Editorial
ChemMedChem doi.org/10.1002/cmdc.202400074
Chemists Invent Drugs and Drugs Save Lives
Donald F. Weaver*[a, b]
Drug molecules are the centrepiece of modern medical
therapies, providing relief from pain, combatting infections and
providing a myriad of other therapeutic effects. The quest for
new and improved drug molecules drives medical research, and
the introduction of a new drug frequently becomes a news-
worthy event capturing the attention of the press and general
public. And yet, misconceptions abound. Often, the general
public thinks that drug molecules are designed, created, and
invented by physicians rather than chemists – a misunderstand-
ing that is merely one aspect of a widespread general under-
appreciation of the role of chemistry in the health and
socioeconomic well-being of humankind. Chemistry as a
Introduction
Every day, millions of drugs, many of which are life-saving, are
dispensed worldwide, and chemistry played an integral role in
the discovery of these drugs. Drug development is very much
an integrated team effort with crucial players from both biology
and chemistry disciplines; but the design, synthesis, purification
and characterization of the drug-like new chemical entities that
ultimately become potent therapeutics are activities that lie
squarely within the domain of chemistry. Computational
chemists, medicinal chemists, organic chemists, biochemists,
chemical biologists, analytical chemists, molecular spectroscop-
ists, process chemists and others collectively contribute to the
fundamental discovery and advancement of compounds
through the drug development path. Regrettably, the integral
and crucial role of chemistry in drug discovery (and thus
medicine) is underappreciated by the general public. Moreover,
as I know from personal experience, many people even harbour
the mistaken notion that physicians invent most drugs; they do
not. Chemists invent drugs – that is why I became a chemist.
I clearly remember the day, indeed the exact moment, at
which I knew I must become a chemist – a moment which I
often recall and which has defined the entirety of my working
life. More than 40 years ago in September 1981, a heartrending
clinical event created “the moment” in time that indelibly
touched my soul, compelling me to become a chemist.
[a] D. F. Weaver
Department of Chemistry
University of Toronto,
Toronto, ON, Canada, M5S 3H6
E-mail: donald.weaver@utoronto.ca
[b] D. F. Weaver
Krembil Research Institute,
Toronto Western Hospital, University Health Network
Toronto, ON, Canada, M5T 0S8
ChemMedChem 2024, e202400074 (1 of 5)
www.chemmedchem.org
discipline needs to change this narrative. Our journals, confer-
ences, societies, mass media presence and social media post-
ings need to better inform the general public about the societal
value of chemistry. Though it is an arduous and time-
demanding process, chemists, both in academia and industry,
invent the drugs that are advancing medical care. We chemists
need to do a better job educating policy makers, politicians,
opinion leaders and fundraisers about the valuable contribu-
tions of chemistry. We need to have people know what we do,
and why we became chemists; we need to engage the general
public.
“The Moment”: A Case Report
September, 1981
I had graduated from medical school in May 1981 and was
working as a junior physician. It was late evening when my
pager notified me that I was wanted urgently on the general
medicine ward. Arriving at the ward, I learned that John (not his
real name), an 82-year old man with early-mid Alzheimer’s
disease, was “sundowning”; he had become increasingly
confused and paranoid, and had grabbed a nurse, dragging her
under his bed. He was shielding her with his arm wrapped
around her, saying that he was protecting her from enemy
soldiers. They were lying motionless beneath the bed –
“hiding”.
There are some things medical school does not teach you.
While I was considering my options, Anna, John’s wife of more
than 60 years, arrived. She lived nearby, and when notified that
John was behaving unusually, had returned to the hospital.
Upon being appraised of the situation, she sighed, tearfully
saying “He’s re-living his nightmare, that dreadful day in 1918
during the First World War.”
I asked Anna for information about this nightmare. Anna
told me that over their six decades of marriage John had
recounted this story only three times, and had struggled
emotionally each time. As I pressed her for details, she began to
relate the events of a day 63 years earlier.
