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Thicker than Water: Dr. Holly Tucker on Blood, Medicine and the Scientific Revolution of the 1600s



Lindley:  Did you discover this story of seventeenth century blood transfusion when you were teaching the history of medicine?

Dr. Tucker:  The short story is that I was.  I teach courses in our Center for Medicine, Health and Society.  I love this program.  I teach students who will become doctors and get to make a real case for the humanities before they go to medical school and get pummeled with science classes.   They get a chance to look at the humanistic aspects of medicine in the classes that I teach.

I teach the class on early medicine from Aristotle to the Enlightenment.  I was prepping for a class on William Harvey’s discovery of blood circulation [in 1628].  I was looking for case reports that are well know from Philosophical Transactions [journal of the British Royal Society] around infusion and transfusion, and that got me interested.

 The longer story is that I stumbled onto a transfusion report comparing blood to sap of plants, and I thought my next book would be on the history of botany and specifically looking at Linnaeus.  The more I dug around on blood, I found there was an interesting story to be told there, and it made the lectures on William Harvey’s discovery of blood circulation more interesting after I combed through those records.

Lindley:  So you found transfusion records when you were looking into Harvey?

Dr. Tucker:  Absolutely.  Specifically, in the Philosophical Transactions of the Royal Society.  I stumbled on a reference to a French case of the first animal-to-human case by Jean-Baptiste Denis.  There were detailed notes on what Denis claimed, and that led me to take a look at the tense relationship of the French and English around blood and the doubly tense relations that Denis had not just with the English but with the French medical elite: the Paris faculty of medicine and the French Academy of Sciences. 

Then I also looked at the third case of  [animal-to-human] transfusion that Denis performed, which was the lethal case.  Much of this story of blood transfusion is well known among medical historians, but what caught my attention is that Denis’s patient, this mentally ill man that he and his benefactor plucked off the streets of Paris, died after the third transfusion.  There were rumors that Denis was responsible for the death.  As a preemptive effort, Denis went to the criminal courts and said, “Wait.  People are saying I did this, but there’s more to this story.”   And there was more to it.   Denis was exonerated and the widow [of the patient] was convicted of poisoning her husband with arsenic.  This was all well known.  The Parliament later decided that there would be no more blood transfusion without the express consent of the Paris Faculty of Medicine.  So transfusion wouldn’t happen because the Paris Faculty did not support transfusion.

That’s where historical accounts typically end.  Most historians say this was an unusual case in the history of medicine, and thank goodness blood transfusion didn’t move forward. 

The court records said yes, the wife did it, but she had help from unnamed physicians. 

Lindley:  And you were the first historian to reveal this complicity of physicians?

Dr. Tucker:  No.  That tidbit was well known.  But that caught my attention because I wanted to know who these people were and why they were so against blood transfusion that they were willing to resort to murder.  That set me off on five years of research. 

Lindley:  And you solved this very cold case by discovering the physicians who abetted the wife’s crime, and they were from the traditional Parisian medical elite?

Dr. Tucker:  We knew of physicians who were opposed to transfusion at the time.  When I decided to expand the stable of cultural documents around the question of transfusion and its detractors, the larger picture started to become clear, and I got a sense of what made blood transfusion so troubling.  But there was nothing I could use to pin the murder on a specific historical figure.  I didn’t have the documents. 

I spent a couple years knowing I had a good story and knowing the names had never been revealed.  I spent weeks and weeks at the Archives of the French Academy of Sciences trying to find anything I could.

Lindley:  Were those archival documents well catalogued and easy to use?

Dr. Tucker:  The French Academy of Sciences is well documented.  Even the notes of secret experiments with [Claude] Perrault, [Louis] Gayant, and [Adrien] Auzout were catalogued and I could get those manuscripts.  Perrault wrote a huge, multi-volume set on animals and the natural world.  There are boxes and boxes of uncatalogued documents associated with Perrault’s work.  I went through a lot of that stuff, and found it unhelpful because I was looking for a smoking gun where I wasn’t going to find it.  

