The point is that with ultrasound – as much as it is very advanced and you can trust a lot of the results – you should never lose track of the fact that those are virtual images, and pathology has real images. This is where things stop: there is no more accurate and real exam than a pathological exam.
Do you feel people are relying too much on technology, almost in order to cheat death?
I recognise that if we do not apply our marvellous technology to these very sick patients, we would not be making the progress that we are making. There are voices that argue very strongly against the application of advanced technology to sustain life, to treat certain conditions in childhood or adulthood. I disagree with that because, as you know, our quality of life is much better now than it was just 20 years ago. And 50, 80 or 100 years ago, when there were no antibiotics and no anaesthesia and things like that, if the doctors of the time had not applied all their efforts to pursuing a particular question, we would never have got to this point. So I think that although the end does not justify the means, we should have the curiosity and the will to apply this marvellous knowledge. But we should do it in a respectful way.
Tell me a bit about your own research.
Well, I have been interested in a particular group of disorders that involves the development of the neural crest. The neural crests are transitory structures of the embryo that are the excess tips of the closing borders of the neural tube. The neural tube gives rise to the brain and to the spinal cord. But as the neural tube closes – because it first begins as a groove – the excess tissue remains there instead of disappearing, and it migrates to different parts of our bodies through a very complex process.
Neural crest disorders are of different types. There are neural crest diseases that are cancer-like, or cancer. And there are neural crest disorders that are the result of an abnormal migration or survival of the cells. The bowel, for example, has a brain of its own. The peristaltic movement of the bowel is coordinated essentially by this brain in the gut, and this nervous tissue, which has many millions of neurons inside, requires for its development the migration of the neural crest into the bowel, and the proper development and survival of the cells in a coordinated fashion. If you look at it under the microscope, it looks like a little piece of brain sandwiched between layers of other tissue in the bowel.
That’s amazing! And is there a lot of it?
Yes. It continues from the oesophagus all the way down to the exit. And the proper development of this gut brain is necessary for our bowels to move. There is a childhood condition called Hirschsprung’s disease, in which babies, usually, are unable to move their bowel, and become distended. And they can explode, literally, with a colon like an anaconda. Just imagine what it is like not to be able to move your bowel for five, six days. There is no peristalsis, because there is an area that is lacking these neurons in the bowel.
The disease was described in 1888. It was poorly understood for the first 50 years and then it began to be unravelled by a surgeon at Boston Children’s Hospital. For the first 50 years the surgery performed on these patients was wrong – they removed a normal piece of bowel and left the abnormal piece because it looks deceptively normal. But then we began to understand that, and the biology of this disease has been unpicked over the last 15 years. I have been more active in determining how to diagnose this disorder than in trying to understand the genetic basis, because for paediatric pathologists this is a serious daily problem. Frequently a biopsy comes to your table that says, ‘Please rule out Hirschsprung’s disease,’ and it is very difficult to make the diagnosis, because it is based on the absence of neurons, and absence of proof doesn’t mean proof of absence.
And is this a common condition?
It occurs in about one in 5,000. But the thing that I am more interested in is a little more uncommon. It’s called neurocutaneous melanocytosis. This is a disorder of neural crest cells that produce melanin – so-called melanocytes. All the pigment in our skin, melanin, is produced by these cells, which all come from the neural crest – with the exception of those that are in the eye. Every other melanocyte in our bodies – including those in the brain – comes from the neural crest. There are babies born with abnormalities in the population of melanocytes, and they develop this condition, neurocutaneous melanocytosis, where they have extensive areas of their bodies covered by moles, or ‘naevi’. These darkly pigmented areas can cover portions so extensive that they are sometimes called ‘bathing trunk naevi’. Or they look like Dalmatians – hundreds, thousands, of little satellite lesions here and there. And the problem with those situations is that not only is the skin abnormal, but the deeper tissues are also abnormal and can develop malignant tumours, melanomas, inside those naevi. Frequently they develop a naevus inside the brain, and that can interfere with the development of other structures. They have seizures, they have hydrocephalus – dilatation of the ventricles of the brain – and frequently they die. The condition is relatively rare, though I can’t give you an exact figure. One in 20,000 newborns will have a giant naevus, and some of those will be neurocutaneous melanocytosis.
But just over 10 years ago, I came in contact with a newly developing support group of parents. They had each had a child born with a giant naevus, and the doctors had freaked out and said, ‘I’ve never seen this. I don’t know what it is.’ Or, ‘It’s a melanoma; let’s treat it like this …’ There was very little knowledge. So parents created this family support group. All of the members are either parents of children with these lesions, or they are patients themselves, because many people have survived 20, 50, 60 years suffering with this situation, and they are ‘freaks’. Sometimes people can hide it. But other times, half your face may be black with a tremendously disfiguring lesion.
So that is where I concentrate most of my research efforts. I was doing that with my late wife – she passed away five years ago.
What are you discovering?
First of all that this is much more frequent than we used to think. People are now aware of this group and are coming forward and saying, ‘I have one of those. I was born with this naevus.’ We are also discovering that it’s a very complex disorder in terms of genetics. We know of no twins, for example, that have this problem, so there is not an inherited basis. It does not repeat in families. There is nothing the mother did during the pregnancy that would represent a particular risk.
So we are first eliminating a number of things. We are sure that these are real clonal lesions – by which I mean lesions that arise from a single cell that starts to reproduce and forms a clone. But we need to gather a lot more samples and make a very organised effort in our research. And when you don’t have such a massive number of patients, it’s very difficult to gather data and get researchers interested.
What made you particularly interested in this condition?
Well, when I was a pathologist in Mexico there was a baby that came to the department of oncology, and it immediately became the ‘patient of the month’ – everybody was talking about it. The baby was born with something in the genital area that was very striking – they couldn’t even tell if the baby was a boy or a girl. They thought it might be a tumour that would kill the baby rapidly, so they took a biopsy. What I saw was something very strange: it reminded me of what is described in congenital naevi, and at the same time it had features of nervous tissue.
Nervous tissue? From where?
From the neural crest. Melanocytes, in my opinion,