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Cracking The Code - Transcript

PROGRAM TRANSCRIPT: Monday, 21 October , 2013

NORMAN SWAN, PRESENTER: Hello I’m Norman Swan from Radio National’s Health Report. What you’re about to see is a breathtaking example of how medicine can be transformed by the determination of ordinary people. Four years ago, Stephen and Sally Damiani’s baby son Massimo was struck down by a mystery disease. Their seemingly impossible quest for answers has made a discovery that’s astonished the international medical community. And it has implications for us all.

STEPHEN DAMIANI, FATHER: Several people have gone and said this is like Lorenzo’s Oil part two, and to be compared in the same breath, I mean it’s just incredibly humbling, because that was never my intention. I just wanted to diagnose my son.

SALLY DAMIANI, MOTHER: I don’t understand, like I don’t know how this can happen to someone. You know, my baby’s suffering and I can’t do anything because I don’t even know what’s causing his suffering.

JO HENDLER, RESPITE CARER: I definitely thought that Stephen was on a wild goose chase, I thought he was going to send himself mad if he wasn’t mad already, because I just thought there’s nothing out there

DR LEAH KAMINSKY, FAMILY GP: I had never heard of this being done before, this was science fiction, this was like wow, how are you to do this?

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD: I think this is actually in the process of revolutionising medicine as we know it. We’re actually changing the way doctors treat their patient and I think that’s truly astounding really.

STEPHEN DAMIANI, FATHER: This was the biggest problem of my life and the biggest problem of Massimo’s life and I think I just fell back on where I saw my strengths and viewed the problem in a different way.

STEPHEN DAMIANI, FATHER (speaking to video diary): Mo, this just came FedEx from the US. This is your genome, personal genome 45. And you’re the 45th person in the world to have had this done…

STEPHEN DAMIANI, FATHER: I wasn’t trying to become a geneticist, I wasn’t trying to become a neurologist, I was just trying to bring my knowledge up to a level where I could talk with neurologists and geneticists You might see in a few weeks time you might see another one of these with me on it and Mum on it…

SALLY DAMIANI, MOTHER: Even before all this my nickname for him was Mr Intensity.

STEPHEN DAMIANI, FATHER: But now we’re going to look at all three billion bits, and go a little bit wider and see what we can find.

SALLY DAMIANI, MOTHER: He doesn’t do grey, it’s all very black and white. You know that’s something we’ll never see eye to eye and I find lots of grey, but it’s not a word in Stephen’s vocabulary.

STEPHEN DAMIANI, FATHER: I was a chartered quantity surveyor once upon a time, which is like a building economist. I moved from that field into the telecommunications and risk management. So I at the time thought genes were things that you wore - I had no idea what was going on and I soon found out that I needed to understand this topic and understand it well

SALLY DAMIANI, MOTHER: Massimo developed like any other kid, rolled when the book said he would roll, started crawling when the book said he would start crawling, pulled up to stand; you know he just did all the things kids do, a really happy child.

STEPHEN DAMIANI, FATHER: I remember the night of his first birthday we had the family over and there was just this sense of unease that something wasn’t quite right.

SALLY DAMIANI, MOTHER: It’s funny how you just remember really specific things. I remember standing at the kitchen bench and we had, at the time, a coffee table up against our window and he crawled up to the coffee table, and we had all his toys out, and he normally would pull himself up to stand, play with his toys and everything. And he crawled up, put his hands up and he couldn’t get up. The other thing that did actually kind of pike my interest was the fact that he, when he was sitting on the floor he would start to lose his balance.

STEPHEN DAMIANI, FATHER: We saw the physio at the Children’s on the day after his birthday, the 23rd July, and that’s when she noticed something wasn’t right and pressed the alarm bell. And we quickly found ourselves in emergency and going through for an emergency MRI and meeting the neurology community for the first time.

SALLY DAMIANI, MOTHER: And, yeah, you know, just felt like one of those things was the longest night of your life.

STEPHEN DAMIANI, FATHER: There was just alarms flashing everywhere, he was screaming in recovery, the faces of everyone in recovery at 2am, were just grim and you could just read something was - something terrible had gone wrong that night

SALLY DAMIANI, MOTHER: And you start to think, oh I’ve done something wrong somewhere along the way, you know, I’ve broken my baby.

