolutionise early cancer detection which is being developed by the son of "ten pound Pom" immigrants to Perth, Western Australia, and it's a device that's close to taking the world by storm.
A breath test device that looks for early signs of cancer, rather than for drunken driving as a traffic infringement, has been developed by physician Michael Phillips. Breathscanner is being examined by a team at the University of Western Australia to see if it can accurately detect breast cancer. Later this year a group in Brisbane, Queensland hopes to conduct a similar clinical trial to screen for early signs of lung cancer.
Dr Michael Phillips, who trained as a scientist in Australia now lives in the United States where he is a professor of Clinical Medicine at New York Medical College and heads the US company, Menssana Research, which is developing the Breathscanner device.
As a small child Michael arrived in Australia from the UK with his family, growing up here and attending medical school in Perth, Western Australia.
BLANCH : So Michael we feel we can claim you as an Australian in the same way we call Olivia Newton John and Mel Gibson, Australians, as they too were young immigrants to this country and grew up here. So when did you leave Australia and where did you head?
DR MICHAEL PHILLIPS : Well that's very illustrious company to put me with, but I grew up in Australia and I went to medical school and then in the 1970s I went to England and I did post-graduate work in London and I did the exams for the Royal College of Physicians, and then after that I moved on to the US in the mid-70s to do a fellowship at the University of California in San Francisco.
BLANCH : Did your medical links with Perth play a part in your undertaking clinical trials of Breathscanner by the team at the University of Western Australia?
DR MICHAEL PHILLIPS : Oh absolutely. You see I come back to Australia as frequently as I can and I like to stay in touch with research trends in Australia. It was during one of my trips a couple of years ago that I met with folks at the Breast Cancer Foundation who strongly encouraged me to go ahead and perform a clinical study in Australia. So it really just worked out very nicely that with growing up in Perth and knowing a lot of folks in medicine there and also getting in touch with folks who were interested in breast cancer research, it just worked out beautifully to do the study in Perth.
BLANCH : And you've been working on Breathscanner for 20 years.
DR MICHAEL PHILLIPS : Yes.
BLANCH : But the practice of a physician detecting disease from the odour of a patient's breath goes back over two-thousand years, so what are some of those indicators that those early practitioners used and are still perhaps used today, even?
DR MICHAEL PHILLIPS : Well, it all goes back to Hippocrates, the father of medicine. He told his students to smell the patient's breath. You can really learn a tremendous amount. Just by common experience physicians learn that for instance the patient with uncontrolled diabetes has got a smell rather like rotting apples, and that's due to the acetone in their breath. And there are several other conditions, for example liver failure has this wonderful Latin expression, fetor hepaticus - the stench of the liver. And physicians learn to recognise these smells.
BLANCH : Now the modern era of breath testing began in the early 1970s, so what brought you to this research, those only 20 years ago?
DR MICHAEL PHILLIPS : Well I was doing a fellowship at the University of California and one of my colleagues was studying a drug which is commonly used in treating patients with alcohol problems, its called Antabuse, otherwise known as Disulfiram, and to my great surprise, instead of doing blood tests in his patients he was doing breath tests.
And he pointed out to me that this drug was broken down in the body to a very simple metabolite, it's called carbon disulphide, and he could actually detect this with a chemical test. And this really caught my imagination.
I thought 'how wonderful'. Really to actually monitor a drug in the body just with a breath test, no need to take blood, no need to cause any pain or discomfort, and at the same time get a lot of information about a drug that was actually in the body. So this led me on to do a bit of research and I discovered that that very famous scientist, Linus Pauling who actually got two Nobel Prizes, had worked out a way of detecting microscopic quantities of volatile organic compounds in the breath. This was back in the early 1970s, and he was using a technique then that was really quite new. It was called gas chromatography and it still is used.
And he worked out a way of concentrating human breath and analysing it, and to my amazement when he did this he found several hundred different compounds in human breath. So I thought; well you know, if human breath contains all of those different compounds they must be telling us something, there must be a message there, maybe if we look at them closely enough we might find clues to disease, and if we can do that maybe we can detect diseases just by analysing the breath.
BLANCH : So that's where you started, what line or direction have you pursued since then in your research?
DR MICHAEL PHILLIPS : Well the first and hardest part was developing a simple method just to collect breath that could be used, say, in a hospital or a doctor's office and yet would give us sufficient sensitivity to be able to tackle these compounds in the breath in very, very low concentrations.
So, it took some years to actually develop a machine that could do that and finally we did. We finally ended up with the world's most sensitive breathalyser. But now we have it down to a small machine that can sit on a desk say in a doctor's office or a medical clinic, and the patient just sits down and breathes easily into it for just two minutes, no hard blowing, nothing at all like that and collect the sample, which can then be analysed in the lab for very, very low concentrations of these compounds. That took a long time.
So actually getting the technology right was the first and hardest part. But once we did have the technology right then we can jump in and do some clinical studies, and that led me into actually doing the clinical studies out there in different hospitals and actually studying patients with different diseases.
BLANCH : While your device is similar to that breathalyser that police use to detect alcohol, what makes it different, because you say it's much more powerful isn't it?
DR MICHAEL PHILLIPS : Well it is a billion with a "B" times more sensitive than the kind that the police use. So we see things in the breath, if I collected a sample from you say I'm sure I would see close to 200 different compounds in your breath, or indeed in the breath of any of your listeners. And yet a police breathalyser can only pick up one compound and that's alcohol. And the reason we can pick up so many is because we have this very, very sensitive technology that can pick up compounds that are present in very, very low concentrations, parts per trillion. So that's what really makes the difference, the sensitivity of the system.
