Program Item Details
TITLE: Dr. David Wishart, Professor, Computing and Biological Sciences, University of Alberta and Researcher, National Institute for Nanotechnology
SUBJECT: #202 Human Metabolomic Project
SYNOPSIS: You’ve heard of the
Human Genome Project. Well, now there’s the
Human Metabolomics Project. University of Alberta scientist Dr. David Wishart has taken on the task of identifying the hundreds of metabolites in our bodies.
AUDIO: Download Audio (mp3 format)
TRANSCRIPT:
#202 May 30, 2006
Interview starts at 1:14
Intro: Just as genes can tell us something about the potential for disease in our bodies, so can small molecules called metabolites. Only we don’t know what all those metabolites are just yet. But by the time Dr. David Wishart is finished his Human Metabolomics Project, we could be well on our way developing a whole new method of assessing the state of human health. David is a professor of computing and biological sciences at the University of Alberta.
Dr. David Wishart
DW: Metabolomics is kind of the new kid on the block. There are fields, we call them “omics” fields, that have been going on for the last 10 years. One is called “genomics”, and that’s the study of the genome. Another field is called “proteomics”, and that’s the study of all the proteins you might find in a cell or organism. And then “metabolomics” is the study of the metabolome, which essentially is all the metabolites or small molecules that you’ll find in your blood or urine or tissues or body fluids that are the chemicals of life. And the metabolome and metabolomics are really the study of the chemicals of life.
CC: YOU’RE INVOLVED IN A PROJECT NOW, YOU’RE ABOUT A YEAR AND A HALF INTO THE HUMAN METABOLOME PROJECT. WHAT’S THAT?
DW: What we’re trying to do with the Human Metabolome Project is do what the Human Genome Project did, which was completed in 2001, about 5 years ago. So the Human Genome Project was tasked with trying to determine the sequence of all the genes and all the chromosomes in a human cell. So there are about 3 million bases and about 25000 genes that had to be characterized. And it took them about 12 years to do and it cost about a billion dollars.
We’re doing the same, although we’re trying to do it over a shorter period of time, for the metabolome. So we’re trying to characterize all of the small molecules or metabolites in the body. And we believe there is something in the order of 2500 small molecules that are in the body. These are different types of molecules that are used to make up the genes and the proteins and the tissues and the things that our bodies typically generate or need to stay alive.
And we’re trying to characterize all of them. We’re trying to identify what they are. We’re trying to figure out how many or what their concentrations are, which compartments and which tissues and which fluids. We have three years to do that. And we have a team of a number of scientists covering many different disciplines to try and achieve that goal.
CC: HOW ARE ACTUALLY DOING IT THEN? DO YOU HAVE TO GO AND DRAW FLUIDS FROM PEOPLE AND LOOK AT THEIR METABOLYTES?
DW: It’s sort of two stage process. The study of small molecules actually was the start to all of biochemistry. And so even as far back as the early 1900’s, people started writing about and characterizing small molecules. And for most of the first half of the 20th century, that’s all that biochemistry was. And then it changed or transformed in the 1970’s when people realized you could do molecular biology and do all kinds of neat things like cloning. And we kind of forgot about biochemistry and about small molecules.
So what we have to do for our first phase of the project is to relearn or rediscover what was forgotten from about 1900 to 1975, and track down all the small molecules that were written about in different journals and in books and papers. So we’re calling that the “backfilling process.” And we’ve been doing that for the last year now, adding to our list of chemicals and compounds things that are long forgotten about or lost in the annals of time to create part of the database.
And then the second part is in fact using clinical samples, patient samples, and measuring and identifying these compounds. In many cases, these are compounds that were reported, so we didn’t want to rediscover the wheel. But in some of these cases these compounds are things that have never been seen or described before, and so now we have to identify them, characterize them, and figure out what their concentration is, the normal and the abnormal levels.
CC: WHAT IS THE APPLICATION?
DW: Metabolomics has the potential for changing the way we do medicine. The same sort of song and dance that people give for genomics and proteomics where with genomics and proteomics we can maybe do new tests identifying the causes of genetic disorders, causes of cancer and other major diseases.