September, 1918
Clearing her throat, Anna started: “It was late September 1918,
and John was stationed in northern France. Several weeks
earlier he had again been injured – knocked unconscious –
during an artillery barrage and had been recuperating behind
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Editorial
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the lines. Since he was suffering from severe headaches and
wasn’t ready for active service, they decided to use him as a
stretcher bearer during the current offensive. Their forces had
pushed the opposing line into a retreat, and he was shuttling
injured soldiers back to a field hospital. Several nurses were also
present for triaging and first aid. John was on his fourth trip
and was standing in a trench talking to a nurse, when
unexpectedly a counterattack occurred as enemy troops tried
to retake a strategic foothold. John and the nurse looked down
the trench and could see soldiers descending the parapet wall.
In an attempt to escape, John and the nurse ran in the
opposite direction, along the trench duckboards, looking for
cover or a means of escape. The nurse noticed a small storage
trench extending away from the main trench line. She grabbed
John’s arm, guiding him into this hiding spot, and the two of
them clambered to the back of the storage trench. With bloated
rats scurrying in every direction, they lay down in the mud of
the trench, she with her back against the rear wall and John in
front. To hide, they pulled some stretchers over themselves. She
wrapped her arm around John’s waist. John and the nurse
remained hidden with the lice and mice for about 10–20
minutes. Believing that all was safe, they emerged and re-
entered the trench, where they were surprised to encounter a
lone enemy soldier, who appeared to be a teenage boy,
ravenously eating from a tin of beef and searching for more
food. In the ensuing struggle, John prevailed.
September, 1981
Pausing and returning to 1981, Anna tearfully continued her
story: “John came home to me in 1919, a changed man, but I
married him, my childhood sweetheart. Thankfully, unlike many
of his comrades, he did not resort to alcohol or violence. John
and I suffered, endured, and flourished together. At first his
nightmares of that day were frequent, but by the 1930s he was
managing rather well. In the 1940s, John came across a poem
by Siegfried Sassoon.[1] John often quoted the last four lines of
this poem:
You smug-faced crowds with kindling eye
Who cheer when soldier lads march by,
Sneak home and pray you’ll never know
The hell where youth and laughter go.
John liked this poem. He said it was therapeutic for him.
From the 1950s onwards, we have had a good life together. But
that has changed recently. His Alzheimer’s disease is weakening
him, and as his mind and thought clarity declines, he is
increasingly confused and has lost the ability to suppress his
personal horrors. Trench life was harsh – cruelty flourished,
compassion suffocated, feelings were futile – John wants to
forget it, but now he can’t. He is regressing to my lonely,
frightened boy in the trenches.”
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I stood there, sombre, deeply moved. However, I at least
appreciated the problem and formulated a practical approach
to this situation. I walked into John’s room, speaking slowly and
firmly. “All is clear. The enemy is gone.” I said in as authoritative
voice as I could muster.
“It’s safe?” came John’s whispered query.
“Yes, it’s over, you’re both safe.” I replied.
John released his arm from the nurse who soon scrambled
from under the far side of the bed. I peered under the bed
directly into John’s eyes – his look of anguish and terror and
horror was truly heart-wrenching. “For Mercy’s sake, help me. I
can’t remember anything but misery, I’m scared. Is there a pill
to help me? Please find a cure, find something, help me …
please help me” implored John in a wretched and pathetic plea.
I was young, I promised him I would. I knelt beside the bed,
staring intensely into his eyes and holding his hand.
That exact moment in time – “The Moment” – has lived with
me ever since. I cannot forget his abject look of terror and his
pitiful, plaintive plea. At that precise moment, I knew I had to
do something for the treatment of dementia. I knew I had to
become a chemist.
Though the remainder of the night was quiet, I did not
sleep. That night, I wrote my first “therapeutic poem”. Since I
had no useful medications, the least I could do in the short
term was “invent” a poem (rather than a drug molecule) –
words meant to be helpful and supportive for a person in need.
