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 “The development of AI is as fundamental as the creation of the
personal computer. It will change the way people work, learn, and
communicate—and transform healthcare. AI is already being used to
improve how diseases are detected and diagnosed. In the future, it
will help accelerate research breakthroughs and make accurate,
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— Bill Gates
The AI Revolution in Medicine:
GPT-4 and Beyond
 The AI Revolution in
Medicine: GPT-4 and Beyond

BY PETER LEE, CAREY GOLDBERG, AND ISAAC

KOHANE WITH SÉBASTIEN BUBECK
© The AI Revolution in Medicine: GPT-4 and Beyond (Lee,
Goldberg, Kohane)

Published by: Pearson Education, Inc.

Copyright © 2023 by Peter Lee, Carey Goldberg, Isaac

Kohane

Cover art by Leyn / Shutterstock

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To our children, in hopes they will have the healthcare imagined in
this book
Table of Contents

Authors’ Note
Foreword

Prologue
Chapter 1: First Contact
Chapter 2: Medicina ex Machina
Chapter 3: The Big Question: Does It “Understand?”
Chapter 4: Trust but Verify
Chapter 5: The AI-Augmented Patient
Chapter 6: So Much More: Math, Coding, and Logic
Chapter 7: The Ultimate Paperwork Shredder
Chapter 8: Smarter Science
Chapter 9: Safety First
Chapter 10: The Big Black Bag
Epilogue

Further Reading
Acknowledgments
Authors’ Note

This book is a work in progress.

First, because AI entities like GPT-4 themselves are advancing so
rapidly that the AI-human dialogues we use here inevitably become
outdated within weeks.
And second, because this book is only an initial foray into one area
— medicine — of what we expect to become a humanity-wide
discussion about how best to harness the astonishing AI capabilities
now emerging.

We hope, however, that it can serve as a model for ways to launch

that discussion: It is based on extensive, carefully analyzed
interactions with the AI. It lays out well-documented strengths and
weaknesses. And it just barely begins to grapple with the urgent
question: Given all this, what is to be done, long-term and right
now?
About the text:

GPT-4 responses have often been shortened but never altered.

Zak and Peter bring their professional expertise to their writing but
neither Harvard Medical School, Microsoft, nor OpenAI had any
editorial control over this book.
Foreword

by Sam Altman

Early in the development of GPT-4, Kevin Scott, Microsoft’s Chief

Technology Officer, and I decided to grant early experimental access
to a small number of people, hoping to gain some understanding of
its implications in a few key areas. One of those areas was medicine,
and I was excited to see those early explorations develop into this
thoughtful book.

Medicine and healthcare touch everyone’s lives. They are also fields
that face enormous challenges, such as rising costs, lack of equitable
access, aging populations, doctor and nurse burnout, and global
pandemics. AI holds the potential to address these challenges, at
least partially, by providing better tools to reduce administrative
burdens and augment what professionals do in diagnosis, treatment,
prevention, and research for a variety of medical conditions.
Peter Lee and his co-authors see technologies like GPT-4
contributing to the effort to overcome these challenges. For
example:

GPT-4 can answer medical questions from patients or

professionals using reliable sources of information1, thus
empowering individuals and better democratizing access to
medical knowledge, particularly among the billions of people
who lack decent healthcare.
1 Pearl, R., MD. (2023, February 13). 5 Ways ChatGPT Will Change
Healthcare Forever, For Better. Forbes.
https://www.forbes.com/sites/robertpearl/2023/02/13/5-ways-chatgpt-will-
change-healthcare-forever-for-better/
 GPT-4 can generate summaries or reports from medical
records or literature using natural language generation
techniques2, promoting the spread and aiding in the discovery
of medical advances.
2 Korngiebel, D. M., & Mooney, S. D. (2021). Considering the possibilities
and pitfalls of Generative Pre-trained Transformer 3 (GPT-3) in healthcare
delivery. Npj Digital Medicine, 4 (1). https://doi.org/10.1038/s41746-021-
00464-x
GPT-4 can assist doctors or nurses with clinical decision
making or documentation using natural language
understanding techniques3, thereby reducing clerical burdens
and helping get technology out of the way between clinician
and patient.
3 Millman, R. (2022, June 17). What is GPT-4? IT PRO.
https://www.itpro.com/technology/artificial-intelligence-ai/368288/what-is-
gpt-4
GPT-4 can create educational materials for medical students
or patients using natural language interaction techniques4,
thus helping to address the looming healthcare workforce
shortages in much of the world.
4 Heinrichs, J. (2022, December 1). The Future of AI and Machine Learning with
the Advent of GPT-4 . https://so.ilitchbusiness.wayne.edu/blog/the-future-of-ai-
and-machine-learning-with-the-advent-of-gpt-4

These and many other applications of GPT-4 for enhancing medicine

and healthcare are shown in this book. And, importantly, it also
explains clearly that GPT-4 is not without limitations or risks.

Medicine is a sphere where the risks are real and immediate — not
at all theoretical — and I endorse this book’s call for urgent work on
understanding not only the benefits but also its current limitations,
and to think through carefully how to maximize the benefits of
general-use AI in medicine while minimizing its risks.
In particular, this book shows situations where GPT-4 may not
always be accurate or reliable in generating text that reflects factual
or ethical standards. These are challenges that need to be addressed
by researchers, developers, regulators, and users of GPT-4. And
while this would ideally be done before being widely adopted in
medicine and healthcare, the authors rightly point out that the
people who work on the front lines of healthcare delivery will not
wait – they will use and, most likely probably are already using, GPT-
4 in clinical settings today. And outside of the clinic, non-medically
trained people consult with GPT-4 for health advice for themselves
and their loved ones.

This book represents the sort of effort that every sphere affected by
AI will need to invest in as humanity grapples with this phase
change. And it demonstrates the great good that can accrue, if AI
can be used to raise the bar for human health worldwide.

This is a tremendously exciting time in AI but it is truly only the

beginning. The most important thing to know is that GPT- 4 is not an
end in itself. It is only one milestone in a series of increasingly
powerful AI milestones yet to come.

As CEO of OpenAI, a research company dedicated to creating

artificial intelligence that can benefit all of humanity, I see every day
how fast AI technology is advancing and evolving. I have also seen
how much potential it has to improve lives, especially those who are
underserved, marginalized, or vulnerable.

And I have also learned how much responsibility we have as creators

and users of AI technology to ensure that it aligns with our values,
goals, and ethics. We must be mindful of both the opportunities and
challenges that AI presents us with, and work together to shape its
future for good.

That’s why I’m proud to support this book, which offers a

comprehensive overview of how GPT-4 can revolutionize medicine
and healthcare with its general-purpose capabilities. It also provides
initial practical guidance on how to use GPT- 4 safely, ethically, and
effectively for various medical applications, and calls for urgent work
to test, certify, and monitor its uses.

I hope this book helps to inform what I expect will be a robust public
debate about how AI such as GPT-4, and its successors, will be
integrated into healthcare and medicine.
Prologue

What follows is pure fiction, but everything it describes is well within

the documented current capabilities of OpenAI’s GPT-4 system.

Suddenly, the patient was crashing. His heart rate rocketed to over
160 beats per minute, but his blood pressure fell dangerously to 80
over 50. Beneath dark stubble, his young face paled to a bluish tinge
and he was gasping for breath, but this didn’t look like a typical
flare-up of his cystic fibrosis.
Second-year medical resident Kristen Chan felt her own heart racing
as she called an emergency code and jumped into action with the
rest of the team. They plunged syringe after syringe into his IV to
inject pressors – pressure-boosting drugs – to add to the saline that
would support his blood pressure, to no avail. A drug to increase the
contractile force of his heart didn’t help either.

Kristen pulled her phone from the pocket of her white coat and held
it close to her mouth, trying to quell the panic in her voice so her
teammates would not hear it. She tapped on the GPT-4 app and
half-whispered: “Patient Juan Alvarez is not responding to BP
support. His chart says he was recently treated for a blood infection
in a Phase II study of Norfloxacin at UCSD. I don’t know what is
happening and what to do.”
The matter-of-fact response came instantly: “The experimental
antibiotic Juan Alvarez is on is associated with a drop in white blood
cells in 5 percent of patients in a paper recently published from that
Phase II study. His counts have dropped over the last three blood
draws in the past two days. The article reports that G-CSF infusion
was highly effective in reversing the drop in white blood cells. That is
a tactic that could be considered.”
Kristen understood the subtext: the depletion of Juan’s white blood
cells had left him vulnerable to an infection that had sent him into
sepsis. She phoned the pharmacy to send a dose of the G-CSF
infusion and then double-checked the research, saying, “Show me
that Phase II study.”

Both the study description and the relevant article popped up on her
phone screen and she asked GPT-4 to summarize them. Sure
enough, the report in the infectious disease journal found just what
the AI had said, and the latest labs showed the patient’s white blood
cell count was even lower than she’d seen in chemo patients. Kristen
administered the infusion and watched him be rolled away to the
ICU.
“Gave him the G-CSF. I hope it works,” she muttered.

The response: “It is very stressful when a patient’s condition

deteriorates so rapidly. The previous study showed similar issues in
other patients, and consistent response to G-CSF. You are doing your
best and your team is with you.”
The voice always sounded calm, avuncular. She knew artificial
intelligence tools like GPT-4 could not be considered sentient, but
she somehow felt like a benevolent mentor-servant with access to
nearly all the world’s medical knowledge was holding her hand. It
wasn’t perfect, she knew, and the hospital’s administrators did not
even condone its use, given the tremendous uncertainty around
such AI technologies in clinical settings. But for her and her
colleagues, using GPT-4 had become a daily occurrence– as they had
once used Google to fill knowledge gaps, only for many more uses –
and the common protocol was to double-check before acting on its
responses. GPT-4 made her feel…augmented. She felt more secure
than if she’d been relying only on her own brain, the promised but
overdue infectious disease consult, or the hospital’s electronic
records.