STEPHEN DAMIANI, FATHER: And I didn’t sleep that night, I was just constantly on the internet you know, what’s an MRI of a brain look like, what's a what’s a normal one, what’s an abnormal one, what’s going on. And I had differential diagnosis is this multiple sclerosis, is it all of these things; none of which it turned out to be. And I returned to the hospital the following morning and that’s where we met Dr Rick Leventer for the first time.

(Excerpt of Dr Rick Leventer showing the Damiani's scans of Massimo's brain)
DR RICK LEVENTER, NEUROLOGIST: The white matter areas here would be much darker than you see on the picture. The fact that they’re not as dark as they should be is a sign to us and to the radiologist that those nerve fibres, they’re not happy, they’re sick, they’re probably don’t have the right amount of insulation around them.

DR RICK LEVENTER, NEUROLOGIST: We went through the story and I told them that I thought there was a problem with Massimo’s white matter, with the cabling networks and then the natural questions are well, what is the problem and how can it be fixed?

(DR RICK LEVENTER, NEUROLOGIST (talking to the Damiani's): It really comes down to whether this is a problem where he formed the insulation, which is called myelin and has now lost it, and those conditions are called leukodystrophies.

STEPHEN DAMIANI, FATHER: Leukodystrophy is derived from the Greek word leuko and dystrophy - leuko meaning white and dystrophy destruction of. When you have a form of leukodystrophy, it will start breaking down your body’s ability to transmit signals from the brain to your body, and that’s why Massimo started to lose skills.

(Stephen filming Massimo as he tries to get him to sit up) Massimo. Up Up Up. Massimo, hey, Massimo. (Massimo crying)

STEPHEN DAMIANI, FATHER: Massimo’s MRI was consistent with a leukodystrophy and his symptoms were also consistent with it. But we needed to find the gene that was causing that because without a gene there was no hope of trying to do something about it.

(Stephen Damiani talking to video diary)
Mo I know you’ve been going through a really rough time the last few weeks and believe me, we all have not knowing what the hell’s going on. But we’re going to rule out what we know that you don’t have and try and focus on what you do have and do something from there. There’s about 38 known forms of what you have, and we’re going to go through a few more tests and we’ve done all the nasty stuff and we’ve put the needles in you, we’ve taken all the pictures, but now a lot of people around the world have to start looking at what these things mean and ruling them out. So this is the big picture of what they all are. There’s some pretty nasty things up here and we hope it’s not one of those.

STEPHEN DAMIANI, FATHER: We tested for all of the known forms of leukodystrophy and all the results came back negative. We knew it was likely genetic, as is the case with most leukodystrophies, but we didn’t know what the gene was that causing this particular condition.

DR RICK LEVENTER, NEUROLOGIST: When we see children with white matter disorders or leukodystrophies, we know at the outset that about fifty per cent of those patients with current methods we don’t find the diagnosis, and even in the other fifty per cent where we do find a diagnosis, there’s very rarely a treatment.

(Sound of Massimo crawling)

STEPHEN DAMIANI, FATHER: Eventually Massimo was categorised as having an unclassified form of leukodystrophy. And that’s like saying you have cancer but you don’t know what type of cancer - nor do you know where it is.

SALLY DAMIANI, MOTHER: And that was the thing like all the advice from the doctors was about you know, remember they’d say take him home and enjoy him and, it’s like, what on earth is that supposed to mean? Over the course of eight weeks we just saw him get weaker and weaker and weaker, so he got to the point where I’d stand him up and his legs just couldn’t hold him up. His crawling just got slower and slower and then it stopped. He was still eating food but he started to, I guess, you know, he’d choke and vomit quite a lot. So it was just like watching your baby just sort of, almost like fall apart in your hands and it was awful because you couldn’t do anything about it.

JO HENDLER, RESPITE CARER: I was working for the local council as a respite carer and my manager came to me and said, we’ve got a new baby on the books. But she said don’t get attached, because in three months they’re expecting him to either be in palliative care or gone

STEPHEN DAMIANI, FATHER: I don’t think anyone was confident he was going to see the end of 2010. And that was just not something I was coping with, I just didn’t accept that you know, we didn’t have a diagnosis and I wasn’t going to lose my son and not know what the hell happened and why, and then there was the risk of not being able to have other children going into the future. So it was a you know, a double whammy of you’re going to lose your son, we can’t tell you why, and you can’t have other children because the same thing might happen again. We needed to work out a way to identify the specific gene causing Massimo’s condition. Then we needed to find other children that had this same defective gene to validate the diagnosis. And then we needed to work out how to fix the problem and develop a therapy. There were two parts which were really difficult to, I guess accept, and one was not being able to develop a therapy and I’d read enough by this stage to know that there was no cure for leukodystrophy, but that didn’t mean we couldn’t come up with one.