I was about to give up the book, but I was inventorying my research at home, and came across a stack of documents that looked familiar, and I hadn’t really looked at them.   I found a letter by a lawyer at Parliament indicating that he was unhappy and nervous for Jean-Baptiste Denis, the transfusionist.  He had every right to be nervous because Person X and Person Y had already shown they were willing to take radical steps to stop transfusion.  That gave me the names that I needed.

Lindley:  So you returned to the Archives in Paris?

Dr. Tucker:  Yes.  They were hiding in plain sight.  When I was sure I had them, I decided I needed to work out at the gym.  I was on my way to the YMCA, and I called my husband.  He said, “What’s up?”  And I started to sob.    I said, “I found them. I found them.”  He said, “What are you talking about?”  “I found the murderers.”

Lindley:  That’s a remarkable story.  Can you talk about the French resistance to Harvey’s theory of circulation compared with the seeming willingness of the English to experiment and question tradition?

Dr. Tucker:  I have a hard time passing judgment on the French.  It’s true that the English were more adventurous and more willing to imagine other possibilities and the French were more traditionalist and looking at the past as a matter of articles of fact and faith. 

We see those same dynamics now.  Change is hard.  Change is scary.  We know Harvey was right now, but when you’re in the middle of it, how can you be sure?  There are a lot of wacky theories circulated in our own day.  There are studies that indicate we have the answer, and two years later we learned the study was flawed or wrong or perfectly wrong.  Or two years down the road you see a study that is replicated and gives you a completely opposite conclusion. 

The resistance in France to transfusion was fascinating, but we can’t judge them by our modern criteria.

Lindley:  Can you talk about Descartes ideas of body-mind dualism and the beginnings then of evidence-based medicine as practiced by “natural philosophers”—the scientists of that era?

Dr. Tucker:  The body is essential because it’s so deeply embedded in philosophical themes of the time.  Specifically, what is a body and what attributes are contained or not in that body?  Descartes comes on the stage with his proposal of mind-body dualism, which is at once attractive yet very unsettling.  It was attractive to natural philosophers who are eager to explore the body’s mysteries, and it gave many natural philosophers and physicians an opportunity to enter into animal experimentation. 

Descartes is often associated with the rise of vivisection because animals function like machines and their bodies are similar to the human body, which is also a machine.  Those animal machines are somehow devoid of the attributes that make humans human: the ability to reason, the ability to speak and the presence of the soul.  So many of the moral obstacles to performing vivisection then are diminished. 

At the same time, to propose that there was the radical distinction between body and soul flew in the face of longstanding tradition. And it also speaks to the role of blood and its attributes.  Biblical references insisted that the blood has a mystical role and is imbued with the soul.  So there’s a lot of resistance to the views of Descartes, and that plays itself out in the differing approaches to blood transfusion in England and in France.

Lindley:  Didn’t the English begin with animal experiments before Denis?

Dr. Tucker:  Yes.  Harvey was doing his experiments in the 1620s.   In the 1650s, Christopher Wren and Thomas Lower were doing infusion trials in animals.  They were injecting fluids—whether water, milk, wine, beer, or opium—into the veins of dogs.  And much of that was counter to the theory of circulation because [before Harvey] the blood was considered a product of the digestive system, and what you ate would be concocted in the stomach, distilled in the liver, or would make a one-way trip to the heart where it would be burnt like a furnace.  Harvey said no, the body can’t make that much blood.  He measured the amount of blood in a single chamber of the heart and multiplied that by the number of heartbeats per half hour.  He asked how much blood would have to be produced and burnt off, and it was a ridiculous amount.  

So this reflects the humoral qualities of blood and the other fluids, and all of those fluids had a deep relationship with the digestive system.  It would make sense to put opium directly into the veins or arteries of an animal and, with the older model, it would go immediately to the heart and be burned off because it would bypass the digestive system.  But the natural philosophers found that [the injection] would have an immediate and lasting, and often fatal, effect on the dog.           