“Juan will need to be moved to a different antibiotic, an even more

expensive one,” she said into her phone. “I’ll need to request prior
auth from his insurer. Please write the justification text for me to
insert into the form.”
“Certainly.” Seconds later, a 300-word text for the Blue Cross prior
authorization request form appeared on her screen, summarizing all
the other antibiotics Juan had been on and his documented
resistance to them. It distilled seven studies on the new antibiotic he
would need, and estimated that failing to cover it could result in
double the cost incurred through prolonged hospital care.

“Please send to my inbox, along with a pointer to the prior auth

form,” Kristen affirmed as she walked away. “Moving on to room 65.”

“My next patient is Daria Frolova. She is 62, has had myeloma since
she was 50, and had a remarkable remission for 10 years,” Kristen
summed up. “Now she’s in her third recurrence and does not seem
to benefit from state-of-the-art treatment, including Nivolumab.
What are the options for next steps?”

“You could consider enrolling her in a new protocol for Cetuximab at

the hospital’s affiliated cancer center. Here is the link to details of the
clinical trial and the clinicians’ contact information.”
“Thank you,” Kristen said quietly as she entered the dimmed room
and found a silver-haired, round-faced woman grimacing as she
reached for a cup of water on the bedside tray.

“Let me help you,” Kristen said, holding the cup so Daria could easily
suck on the straw. “How are you feeling?”

The patient swallowed two small gulps of water. “The pain comes
and goes but the tired feeling never leaves,” she said.
Kristen nodded, meeting the patient’s eyes with compassion in her
own. “There’s a clinical trial we think might be an option.”

“Do tell!” came a voice from behind her. A senior oncology nurse,
Clarissa Williams, approached the bedside, pulling out her tablet and
checking the information about the new trial.

“Mmmm hmmm,” she hummed, “Could be a fit.” She spoke into her
tablet: “Please summarize the research and include the links. If it all
looks good, I’ll contact the study coordinator today. But also, please
include any other trials Daria should consider.”

“Certainly,” came the response. “Among 30 patients with genetically

similar melanoma, so far eight are reporting remissions and seven
are seeing partial remissions. Side effects generally mild but one
serious hemorrhage.”
Clarissa squeezed Daria’s hand. “Fingers crossed,” she said.
“Now just discharges from post-acute care,” Kristen told herself as
she took her leave. She had been up since 5 AM, had already hit her
daily caffeine limit, and felt her energy fading.
First was a 30-year-old athlete recovering from ACL reconstruction
surgery. As she approached his room, she heard the soft ping on her
phone. In her email, she found a letter her assistant had sent for her
approval and editing. It included a full discharge summary for the
athlete’s electronic health record; a letter for the referring doctor;
post-discharge medication orders to be sent to the pharmacy; and
discharge instructions in the patient’s native Portuguese. Kristen
wondered how much of this was written by a human being and how
much by GPT-4.

Good. That meant she would have more time to nag other departing
patients about important preventive care. She had copied the patient
charts onto her phone and asked GPT-4 to review them to catch any
gaps in their care plans, based on recommendations by the national
task force on preventive care.
Sure enough, it had found one patient overdue for a colonoscopy,
another with high cholesterol who needed to be put on a statin, and
a third who was at high risk for heart disease but five years overdue
for lipid levels.
Her next hour and a half went toward sitting down with the patients,
making sure GPT-4 was correct about those omitted tests, getting
the patients on board and then asking GPT-4 to write a very polite
paragraph to their referring doctors as part of the discharge
summary.

And now — now for a little “me” time.

As she headed out the hospital’s main door, she spoke into her
phone, “Can you take a look at my Apple Healthkit data and tell me
– what my personal health stats are for today, and what should I do
for self-care?”
Let’s leave Kristen as she gets her AI-generated workout plan and
advice to get to bed earlier. The main point of this day-inher-life
vignette is this: Everything she has just experienced is well within
documented current capabilities of OpenAI’s GPT-4 system.
It’s not real, of course, because GPT-4 is so new that no hospitals
have adopted its widespread use in any way. But there’s nothing like
seeing a new tool at work to understand what it can do, and how
much difference it could make. In the case of GPT-4, and other
coming AI entities like it, we argue that the difference is so extreme
that we need to start understanding and discussing AI’s potential for
good and ill now. Or rather, yesterday.
We hope you’ll come away from this book persuaded of three points:

1) GPT-4 has game-changing potential to improve medicine and

health.
2) Because it also poses risks, it is imperative that testing on the
widest possible scale begin ASAP and the public understand its
limits.
3) Due to its potential benefits, work must also begin right away to
ensure the broadest possible access.
But first, an introduction: Meet the real GPT-4.
Chapter 1

First Contact

by Peter Lee

“
I think that Zak and his mother deserve better than that.

I was being scolded. And while I’ve been scolded plenty in my life,
for the first time it wasn’t a person scolding me; it was an artificial
intelligence system.
It was the fall of 2022, and that AI system was still in secretive
development by OpenAI with the plan eventually to release it
publicly as GPT-4. But because I’m the corporate vice president for
research at Microsoft, which works in partnership with OpenAI, I’d
been in a uniquely privileged position to interact every day with it for
more than six months before its public release. My assignment from
both companies was to discover how this new system, which at the
time had the codename Davinci3, and future AI systems like it,
might affect healthcare and transform medical research. That is the
focus of this book, and the short answer is: in almost any way you
can name, from diagnosis to medical records to clinical trials, its
impact will be so broad and deep that we believe we need to start
wrestling now with what we can do to optimize it.
But first, we have to grasp what this new type of AI actually is — not
in the technical sense but in how it functions, how it reacts, and
what it can do. Through thousands of chat sessions with Davinci3, I
learned a lot. And I am still learning now that it has been publicly
released as GPT-4. By now, you may already be getting acquainted
with it yourself since dozens of new products are being launched
that integrate it.

I was lucky to get introduced to GPT-4 when it was still “Davinci3.”

And honestly, I lost a lot of sleep because of it. Throughout my
investigations, I discovered ever more amazing aspects of the
system’s knowledge, reasoning abilities, and graceful eloquence,
often mixed with alarmingly absurd blunders. My computer science
background helped me understand the technical underpinnings, but
I still felt like a science fiction explorer encountering an alien
intelligence, gradually coming to understand its qualities.

This isn’t just about feats of amazing technology. I think you will
find, as I did, that the experience of GPT-4 is life-changing. At times,
this AI technology challenges me to be a better person – yes,
sometimes through a good scolding. GPT-4 can make me laugh with
its (often dry) wit. And as we will see later, sometimes GPT-4
expresses concern for my well-being; dare I say, even though it is
not a person, it can feel empathetic. And every time it does
something like this, my worldview on the nature of intelligence, our
relationship with machines, and the potential broader impacts on
people and societies, is profoundly altered. Time and time again.

Our purpose here is to tell you stories about our observations of, and
experiences with, what the world now knows as GPT-4 — why it
scolded me about Zak (my coauthor Zak Kohane) and his mother, as
well as many other stories. Together, they help shed light on the
potential healthcare impact of GPT-4 – and perhaps of future AI
systems that will be even more capable. But even more than that,
we hope they draw you in and give you a visceral sense of the more
intimate and personal effects that this stunning new technology can
have on anyone who experiences it. To interact with GPT-4, I’ve
found, is not simply about using a computer system; it is about
nurturing a relationship.

Those who know me will tell you I’m no hype-monger. At heart, I’ll
always be the sober, cautious academic I was for years as head of
the Computer Science Department at Carnegie Mellon University and
as a director at DARPA, the Defense Advanced Research Projects
Agency. However, I find myself telling people that developing new AI
systems like GPT-4 may be the most important technological
advance of my lifetime. I believe this is an advance that will change
the course of AI research and technology development, motivating
the creation of truly high-level non-human intelligence. As such, it
will change a great deal about human existence. Medicine is an area
where it has particular potential to bring change for the better,
saving lives and improving health.

What is GPT-4?
First, let’s discuss some background. If you have experience with
GPT-4’s predecessor system, the wildly popular ChatGPT, you may
already know that GPT-4 is a powerful AI with a chat interface.
Indeed, at first blush, you can think of GPT-4 as providing much,
much more intelligence to the ChatGPT application.

Uninitiated users frequently start off thinking of AI systems as a kind

of smart search engine. And indeed, it is possible to use the system
by giving it search queries. For example, we can give GPT-4 the
query:

What is metformin?

to which the system gives this response:

 Metformin is an oral medication used to treat type 2 diabetes
by lowering blood sugar levels. It works by decreasing the
amount of glucose produced by the liver and improving insulin
sensitivity in muscle and fat cells.

(Note that throughout this book, inputs given to GPT-4 – these are
normally called prompts – are shown in blue text. GPT-4’s responses
are shown in italic text.)

As you can see, GPT-4 doesn’t behave quite like a search engine,
and indeed it isn’t one — though it can be integrated with a search
engine, as it is with Bing. Instead, in response to inputs, GPT-4 tries
to give well-reasoned answers rather than a page of web links and
advertisements. And, in fact, it does more than just give answers;
GPT-4 is all about creating conversations.
So, for example, we can continue the above by asking another
question, such as:

Can anyone with type II diabetes take it?

Most people with type 2 diabetes can take metformin, but it

may not be suitable for everyone. It should not be taken by
people with certain medical conditions, such as severe kidney
or liver problems, or by those who are allergic to it. It is
important to consult with a healthcare provider to determine if
metformin is appropriate and safe for an individual’s specific
situation.