STEPHEN DAMIANI, FATHER (Talking to Sally): So imagine if this was all of Massimo’s DNA, we’ve looked at just the little bits here - these genes that are causing these conditions. But if we sequence his whole genome, we’ll get all of the information of the genes in between here which may be causing his problem.

SALLY DAMIANI, MOTHER: So when we finally did sequence Massimo’s genome the cost was just over $10,000. It’s not something that’s funded through any health care system, certainly can’t swipe your Medicare card for it.

STEPHEN DAMIANI, FATHER: I was full steam ahead with a business I’d just started, but we effectively had to put tools down and focus all of our energies on understanding the technology and understanding what was required to achieve that diagnosis.

SALLY DAMIANI, MOTHER: The routine was pretty much you know once Massimo was asleep at night, Stephen and I were at opposite ends of the couch with laptops out just Googling; finding things we could find. And you know, we’d just read anything we could get our hands on to understand what we’re dealing with.

STEPHEN DAMIANI, FATHER: We were both numb and the way I dealt with that was to lock myself in my study and drink, I don’t know dozens of coffees during the day, and just read and read and read and lock myself out from the world.

(Excerpt from video diary of Sally Damiani with Massimo)
SALLY DAMIANI: Okay, Massimo, let’s go pay a visit to Dad. And Dad’s in his study where he always is and oh he's on the computer.
SALLY DAMIANI: Hi, Dad. What are you doing Dad, what are you looking at?
STEPHEN DAMIANI: I’m having a look at your genome again Mo. I’m having a look at a few of the genes in here.
(End of excerpt)

JO HENDLER, RESPITE CARER: You know I’d been working in the disability field for a while and I just thought this poor man can’t accept that his child's sick, and I think that it wasn’t that he couldn’t accept that he was sick, he just couldn’t accept that that was going to be it, and he thought you know what he’d been told couldn’t be the only option.

DR LEAH KAMINSKY, FAMILY GP: Massimo was deteriorating in all ways. I guess Stephen and Sally were kind of almost preparing for the worst. But after a while he seemed to plateau out, and that seemed to shift the focus from having brought a child home and starting the grieving process to - the strongest determination I have ever seen in my entire career. I think from the outset there was a division of labour, so Sally was taking over the care aspect and that freed Stephen up for really being, you know, the numbers guy. He took it on as a project, and I guess I have to put up my hand as being, if I’m honest with myself, of being the biggest sceptic initially.

(Excerpt of reading from DNA papers)
DR LEAH KAMINSKY: Okay, what’s this, genetic diagnosis by whole exome capture and massively parallel DNA sequencing.
STEPHEN DAMIANI: If you imagine that what we’re trying to do...
(End of excerpt)

STEPHEN DAMIANI, FATHER: The concept to me was still simple, it was about data, it was just mining data.

(Excerpt continues)
STEPHEN DAMIANI: Step two is to get Sally’s genome and my genome and we’ll line up all the letters from these...
(End of excerpt)

SALLY DAMIANI, MOTHER: And you know in Stephen’s logical brain it was like, we'll sequence it, we’ll get some data and you get a really super duper computer that can analyse it and an answer will pop out. Because that made sense to him, that was logical, it was mathematical.

DR LEAH KAMINSKY, FAMILY GP: A lot of people around the world that he’d been contacting, I think, you know, the message, take home message was oh another maverick scientist, another you know, backyard geneticist and there are plenty of them out there.

(Dr Rick checking Massimo's legs)
DR RICK LEVENTER: They are pretty stiff, he's just had the botox recently.
SALLY DAMIANI: Yeah just last week.

DR RICK LEVENTER, NEUROLOGIST: I remember quite well the day he said, we must be able to find this, there must be a way, there must be a broken gene, it’s just technology, it’s just statistics, it’s just data, it’s just money, it’s just whatever we need to do, it can be done. And in some ways I really had to agree with him.

STEPHEN DAMIANI, FATHER: You could count on one or two hands how many people could do this in the world, and we were struggling to find those people. It goes back to that analogy of almost being the architect that has this grand vision of what needs to be done, you know architects love to come up with these visions, but then you need to find a builder that’s going to be able to do that and that’s where we found a builder in Ryan Taft.

