The Thesis (5 of 7)

A tome well over an inch thick, there we are on the cover as “associate members” of the jury.
Thumbing through it before bed, I see the example pedigree I sent Jamal last week, along with my explanation, word for word. This makes me wonder how much of the rest of the text its author understands. I might read and nod ‘yes, that’s right’, and the student has no clue after all. .
That might in fact be the case. There are a lot of telling mistakes, more than you can just attribute to awkward phrasing. In a section on the epidemiology, the author states that the average age at breast cancer in Algeria is 23.3 years old; that in France 91.1 years. This is obviously not true. Those are the standardized incidence rates from 2001, meaning 23.3 (or 91.1) cases per year per 100,000 population. A typo? The whole paragraph concerns age, so I don’t think so.
What the student has done for her medical thesis is compile all characteristics of 31 of the cases they sent us. That takes up quite a lot of space, because each parameter is both stated in the text and repeated in a table - even if all the cases are in the same category. And we get both the fraction of 31 for each parameter as well as the percentage, calculated to two decimals.
I hope to find in here whether the cases we’ve studied are like the French (because the rates of mutation discovery are the same), or like the Algerians (because the lifestyle is similar). First good thing, all 31 cases here are breast cancer patients. Next thing, they resemble the Algerians overall. So the data is in there. Excellent. It isn’t arranged in a way we can publish, but that should be a question of reorganization. I hope.

All these criticisms are my Western world-view showing through. The Moroccans are starting from nothing. They’re not even set up to extract DNA, let alone analyze it. The genes and mutations I talk about are utterly theoretical to them - I can’t expect them to be expert on the details. It’s actually fabulous that they are interested in getting something going for preventive breast care. They want to learn. They do everything they can to get over to Europe, or the US, to learn.
Putting that learning into practice, however, is another matter. Morocco is dirt poor. Yes, there are some incredible palaces, and an emerging middle class, but on the whole it’s more or less a third-world country trying to pull itself into the 21st century by its bootstraps.
Take every woman at high risk of breast cancer and give her an annual mammogram by a competent radiologist? Only the top few % can afford it, and health insurance is not widely available to the masses. Forget about bi-annual screening for everyone. Switching to MRI’s rather than mammography is just pie in the sky: I’m not sure there’s a single MRI machine in the whole country, much less one available for routine screening of millions of women.

So I have to consider where this thesis is coming from. It isn’t from one of my students, and I need to keep that in mind. At the same time, a diploma is meant to mean that one has acquired a certain body of knowledge, and it’s no favor to anyone to hand degrees out for free.

At the defense in the morning it’s not the kind of thing I’m used to, of course, even though much of the structure is there. The student gives a 15-20 minute talk. The various jurors hold forth on their domains of expertise, offering congratulations as well as criticism. Then the jury retires to deliberate on the “mention”, the grade if you will: Honorable, Very Honorable, Stupendously Honorable, etc. We get to sign all manner of forms. We even get to wear voluminous crimson robes with huge sleeves. What’s different is that, while I can ask questions, they aren’t answered by the student.
?huh?
Whose thesis is it?
No, the person who directed the thesis answers the questions. A rather paternalistic system! The student just stands there at the podium, which is off to the side, while the jurors debate among themselves at the table. Because we’re looking at each other during all this, which takes far longer than the presentation did, we’re not ever looking at her. It’s as if she were just decoration.
One thing I was hoping for here was to see at last the pedigrees of the families under study. It’s my boss who brings it up; we really can’t let it go. The whole point of this thesis is to analyze the cases under study, and this she has done every which way except showing us the reasons for them being included, their genetic risk. Every treatment, every parameter, every detail of the reproductive history of 31 cases are here. Add the 31 pedigrees, and OK for the diploma.

Organized as my lab is, this would be the work of a day. In fact, it would have to be done before anything else, because how else can you decide who to study? In Marrakech, I fear, it could take a while.
In fact, I discover the next day when we meet as a small group, that while the age at diagnosis of each case is known, and there are scattered notes as to other cases in the family, nothing like complete pedigree information has been collected. She’s going to have to recontact every single case and collect that information from scratch. A task indeed. I just hope I have made it clear enough that we need to know who is not sick as well as who is. We’ll see. I’m available for advice, and their new geneticist knows her business. We’ll get this thing out, pronto.

Public Squalor, Private Splendor (4 of 7)

Trucks in Morocco tend to be decorated. Not as much as Pakistani or Indian ones, but it's a cool personal touch.
One of the sadder public spaces.

These hats are just for tourists. I never saw a Moroccan wearing anything but subdued, neutral colors.

Walking through the souks, I was constantly removing and replacing my sunglasses. And the cats are everywhere.