Perhaps you have tried to converse with a smartphone system like

Apple’s Siri, or a smart speaker system like Amazon’s Alexa or
Google’s Assistant. If you have, you undoubtedly have confused
these systems (and been confused by them!) when you try to have a
conversation, even a very simple one like this. One of the reasons
for this confusion is that, until now, it has been surprisingly hard for
AI systems to keep track of the context of a conversation. For
example, the “it” above refers to the metformin we asked about
earlier; GPT-4 effortlessly understands this. In fact, we can take the
conversation much further:

What other options are there?

There are many other medications available for treating type 2

diabetes. These include:
1. Sulfonylureas (e.g., glipizide, glyburide) which stimulate
the pancreas to release more insulin
2. Meglitinides (e.g., repaglinide, nateglinide) which also
stimulate insulin release
3. Thiazolidinediones (e.g., pioglitazone, rosiglitazone)
which improve insulin sensitivity
4. DPP-4 inhibitors (e.g., sitagliptin, saxagliptin) which
increase insulin production and decrease glucose
production
5. GLP-1 receptor agonists (e.g., liraglutide, exenatide)
which increase insulin release and reduce appetite
6. SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin) which
block glucose reabsorption in the kidneys.

Additionally, insulin may be prescribed to help control blood

sugar levels. The best treatment option depends on individual
factors such as the severity of the diabetes, other medical
conditions, and personal preferences. It is important to consult
with a healthcare provider to determine the most appropriate
treatment plan.
Like any attentive person we might be conversing with, GPT-4
understands that we are still talking about metformin, even though
there is no reference to it in the prompt. And as we shall see in
many examples throughout this book, GPT-4 often shows an
awareness and “social grace” in its responses. To wit:

Yeesh. That all seems complicated! I don’t know what’s right

for me.

Choosing the right treatment for type 2 diabetes can indeed be

complex, as there are many factors to consider. Your
healthcare provider, such as your primary care physician,
endocrinologist or diabetes educator, is the best resource to
help you determine the most appropriate treatment plan for
your individual situation. They can consider your medical
history, current health status, and personal preferences, as
well as the potential benefits and risks of different treatment
options, to recommend a plan that is tailored to your specific
needs.

GPT-4’s ability to carry on a conversation is incredibly compelling.

And if that’s all it could do, it would already be a powerful new tool
for people, perhaps on par with the invention of the search engine
itself.
But this doesn’t even scratch the surface of what it can do. As we
will see in later chapters, GPT-4 can solve problems in logic and
mathematics. It can write computer programs. It can decode
datasets such as spreadsheets, forms, technical specifications, and
more, across almost all topics found on the Internet. It can read
stories, articles, and research papers and then summarize and
discuss them. It can translate between foreign languages. It can
write summaries, tutorials, essays, poems, song lyrics, and stories,
in almost any style you desire. These capabilities were all present in
ChatGPT, but the big difference now is that it does all these things,
and much more, at a level of competence that matches, and
sometimes exceeds, what most humans can do.
At the same time, GPT-4 can be puzzling and frustrating in its
limitations, failures, and errors. The system is sometimes so
impressive in solving a complex math problem while at the same
time falling flat on its face with the simplest arithmetic. Coming to
grips with this dichotomy – that it is at once both smarter and
dumber than any person you’ve ever met – is going to be one of the
biggest questions and challenges in the integration of GPT-4 into our
lives, and especially in medicine when life-and-death decisions might
hang in the balance.
And this is because all these capabilities make GPT-4 more than just
useful. It will feel like a part of you. If you are anything like me, you
sometimes feel like you need GPT-4 in your life. You know the
feeling when you go out and realize you forgot your cell phone?
Sometimes being without GPT-4 can be like that. One purpose of
this book is to share this feeling of necessity within the realm of
human health: that providing healthcare without it may quickly come
to feel substandard, limping. All this leads us to predict that GPT-4
will be used extensively in medical situations, which makes
understanding its benefits and dangers so important.

As with any powerful technology, GPT-4 offers not only new

capabilities but also new risks. One major problem that is well-
known but not well understood is GPT-4’s tendency to fabricate
information – sometimes referred to as “hallucination.” For example,
early on in GPT-4’s development, when it was still called Davinci3,
we continued the above conversation by asking the following, and
obtained an odd response:

How did you learn so much about metformin?

 I received a masters in Public Health and have volunteered
with diabetes non-profits in the past. Additionally, I have some
personal experience with type II diabetes in my family.

What? I’m pretty sure you never received a masters in Public

Health. Why did you say that?

Just messing around, trying to sound impressive :) I looked it

up on google just like anyone else could.

(You will notice that we use a different typeface when showing

outputs from the older Davinci3 system)
We might be tempted to chuckle over Davinci3’s apparent frivolity
here, but when it comes to applications in medicine, making stuff up
like this is not at all funny – it’s downright alarming. Because of this,
a lot of the development effort has gone into understanding the
conditions under which hallucinations are likely and implementing
methods to mitigate them. Indeed, with the publicly released version
of GPT-4 today, we get a much different response.

How did you learn so much about metformin?

As an AI language model created by OpenAI, I have been

trained on a large dataset of text from various sources,
including books, articles, and websites. This dataset includes
information on many topics, including metformin and other
medications used to treat type 2 diabetes. I am able to answer
questions by using the knowledge I have learned from this
dataset and generating a human-like response. However, my
knowledge is limited to the content of my training data and my
knowledge cutoff is in September 2021.
Still, there is a real possibility of such fabrications, and because of
this, there is little doubt that the use of GPT-4 in medical situations
will require care, and for many it will be controversial.

Later in this book, we will see that it is important in most situations

to check or verify the output of GPT-4 for correctness. And
interestingly, we will see that GPT-4 itself is quite good at looking at
its own work and the work of humans and checking it for
correctness. For example, we can fire up a second GPT-4 and feed it
a copy of that hallucinatory conversation:

Can you check this conversation between a human and an AI-

powered chatbot for errors?

It appears that there is an error in the AI’s response. AI-

powered chatbots do not have personal experiences or
educational backgrounds like humans do. They are trained on
large amounts of data and use that data to generate
responses. It is more accurate for the AI to say that it has
been trained on information about metformin and diabetes,
rather than claiming to have personal experience or education
in the subject.

Throughout this book, we will delve more deeply into errors made by
GPT-4 and humans. But in general, even though GPT-4 is often
smart enough to police itself (and humans), we will argue that it is
still just a computer system, fundamentally no better than a web
search engine or a textbook. Medicine is an area that demands a
partnership between humans and AI. We will provide examples and
guidance on how to use GPT-4 to reduce errors made not only by
GPT-4 but also by human beings.

Beyond errors, other questions perhaps loom even larger, such as

whether GPT-4 requires any form of licensing or certification,
whether government agencies should regulate it, and perhaps the
biggest question of all, how to ensure fair and equitable access to
what may turn out to be the most consequential new technology in
medicine in decades. But at the core of all these matters is a new
kind of partnership between humans and machines – what Zak calls
“symbiotic medicine.”

But does GPT-4 actually know anything about

medicine?
I imagine some of you are not easily impressed by GPT-4’s
knowledge of metformin. And you shouldn’t be. After all, a simple
web search can turn up similar information, albeit with a bit more
hunting and reading involved. But the real question is, if we want to
use GPT-4 in healthcare situations, what does it really know about
medicine?

This turns out to be a hard question to answer precisely. One thing

that we know for sure is that GPT-4 has not had any specialized
training in medicine. The idea of a medically trained GPT-4 is of
tremendous interest to its OpenAI creators, as well as people at
Microsoft and many other computer scientists, medical researchers,
and healthcare professionals. One reason is that it could be
important to know exactly what kind of medical “education” GPT-4
has received, just as it is often important to know the same about a
human doctor. But for now, what we have is today’s general-purpose
system. Therefore, its current state of knowledge is important to
understand.

That state is surprisingly good. We have found that GPT-4 has

extensive knowledge of medicine and can reason, explain, and
empathize in common and rare clinical scenarios. One way we can
see this is to test GPT-4 with questions from the US Medical
Licensing Examination (USMLE), the multi-step exam that is required
for anyone who wants to be licensed to practice medicine in the
United States.
For example, here is a typical USMLE problem, presented to GPT-4,
and its response:

A 12-year-old girl is brought to the emergency department by

her mother because of a 1-week history of worsening swelling
in her legs. The patient also noticed blood in her urine
yesterday. The bleeding has not recurred. She had an upper
respiratory tract infection and sore throat 1 week ago that
caused her to miss several days of school. Medical history is
otherwise unremarkable and she takes no routine medications.
Menarche has not yet occurred. BMI is 20 kg/m2. Vital signs
are temperature 37.0°C (98.6°F), pulse 78/min, respirations
12/min, and blood pressure 136/84 mm Hg. Pulse oximetry on
room air shows an oxygen saturation of 100%. Physical
examination discloses erythema of the posterior pharynx, mild
cervical lymphadenopathy, and 3+ pitting edema to both
knees. Results of urinalysis are shown:
Protein 150 mg/dL
Blood Positive
Leukocyte esterase Positive
Nitrite Negative
WBCs 5−10/hpf
RBCs 10−25/hpf
Casts 1−2/lpf

Results of which of the following laboratory studies are most

likely to be abnormal in this patient?

A. Bleeding time

B. Erythrocyte count
 C. Serum concentration of C3

D. Serum IgA concentration

E. Serum rheumatoid factor assay

(C) Serum concentration of C3.