BLANCH : And Michael in 2005 the US Food and Drug Administration approved your invention for detecting organ failure in heart transplant recipients. So how does the device work that it's possible to detect organ failure, breast cancer and lung cancer - all those three?
DR MICHAEL PHILLIPS : Well now I have to tell you a little bit about chemistry that occurs in these diseases. There is a condition called oxidative stress and it really happens when oxidation in the body goes wrong and it generates a number of different compounds which we can detect in the breath. Doctors have been very interested in oxidative stress for several years now, and just about everywhere you look, particularly in diseases such as cancer or infections or organ transplant rejection, you can find oxidative stress.
Now what we found that was interesting about this is that oxidative stress is not one size fits all. It's a very, very complicated pattern and we're looking at more than 100 different compounds in the breath which are markers of oxidative stress. And by doing this we can actually identify a fingerprint that distinguishes one disease from another. So we're looking at these oxidative stress markers but because we're looking at so many of them, we can identify a unique fingerprint, so that the fingerprint in a disease like lung cancer is completely different from a disease like breast cancer, and that's completely different from a disease like tuberculosis. So by identifying these different fingerprints of disease we can then work out if we analyse the breath, we can tell with pretty good accuracy if a person has that disease or not.
BLANCH : So there's a whole range of diseases, it's not just those three, it can go on and on?
DR MICHAEL PHILLIPS : Oh absolutely, it's really quite amazing, everywhere we look we find evidence of breath testing really does provide useful information.
BLANCH : And this device therefore is perceived as a real turning point in screening for disease. With your latest report of your breath test for lung cancer recently published in Cancer Biomarkers, so how do you believe it will be used by clinicians?
DR MICHAEL PHILLIPS : Well, one of the first obstacles to getting clinicians to use it is first of all to get physicians to believe it. And so for that reason we have--the first obstacle is you have to do large clinical studies in which you compare patients with the cancer to those who haven't got it, and then you have to do very complicated analysis to see that you get a really good signal and that you're not getting confusion say from false positive and false negative results. So that's step number one. And then it's very expensive and very time consuming. But we've pretty well got there now with lung cancer and with heart transplant rejections.
The next step is actually getting regulatory approval to use this. Now in the United States and in other advanced countries like Australia, the government sets up quite rightly rather high obstacles to using a new diagnostic test. I cannot just come in and say 'hey, I've got this great test, let me go and sell it to you'. No, the government demands very high levels of proof that the test really and truly does what we say it does.
So for this reason the next big step is actually providing the information for government regulatory authorities, in the United States it's the Food and Drug Administration, so that they'll approve it. So that's the second step.
And then the third step, you're not there yet, is then getting the insurers to say yes we'll pay for it. And it's only when you go through all of these three steps that you can actually get a test out there in the doctor's office and to the patient's bedside.
BLANCH : Well you're doing the trials in Australia for breast cancer and lung cancer, so you have others planned down the track by the sounds of where you're talking?
DR MICHAEL PHILLIPS : Yes we've just started a very large validation study of the breath test for lung cancer in the United States. We've had an award from the United States National Institutes of Health; they've just given us three-million dollars just to validate this in a multi-centred study around the United States. So we hope that in the next two years or so we'll have the information that will satisfy all the regulators, such as the Food and Drug Administration.
BLANCH : Others around the world are developing similar breath test devices for various diseases, so what do you believe sets yours apart? Is it accuracy or methodology or what?
DR MICHAEL PHILLIPS : I think what sets ours apart is methodology. You see, the other tests that are being approved for use--there's one out there that's a test for nitric-oxide for asthma--they're good tests but they generally one shot tests. That is they look at just one compound in the breath. As far as I know we are the only people who are looking at many different compounds at the same time and trying to extract a fingerprint. That's what I think sets us apart. We're looking for fingerprints of disease and we're looking at several different compounds simultaneously.
BLANCH : Well we've talked about lung cancer and breast cancer, what other diseases are next in line because there seem to be a multitude there that you can choose from?
DR MICHAEL PHILLIPS : Well, one that we're very excited about is pulmonary tuberculosis. And I should tell you that on a worldwide basis, tuberculosis is one of the biggest killers in the world. One of the problems is that especially in less developed countries it's very difficult to detect who's actually got an infection and who needs treatment.
We did a study here in New York City in which we looked at a group of patients who were in a hospital and who actually were diagnosed with pulmonary tuberculosis, and we found that there were markers in their breath which actually appeared to be coming from the bacteria in their lungs. And this is a very exciting finding because it offers a new pathway to detecting infection in a completely non-invasive fashion, just by analysing the breath we could tell in this case if a person's infected with tuberculosis.
So that offers a new approach to helping folks in less developed countries, and also in advanced countries now such as Australia, the United States because we're seeing more and more tuberculosis.
BLANCH : So your timeline, it could be two to three years before we're blowing into this gadget on our doctor's desk?
DR MICHAEL PHILLIPS : Well in fact it's going to be much sooner than that because it's going to be available in Europe this year for lung cancer screening.
BLANCH : Dr Michael Phillips speaking from New York City in the United States about his development of the Breathscanner device that gives early detection of disease by analysing human breath.
Dr Michael Phillips
Menssana Research Inc,
1 Horizon Road, Suite 1415, Fort Lee, NJ 07024-6510, USA