"The new tests are improving our capacity to categorise diseases better, and in some particular fields like haematopathology they are becoming very important. But for most solid tumours, the microscopic examination remains essential – and often the only thing you need"
Juan Rosai (Argentina, USA and Italy)

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The advances in technology during the lifetimes of these interviewees has been massive.  Immunohistochemistry, monoclonal antibodies, molecular genetics, and advanced imaging techniques have all come in since the 1970s, and have enhanced the practice of pathology immeasurably. 

The development of ever more sophisticated techniques has, however, raised nagging questions of whether morphology as a means of diagnosis will become redundant. “Pathologists have always been in danger,” says Juan Rosai.  “There is always someone predicting that tomorrow they will describe a DNA test [or something] that will put us out of business.  It hasn't happened yet, and I don't think it's going to happen any time soon.” 

This era of anatomical pathology is over... It’s over because techniques are changing.Most interviewees hold the view that morphology remains the gold standard in diagnosis, although a few people are pessimistic.  “This era of anatomical pathology is over... It’s over because techniques are changing.” (Richard Hewlett)

Jeffery Taubenberger’s research on flu viruses provides a graphic illustration of the quantum leap enabled by technological advance: “In the 1890s...they had no electron microscope and you couldn’t see a virus through a light microscope, so they had no way of knowing really what a virus was.  There was just this infectious ‘thing’ that slipped through the filters.” Today not only can you see viruses, but “techniques have been invented that allow you to make, in a sense, influenza viruses from cloned genes.  It’s a technique called ‘reverse genetics’... It’s amazing.”

Of immunohistochemistry David Levison says, “Before this technology became available I could make an educated guess [about the nature of a tumour]. ... But this technology has made diagnosis much, much more specific.”

This technology has made diagnosis much, much more specific.For Elaine Jaffe it was the introduction of monoclonal antibodies that provided one of the “eureka moments” of her career.  “Then we had a wealth of tools that were available – there were no limits to what you could dissect out and the various sub-populations [of blood cells] that you could discover.”

One or two people sound a warning about becoming too enthralled by new technology, and losing sight of the importance of the patient’s quality of life.  Miguel Reyes-Múgica, for example, argues that “we should really have the curiosity and the will to apply this marvellous knowledge.  But we should do it in a respectful way.”

Key interviewees: Kenneth Hillan, David Levison, Jeffery Taubenberger, Elaine Jaffe, Julia Polak, Waney Squier, Richard Hewlett, Dhiren Govender, Maesha Deheragoda



Miguel Reyes-MúgicaFrequently I have situations in which I come to see a case where the clinicians want to know what happened, and they have spent weeks -- sometimes months -- treating a patient with different types of complications.  They know all these parameters -- respiratory, cardiac and many others -- and they are following those and they see the curve of the progress up…down etc, and then finally when the patient dies they come to me and say, ‘What happened?  We don’t understand how this patient died.’ And my answer in several of those situations has been, ‘Well, I can’t understand how this patient lived.’  They lose track of what life is all about.
 - Miguel Reyes-Múgica (Mexico and USA)

David LevisonImmunohistochemistry has made a huge difference.  Before we had this, if we saw a mass of malignant cells, we could tell it was a tumour, but not definitely if it was a lymphoma, which is treatable, curable; or if it was an undifferentiated carcinoma which virtually nothing will touch, will kill you in a few weeks or months; or if it was a sarcoma for which there might be some other specific treatment. 

Now, with immunohistochemistry and the molecular techniques as well, we can tell in almost every case, "Yes that’s a lymphoma, it’s a B-cell lymphoma, usually curable.” The chances are that 90% of people who have this sort of tumour will be still alive in five years, if they are treated with this particular regime. 

 - David Levison (UK)

Kenneth HillanThere's been a huge explosion [in identifying the specific genetic mutations of different cancers], and part of the fun of being in pathology is matching back this kind of tumour with that gene mutation.  What needs to happen next takes a lot of time.  When you have a pathway that's driving a particular tumour, if you want to interfere with that pathway with a drug, for example, you have to do a full clinical development programme, and that takes seven to 10 years. 

Pathologists are going to be hit with an explosion of new tests, and it's beginning.   I think you'll see, over the next five to 10 years, this whole thing exploding.  And poor pathologists will suddenly be faced with, ‘Wow, how do we manage all these tests?!’  As well as making the diagnosis, now we have to go further so we can help with treatment decisions.

 - Kenneth Hillan (UK and USA)

Jeffrey TaubenbergerSometimes when you look at a lymphoma or a leukaemia, for example, under the microscope it may be so classic in terms of its histology that you can say, "Well it’s this sort of lymphoma.”  But very often it’s difficult, so you look for additional tools.  Immunohistochemistry, which looks for the expression of certain proteins, is an adjunct tool, and there are certain other tests you can do too.  It became more and more apparent, as basic science was advancing, that these kind of molecular tests could be used diagnostically -- and in fact, in a sense, would be the definitive diagnostic tools.  Histology might not be definitive, but these molecular tests might actually be definitive.
 - Jeffery Taubenberger (USA)

At that time, in the early 1990s, most people thought you actually couldn’t even recover nucleic acid from fixed tissues.  So it was an interesting technical challenge, a practical challenge, and we thought it was very exciting.  My colleagues and I worked out techniques that we could reliably extract both DNA and RNA from fixed tissue and we developed assays to do a lot of these diagnostic tests.  We became the only facility, at least initially, that we were aware of that could do these kind of tests, so people would send us cases from all over.
Jeffery Taubenberger (USA)

Juan RosaiOf course the new tests are improving our capacity to categorise diseases better, and in some particular fields like haematopathology they are becoming very important. But for most solid tumours, the microscopic examination remains essential – and often the only thing you need. 

Actually, I think there is an excess of special tests being done which are not truly necessary for the diagnosis and treatment of patients, because morphology is like a grand summary of all the genetic events that occur in a cell.  I mean, any genetic event of any biologic significance is likely to translate into a morphologic change that one should be able to see under the microscope. 
Juan Rosai (Argentina, USA and Italy)

Richard HewlettThe position is hopeless.  The era of anatomical pathology is over.  It started with Virchow and those people, and it's gone on for nearly two hundred years and it's now over; that's the only way to see it.  Molecular genetics is taking over, and though it hasn’t replaced conventional path, it has enough force to seriously interfere with the value we used to place on simply looking at tissues down the microscope. That's the way it has to go.  This is steam age stuff that I'm doing.
 - Richard Hewlett (South Africa)

TB of the brain became my main interest, and of course the images that go with it.  We wrote the first detailed account of imaging and pathology of tuberculosis of the brain, which I think is more or less accepted now.  Because we looked at the bits, we were able to interpret some of the changes on the images.  And because we looked at the images, we could see the changes that occurred over time in the brain, which you can't otherwise.  That's the big difference -- the pathologist gets the brain once [after the patient has died]. The imager can scan the brain repeatedly and see how a structural abnormality is changing over time, which is crucial to understanding the disease process.

 - Richard Hewlett (South Africa)

Waney SquierMRI gives us so much information, but it's actually seeing the structure with the naked eye and then looking at it under the microscope that really teaches us so much... Good, old fashioned, observational pathology has such an enormous amount to offer... And we've forgotten it, moved away, and we think we know better.  Well we don't, because we're missing things with some of our new investigations.  Although the imaging is so good, it doesn't give us the same amount of information.
 - Waney Squier (UK)

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