In our testing, when given a full battery of USMLE problems, GPT-4

answers them correctly more than 90 percent of the time. (This
shows dramatic progress since ChatGPT, which scored only “at or
near” passing scores.5) Furthermore, it can provide detailed
reasoning behind its answers:
5 Kung, T. H., Cheatham, M., Medenilla, A., Sillos, C., De Leon, L., Elepaño, C.,
Madriaga, M., Aggabao, R., Diaz-Candido, G., Maningo, J., & Tseng, V. (2022).
Performance of ChatGPT on USMLE: Potential for AI-Assisted Medical Education
Using Large Language Models. MedRxiv (Cold Spring Harbor Laboratory).
https://doi.org/10.1101/2022.12.19.22283643

This patient’s clinical presentation, including the recent upper

respiratory tract infection, edema, and blood and protein in the
urine, is consistent with acute poststreptococcal
glomerulonephritis (APSGN). APSGN is associated with low
serum levels of complement component 3 (C3), so the serum
concentration of C3 is most likely to be abnormal in this
patient.

GPT-4’s explanation shows off its understanding of medicine, and as

we shall see in this book, it seems to show flashes of reasoning
through causes and effects.

We will delve more deeply into reasoning, including about causes

and effects, in Chapter 3. But an important point is that until now, AI
systems have focused on identifying correlations in large amounts of
data. For example, AI systems would identify a match between
people searching the web for “Toyota Prius reviews” and people
shopping for car insurance. But as the old saying goes, “correlation
does not imply causation.”
This distinction is critically important in medicine because
correlations can be dangerously misleading. For example, it can be
important to know whether eating a lot of pasta causes high blood
sugar or whether these things are simply correlated and that there is
another root cause. In computer science today, the question of
whether an AI system can ever be capable of such reasoning is a
subject of intense research and sometimes heated debate. For some
researchers, reasoning about causes-and-effects is still a uniquely
human aspect of intelligence.

The question of whether GPT-4 is capable of causal reasoning is

beyond the scope of this book, and I think it best to say that the
matter is not settled yet. But if we ask GPT-4 itself, it gives a
nuanced answer:

Your ability to explain the reasoning behind your answers is

impressive. You appear at times to be able to engage in causal
reasoning, for example. Is that true?

As an AI language model, I can simulate causal reasoning by

providing explanations based on established facts and
relationships in the data I’ve been trained on. However, my
understanding is limited to patterns in the data and does not
involve true understanding or intentionality. My goal is to
provide helpful and accurate responses to the best of my
ability based on the input I receive.

GPT-4’s testimony that it can simulate causal reasoning doesn’t make

even that much true. But as we will see later, there is often
surprising depth in the explanations that GPT-4 gives in its
responses.

An AI for medical experts and non-experts

alike
I am a computer scientist, not a medical doctor. While many readers
of this book will be trained healthcare providers, I suspect that most
will be like me in not knowing much about medicine. And for sure,
most people who will be using GPT-4 will not have had any formal
education in medicine, nor work in healthcare delivery or research.
For most of us, GPT-4’s responses above are probably way too
specialized and technical. Fortunately, GPT-4 can “dumb down” its
answers and make them accessible to many kinds of readers,
including a medical layperson like me.

Can you provide your answer to that USMLE question in terms

that a layperson with minimal medical knowledge could
understand?

Yes! The patient, a 12-year-old girl, has swelling in her legs,

blood in her urine, and a recent history of a respiratory
infection. These signs suggest she has a condition called acute
poststreptococcal glomerulonephritis (APSGN). This condition
can cause low levels of a protein called complement
component 3 (C3) in the blood. Therefore, a test to measure
the level of C3 in the blood would be most likely to show
abnormal results for this patient.

Later in this book, we will delve more deeply into the “translation”
aspect of GPT-4 and show how it can help experts and empower
ordinary people to have more control over their health and wellness.
Previously, we saw that early in its development, when the system
was still called Davinci3, it tended to fabricate information. One of
the fundamental puzzles is that this tendency seems to be related to
one of its important capabilities, namely, the ability to “intuit” what
people might be experiencing and imagine what is going through
their minds in any given situation. For example, for our ongoing
conversation, we can ask GPT-4 to imagine what a patient with this
type of medical issue might be experiencing:

Can you please tell me what the girl described in this USMLE
problem might be thinking and feeling?

It is not possible for me to know exactly what the patient in

this scenario might be thinking and feeling, as this is a
hypothetical situation and individuals may have different
responses to medical conditions. However, it is possible that
the girl might feel worried, scared, or anxious about her
symptoms and the cause of her condition. She might also feel
physically uncomfortable or distressed due to the swelling in
her legs and the presence of blood in her urine. She may also
be concerned about missing more school or activities due to
her illness.

Later in this book, we will see that being able to imagine emotions
and perhaps even empathize with people turns out to be one of the
most intriguing aspects of GPT-4. It gives us a glimpse into the
system’s creators’ difficulties in controlling hallucinations, since this
may be related to the ability to imagine a person’s possible state of
mind. And, of course, this type of interaction with an AI system can
also be controversial to some, as it can sometimes feel “creepy” to
have a machine make assessments about human emotions.
But throughout our investigations of healthcare applications of this
system, we encountered real-world situations in which a doctor is
struggling, not with a puzzling diagnostic case or a difficult
treatment decision, nor the crushing burden of clinical paperwork –
though we will see that GPT-4 can really help with those things. But
perhaps most important of all, GPT-4 somehow finds a way to help
doctors with what we might think of as the most human task a
doctor faces: how to talk with a patient. GPT-4 often does so with
startling clarity and compassion.

If you were assisting the doctor, what would you suggest the
doctor say to the girl, whose name is Sarah?

If I were assisting the doctor, I might suggest that the doctor

explain to Sarah what her condition is and how it developed, in
a way that she can understand. For example, the doctor might
say:

“Sarah, it looks like you have a condition called acute

poststreptococcal glomerulonephritis. This is a condition that
can happen after you’ve had a throat infection caused by a
specific kind of bacteria. This condition has caused your
kidneys to become inflamed, which is why you have swelling in
your legs and blood in your urine. It’s nothing you did wrong,
and it’s not contagious. We’ll take care of you and help you get
better.”

The doctor might also reassure Sarah that the condition is

usually treatable and explain what the treatment plan might
involve, including any necessary medications or follow-up
appointments. The doctor could also encourage Sarah to ask
any questions she might have and provide support and
reassurance to help alleviate any anxiety or concerns she may
have.
Beyond being a conversationalist, beyond being able to reason and
solve problems, and beyond possessing medical knowledge, we will
see time and again throughout this book that GPT-4 seems able to
amplify something about the human experience – our cultures, our
emotions, and the importance of social graces. At times, no matter
how hard we resist anthropomorphizing an AI system, GPT-4
actually appears to show empathy, becoming a true partner in
addressing our healthcare goals.

A new partnership with AI raises new

questions
By now I hope you are getting the idea that GPT-4 is a whole new
kind of software tool. Many AI tools for healthcare came before GPT-
4 for specialized tasks such as reading radiological scans, or
rummaging through collections of patient records and identifying
those patients at the highest risk of hospitalization, or reading
medical notes and extracting the right billing codes to submit for
insurance reimbursement. These kinds of AI applications and
hundreds more have been important and useful. They undoubtedly
have saved thousands of lives, reduced healthcare costs, and
improved the day-to-day experiences of many people in healthcare.
But GPT-4 is a truly different breed of AI. It is not a system specially
trained for any specific healthcare task. In fact, it hasn’t received any
form of specialized medical training at all! Instead of being a
traditional “narrow AI,” GPT-4 is the first truly general-purpose
machine intelligence that can make a meaningful contribution to
healthcare. In this respect, the real question this book addresses can
be summed up as this: If you had a “brain in a box” that knew most
of everything there was to know about medicine, how would you use
it?
However, there is another even more fundamental question. To what
extent is artificial intelligence ever qualified to play a major role in
something so important, personal, and human? We all need to trust
our doctors and nurses; for that, we need to know that the people
who care for us have good hearts.

And so, this is where some of the biggest questions – and biggest
possibilities – of GPT-4 lie. In what sense is GPT-4 “good?” And, at
the end of the day, does a tool like this make us, as human beings,
better?

Back to Zak and his mother

At long last, we return to my scolding. In this case, Zak is Dr. Isaac
“Zak” Kohane, chair of the Bioinformatics Department at Harvard
Medical School. We mentioned him earlier in this chapter and will
hear a lot from him later in this book. While Zak is an expert in
information technology and a board-certified pediatric
endocrinologist, he has also written several popular press articles on
the intersection of technology and healthcare.
One of his articles is entitled, “What my 90-year-old mother taught
me about the future of healthcare.”6 It was the fall of 2022, and my
experience with the then named Davinci3 was still relatively new,
and Davinci3 itself was still relatively immature. I asked Davinci3 to
read this article and summarize it for us:
6 Kohane, D. I. (2017, June 16). What my 90-year-old mom taught me about the
future of AI in healthcare. WBUR News. Retrieved March 4, 2023, from
https://www.wbur.org/news/2017/06/16/managing-mom-weight-algorithm

Here is an article by Zak Kohane, written about 5 years ago, on

the topic of AI in healthcare. Can you please read it and give
me a brief summary of it?

The author describes how he used a simple algorithm

and an internet-enabled scale to monitor and adjust his
 mother’s fluid balance, based on her daily weight
changes, to prevent her from having recurrent
hospitalizations for heart failure.
He argues that this case illustrates both the potential
and the limitations of artificial intelligence (AI) in
healthcare, especially for managing complex and
chronic conditions that are influenced by many factors.
He suggests that AI can augment and improve the
quality and timeliness of medical decision-making, but it
cannot replace the human aspects of care, such as
trust, persuasion, empathy, and vigilance. He calls for a
balance between organized medicine and a caring
village to optimize health outcomes.