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : So the Damiani’s came into my life very unexpectedly. My wife had lunch with their general practitioner, Leah Kaminsky, and they’re both writers and Leah got to talking about this family she had where the father had paid to have his son’s genome sequenced and asked my wife you know, doesn’t your husband do something with genetics and genomes and my wife was pretty sure I did.

STEPHEN DAMIANI, FATHER: That to us was a miracle, you know, we had banged our head against the wall all over the world to try and find someone and that someone was here in our backyard in Brisbane. When Ryan and I initially first had that conversation, I'd really wanted a sounding board to just com-check whether what we wanted to do was realistic. This wasn’t Ryan’s field, it was like he was building nuclear submarines and we were coming to him and saying we need to build a rocket ship. Both extremely complex, but not quite related to one another.

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : This was totally different, this was somebody with a sick kid came to me and said, can you figure this out? And that was a whole different level of daunting, because that was - there’s something on the line here now, this work really matters right now today. I think it was invigorating, it was just really pushing the envelope, it was taking things to the very edge of what we thought we could do.

STEPHEN DAMIANI, FATHER: Ryan took an approach, which was very pragmatic saying, this hasn’t really been done before. But then when he came back and said I’d like to give this a go, we knew we’d found that one in a million person.

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : (talking to Stephen on the phone): It could be a week, it could be a month, but hopefully we’ll do it as quick as we can.

SALLY DAMIANI, MOTHER: We decided very early on we wanted to have more children, and so we had to look at alternatives for doing that because we didn’t want to take the risk of having another child with the same condition as Massimo and put another child through that level of suffering.

STEPHEN DAMIANI, FATHER: We did lots of research, and there was a greater chance that Massimo's condition was passed down maternally, so we concluded the lowest risk option was to move forward with an egg donor.

SALLY DAMIANI, MOTHER: And the big thing that drove us to that was we didn't want Massimo to be just a child in a frame on the wall, that one day a younger sibling would sort of just see pictures of - we thought even if they only have six or twelve months or one or two years together, we wanted whoever his siblings were to meet him and to live with him.

(Images of the Damiani's next two children with Massimo)

SALLY DAMIANI, MOTHER: We’re just glad that they’re with us and that there’s two other people in the world that I think love Massimo as unconditionally as Stephen and I.

STEPHEN DAMIANI, FATHER: It was the best decision we could have ever made.

SALLY DAMIANI, MOTHER: Ryan was doing this in his own time, so this wasn’t his day job. He sacrificed basically his evenings and his weekends. He’d just be locked away in his study you know writing codes and trying to work things out.

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : I thought our chances were pretty slim to be honest, but I don’t know I was naive and optimistic enough to go for it. There were really at the time very few cases globally of anybody having success at this scale.

STEPHEN DAMIANI, FATHER: The unique thing with Massimo was we only had one child - we were trying to diagnose one individual. There were no other Massimo’s in the world.

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : The successes had been if you had lots of kids who had the same disease, and then doing this kind of analysis. You kind of had a broader pallet to work with. We had to figure out what was wrong with one child. I think sometimes I get a little ahead of myself. I’d disappear into the office for hours at a time and pop out and say, I think I’ve got it, you know. And then Erica, you know, my partner, my wife - she’d say great, that’s really good honey you know, and give me something to eat and I’d go back into the office and then come back an hour later and go no that wasn’t it. It felt a little surreal in a way, when that first piece of evidence came in, where I went I don’t know I think this might be something. And then within five minutes to drill into it a little bit and it made more sense, and then ten minutes later it’s still making sense and then a day later it’s really starting to make sense, you know, it was great.

DR RICK LEVENTER, NEUROLOGIST: Ryan contacted me, and said he’d found a gene that he thought was the cause of Massimo’s disease, or a disease, a gene of interest at least. And when you just have a new gene and disease that hasn’t been described it’s really difficult to prove that - you can’t just prove it with one patient.

STEPHEN DAMIANI, FATHER: And I remember receiving a call in September of 2012, so by this stage Massimo was just over four. And it was from his neurologist Rick. And he was very excited on the phone and he said we need to have a video conference, I’ve got Ryan, we need to have a chat very quickly, very animated.

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : So we had a conference call and Stephan was notified that we had it you know, and I had to be there for it and it was, it was monumental.