And in the 1660s, Richard Lower and Robert Boyle wondered if you could inject these fluids into animal veins and arteries, what would happen if you could move blood from one animal into another animal.  They were very close to performing the first animal-human experiment when the French scooped them.

Lindley:  And Denis had also done animal-to-animal experiments before the first animal to human transfusions, and used animal blood to transfuse humans because he believed it was “purer” than human blood.

Dr. Tucker:  That’s not Denis’ idea.  That’s also coming from the English.  Denis is fascinating because he’s a big copycat.  There’s very little that he brings to the table that is new.  He replicates all of the English animal-to-animal experiments.

Lindley:  And he’s reading the English documents on their experiments.

Dr. Tucker:  He’s actually reading the French translations of them.  He is performing the experiments almost identically to what Edmund King, Richard Lower and the other English transfusionists are doing.   The one difference that Denis adds is that he starts putting in new species like a fox and a dog, and a cow and a dog.  I imagine that he knew the English were imagining trials with humans as well.  

The difference between Denis and the English is that he got there first.   They were all filled with hubris, but Denis had a very special kind of hubris in wanting to make a name for himself first and then pursuing science.  And for the English that balance between making a name and unlocking the mysteries of nature is a little bit different.  For Denis, it’s all for self-publicity.

Denis also is aggressively flying in the face of the French elite to such a degree that, after he does these animal to animal experiments in his home on the left bank of Paris, he ends up doing a “come-one, come-all [demonstration] on Sunday at two p.m. on the banks of the Seine.  I’m going to transfuse an old, mangy dog with the blood a healthy and spritely dog.”  All of his experiments were conducted in a carnival atmosphere.  There are lots of people around, elbowing each other.   Denis takes it out of the Academy and does it on the banks of the Seine.

Lindley:  Denis seems like a self-promoter in the vein of our P.T. Barnum.

Dr. Tucker:  Yes.  In the way he describes those public experiments it is clear he was at it for the excitement and entertainment value.

Lindley:  Your description of the fear of contamination of blood and animal-human hybrids is fascinating.

Dr. Tucker:  The fear of interspecies creatures is very interesting.  The English addressed that head on.  In 1666, Robert Boyle notes a list of research questions he hoped Richard Lower would pursue.  The first one is would it be possible to nourish an animal using the blood of another animal.  And each question gets more and more hypothetical.  What would happen if we transfused the blood of a dog that liked to fetch with a dog that didn’t like to fetch, what would the animal’s disposition be?  What would happen if we transfused a furry animal with the blood of a feathered creature?  And at the end, he wondered if something tending toward a change of species could happen.  And Boyle didn’t think that would happen, but he thought it was worth pursuing the question and confirm it by experiment.  So they’re already fascinated by the possibility. 

The [French] scientists, on the other hand, don’t address the possibility head-on until much later, and instead of being curious about the possibility, they are frightened by the possibility.  And my research showed [that fear] ended up in the eventual murder of the mentally-ill man.

Lindley:  And before the transfusions of the mentally ill man, Denis treated two other people with transfusions of animal blood.  Wasn’t the first patient a child with a seizure disorder?

Dr. Tucker:  The child had a long history of fevers of unknown etiology.   Denis transfused him with lamb’s blood, and the child didn’t die, which seemed to be the criterion for success.  The second transfusion was on a butcher who provided the lambs for Denis’ first experiment.  That was purely non-therapeutic and experimental because there seemed to be no illness they were trying to cure. 

Then the English transfused Arthur Coga with lamb’s blood.  Coga was mentally ill.  Then Denis transfused his own mentally ill man, Antoine Mauroy.

Lindley:  How did Denis decide to use calf’s blood on Mauroy rather than lamb’s blood?

Dr. Tucker:  I couldn’t find any clear rationale for the shift, and all the other experiments with humans were done with sheep.  That makes sense with the “Lamb of God, blood of Christ.” And of course, the sheep is very calm.   The only thing I think about is a cow in a pasture, and the cow is a mellow creature.  But Denis gave no reason for calf’s blood.