My poem for John was as follows:
There are no wars to end all wars, And every war is like the last;
Scorched souls and human shells remain;
For those who fought, for all the souls
Their sacrifice and courage great,
We grieve,
We must abhor war’s carnage strife,
We must embrace each human life.
The following afternoon I returned to visit John and give
him his poem. Although he didn’t recognize me, he seemed
aware that he had experienced one of his nightmares and
wanted to talk. “My life was saved by a nurse. You know, I don’t
even remember her name. And I confronted a young soldier, a
teenager like me, but he looked even younger, maybe 16. I can
still see his face. I can still remember looking into his eyes. The
events of that day have haunted me and our marriage ever
since. And the nightmares… thought I had beaten them down,
but they’re coming back. This dementia, the confusion and the
memory loss for things I want to remember, it’s crushing me,
it’s awful… awful, awful.”
I handed John the poem. He read it. He smiled, and then he
cried. Thanking me, John grasped my hand. “It seems we
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Editorial
ChemMedChem doi.org/10.1002/cmdc.202400074
cannot cure humanity of war, but maybe you have a chance at
dementia. Please … may my misery, our misery [looking at
Anna] not have been in vain. Please help.”
After “The Moment”
Within eight months of “the moment”, I had submitted an
application to graduate school in chemistry. I felt compelled,
intellectually and emotionally, to dedicate my life to discovering
a cure for Alzheimer’s disease, and chemists are the people who
invent drugs. Though I had to complete almost two years of
“refresher” undergraduate chemistry courses, I was eventually
admitted to graduate school completing a PhD thesis that was
70 % organic chemistry and 30 % computational/theoretical
chemistry. I also completed my residency training in clinical
neurology.
About a year after “the moment”, John died of pneumonia.
At the time of his death, Anna said “John never really survived
the war … a war that inflicted him with the concussions and
horrors that probably caused his dementia … and that damn
Alzheimer’s brought back all those horrors … so cruel”. She
died several months later. With no family, children or
descendants, John and Anna had worried that his/their plea
would die with them. It will not. It has been 43 years since John
hid beneath a hospital bed (and 106 years since he hid beneath
a stretcher), but I have never forgotten “the moment”, and my
commitment to him and to myself.
I have now spent the past 30 years working as an academic
medicinal/computational chemist at three different universities,
while seeing patients at various university-affiliated teaching
hospitals. I have researched dementia, developed new theories
of Alzheimer’s disease, taught undergraduate chemistry
courses, supervised chemistry graduate students, published
papers, filed patents, wrote the third edition of a medicinal
chemistry textbook, done emergency room shifts and overnight
on-call duties for neurology, assessed patients in Memory
Disorders Clinics, and held people’s hands when I told them
they had an incurable lethal brain disease. I was an inventor of
the drug tramiprosate, one of the early agents to reach Phase III
human trials as a disease modifying drug for Alzheimer’s
disease; it failed.[2] Indeed, much of my past research has failed
– the challenge of Alzheimer’s is formidable. However, when-
ever I look into the eyes of one of my patients with Alzheimer’s,
part of me sees John staring back, and my many failures are
immediately transformed into stepping stones, guiding my
journey to use chemistry as a therapeutic weapon in the fight
against Alzheimer’s disease.
The search for a curative agent for Alzheimer’s is a human
healthcare priority. By 2030, 80 million people globally will be
living with and dying from Alzheimer’s disease; by 2050 this
number will have reached 150 million since every three seconds
someone in the world develops dementia and 70–75 % of these
people will have Alzheimer’s.[3] Though it affects millions,
Alzheimer’s is a very personal disease. It devastates a person’s
thoughts, judgments and memories – the very essence of what
makes them a unique individual human being. It is a direct
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assault on the “self”; as Auguste Deter, the first person officially
diagnosed with Alzheimer’s disease stated “Ich habe mich
verloren” (“I have lost myself”).[4] Auguste Deter’s initials are
“AD”, which is what I recall when I use the same abbreviation
for Alzheimer’s disease – it reminds me that our research is not
just about the disease as a pathological process, rather it is for
the people (and their families) living with the disease.