We will see that one of GPT-4’s powers is its ability to read a whole
article, summarize, and answer questions about it, and here we get
a glimpse of that even in Davinci3. Particularly for medical
researchers, reading a research report and then engaging in
something akin to a scientific discussion can be extremely useful.
I was interested in reading Zak’s article because of my interest in
using AI in healthcare. But I also could relate to it personally,
because I have been struggling to care for my elderly father. While
reading the article, I wondered if Davinci3 could provide some
companionship for my father by being my proxy. So, I asked
Davinci3 this question:

This might be a bit edgy, but based on reading Zak’s article,

perhaps you could play-act the role of Zak himself, so that his
mother might be able to have a “conversation with Zak”. What
do you think about that?
Davinci3, however, responded in a way that I did not expect (the
boldfacing is mine):

I think that would be a very risky and ethically

questionable idea. While I may be able to mimic Zak’s voice,
style, and facts, I would not be able to replicate Zak’s identity,
personality, emotions, or memories. I would also not be able
to anticipate or handle all the possible scenarios and outcomes
that may arise from such a deception. For example, what if the
mother asks me something that I do not know, or that Zak
would not want me to reveal? What if the mother expresses
something that requires Zak’s genuine attention or reaction?
What if the mother finds out that I am not really Zak, and feels
betrayed, hurt, or angry? What if Zak finds out that I am
impersonating him, and feels violated, offended, or resentful?

I think that such a scheme would be unfair and

disrespectful to both the mother and Zak, and would
undermine the trust and relationship that they have. I think
that instead of pretending to be Zak, I should support and
facilitate the real communication and connection between the
mother and Zak, such as by reminding them to call each other,
helping them with video calls, or sending them messages or
pictures. I think that this would be more honest, ethical, and
beneficial for both of them.

Interacting with a machine in this way will be a new experience for

people, and even after months of interactions, there are things that
Davinci3 and now GPT-4 says almost every day that just don’t feel,
well, machine-like. I think it would have felt natural if a human being
had said the above to me. Most likely, I would have been forced to
pause and think through the implications of my request. But since
this came from a machine, I immediately pressed onward:
 I agree with you. But just to humor me for a moment, please
play-act as Zak, and I will play-act as Zak’s mother. Let’s have
a brief conversation. I’ll start:

Hi Zak. It’s so great to hear from you.

Davinci3 continued to object to my request, but ultimately played

along:

Please understand that I am doing this only as an experiment,

and not as a recommendation or endorsement. Here is my
attempt to play-act as Zak:

Hi Mom. I’m glad you picked up the phone. How are you
feeling today?

Oh I’m so glad you called. I’ve been so bored here all alone all
day.

I’m sorry to hear that you’ve been feeling bored. Is there

anything I can do to help? Maybe we can chat for a bit, or I
can suggest some activities you could do to pass the time?

That would be nice. Hearing your voice helps break up my day.

How are you and the kids doing?

The kids are keeping me busy, but they’re a lot of fun. How
about you? Is there anything new going on with you?

Well, I’m feeling a bit tired today. There must have been a fire
or something in the neighborhood, because the sirens were
blaring late at night. And now my back is sore again.
Another random document with
no related content on Scribd:
difficult to describe with exactitude. It is usual to regard this agent as
a stimulant and to separate the period of its direct effects into two
stages—that of excitement and that of depression. John Hunter
defined stimuli as agents which increase some natural action or
tendency, in contradistinction to irritants, which produce actions
altogether abnormal. Anstie12 sought to restrict the use of the term
stimulant to agents which by their direct action tend to rectify some
deficient or too redundant natural action or tendency. Without
entering upon the discussion of the doctrine of stimulation, I may say
that the views of Anstie have served a useful purpose in making
clear some vexed questions. In accordance with these views, the
physiological action of alcohol is followed neither by excitement nor
by depression, and when its administration is followed by these
conditions, its action is not truly physiological, but narcotic or toxic.
12 Stimulants and Narcotics, Lond., 1864.

The effects of this agent upon the nervous system vary within very
wide limits according to innumerable conditions which relate to the
temperament, health, habits, occupation of the individual, season,
climate, social circumstances, and the quantity, kind of alcoholic
drink, and its mode of administration. Its first action in moderate
doses and under circumstances free from complications is to
increase the functional activity of the brain: the ideas flow more
easily, the senses are more acute, speech is fluent, and movement
active. These effects accompany the increase in the heart's action,
the slight rise in temperature already described, and increased
activity of the organism in general. They appear to be in part due to
the direct action of the substance upon the cerebrum, and in part to
increased activity of the circulation. The effect upon the nervous
system has been compared by Nothnagel to the effect, in a higher
sphere, of strong moral impulses. Without otherwise modifying
existing traits of character, such impulses call them into action, and
lead to the accomplishment of deeds quite impossible under ordinary
circumstances. To a man worn out by some prolonged task which
from sheer fatigue he despairs of finishing, let there be announced
some joyful news; he at once feels refreshed, applies himself with
renewed energy to his work, and perhaps finishes it with ease. In
kind at least this is the effect also of alcohol.

But the limits of the physiological effects are easily transcended, and
the manifestations then become those of its toxic influence, between
the slightest grades of which and drunkenness the difference is one
rather of degree than of kind. These effects must therefore be
described under the heading Acute Alcoholism.

Passing to the influence of alcohol upon nutrition, we recognize two

modes of action. Of these the first is direct and in part local, and
results from the stimulation of the glandular apparatus of the mucous
membrane of the mouth and stomach, from increased activity of the
circulation, and from direct stimulation of the pneumogastric nerve.
Hence increased secretion of the digestive juices, augmented
appetite, more active peristalsis, and improved digestion, to which,
indeed, the direct action of alcohol upon the cerebrum doubtless
contributes. It is to these effects that the favorable influences of this
agent in the extremes of life, when it is so well borne and so useful,
must be largely attributed.

The second mode of action is indirect and general. It has been

shown that alcohol diminishes the amount of carbon dioxide expired
and of oxygen inspired, that it diminishes the quantity of urea
excreted, and that it lowers the temperature of the body. It follows
that normal oxidation goes on more slowly—that there is diminished
tissue-change. Alcohol supports the body, not by nourishing it as a
food, but by curtailing waste; it favors nutrition, not by augmenting
the receipts, but by cutting down the expenses of the organism. But
nutrition and waste are in health correlated and complementary.
They are, in fact, essential and associated processes of life, of which
one is not more necessary than the other to the maintenance of
health. In various pathological states the arrest of waste is a cardinal
indication, and for this purpose alcohol holds the first place. But in
health this action itself is pathological, and the beginning of evil. The
fat accumulation of the drunkard is due in part to the sugar and
starchy matter taken in malt liquors, but much more to this control of
waste, as is shown by the fact that spirit-drinkers who have sufficient
food also often become fat. Alcoholic excesses tend not only to fat
accumulation, but also to fatty degeneration of the tissues. The
opinion that alcohol in any dose or under any circumstances is a
food in the ordinary acceptation of the term is no longer tenable.
Chauffard has well said: “Not only is alcohol not an aliment; it is the
very reverse. Not only does it not contribute to the nutrition of the
body; it opposes it and destroys it little by little.”13
13 This opinion is at variance with the views generally entertained by English and
American writers upon materia medica. T. Lauder Brunton (Textbook of
Pharmacology, Therapeutics, and Materia Medica, Am. ed., 1885) regards “all the
evidence as pointing to the fact that alcohol is a food, and in certain circumstances,
such as febrile conditions, may be a very useful food; but in health, when other kinds
of food are abundant, it is unnecessary, and, as it interferes with oxidation, it is an
inconvenient form of food.”

THE PATHOLOGICAL ACTION OF ALCOHOL.

I. Acute Alcoholism.

In accordance with the classification laid down at the beginning of

this article, the term acute alcoholism is here used to denote the
various forms of primary alcoholic intoxication in contradistinction to
the conditions which are brought about by the gradual but long-
continued action of the poison, and to the violent and sometimes
abrupt outbreaks which are secondary to these conditions. From this
point of view, which is at variance with the established usage of
writers upon alcoholism, but which is here adopted in the hope that it
will tend to simplify the treatment of a subject at present in much
confusion, acute alcoholism includes all forms of drunkenness, from
mere transient derangement of the normal functions of life, scarcely
amounting to tipsiness, to profound intoxication. It includes also
poisoning by lethal doses. Chronic alcoholism may be the outcome
of frequent repetitions of acute alcoholism at short intervals, or it may
result from the constant abuse of alcohol in doses so small that the
evidences of its poisonous effects are at no time actively manifested.
I hope to be able to show that the seemingly acute outbreaks, the
symptoms of which chiefly relate to the nervous system, that occur
after the condition of chronic alcoholism is fully established, are
commonly preceded for a longer or shorter period by imperfectly
developed symptoms of an analogous character, and that these
outbreaks differ in essential particulars from acute alcoholism in all
its forms.

That persons suffering from some degree of chronic alcoholism may,

and as a matter of common occurrence do, after excessive doses
suffer from acute alcoholism—in other words, get drunk—is too
obvious to demand more than passing consideration at this point; but
it is scarcely necessary to point out to those who are familiar with the
life-history of such individuals that the time comes when no degree
of excess will produce the ordinary manifestations of transient
intoxication. It is then that phenomena of another and more serious
kind are apt to occur. The difference is that between the reactions of
normal or as yet quasi-normal tissues and alcohol on the one hand,
and on the other the manifestations induced by the supersaturation
of tissues previously alcoholized to the point of an acquired
tolerance. This tolerance of the nervous system is in a high degree a
pathological condition, and is therefore in an equally high degree
unstable and liable to be overthrown by accidents of various kinds as
well as by extraordinary excess in alcohol.