DR RICK LEVENTER, NEUROLOGIST: He really was just stunned, I think, I don't think it had really sunk in initially when we spoke to him.

STEPHEN DAMIANI, FATHER: I just didn’t know what to say, and that’s when Rick chimed in and said oh but there’s more, and several more families from a database in the United States in parallel have been identified in having mutations in that same gene and as a result of this a new condition had been discovered.

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : I literally jumped up and down (laughs). I will never forget that, that was an amazing moment.

STEPHEN: And that, that was the moment, that was eleven hundred and sixty one days after that first MRI.

SALLY DAMIANI, MOTHER: It was like you know, done it, everyone said this would almost be impossible, we’ve done this, we’re definitely going to do the next two steps.

(Stephen talking to video diary)

STEPHEN DAMIANI (talking to video diary): It’s just incredible, this is what the future of medicine is and genomic science is to work out what’s wrong with us and how we can fix it and make us all better.

STEPHEN DAMIANI, FATHER: In essence, we discovered Massimo's Disease - we discovered a completely new disease. And they called it HBSL for short, which is Hypomyelination with Brain Stem Involvements, Spinal Cord Involvement and Leg Spasticity. Yeah, I guess neurologists aren’t good marketers are they (laughs) Getting this diagnosis broke that isolation of three and a half years. Massimo wasn’t alone anymore and I think to date we’ve identified about a dozen children around the world that have this condition

(Washington DC)
DR ADELINE VANDERVER, CHILDREN'S NAT.MEDICAL CTR (Talking to Stephen Damiani): And we have a, over 900 patients now in our unsolved bio-repository.

DR ADELINE VANDERVER, CHILDREN'S NAT.MEDICAL CTR: It’s the only time I’ve ever heard of a father spear-heading a diagnosis in this way, the way Stephen did, you know he sent us all these huge tera-drives of data all over the world to try to make this happen for Massimo.

STEPHEN DAMIANI (Talking to Dr Adeline): So it gives us time to hopefully come up with a therapy.

DR ADELINE VANDERVER, CHILDREN'S NAT.MEDICAL CTR: The way that Ryan uses these tools is fairly unique in that he manages to apply bioinformatics, or computers, to these huge amounts of data. It’s going to permit not just diagnosis of rare diseases in a more effective way, but it’s going to permit us to better understand common diseases, it’s likely that diseases like diabetes, cancer, cardiovascular risk, are all genetically mediated to some degree.

(Excerpt of Dr Ryan Taft speaking at Institute of Molecular Bioscience, UQ)
DR RYAN TAFT: I’m going to start with Mission Massimo, which is really, in a way, the whole reason all of you are in the audience today.
(End of excerpt)

DR RYAN TAFT, GENETIC SCIENTIST, UNI OF QLD : There are a lot of people I think scratch their heads when I try to explain what we’re doing. But I think you can really boil it down. Yeah we’re using some exciting techniques and some computer algorithms and computer programs to try and sort this out, but at the end of the day we’re really asking a fundamental question - what makes us us? What are those instructions doing and what happens when they go wrong? And I think what’s even more amazing is what we’re going to see what happen next, you know, we’re just at the beginning.

DR ADELINE VANDERVER, CHILDREN'S NAT.MEDICAL CTR: It’s like finding a needle in a haystack and you, if you don’t know what gene you’re looking for, you couldn’t get an answer and now you’ve blown the haystack to pieces and the needle's right there.

SALLY DAMIANI, MOTHER: I guess what makes me so proud of Massimo is he hasn’t given up in all of this either. He’s regained some of the skills he lost originally, he’s now at he’s local kindergarten absolutely loving it. I know he’ll embrace school with everything that he’s got and try and make the most of it.

STEPHEN DAMIANI, FATHER: I think if we use the analogy of achieving a diagnosis was getting to the moon, coming up with a therapy would be going to Mars, it is that big a leap. But I am absolutely confident with the right team and with the will that we will be able to make a life changing difference to Massimo and I hope other children in the not too distant future.

SALLY DAMIANI, MOTHER: Who knows what his future holds? I think whatever it is he’ll write his own story and it will be a good story.


Dr Ryan Taft and Stephen Damiani, with colleagues from around the world, published the discovery of Massimo’s disease in The American Journal of Human Genetics.

Dr Taft's laboratory continues to develop the method used to diagnose Massimo in collaboration with the Global Leukodystrophy Initiative.