AD destroys cherished memories, fond family recollections,
hopes and dreams – it attacks the person. AD is a tragedy of
despair and suffering, placing a human face on the havoc
wrought at the molecular level by protein misfolding – we must
keep this face in mind while we pursue our molecular level
research: synthesizing, purifying and characterizing compounds.
We must stare this disease in the eyes and ultimately win.
Regrettably, to date the history of chemistry-driven drug
discovery for AD has been a seemingly unrelenting series of
failures. Although there were some successes in the develop-
ment of cholinesterase enzyme inhibitors (donepezil, galant-
amine, rivastigmine) as symptomatic agents, the quest for a
disease-modifying drug has yielded hundreds of
disappointments.[5] Recent trials with biologics (aducanemab,
lecanemab, donanemab) have hinted at improvement, but
these are still not curative agents.[6,7] This litany of failure that
characterizes AD drug discovery research is however not
surprising given the complexity of the challenge: the brain is
the most complex organ in the human body, and arguably AD
is the most complex disease of the brain.
For decades, AD research has been focused on the
misfolding and aggregation of proteins, principally β-amyloid
(Aβ).[8] But Aβ’s pathogenic role in AD remains debated and
contentious: some claim Aβ commands centre stage as the
principal performer; others disagree, contending that its role is
merely as a supporting actor in the pageant of pathology that
characterizes AD. The failure of multiple drugs targeting Aβ
over the past two decades has only served to deepen the doubt
surrounding the amyloid hypothesis. A comprehensive mecha-
nistic understanding of AD thus remains elusive, leading to
many different proposed disease models including proteopathy,
tauopathy, immunopathy, gliopathy, mitochondriopathy, syn-
aptopathy, membranopathy, metal dyshomeostasis – all invok-
ing different biochemistries; all striving for explanatory
dominance.[9] This complex and unresolved pathogenesis has
been a barrier to the attainment of a complete molecular-level
understanding of AD and correspondingly to the design and
implementation of an effective disease modifying therapeutic.
Nonetheless, we must remain optimistic. The history of
chemistry as an inventor of therapeutic magic bullets is long
with many small-molecule drugs having contributed to medical
progress and to improving the lives of people. The first
synthetic drug, chloral hydrate, initially synthesized in 1832, was
introduced into medicine in 1869 when Liebreich identified its
effectiveness as a neuroactive sedative-hypnotic.[10] The first
blockbuster drug was aspirin: bitter tasting salicylic acid, an
extract from the bark of the willow tree, had been used for
centuries to treat various pains and its simple chemical
modification into acetylsalicylic acid promoted widespread use;
aspirin was first synthesized in a pure, stable form by Bayer in
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Wuppertal, Germany, and registered in 1899 as a safe,
affordable analgesic.[11] The first pharmaceutical companies
were spin-offs from synthetic dye chemical industries based on
coal-tar by-products, such as aniline and p-nitrophenol, which
were derivatized in the 1870s to produce analgesics such as
phenacetin. The first major therapeutic drug class discovered in
the 20th century was the neuroactive barbiturates exemplified
by phenobarbital and thiopental, which have been employed
for more than a century as anticonvulsants and anaesthetics;
they are derivatives of barbituric acid, first synthesized in 1864
by von Baeyer when he condensed urea with diethyl malonate.