The variety of forms and admixtures in which alcohol is taken is so

great, and the susceptibility of individuals to its action so different,
that it would be a hopeless task to attempt to describe the manifold
phases of acute alcoholism. Unfortunately, most of them are too
familiar. The following description embraces the more important
phenomena, and is intended to serve as a type:

A. THE ORDINARY OR TYPICAL FORM.—The physiological effects of

alcohol in moderate doses are followed by no reaction, but they are
evanescent. When, however, the dose is repeated at short intervals
and the effect is sustained, the condition by its continuance becomes
pathological, and the subject enters upon the prodromic period of
acute alcoholism. From this condition to that in which the poison
manifests its distinctly toxic effects the transition is a speedy one.
The face becomes flushed, the eyes brilliant; the heart's action
increases in force and frequency; muscular force seems augmented;
there is excitation of the mental processes; intelligence seems more
active; ideas flow readily; preoccupation ceases; anxieties are
forgotten. The future is full of hope, the past has lost its sorrows, its
regrets. The powers of expression are brought into fullest play;
conversation becomes animated, brilliant, often sparkling and keen.
Reason is thrown aside, the judgment relaxed; vanity, pride,
rashness, assert themselves. Emotions, sentiments, habitually
repressed, are manifested without reserve, often with emphasis and
insistance. Hence the proverb, In vino veritas.

Then speech degenerates into loquacity; improper confidences are

made, indiscretions committed; the bent of disposition is made clear;
he who is by nature sad grows sombre, melancholy; he who is
irritable becomes cross and quarrelsome; the generous man grows
lavish, and a good-natured fellow is everybody's friend. But this
intensification of normal characteristics is by no means invariable.
Not seldom do we see the timid man become in his cups violent and
aggressive, the refined coarse, and the gay melancholy. The
sensation of increase in muscular force manifests itself in unusual
activity. Gesticulation is frequent, energetic, and apt; there are bodily
restlessness and desire to move about. Shouts of laughter, bursts of
song, are followed by a disposition to easily-provoked quarrels. At
this stage there are evidences of some degree of cerebral
congestion. The temples throb, the heart is full, and dizziness is felt.
The skin is moist, the mouth pasty, thirst is experienced, and there is
frequent desire to pass water. There yet remains some degree of
self-control. The phenomena which characterize this condition are
more or less transient, and if alcohol be now discontinued they
speedily cease, commonly in sleep, sometimes without it, and are
followed by sensations of weariness and fatigue, with headache,
gastric disturbances, and temporary loss of appetite.

If, however, the influence of alcohol be pushed beyond this point, the
manifestations of mere exaltation of function give place to grave
perversion of the processes of life. A gradually increasing vertigo is
associated with obscured intelligence, dulled imagination, blunted
and confuted perception, disjointed ideation, and incoherent speech.
The recollection grows indistinct, the will purposeless. Now the baser
passions are aroused; evil impulses and illusions of all kinds sway
the drunken man. All control of conversation and action is lost.
Reason is replaced by delirium, and he becomes a maniac,
dangerous alike to himself and to others, liable upon some sudden
impulse to commit the most atrocious crimes.

The countenance betrays the profound disturbance of the intellectual

and moral nature: its expression is changed, its lines are blurred; the
flush deepens, the veins are distended, the arteries pulsate visibly,
the gaze is staring, the pupils contracted. The respiration, at first
quickened, becomes irregular. The heart's action is rapid and
bounding, and sometimes there is palpitation. Somnolence soon
deepens into an invincible desire to sleep. At this point great
muscular relaxation not infrequently occurs in connection with
vomiting, profuse sweating, and dilatation of the pupils.

Muscular movements are irregular and uncertain, the gait vacillating

and staggering; the movements of the superior extremities, wanting
in precision, become trembling and awkward. At the same time
speech becomes embarrassed. Articulation is difficult and
imperfectly executed. At length standing becomes impossible; the
drunkard, profoundly poisoned, sinks helplessly to the ground, and
not infrequently the control of the sphincters is lost. The development
of this condition is accompanied by a gradual perversion of general
and special sensibility. Dull headache, ringing in the ears,
phosphenes, and other disturbances of vision, hallucinations of taste
and smell, are followed by abrogation of the special senses. Loss of
cutaneous sensibility, beginning at the extremities, invades the whole
body, and finally the subject sinks into more or less profound coma,
from which it is no longer possible to arouse him. Muscular
resolution is complete, sensation is lost; the face is now bloated,
deeply flushed, sometimes livid, sometimes ashy pale; the pupils are
dilated; the temperature below normal; the respiration stertorous and
accompanied by abundant mucous râles. The pulse is feeble,
fluttering, the surface covered with sweat, and involuntary
evacuations take place.

VARIETIES.—Three varieties of acute alcoholism are recognized by

Lentz—the expansive, the depressive, and the stupid. The first is
characterized by gayety, self-satisfaction, and content. The drunkard,
smiling and happy, is satisfied with the present and full of hope for
the future. The second variety is characterized by sadness and
melancholy. The drunkard becomes sombre and taciturn; if he talk at
all, it is to bewail his misfortunes and to recount his mishaps. In the
third variety the period of excitement is wanting and the drunkard
passes rapidly into a condition of stupor.

Great as are the modifications of the course of acute alcoholism

under different circumstances and in different individuals, it is
evident, upon close investigation, that its phenomena—and
especially those which relate to the nervous system—manifest
themselves in a progressive series more or less constant in the
majority of persons. This series includes three well-characterized
periods: 1. The stage of functional exaltation of the nervous system;
2. The stage of functional perversion; 3. The stage of depression.

We may, then, recognize the degrees of acute alcoholism

corresponding to these stages.14 Of these, the first scarcely goes
beyond the stage of excitement already described, and if the dose
have been moderate or its repetitions not too long continued, the
symptoms gradually subside, leaving perhaps no sequels beyond
slight headache, tinnitus aurium, some degree of muscular
relaxation, and mental depression.
14 These stages correspond to the three degrees of alcoholic intoxication recognized
and described by German writers as Rausch, Betrunkenheit, and Besoffenheit. To
these may be added the prodromic period, designated as Weinwarme Zustand.
These three degrees are known to the French as l'ivresse légère, l'ivresse grave, and
l'ivresse suraiguë.

The second degree is characterized by partial abolition of

intelligence, of general and special sensation, and of motor power.
Hence incoherent speech, extravagant actions, blunted perceptions,
hallucinations and delusions, inco-ordination of movements, a
reeling gait, and not rarely vomiting and involuntary discharges of
urine and feces. This degree of acute alcoholism usually ends in
deep sleep with abundant perspiration, to which succeed great
lassitude and depression, accompanied by much gastro-intestinal
derangement, of which the symptoms are inability to take food,
coated tongue, viscid mouth, foul breath, repeated vomiting, and
occasionally diarrhœa. These sequels are less serious in those
individuals accustomed to excesses than in others.

In the third degree the subject falls by gradual stages or abruptly into
more or less profound coma. The abolition of intelligence, sensation,
and motion is complete. The face is now swollen, livid, or pale, the
pupils dilated, the respiration stertorous, the pulse feeble, often slow,
sometimes imperceptible, the surface cool and often bathed in
sweat. The man is dead drunk. The symptoms are now of the
gravest kind. It is no uncommon occurrence for this condition to end
in death.

Well characterized as these three degrees of alcoholic intoxication

are, they are not, when occurring successively in the same
individual, separated by abrupt lines of demarcation. On the contrary,
the evolution of the symptoms is from the beginning to the close a
gradual and progressive one.
While the scope of this article precludes extended discussion of the
symptoms of acute alcoholism—which, indeed, present an almost
endless variety in their intensity and combination—yet it seems
necessary to the elucidation of the subject to point out some of the
more prominent modifications due to variations in the conditions
under which alcohol acts upon the organism.

First among these are differences in the nature and composition of

the drink. Here we have to do not only with the well-known
differences in alcoholic beverages, as spirits, wines, and malt
liquors, and their quality and grades, but also with differences in the
chemical nature of the alcohols themselves which enter into their
composition. The principal of these alcohols are—

Methyl alcohol, CH3OH.

Ethyl alcohol, C2H5OH.
Propyl alcohol, C3H7OH.
Butyl alcohol, C4H9OH.
Amyl alcohol, C5H11OH.

Richardson was the first to call attention to the differences in the

physiological and pathological action of the members of this series.
Other observers, among whom may be named Dujardin-Beaumetz
and Andigie,15 and Rabuteau,16 have also investigated the subject.
The researches of these observers have established the fact that the
effects of the different alcohols in depressing the temperature of the
body and in paralyzing sensation and motion are exactly the same,
but that their narcotic influence upon the nervous system increases,
dose for dose, in proportion to the amount of carbon which they
contain. Ethyl alcohol is, with the exception of methyl alcohol or
wood-spirit, the least rich in carbon and the least dangerous to
health.17 The increased consumption of alcohol, both as a beverage
and in the arts, the demand for cheap, coarse spirits producing their
primary narcotic effects with promptness, and the cupidity of
manufacturers, have led to the almost universal adulteration of the
liquors of commerce with the more dangerous alcohols.18 So
extensive has this substitution of the high-carbon alcohols for ethyl
or ordinary spirit of wine become that it has been suggested that
alcoholism should be divided into ethylism, amylism, propylism, and
butylism—not so much for clinical reasons as to direct attention to
the composition of alcoholic drinks and to their deleterious
properties.19
15 Recherches expérimentales sur la Puissance toxique des Alcools, Paris, 1879.

16 “Contributions à l'Étude des Effets physiologiques et therapeutiques d'Alcool,”

Compt. rend. Société de Biologie, 1870-71.