In Marrakech, and in the Maghreb in general, there’s a tremendous contrast between people who have and people who don’t.
Most of the population is very poor. Many beg on the streets, especially women whose husbands have died or left them. Children in the Medina are put to work as soon as they’re able to carry a load, instead of going to school. Everywhere men are idle on streetcorners and squares, wearing rags and looks of desolation.
The state doesn’t spend much on infrastructure, either. The cracked and broken sidewalks, the trash accumulating under every bush and all along the streets, the dirt everywhere: all contribute to making the city look uncared-for and broken. Construction is shoddy, with plaster flaking off façades before buildings are even finished.
Yet in the midst of all the squalor, behind high walls in the Medina or in gated neighborhoods, are oases of luxury.
Open the door to a hidden riad in the Medina and step from a world barely scraping by to the tinkling of fountains under the shade of well-watered palms, couches piled with heavily brocaded cushions. The houses in the rich areas rival their wealthy American counterparts.

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My host, on Wednesday after a session of going over the family data and pinpointing what needs to be done (I’ll post about the thesis tomorrow), took me to see her future new house, now in its third year of construction.
Our way there is along a potholed and trash-lined boulevard. When we turn off into the nice neighborhood, still nobody picks up the trash along the public street, but the new houses loom huge and perfect behind their high walls and lush landscaping.
BB’s yard has been planted with fruit trees, but as yet nothing else because of the work still in progress. The structure of the 4-bedroom house is complete. It’s now a question of finishing work - installing sinks and light fixtures and banisters. Another six months, perhaps, maybe more at the Moroccan pace. Inside I see why it has taken three years already and the place is not yet livable. The ceilings are masterworks of traditional hand-cut plasterwork designs such as you see in all the pretty picturebooks of Moroccan style. There’s a central light well illuminating the three stories. Every door and windowframe is hand carved from top to bottom. Colorful tile designs line the bathrooms and floors. Everything has been made by hand, here on site. Two men are working on a pair of carved slatted closet doors laid out on benches in the garage. No buying machine-tooled fixtures from Home Depot around here. The artisans are hard at work.
Perhaps the populace as a whole isn’t so very poor. Certainly many live in shacks and can barely feed themselves, but there’s a whole society of artisans and taxi-drivers and grocers who are doing alright. Not the same standard of living as in the US, but living alright for Morocco.It’s the tragedy of the commons that perhaps makes things look worse than necessary. It’s the trash everywhere. The crumbling buildings, the derelict wrecks, the potholed roads. The green spaces look so inviting from afar, but closer up you see the old bottles and papers and homeless men in every direction, and the stench of decay hits you and the beauty and peace disappear. Only inside the private spaces are things cared for and clean.
Too bad I didn't have the camera with me for this visit! But after hauling it around all morning through the souks, it just seemed so darned heavy. In the post after-next I'll show you the luxurious side of Marrakech.

Marrakech (3 of 7) Arriving

While visiting Crete a dozen years ago, it was explained to me that the reason the upper floors of so many houses remained unfinished (just a forest of reinforcement rods sitcking up out of the de facto roof) was because of taxes: no property tax until the construction was complete. So only the rich completed their houses.
Told to me by a local, so I believed it.
When I visited Algeria I noticed the same phenomenon. Then again to a lesser extent in Morocco. Not knowing the local tax codes, I thought it might be the same reason, but I didn’t go so far as to ask. Then something I just read suggests another explanation: An Algerian character in a memoire cites an old arab proverb -
When the house is finished, death walks in the door.
How’s that for incentive to leave an extra floor open to the heavens?
And there aren’t so many Arabs in Greece; why should there not be multiple origins for the same effect?

Mohammed V airport in Casablanca. Just like small airports all over France. Clean. Non-smoking. Shops all over the place. Spacious. Carts selling pastries and Diet Coke.
All the men, and the great majority of women waiting here in the domestic departures area for planes to Fez, Oujda, Agadir, or Djalkeh are wearing western dress. Maybe a third are Europeans, but it’s hard to tell. The Eagles are playing on the loudspeakers, alternating with panpipes versions of old saws, exactly like the faux-American Indian stand at the weekly market in Aubière.
Ah, globalisation.
The fields around Casablanca are a delicate spring green, here and there an early crop of colza is beginning to come into lemon-yellow blossom. The city blocks, tight-packed with whitewashed houses topped with antennae and satellite dishes, stop short at the edge. City. Country. City. Country. No intermediate zone of houses with yards or piles of junk, or semi-industrial areas, at least on this part of town.
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Approaching Marrakech only half an hour late, we discuss our lodgings. Having not heard from our host, YJ’s wife went ahead and reserved them a luxurious riad in the Medina. I have no plans at all, trusting that, like last time, arrangements will have been made. In an email that did get through, Jamal mentioned a reservation. I just don’t know where, though I assume it’s in the same hotel as last time (the owners being good friends of BB’s, after all). If not, it’s not as if the city lacks hotels, it’s mostly a question of finding a nice one without paying a fortune. YJ’s palatial riad is not in my budget, even with the stipend we’ll be given.
Not to worry. At the airport a familiar group of three is waiting. Jamal and two young doctors I met on the last trip are here for us, bearing flowers. This time I myself am prepared with good French chocolates for them.
They have reserved, and are taken aback that YJ is declining that hospitality, but agree that not knowing, it’s understandable. Apparently there is a real problem with BB’s email getting through, and we find out later it’s mostly been identified as spam by our hospital’s filters. Going to have to see about that. Oh, and here’s a copy of the thesis for each of you.

