Um, let's

get into it right after this break. I want to start off the history section with a

quote, love that

quote. One of the more frustrating endeavors for those interested in the history of medicine can be the desire to discover the first published description of a disease, operation or procedure. Having attempted this on several occasions, I have concluded that it requires more than a large medical library, a good memory, luck, perseverance, or a high degree of suspicion for quoted sources. I am always left with the uneasy feeling that only the personal perusal of the original publication will convey the author's true thoughts. Existing seemed to change in quoted sources and often contain errors in regard to context, interpretation, translation, and bibliographic data. Osteogenesis imperfecta is a case

in point. Mm-hmm.

So what you're saying is we don't know. Yeah.

That was the paragraph to say three words. We don't know. So that was from a paper titled Osteogenesis imperfecta historical background by Ulrich H. Wheel MD published in 1980. And when I read it, first of all, I was like, this is an amazing quote. Also I love that this author devoted so much space to this sentiment. That's great. But it's a great quote I thought to begin the history of Osteogenesis imperfecta. And honestly, it's applicable to many other topics that we've covered. Because I think it does force us to think about what is important when tracing the history of a disease and why is it important? Is it that Dr. So-and-so was the first to name something? Maybe, especially if you're that Dr. So-and-so or related to that Dr. So-and-so. Or is it the order that things were discovered about a condition? Or how the timing of discoveries influenced the perception of a disease because of the current social or political climate? Or how the discovery of a condition altered the experience of those who had it? Or how the discovery changed medicine itself? Or maybe it's like a combination of all those things and it can be. And don't worry, this is not going to be just a giant philosophical discussion or a lecture on how to construct a narrative on the history of medicine. I just thought that this quote kind of served as a good reminder that the stories that we tell are exactly that, their stories. And the storytellers themselves choose what does or doesn't go into a story and they're human. We're human with biases and flaws and sometimes typos, oftentimes typos. So what does that mean for osteogenesis imperfecta? It means that what I want to focus mostly on today is not who gets priority for the first description of this disorder, but how our understanding of it has grown over time and what that is meant for the people living with this disease, especially as the divide between knowledge and application has shrunk, but not entirely at

all.

Okay, so let's get started with this history by heading back as we often do to ancient Egypt. Since osteogenesis imperfecta is associated, of course, with skeletal changes, we can make fairly confident diagnoses in skeletal remains that have evidence of the disease. And the earliest of these that I came across is from an ancient Egyptian mummy, an infant, from around 1000 BCE. The infant skull and bones were consistent with osteogenesis imperfecta, specifically types three and four. I think there couldn't distinguish between those two. But from what I can tell, there aren't references to osteogenesis imperfecta in any ancient texts or at least any that aren't incredibly vague, which I thought was kind of interesting.

That is because it's... I mean, bones are often what we look to to see about so many other diseases. And so it is interesting. It is, it

is. And also, like what proportion of medical writings from ancient... from the ancient world remains today, what is still waiting to be translated, etc. Like, you know, it's... I'm not saying that they don't exist. It's just that A, I didn't read about them, B, no one's read about them yet. I don't know. It could be both. But there is a legendary figure from the ninth century CE that has been said to have osteogenesis imperfecta. Ivar the boneless. Ooh. Sometimes translated as Ivar, I hope it's Ivar, not Ivar, Ivar the legless. Ivar the boneless was a Viking king slash leader slash person of importance who I couldn't get a handle on what position he held. But in any case, he makes an appearance in the 13th century epic poem, The Tale of Ragnar Laudbrok. He was the son of Ragnar. And in this poem is the story of how Ivar travels to East Anglia and Northumbria to avenge his father who was murdered by the king of Northumberland. He was successful, allegedly killing the king Ivar and a horrible way, the blood eagle. Maybe read about it, maybe don't. Ultimately, Ivar dies in Dublin, like peacefully in the year 873. Before he died, he instructed that his body should be buried in a mound on the east coast of England, saying that as long as his grave was undisturbed, no invasion of England would be successful. And that apparently held true until William the Conqueror landed there in 1066 and burned Ivar's remains. Just a fun little story that has nothing to do. That's just mostly backstory on this

guy. Ivar.