Lindley:  How did anyone survive these transfusions before any knowledge of blood incompatibility or the need for antiseptic conditions?

Dr. Tucker:  I tried to figure this out also.  In the end, it boils down to three simple criteria when you try to figure out whether there will be a blood incompatibility reaction and how serious it will be: how much blood gets in, how fast it gets in, and whether there has been any previous exposure.  For how fast and how much, they’re using goose quills, and the problem with goose quills is that not a lot of blood is getting in.  Also, the blood is clotting so fast that we don’t know how much is getting in.  We can only speculate very little, if any [was transfused].      Immunologists will tell you that the human body can handle an assault of animal blood if it’s a small quantity and only once.   But the English were having good success with the animal models and the French Academy of Sciences did not. I couldn’t make sense of that because they were using essentially the same procedures.  It was only after looking at the manuscript minutes from the secret [French] experiments showing an inventory of the dogs that I realized Perrault was reusing his dogs so the dogs had previous exposure, which meant they were prone to incompatibility reactions. 

Lindley:  And dogs have different blood types too?

Dr. Tucker:  Absolutely.  In fact, they have even more blood types than humans.  I had veterinarians look at translations of the canine-to-canine experiments.  It’s just like the human experiments: sometimes you’re lucky and sometimes you’re not, and it all depends on how much blood gets in. 

Lindley:  It seems that some scientists in this era believed that transfusion could cure madness, and you vividly describe the Bedlam asylum (St. Bartholomew’s Hospital, London] and how English scientists sought a suitable mentally-ill subject and recruited Arthur Coga.

Dr. Tucker:  One of the explanations for mental illness in this time was that the blood would become overheated, either by illness or passion and vapors would rise to the brain and trouble the mind.   One of the first courses of action they would take was bloodletting to reduce the heat of the body by reducing the amount of the blood, or dunking in very cold baths to cool the body and reduce the vapors.  My sense is that they [used] animal blood, and particularly lamb’s blood because it was considered to be purer and more cooling than human blood.  They hoped that could actually cool down Coga’s humoral complexion and reduce his frenetic behavior.

They did not get Coga from Bedlam though.  They first tried Bedlam, and the director of Bedlam refused to provide [a subject].  I spent a lot of time trying to figure out why, and thought this may be a rare instance of bioethical hesitation, and I couldn’t find anything to document that.  I suspect that the director of Bedlam didn’t want to submit his patients to [the experiments] but, at the same time, there would be a contradiction because the patients were not treated well to begin with.

Lindley:  Weren’t mentally ill people used as subjects because they were a vulnerable population and less likely to object to experimentation?

Dr. Tucker: Look at the patients [Denis] had:  A young boy, a butcher of a lower class, and a mentally ill patient.  You have primary definitions of vulnerable populations.

Lindley:  Your writing and storytelling is very compelling.  Who do you see as your influences as a writer? 

Dr. Tucker:  The historians who have done a great job writing narratively are Natalie Zemon Davis, David Kertzer, Carl Ginsberg, Jill Lepore, and Jane Kamensky, who do compelling research and also tell great stories that brings you into this past world you’re describing. 

I outlined other nonfiction books like Seabiscuit [by Laura Hillenbrand] and Debbie Applegate’s Pulitzer-prize winning The Most Famous Man in America about Henry Ward Beecher. I figured out how they brought readers into the narrative, how the narrative pacing worked, how the stories opened.  That was invaluable to me. 

Lindley:  And you must have done extensive research for your vivid and exacting descriptions of London and Paris and medical experimentation.

Dr. Tucker:  Yes.  I found the modern equivalent of a [Paris] yellow pages [with] addresses in the 1660s of where things were bought and sold and who the owners of the shops were.  I knew that not far from Denis’ house was a woman who sold fish, and that allowed me to say that part of town would be a little bit stinky.  