The fabulous new train station, and the freight area next door.

The university campus.

Some pictures from a walk around the Khoutoubia and surrounding parks.

Marrakech (2 of 7): Snapshot of Breast Cancer

It’s always instructive to see where other people are in their ideas and assumptions. YJ and I saw, with the whole Marrakech team present - Mr the Gynecologist, Mme the Pathologist our host, a bevy of students and young doctors interested in oncogenetics, an intimidating total of nine people - four families in consultation. Well, the first came as a family, the others one person represented the family.
We first spoke to a woman and three of her daughters. The matriarch, at 61, was the only one to have had breast or ovarian cancer in the extended family as far as we could tell. She’s relatively old, for Morocco, to have breast cancer, and without any other cases, there’s no reason to suspect a genetic origin for her malady. There’s a slight excess risk for her daughters, but very modest. In our own consultation, we would never have performed BRCA screening.
YJ explained that they should not be worried about a strong genetic risk, but for everyone to get mammograms regularly. A glance between us showed we were both thinking, well this is the reason there are no BRCA mutations in the group we studied: if this family is typical, we’re not studying the right people.

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The second case was a young woman. YJ started off asking about the family history, and it turned out that the only relative to have had breast cancer was a cousin of the woman’s father. Nobody else? Nobody with ovarian cancer? Nobody on the mother’s side? Well, it seems there really is no genetic risk at all.
The young woman has some questions about the treatment she’s been receiving, and we begin to perceive our error in not starting off with the right question. The 26-year-old facing us is herself the index case of the family. In France it’s exceedingly rare for breast cancer to occur so early; even in families with mutations it’s uncommon. This changes the whole picture. Yes indeed, there is a definite genetic risk, and although all the tests we’ve done so far have not revealed an anomaly, we will keep searching, by other means and in other genes, and will stay in contact.

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The third family is typical of those we see in the west. Two sisters, breast cancer at age 37 and 44. Oddly, the older sister, who is not here today, never had any kind of treatment beyond the initial surgery. So we’re left wondering, was it really cancer, or a benign lesion? There’s no way to get this information. Even a single case at age 37, however, fits the criteria for BRCA analysis, so that’s two out of three good families. We seem to be more or less on the same page with our African colleagues.

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The last family we see illustrates the tragic state of women’s health care in Morocco. In a family with several cases of breast cancer, the women saw for themselves the hereditary risk. Two years ago, the woman before us was dealing with her sister and niece being diagnosed with breast cancer. She went to her doctor for examination. She was told that the mammogram was normal, but that she had some benign ovarian problems causing cysts in her breasts that were nothing to worry about; they would resolve on their own. Reassured, the woman stopped doing self-exams. Six months later, she noticed a lump her breast anyway, and went back to her doctor, who again told her that it was nothing to worry about. Come back next year.
But she did worry, and insisted on having the lump, whatever it was, removed immediately. Reluctantly the doctor complied, and discovered on surgery not one, but two good-sized malignant tumors. The follow-up treatment continued the disaster, using radiation in a way that caused severe damage to all the normal tissue in the area treated. This poor woman’s trials are not yet over, though I sincerely hope she has changed doctors.
She had the original mammography films with her to show us. Even I, often at sea in looking at such images, could tell that the large white splotch was something fishy. Right there for any competent radiologist to see was breast cancer.
I hope I’ll be able to find the mutation in this family, but it may be difficult. Every person with breast cancer (the ones to study) is either in treatment or deceased. And we know from experience that collecting blood from a person currently undergoing chemotherapy gives very poor quality DNA. There are some new tricks coming up in the laboratory, though, and we’ll make it work.

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This kind of situation may be widespread. Many women aren’t aware that a close relative having breast cancer, especially several relatives or young ones, means their own risk of breast cancer is elevated, perhaps extremely so. Even when women do know that something is up and they need to be cared for, they may not be taken seriously by their doctors. Family stories are seen as just anecdotes, not medical information. Many doctors are not competent in techniques relatively new here such as interpreting mammograms.
Things are changing, and my colleagues at the Mohammed VI university hospital are working hard to make them change. It’s a long road, though. There are about 3 million people in the Marrakech area. There is no oncogenetics department, or even an office. There is exactly one geneticist, to deal with all genetics not just cancer genetics, and she just arrived a couple of months ago. In the basement of the pathology building, my friend Jamal is just unwrapping some of the apparatus needed to do their own DNA extractions and the preliminary steps of genetic analysis. There’s a lot of willpower involved, the enthousiasm of a small group of people in the midst of an ocean of inertia.