Okay. And because we don't know where Ivar was buried or if he existed at all or was just like a composite figure in this poem, but if he did exist, his body was possibly burned. So like we can't make a diagnosis based on his remains. We can't know whether or not he had osteogenesis imperfecta. Okay. Ivar's mother was said to be cursed while she was pregnant with him and he was unable to walk and was carried on a shield into battle where he would use a long bow. So maybe he had O.I. But another explanation for his name that some authors suggest was that it was like an insult suggesting that he wasn't really up to the task in

certain ways.

But

it was just that he couldn't walk. That's the only. Yeah.

Oh, interesting. I know. So this is what like the amount of conjecture that comes out of some of these early histories of diseases is simply staggering.

Yeah. Mm-hmm.

And we're never going to know. But I did want to mention him because his name comes up in like every history of osteogenesis imperfecta more or less. And there are a few other possible references to what could be osteogenesis imperfecta in like ancient and medieval times, but very much in theme with the quote at the beginning, the original ancient source can't be found or it's been mistranslated or whatever. So let's move on to the 17th century where we have to go from here. And that's when the next possible reference to osteogenesis imperfecta shows up in France in 1675 from the philosopher Nicholas de Malabrash who wrote that quote. About seven or eight years ago, a young man could be seen at the incurable's hospital who was born mad and whose body was broken in the same places as murderers bones are broken. He lived for about 20 years in this condition. Several people saw him and the late queen mother when paying a visit to this hospital was curious to see him and even to touch the arms and legs of that young man where his limbs were broken. End quote. de Malabrash then provided his reasoning for why this man had this condition.

Quote, the

cause of this terrible accident was the fact that the mother having heard that a criminal was to be put on the wheel went to see the execution. All the blows that were given to that wretch struck the imagination of that mother forcefully and as an indirect consequence, the tender and delicate brain of her child end

quote. What?

So yeah, he is not even like suggesting but just like stating very firmly that this guy's mother who when pregnant with him saw this public execution and that every blow that landed on the guy who was on the wheel, the person put to death, then when he was born, he later had breaks and all the same. It sounds. It not

only makes no sense, it also why does it sound weirdly familiar?

Oh, I think epilepsy was a lot about when someone was pregnant and they witnessed something and then I think it was epilepsy. And that sounds that sounds familiar. I mean, to be honest, Erin, we know that it's going to be a thousand different things, right? Anything that you can blame a woman for. Yeah.

Yeah. It's always

mom's fault. Yeah.

Yeah. It's it's doesn't make any sense. The next reference to what is likely osteogenesis imperfecto was written with slightly less conviction about what caused it. Okay. This is from a medical report from France in 1690 quote. On March 8th, 1690, a woman in her late 20s was admitted to the Hotel du in Paris. She complained that over the past four months, she had suffered extreme and diffuse pain all over the body with no apparent feverish episode. Although she could walk and move without restriction, she suffered unbearable pain when anyone touched her. After three months of forced bed rest, she could no longer walk. All bones fragmented and it was impossible to touch her without causing new fractures. The pain increased progressively until she died. On dissection, we found that the upper and lower limb bones, clavicles, ribs, vertebrae, and the pelvis were broken. Not a single unbroken bone was found. The bones were thin, tender, and full of red marrow. Upon manipulation, they pulverized and dissolved like a rotten, wet tree bark. They could sink our fingers into her skull bones, the consistency of which was similar to that found in a 15-day old neonate. Cartilages and articulations showed no sign of alteration. The internal organs were healthy and no other signs of her pathological condition were found. It is known that smallpox can cause bony erosion, but in this case, the bones were melted and softened. What was the cause and nature of their dissolution?