But it turns out that studying small molecules or measuring small molecules is, in fact, way we’ve been doing medicine for the better part of a hundred years. If you go into the doctor’s office and they ask you for a urine test or they take a blood test, the things they’re actually looking at are small molecules. And small molecules give a wonderful indication of exactly what’s going on in the body. In fact, more so than what many genetic tests can do and many proteomic tests can do.
Now, the problem has been the number of molecules that doctors can measure has been in the order of 10 or 20. It’s a small set of tests. With metabolomics, we’re going to have a list now of 2500 molecules and the technology to potentially measure maybe 300 or 400 of those all at once.
And now instead of getting a little slice of the picture of what’s going on in your body, sort of a short biography that’s got 10 words, we’re going to have a description of you, a chemical description of you, which might constitute 300 or 400 words or components. And we’ll be able to tell you what’s high or what’s low or what’s normal. And those may be able to indicate what things might be wrong, or what’s ailing you or what might have happened to you the night before or what could happen to you further down the road.
So small molecules are wonderful tools for both diagnosis of disease and for prognosis of disease outcomes. And we’re just essentially expanding the library or dictionary so we can make more precise assessments. And we’re also trying to expand the technology so we can do this better, faster, cheaper.
CC: NOW I UNDERSTAND THAT THERE’S A COMPANY IN EDMONTON THAT’S ALREADY WORKING ON SOME OF THIS AND YOU DO HAVE A RELATIONSHIP WITH THEM, THE COMPANY CHENOMX. WHAT’S HAPPENING THERE?
DW: Well one of the things that Chenomx is doing, its one of the first metabolomics companies to start up, they have a technique for rapidly assessing, identifying and quantifying metabolites in urine or in plasma or other body fluids and body tissues. But their technique depends on having a library of known compounds. So right now our library is limited because our knowledge is limited. With the Human Metabolome Project we’ll have the potential of expanding that library by a factor of 10, say from 200 molecules to 2000 molecules.
If Chenomx or other companies were to use this library and use the knowledge that comes out of the Human Metabolome Project, then they would essentially have a testing tool or testing device that integrates and NMR or a nuclear magnetic resonance spectrometer or a mass spectrometer and within perhaps a minute of collecting a sample and processing it, would have a readout of 200, 300, 400, a 1000 molecules and their concentrations.
And given that it costs using conventional technology today to get a readout of maybe 20 compounds , that might cost 500 to 1000 dollars, and it might take a week or two weeks to get the results back. This sort of thing that metabolomics promises or the tools that Chenomx or other companies around the world are developing, promises to make the delivery of diagnostic tests much, much cheaper, and the quality of diagnostic tests much better. It would be a transformation or as they call it, a “disruptive technology” that totally changes the way we do medicine.
CC: YOU’RE BACK TODAY FROM YOUR MIDTERM REVIEW OF THE HUMAN METABOLOMICS PROJECT. YOU’VE FINISHED UP THAT BACKFILLING PHASE OF IT. WHAT’S NEXT?
DW: The next phase is to move forward and start actually identifying and confirming the metabolites that we can in blood and urine and in cerebral and spinal fluid and in cells. We’re also looking at other body fluids like saliva. We may even look at tears. These are all things that are relatively easy to access. So this is another appeal for metabolomics that we don’t have to do biopsies. We just take things that are very easy to access and not too painful to get, and essentially measure health.
So what we’re trying to do now is measure those metabolites, confirm what was reported in 1923 is still true today, or correct the concentrations for the metabolites. So the forward filling process is going to occupy us for the next 18 months
And if all goes well, we should have the first release of the Human Metabolite Database or the complete collection of all human metabolites and their relationship to genes and proteins, pathways and disease, released to the public for January 1st, 2007. And we think it will be as significant to medicine and hopefully as significant to Canadian science as the Human Genome Project was when it was announced in 2001.
CC: THANK YOU VERY MUCH, DAVID.
DW: You’re most welcome, Cheryl.
Dr. David Wishart is a Professor of Computing and Biological Sciences at the University of Alberta and a researcher with the National Institute for Nanotechnology. He is also the lead investigator on the Human Metabolomics Project which is supported in part by the Alberta Ingenuity Centre for Machine Learning.
FEATURED LINK: Dr. David Wishart's home page
FEATURED LINK: The Human Metabolomics Project
FEATURED LINK: Alberta Ingenuity Centre for Machine Learning