Marrakech (1 of 7): Welcome!

It’s definitely a North African trip. You can tell from the organisation.
Over the summer I was supposed to fix a date for this 5-day visit with our Moroccan collaborators. But I was gone some weeks, my boss YJ gone others, the summertime and all, and by the time I got around to it, there was not a single 5 day block available to both of us that was at least two months away (a rule of our sponsors, the INSERM) and still in 2008. So I thought, Failure Tax, and let it go.
Then in November, email from the INSERM wanting us to confirm dates for our visit - our partners in Rabat wanted to know.
??
The woman at INSERM was very nice, saying, in complete defiance of all the beloved rules, that sure, they understand how hard it is to schedule. Just plan now, and take the trip as soon as possible.
Which turned out to be today.
In the meantime, I’ve been more or less in contact with our Moroccan hosts, mostly with the junior guy who stayed in my lab for a month, learning the ropes. Jamal. He’s a good egg.
About a month ago, he said they’d love for us to give talks, my boss and I.
Okay, no problem.
But then, nothing. No idea what sort of audience we’ll be talking to. No idea if we’ll be seeing patients, as YJ wants to.
Friday, after one last request for information, I get news that we’ll be speaking in front of a group of doctors. That’s fine; I’ve prepared a very basic slide show, only 18 slides, including the bla-blah. Anything more and I’ll lose them.

Meeting up at the airport this morning, it seems he’s had additional information. We’ll be met at the airport (good to know, since we never were sent our hotel information). And Tuesday we are to preside at the thesis talk of one of their students. As part of the jury.
???
Ummmm.
I vaguely remember Jamal mentioning late last year that somebody on their staff was doing a thesis on the breast cancer families they had sent us for analysis. I said great, glad to help out. But never hearing any more of it, the student had completely slipped my mind. YJ seems to have forgotten too. Or perhaps the boss in Marrakech, BB, assumed that her guy Jamal in telling me would automatically be inviting my boss to be on this jury. Well, I thought that any such invitation would surely be passed directly boss to boss. That's how these things are done.
But wanting to help out with this thesis or not, how can we be expected to do so having never seen it?
We’re happy to listen, even to ask questions off the cuff, but that’s not how you judge a thesis. You have to read it first! Consider the strengths and flaws. See how the oral presentation complements the written. Mostly, the written document allows you to formulate pertinent questions and have a meaningful discussion.
And it’s being sprung on us for tomorrow?
Well, I hope they don’t absolutely need us as jurors, because we’re not happy to rubber-stamp our approval.
This is symptomatic of the whole North African system. All seat-of-the-pants, under-the-table, handshake-between-friends. It’s not serious. Well, the definition of serious is vastly different.
Will there be any science in there? The student in question has never - not once- contacted us. If you’re doing a thesis on familial breast cancer, why not take advantage of our expertise?
I’ve not got a good feeling about this. Whatever knowledge Jamal took back with him - and he gained a lot in his month here - just last week he asked me for directions on how to draw pedigrees.
Um, last week you guys were at Lesson One in genetics?
I’ve been looking forward to seeing the pedigrees of the 40 families we’ve analyzed for them. Tomorrow I’ll see how they’ve got on with drawing them out.

This all reminds me of our collaboration with the group in Algiers. Amina A is just as hard to get in touch with (in fact, I invited her to join us in Marrakech because the comparison of the Algerian and Moroccan populations I’ve analyzed is really interesting, but never heard back), and it was just as hard to get the message across that only breast and ovarian cancer count when you’re looking at genetic breast/ovarian cancer risk. Please do not send us leukemia patients! But there’s also a parallel that hereditary breast cancer risk is just a curiosity to them. AA and BB are so hard put to keep up with basic medical care, that treating breast cancer is all they can do. Going out and finding it with screening programs is for tomorrow sometime. Finding families at risk and following up on women who aren’t even sick yet is just beyond their resources, and beyond even their ideas of what resources should ever be used for. Genetic testing is a Western luxury.
I wonder if the difficulty in convincing them that breast cancer risk is related to breast cancer cases in families is finally the reason why in the Moroccans we have almost no mutations at all - they’ve sent us whatever samples were available, not pertinent ones. I know they sent us samples from husbands (set aside), and from young children (set aside), but are the women really women with breast cancer, as promised? If they are, there’s something to look into.

I’ll try to get on line again later, but it isn’t easy!
Ciao.