Wow.

Yeah.

That's a pretty gnarly description. Yeah. That

sounds like a very severe

form. What struck me about this was the mention of pain, because you didn't really talk about pain very much, but is pain a major feature of some of these different types of osteogenesis imperfecta?

I mean, certainly, yes,

especially because

these fractures are painful. Like breaking a bone is incredibly painful. So, it's not that this disruption in collagen disrupts in any way all of the nerves and everything else that's involved. So, the fractures themselves are going to be painful. The way that bones heal might lead to additional kind of damage down the line, like we talked with the scoliosis and things like that, which can be painful. So certainly pain can be a component of osteogenesis imperfecta. Okay. Yeah.

Okay. Well,

anyway, so still traveling through these early mentions, there is sometimes people mentioned someone named Armand as providing the next description of OI in 1716, but I didn't really find any more about that. Like, that was it. Then we have the dissertation of Swedish surgeon Olaus Jakub Ekman published in 1788, which had previously been considered the first scientific description of the disease, even though he considered them to be cases of osteomalacia that ran in families. So, he described four generations living in a mining district with bony disorders resulting in disability. Mm-hmm. But he just thought that it was osteomalacia. Yeah.

That is interesting because Ricketts, which we already did this season, and Skurvy are all definitely on the differential. That is when it comes to osteogenesis imperfecta. Yeah. Yeah.

But are you seeing how the quote at the beginning is like so relevant? Yeah. I love it. And then there's this. And then like, there are so many different instances of the first description of this and that anyway. Personally, what I think is that the first description that really matters is the one from Edmund Axman in 1831, where he describes for the first time the four major characteristics of osteogenesis imperfecta, bone fragility, joint hypermobility with easy dislocation, blue sclera, and a frail body. A couple of years later, Lobsdine described a condition he called osteosathorosis idiopathica, an abnormal brittleness of bones, particularly afflicting children and the elderly, also mentioning that it can run in families. It's unclear whether he was actually talking about a combination of osteoporosis and Ricketts or actually OI. And so at this point, we have, okay, we don't have a complete clinical clear picture, but we have now gotten a distinct condition. So this is not just like a symptom that people are talking about. This is a collection of symptoms that are recognizable features and that makes diagnosis a possibility by around like the first half of the 19th century. But like a diagnosis of what? Because what we now know is osteogenesis imperfecta didn't yet have that name. Right. So how did that happen? Gerardis Vrolik was a professor of anatomy and physiology and of theoretical and clinical obstetrics at the University of Amsterdam in the early 19th century.

Sorry, what is theoretical obstetrics?

It's just imagining how everything happens. Okay. Cool.

Yeah.

Okay. Malpractice insurance

is

very low. That's my dorkiest joke yet.

I really liked it. Thank you. As if

anyone needed malpractice insurance in the 19th century. Yeah. One of Vrolik's special interests was congenital disorders. And that was a topic that was very popular at the time. I saw it described in one paper as the golden era of descriptive pteratology.

Hmm.

Anyway, Vrolik, in addition to publishing case studies of some of the congenital disorders that he treated or came across, he also began a private collection of specimens, humans and other animals.

That sounds questionable. Yeah.

I think it still exists. His son, Willem, who was also a physician with an interest in congenital disorders, inherited this collection after his father's death and studied it. One of the samples that he came across and found worthy of description was the skeleton of an infant that had died three days after birth with numerous fractures. Willem dissected the skeleton and found that there were fractures in every intact bone. The skull, large and with a high forehead, was fractured. The ribs were very thin and development overall seemed incomplete. In 1849, he published his description and his belief that the infant had a condition he termed osteogenesis imperfecta. Meaning that he believed, unlike most of his contemporaries, that it was a condition that the infant had been born with rather than something they had acquired after birth, as in like Ricketts. Right. Later reexamination of the skeleton in the 1990s led to the diagnosis of osteogenesis imperfecta type 2.

Mm-hmm.