I had to think about whether they had curtains or windows in carriages at the time because, as Denis moves from the Left Bank to the Right Bank.  I’m trying describe what Paris looked like and to put the reader in that carriage with Denis, and it makes a difference whether we’re looking out a window or drapes. 

Other instances aren’t front and center in the book but I had to look at.
In 1667 Louis the XIV appoints the first police chief because of the crime in Paris.  The first thing the police chief does is light the streets of Paris.  It makes a big difference if I’m moving people through the streets of Paris before or after.  I can promise you I wouldn’t want to be a darkened Parisian street in 1667.  That didn’t play out directly in how I wrote, but meticulous research on the small elements of daily life made a difference for the tone that I set for moments in the book,

Lindley:  You used a Paris city directory and other materials for the details?

Dr. Tucker:  Yes. I also worked a lot with maps for a sense not just of the city street layout and how one would move through the streets but one map gave a bird’s eye view so you could see the city from the air and into courtyards.  You have to take care that it’s historically accurate, but in the case of the Montmor estate where the blood transfusions were conducted, I actually worked with the primary documents first—everything I could get on the building down to early tax records.   It was only after I finished the first draft of my book that I had a chance to go into the Montmor estate and, interestingly enough, it was exactly as I had imagined it based on my primary research.

And I used illustrations too, whether portraits of the people [I was] describing, or images of what people of the same class are wearing in 1667. 

Lindley:  You did selected compelling illustrations of the experiments.

Dr. Tucker:  Most of those are fairly well known, and thank goodness for digital collections.  The National Library of Medicine has an extraordinary collection with modest reproduction fees and they’re all fair use so I didn’t have to pay a fortune to get access.

Lindley:  You bring a fascinating background to this book with a doctorate in French and then teaching medical history.

Dr. Tucker:  My graduate work has come in handy in writing a book like this, [such as] the ways to shape and pace a narrative and establish a voice.   I didn’t realize the extent to which I’d be reaching into that work as well to create the Blood Work narrative.

Also, my [ten-year-old] daughter became something of a writing partner for me.  When I was approaching the book deadline, I was getting nervous.  She looked at me and said, “Mommy, you need help.”  She asked, “How many pages do you have to do?  And how long do you have?”  And she went off into another room and came back about a half hour later with a calendar and told me how much I had to write each day.  And every Sunday night, she would write me in her grade school handwriting a contract that I would have to sign.  I kept careful records of how long I worked and how many pages I wrote.  And every Sunday night she would review my progress and then write me a new contract.  So she kept me on task. 

Lindley:  Can you talk about the history of transfusion after Denis?  It seems the experiments stopped not only in traditional France following the Denis case, but also in progressive England for 150 years.

Dr. Tucker:  That was a mystery I have not found a satisfying answer to.  You’d imagine that since the English were so excited about blood transfusion they would have said, “The French are just nuts and we’ll continue on our own path.”  The only thing I can figure out is that they were waiting to see the outcome of this highly publicized case, and then they were distracted by other things. 

Richard Lower observed blood in a vial and noticed that when he exposed it to air, it turned red.  They didn’t know the relationship yet between the pulmonary system and the circulatory system, and that set off a line of questioning about the contact with blood and the outside, and they weren’t yet aware of oxygen.  That’s sets off a series of other questions they begin to answer. 

That takes it to the present.  There was a recent article in Cell, the premiere journal of cell biology, [in which] they interviewed researchers who work with adult stem cell research, human embryological stem cell research, and induced pluripotent stem cell research where you use an adult stem cell and try to make it act like a pluripotent embryological stem cell.   They asked these researchers: “What does the current climate of uncertainty surrounding federal funding for stem cell research and human embryological research done to your research?”  A strong majority of the researchers for human embryological research said “I have been pulling back on what I’m doing until I know for sure what’s happening.”  But even those studying adult stem cell research—not a part of the controversial aspects—also said it had a limiting impact on what they’re doing in their labs. 