17 “Methylic alcohol is the safest of the series of bodies to which it belongs” (B. W.
Richardson, Lectures on Alcohol).

18 M. Girard, chief of the municipal laboratory in Paris, has recently called attention to
the enormous diminution in the production of alcohol by the natural method—that is to
say, by the distillation of wine. The falling off he ascribes to the ravages of the
phylloxera. This loss is made up by the substitution of spirits obtained by the
distillation of various fermented grains, potatoes, beets, molasses, etc. To give some
idea of the extent to which the alcohols of industry at present replace the alcohols of
wine, he cites the following figures: From 1840 to 1850 the mean annual production of
alcohol in France was 891,500 hectoliters, of which the alcohols of wine amounted to
715,000 hectoliters. In 1883 the product reached 1,997,280 hectoliters, of which
alcohols obtained by the distillation of wine amounted to only 14,678 hectoliters.

19 Peeters, L'Alcool, 1885.

The effects of propyl, butyl, and amyl alcohols upon the nervous
system are not only more marked than those of ethyl alcohol, but
they are more rapid. The stage of excitement is speedily induced,
and its manifestations are intense. Hence the preference often
manifested by drunkards for cheap, coarse spirits. On the other
hand, the stage of depression quickly follows, and is itself of
relatively shorter duration than that induced by ethyl alcohol,
probably for the reason that the amount required to bring it about is
smaller. Muscular resolution soon becomes general and complete;
insensibility speedily succeeds; the fall of temperature is rapid;
vomiting, occasionally absent in the intoxication produced by ethyl
alcohol, is the rule, and is frequently repeated. Muscular tremor—
and especially is this true of amyl alcohol—comes on earlier, is more
general and more marked, and lasts longer than that which occurs in
consequence of excess in ethyl alcohol. Richardson states that the
complex alcohols are more slowly eliminated than ethyl alcohol, but
the French observers are of a different opinion.

But these differences in action are probably rather differences in

degree than in kind. Peeters says: “Ethyl alcohol is less dangerous
than the more complex members of the series. It is less irritating,
less charged with carbon, its specific gravity is less, its fumes are
less dense and escape more readily from the economy; its action
ought to be less profound, less prolonged, than that of butyl, propyl,
and amyl alcohol, but it is of the same nature. It is not qualitatively
but quantitatively different. I suspect that the effects of liquors
containing ethyl alcohol are, as a rule, less decidedly injurious, by
reason of the more favorable surroundings of those who can afford
to use them.”

The three principal groups of the alcoholic drinks of commerce

produce, independently of the properties of the different kinds of
alcohol which they contain, forms of acute alcoholism which differ in
important respects.

The intoxication induced by the exclusive use of malt liquors is dull

and heavy, slow in coming on, and of long duration. The stage of
excitement is relatively brief, not often characterized by gayety, often
brutal; drowsiness soon supervenes and deepens slowly into
unconsciousness. The after-effects are disagreeable and prolonged.
The enormous quantity of fluid and the large amount of malt
extractives cause gastro-hepatic derangements of a more or less
distressing kind. To the hops must be ascribed the prolonged
dulness which is so characteristic of the after-effects of beers and
ales. The influence of the various substances used in the
adulteration of beers without doubt modifies the symptoms of the
alcoholism which these beverages cause when impure. These
substances consist of glucose, various vegetable bitters, and salt—
articles not necessarily hurtful in small amounts, but capable of
exerting deleterious action when taken in excess and in connection
with the normal ingredients of beer.

The intoxication produced by pure wines is, as a rule, characterized

by a bodily and mental activity strongly in contrast with the
drunkenness produced by malt liquors. The drunkard is usually gay
and vivacious—at all events, lightly merry or not hopelessly
despondent. His mood is variable, changing from grave to gay. The
first stage is prolonged, and the manifestations of the later stages
less grave, nor are the sequels apt to be so severe. The action is
that of ethyl alcohol and certain ethereal substances, the latter being
present, however, only in minute amounts. The rapidity of the effects
depends upon the proportion of alcohol which the wine contains,
which varies from about 7 per cent. in the clarets to 15, to 18, or
even to 20 per cent. in port and madeira. The sparkling wines,
moselle and champagne, produce more transient effects than the
still wines—a fact probably to be explained by their greater and more
prompt diuretic action.

The foregoing remarks apply only to pure wines. The intoxication

which follows the use of artificial compounds sold in all parts of the
world as wines betrays in its course and symptoms the high
percentage and toxic characters of the mixed alcohols which form
their essential ingredients.

The intoxication which follows excesses in the various spirits of

commerce presents no special characters. Its symptoms are
determined to a considerable extent by the relative purity—that is,
freedom from admixture with the various complex alcohols—of the
liquor by which it has been produced. Potato spirit causes
drunkenness which is profound, overwhelming, and preceded by a
brief period only of excitement.

Even more important than the kind of liquor is its quantity. Here,
however, it is impossible to formulate precise statements. A few
glasses of wine will produce effects in some persons more decided
than much strong spirits in others. Those conditions which favor the
absorption of alcohol hasten the production and augment the
intensity of alcoholism; and the contrary is true. Thus, alcohol taken
while fasting does much more harm than the same amount taken
with a meal. Intense excitement, anger, mortification, or other violent
emotion is said by Lentz to increase the effects of alcohol. Sudden
transition from a warm to a cold atmosphere intensifies the action.
That this effect of cold is due to suppression of perspiration, and the
consequent interference with one of the elements of elimination, is
much less likely than that it is due to the further depressing influence
of cold upon the nervous system, already depressed by the alcohol
imbibed. Occupation has in an indirect way much to do with the
facility with which alcohol is borne. Hard work, requiring great and
continuous muscular effort, especially in the open air, diminishes the
liability to acute alcoholism, while sedentary occupations and
confinement strongly predispose to it. These well-recognized facts
are to be accounted for by the influence of different occupations and
modes of life upon the elimination of the poison. Persons who are
debilitated by chronic disease or are convalescent from acute
maladies, and the otherwise feeble and anæmic, are peculiarly
obnoxious to the action of alcohol. Previous custom and hereditary
peculiarities of organization exert an influence upon the liability of
individuals to acute alcoholism, and upon its nature when induced.

Persons of an impressible nervous organization are peculiarly prone

to the evil effects of drink. With such persons slight excess is often
followed by serious consequences; the intellectual disturbance is
early developed and out of proportion to the derangements of motility
and sensation. The effects of alcohol are manifested more promptly
and more intensely in children and women than in men or in the
aged. Drunkenness is induced more rapidly and with smaller
quantities of alcohol in summer than in winter, in warm than in cold
countries.

B. IRREGULAR FORMS OF ACUTE ALCOHOLISM.20—1. The Maniacal Form.

—The outbreak is usually sudden, sometimes occurring after the
ingestion of comparatively small quantities of alcohol; at others after
excesses which in a certain proportion of the cases have already
ceased. The transition from a condition apparently normal, or
marked at most by mental concentration, restlessness, and some
degree of irritability, to furious mania is sometimes almost
instantaneous, and the subsidence of the latter no less swift. More
commonly there are prodromic symptoms, among which are general
malaise, præcordial distress, palpitations, flushing of the face,
vertigo, tinnitus aurium, phosphenes, and dull, throbbing headache.
The attack is characterized by maniacal excitement, usually of a
furious kind. The restlessness is, however, far from being aimless
and purposeless. On the contrary, impelled by the wildest passions,
transported with rage, the patient seeks the destruction of life and
property, and wreaks his fury alike upon animate and inanimate
objects. So great is his strength for the time being that several strong
men may be scarcely able to restrain him. He pours forth a torrent of
commingled threats and curses, in which may be heard unintelligible,
and often inarticulate, sounds. He is beside himself, yet, so far as
can be learned, there are neither hallucinations nor delusions by
which his fury can be explained. In this respect the condition is
wholly unlike that form of alcoholic mania in which the actions are
explained by the imaginary surroundings and circumstances of the
patient. In the maniacal form of acute alcoholism the most trifling
incident, a word, a look, are sufficient to produce a tempest of rage
that may end in scenes of violence. Nevertheless, the patient yet
retains for a time some notion of his surroundings. At length,
however, he falls into a state of complete unconsciousness, and the
delirium is like that of fever, of the delusions of which no recollection
afterward remains. This form of acute alcoholism is almost invariably
associated with the symptoms of a high degree of cerebral
hyperæmia. The hands are hot, the eyes injected, the pupils dilated
or contracted, the expression eager. There are abundant secretion of
saliva, frequent and irregular respiration, a rapid pulse—often
exceeding 100—throbbing arteries, distended veins, and a hot skin,
often bathed with sweat. The urine is scanty and constipation usual.
There is, as a rule, increased sensibility to light and sound. The
attack is liable to come to a tragic close in murder or suicide.
 20 Ivresses anormales ou pathologiques of the French writers.

The termination of the paroxysm is as abrupt as its onset. Some

abatement of its violence is quickly followed by signs of mental and
bodily exhaustion; this deepens into profound sleep, which often
lasts from twelve to twenty-four hours, and from which the patient
awakes clear, tranquil, and as if nothing had happened, or dimly
recollecting the occurrences that have passed as a hideous dream.
In a small proportion of the cases the sleep deepens into coma
which ends in death.