The only thing I can imagine is that technology is under scrutiny even for those people who don’t have a problem with that line of research, and it has a chilling effect on their going forward.  I suspect that may have happened as well in England.  That may be a case where the present informs our understanding of the past.   History is unsatisfying at times.

Lindley:  You describe the bloodletting of George Washington on his deathbed in 1799.  Doesn’t the belief in bloodletting go back to Galenic medicine?

Dr. Tucker:  Galenic medicine coexisted with [the discovery of] blood circulation and transfusion.  Bloodletting continued well into the nineteenth century.  When George Washington was blood let to death that’s not at odds with other understandings of the body because Galenic medicine persisted for so long. 

Lindley:  And what prompted the resurgent interest in transfusion and James Blundell’s human-to-human transfusions in about 1818?

Dr. Tucker:  That’s another instance where history is unsatisfying and we can’t always find clear cause and effect.  In 1818, James Blundell, an obstetrician in Guy’s Hospital in London, sees new mothers hemorrhaging to death and wonders if there’s something he can do.  He first injects human blood into animals and the animals die, and he realizes that interspecies blood transfusions may not be the best way to go.  He then begins the first human-to-human transfusions with the husbands of these women or staff members.  He didn’t do a lot of these, and they didn’t have great success, but that set off a line of questioning about the possibility of blood transfusion and how to stave off clotting. 

That will continue throughout the nineteenth century and will end up with the discovery of blood types by Karl Landsteiner in 1900/1901.   It’s a sublimely simple experiment that he performs as he takes blood from a variety of lab mates and puts different blood samples together and finds blood A coagulates with blood B, blood B with blood C, and he finds patterns in coagulation and proposes the idea of blood groups.  And in 1914 they discover sodium citrate as an anticoagulant on the battlefields of World War I.   The anticoagulant discovery allowed them to administer blood remotely so you don’t [need] the donor and patient hooked up together.  Then, in the 1930s, you have the first blood banks established.

So you of course have the question why the nineteenth century [advances]?  The nineteenth century is associated with another moment of huge biomedical progress.  You have the discovery of germ theory, anesthesia, and antisepsis with new ways of understanding diseases and perhaps a willingness to push against traditional ways of looking at the body and fighting illness.     

Whether in the nineteenth century or in our genomic era, blood always is at the center of debates, concerns and progress surrounding medicine.

Lindley:  You also discuss the segregation of blood supplies by race, which lasted in the South until the 1970s, representing a fear by some that transfusion recipients might take on the characteristics of another race.

Dr. Tucker:  That’s a sad but classic example of the conflicts between science and society.  It’s my understanding that at no point during discussions of whether blood should be segregated by race was there any clear-cut scientific evidence that would show differences between races.  But, for social reasons, it was considered necessary to separate the blood of whites and African-Americans.  Some of it was to help transfusions to be more accepted because there were fears about racial contagion, and better to segregate that blood to get rid of that fear, even if it is an unfounded fear. 

In the end, science and society are often at odds, and when it gets to questions about blood, it gets to deep, deep questions about identity, how firm the lines of identity are, and how blood allows us to define ourselves and define who we are and who we are not.  In the end, those definitions are quite fluid, and just as fluid as the blood itself.

Lindley:  The issue of hybrid animals even has resonance in medical research now.  You wrote that a 2006 speech by President George W. Bush was a prompt for your book.  He mentioned a need to prevent research abuses including human-animal hybrids.

Dr. Tucker:  We’re in the thick of discussions now about what the relationship between society and science should be.  Should science be allowed to move unhindered in its work to unlock natural mysteries, and to what degree are members of society stakeholders in those efforts? 

All of this gets back to how society responds to biomedical technology.   Blood transfusion was so frightening in the seventeenth century that physicians would be accomplices in a murder to make it stop.  Now it’s part and parcel of medical procedures.  You can’t find a physician now who could imagine modern medicine without the benefits of blood transfusion, and I wonder what history will say about us at 50, 100, 150 years from now as we try to navigate this rocky landscape of our own biomedical innovation.  I just hope history will be kind to us.