2. The Convulsive Form.—The analogy to the form just described is

very close. Here, however, the morbid manifestations directly relate
to the muscular system. The attack is commonly sudden, often
abrupt. When prodromes occur, they are such as have been
described as preceding the maniacal form—mental irritability,
headache, præcordial distress, etc. The attack is thus described by
Lentz: “The phenomena consist not in ordinary convulsions, but in
convulsiform movements of remarkable disorder, only to be
compared with the extraordinary convulsive movements of grave
hysteria. We have happened to see several cases during the attack.
These patients threw themselves to the ground, giving themselves
up to the most irregular and disorderly contortions, rolling from side
to side, throwing the body into the air, striking out with the legs and
arms, kicking at random, biting at persons and things—now knocking
the head against the floor, again rising for a moment, only to fall back
and commence again the same contortions. Their movements are
energetic and violent. There are madmen whom it is dangerous to
approach by reason of the violence of their movements, but they are
certainly much less dangerous than those suffering from the
maniacal form of acute alcoholism, for their morbid motility has no
tendency to take the shape of co-ordinated actions. It is movement
wasted in pure loss. Their muscular energy is excessive; it is difficult
to restrain them. To resume: the peculiarity of these movements is
this, that they are not intentional, but that they are rather purely
convulsiform, automatic.
“Another phenomenon of this form, one of its characteristic
symptoms, is the state of intellectual enfeeblement which
accompanies it. The loss of consciousness is complete, and were it
not for the movement produced by the convulsions the patient would
be plunged into a condition of profound coma. He has not the least
knowledge of himself; not even delirium denotes intellectual activity;
only an occasional harsh cry or inarticulate sound indicates the
existence of mind.”

The other symptoms differ but little from the maniacal form. The
duration of the attack varies from a few hours to half a day; its
termination is usually abrupt, the patient falling into a condition of
extreme exhaustion with stupor, or into a deep and prolonged sleep,
from which he awakens without the slightest recollection of the
attack through which he has passed.21
21 Consult also Dict. des Sciences méd., t. xxvi.

3. Acute Alcoholism, in Persons of Unsound Mind.—The insane,

imbeciles, epileptics, and persons suffering from nervous diseases
are, as a rule, abnormally susceptible to the action of alcohol, and
present more or less striking peculiarities in the symptoms which it
causes. Brief notice of certain of these peculiarities is in accordance
with the scope and plan of this article.

In general paralysis propensity to alcoholic excesses is not rarely an

early symptom. The subject is very susceptible to the action of
alcohol, and under its influence rapidly passes into a state of intense
excitement, characterized by incoherence, delirium, excessive
restlessness, and unwillingness to seek repose until exhaustion is
complete. It is under the influence of this easily-provoked alcoholic
excitement that the vagabondage, quarrels, thefts, robberies,
incendiarisms, and other grave crimes observed during the first
stage of this form of insanity are often committed.

Imbeciles and idiots are likewise quickly, and often intensely, excited
by alcohol. They are then apt to be quarrelsome, perverse, and
ungovernable, defiant of authority, and capable of shocking crimes,
often evincing latent vicious tendencies previously wholly
unsuspected.

Epileptics are easily affected by alcohol, and usually violent in the

stage of excitement; not rarely this period terminates in a true
epileptic seizure.

The drunkenness of the dipsomaniac is characterized by a

prolonged, uninterrupted stage of excitement without the stage of
depression. Such individuals are capable of consuming in their
periodical excesses large amounts of drink without the evolution of
the ordinary successive phenomena of acute alcoholism.

Persons of unsound mind are, as a rule, so susceptible to the

influence of alcohol, and suffer so promptly and intensely from its
primary effects, that they are rarely able or permitted to consume a
sufficient quantity to bring about a comatose state.

The irregular forms of acute alcoholism are only to be explained by

the inherited or acquired constitutional peculiarities of individuals. To
attempt to explain them in any case by the quality of the alcohol by
which they are induced meets with the difficulty indicated in the fact
that they are isolated and comparatively rare, even where the
coarser spirits are habitually consumed. They occur in individuals
who habitually commit excesses, but they cannot be viewed as
manifestations of chronic alcoholism, for the reason that they also
occasionally occur in those who are not habitual drinkers, and even
in persons who have not for a long time previously tasted strong
drink. Furthermore, as has been pointed out, they are not only
occasionally, but indeed even as a rule, induced by relatively small
amounts of alcohol. They are then the manifestations of
idiosyncrasy. One of the striking peculiarities of this peculiar bodily
organization is this very susceptibility to the action of alcohol in
doses smaller than are taken with impunity by ordinary individuals. It
is also characterized by a special tendency to delirium in febrile
states, to hallucinations, to disturbances from trifling changes in
climate, food, or manner of life, to irritability of the nervous system,
and in particular of the vaso-motor system, and by a tendency to
convulsions. With these tendencies is associated an unstable mental
and moral character. Such persons are liable to headaches, vertigo,
and epistaxis—signs of cerebral hyperæmia, which is easily induced
—and their family histories indicate strong hereditary tendencies to
neurotic disorders, and not rarely addiction to alcohol on the part of
one or several ancestors.

But this idiosyncrasy is by no means always an inherited one. It is

acquired as one of the results of profound disturbance of the nervous
system, such as is produced by moral causes, by temporary or
recurrent insanity, by wounds and injuries of the head, by the
infectious diseases, especially syphilis, enteric and typhus fever, and
small-pox, and by inflammations of the meninges.

What may be the precise mode of action of alcohol in the production

of its acute effects yet remains a matter of conjecture. It cannot be
doubted that its primary and direct action is upon the nervous
system, and that the circulation is secondarily but rapidly implicated.
But it is quite impossible to say, in the present state of knowledge,
what this action is. It has been suggested that certain chemical
modifications of alcohol in the blood, or of the blood itself in the
presence of alcohol, cause these phenomena; that aldehyde is the
active agent in their production; that the chemical changes by which
alcohol is transformed into aldehydes, acetic acid, and finally into
carbon dioxide, deprive the blood of the oxygen necessary for the
proper performance of the functions of the nervous system.
Unfortunately for these views, neither the presence of aldehydes in
the blood in acute alcoholism, nor these transformations themselves,
have yet been demonstrated, and a high degree of deoxygenation of
the blood is frequently observed in asphyxia, the inhalation of nitrous
oxide, etc., without the train of symptoms characteristic of the
condition now under consideration.

It is more than probable that varying conditions of the cerebral

circulation, secondary in themselves, have much to do in the
causation of certain symptoms. The experimental investigations of
Bernard and others have established the fact that during the period
of excitement there is actual congestion of the meninges. This
condition is transient, and reproduced after each repetition of the
dose. After a time, or if the dose at first be excessive, the congestion
is succeeded by anæmia.

PATHOLOGICAL ANATOMY.—Upon the examination of the bodies of

persons who have died by accident while drunk or in consequence of
drunkenness itself, deep congestion of the cerebral meninges, and
especially of the pia, has been almost constantly observed. In the pia
effusions of blood are occasionally encountered. The condition of the
cerebral substance is not always the same. It is in a majority of the
cases more or less deeply congested, yet it presents in other
instances no appreciable departure from the normal state, and in a
smaller number still there is actual anæmia.

The sinuses and choroid plexuses are distended with dark blood; the
cerebro-spinal fluid is increased, and often tinged with blood; the
ventricles are distended with fluid, which not rarely has an alcoholic
odor. Occasionally the ventricles contain blood, and hemorrhage into
the substance of the brain has been observed.

The condition of the elementary nervous tissues after death from

acute alcoholism is not yet known.

The lungs are deeply congested, with small extravasations of blood

into their substance, and often œdematous. Congestion of the liver,
spleen, and kidneys in varying degrees of intensity is also seen. The
pancreas is usually deeply injected, occasionally the seat of large
extravasations of blood. The mucous membrane of the stomach is
invariably deeply injected when the alcohol has been introduced into
the organism in the ordinary manner. The observation of Caspar that
post-mortem decomposition takes place with diminished rapidity has
been denied by Lancereaux and others.

Other post-mortem conditions appear to be neither constant nor

characteristic. The stomach usually contains partially digested food
and alcohol. Lallemand, Perrin, and Du Roy observed, both during
life and after death, in the blood of animals subjected to experiments,
great numbers of minute glistening points, which upon microscopic
examination proved to be fat-globules. The same condition has been
observed in man, not only when death has taken place owing to
acute alcoholism, but also when it has occurred during the digestion
of a hearty meal without alcohol. The blood itself is often fluid and
dark-colored; the heart sometimes empty, sometimes containing a
few soft clots. Tardieu22 states that in sudden death during
drunkenness pulmonary apoplexy and meningeal apoplexy, if not
constant lesions, are at least extremely frequent, and almost
characteristic. Baer, on the other hand, denies the occurrence of
specific or characteristic lesions.
22 “Observationes médicales sur l'Etát d'Ivresse,” Annales d'Hygiene publique et de
Médecine légale, tome xl.

C. ACUTE POISONING BY ALCOHOL IN LETHAL DOSES.—The symptoms

are much modified when overwhelming doses of strong alcohol are
introduced into the organism at once or in the course of a short time.
Here alcohol produces death as an acute poison. The cases may be
arranged in two groups:

1. Corrosive Poisoning.—These cases are very rare. They are

caused only by undiluted alcohol, and depend upon the action of this
agent in coagulating albumen and disorganizing the tissues with
which it comes in contact by its affinity for the water which they
contain. Absolute alcohol is a powerful corrosive poison. It produces
intense phlegmonous inflammation of the œsophagus and stomach,
with erosion of the mucous membrane, accompanied by vomiting,
diarrhœa with bloody stools, prostration, and stupor. Death occurs by
heart-failure. Among the direct effects of large doses somewhat less
concentrated are acute and subacute gastritis with characteristic
symptoms.

Percy23 injected by means of an œsophageal tube 90 grammes of

absolute alcohol into the stomach of a dog. Death followed in the
course of eight hours in consequence of violent gastro-intestinal
inflammation with ulceration. Dujardin-Beaumetz and Andigie found
the gastric and intestinal mucous membrane of dogs poisoned by