[12]
Following this strong start in the late 19th century, chemists
have invented thousands of drugs that have provided relief or
cures for many of the maladies that afflict humankind. There
have been tremendous advances against infectious disease,
cancer, as well as cardiovascular, respiratory, gastrointestinal,
endocrine, renal and musculoskeletal disease. The conspicuous
outlier on this list is neurological disease. The management of
neurodegenerative brain disorders remains a no man’s land of
pharmacological futility. Indeed, it is sometimes stated that
neurology is the “diagnose and adios” speciality because of our
therapeutic nihilism for chronic brain disease. This is regrettable
in view of the observation that the origins of medicinal
chemistry in the late 1800s arose from the invention of
promising neurologically active drugs such as chloral hydrate
and phenobarbital. Unfortunately, this momentum did not
persist throughout the 1900s. However, humans constitute the
only species that thinks about thinking, and the 21st century has
been wishfully called “Century of the Brain”. Hopefully, the
coming century will witness a new wave of effective neuro-
active drugs that will revolutionize the management of chronic,
neurodegenerative disease.
The many recent advances in chemistry-driven drug discov-
ery methods will contribute to this anticipated new wave of
neuroactive drug discovery.[13] These advancements have
included a multitude of new and improved techniques,
technologies and strategies: computer-aided drug discovery
(machine learning, artificial intelligence), in silico 3D protein
structural prediction, in silico virtual screening (structure-,
ligand- or fragment-based), virtual target profiling, molecular
docking studies, in vitro high throughput screening, combinato-
rial synthesis, diversity-oriented synthesis, activity-directed syn-
thesis, bioisosteric substitutions, scaffold hopping, structural
alerts, receptor profiling, OMICs technologies (genomics, pro-
teomics, and metabolomics) and microfluidic lab-on-a-chip
technologies. These technological advances are heralding a
new wave of therapeutic molecules for AD. In 2023, there were
187 ongoing clinical trials assessing 141 unique treatments for
AD: 28 % of candidate therapies were repurposed agents, the
remainder were new chemical entities reflecting a structurally
diverse range of chemotypes that explore a similarly diverse
array of druggable targets.[14] These new compounds and new
drug discovery methods, coupled with our ever-improving
molecular level mechanistic understanding of AD, will hopefully
translate into globally available curative agents – global
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diseases deserve global solutions, and AD is a global disease.
Given time, chemists will deliver once again.
Conclusions
Drugs are invented by chemists. Physicians administer drugs,
they usually don’t invent them. Yet, in my 40 years of seeing
patients I can attest to the fact that most members of the
general public are completely unaware that drug molecules are
invented by chemists. This needs to change. Our journals,
conferences, societies, mass media presence and social media
postings need to pull back the curtain to shed light on this
important truism. We need stories (publicly accessible, widely-
distributed, interesting, readable, engaging stories about new
drugs, new materials, new approaches to major issues) that
describe the successes of chemistry and chemists in helping to
resolve the myriad of problems confronting humankind. We
chemists need to do a better job informing policy makers,
politicians, fundraisers, donors, opinion leaders and influencers
that chemists invent the drugs that cure diseases – because
with greater acknowledgement and support will come ex-
panded opportunities to discover the drugs that improve the
lives of people, people living with diseases like AD.
As I sit here writing this guest editorial and remembering
“the moment” when I looked into John’s sorrowful eyes, a
number screams irrepressibly within my brain: 10,000. John
may have been one of my first patients with AD, but over the
past 30–40 years I have diagnosed more than 10,000 people
with dementia. And I have cured no one. This is an over-
whelming, disheartening realization with which I have difficulty
coming to terms and accepting. I vividly remember the moment
when I got down on my knees and looked into the eyes of a
man broken by a disease and pleading with me for help –
pleading with me to find a cure or anything so that other
people would not have to suffer what he is suffering. I have
spent decades as a medicinal chemist endeavouring to discover
such a drug: no curative successes yet, no drug yet, but I’m still
searching and researching. Concomitantly, I have spent decades
as a neurologist telling people that they have dementia and
that there is nothing I can do for them. I yearn for the day
when I can look into the eyes of my patients (or their families)
and tell them “I have a drug that can help you, you are not
going to die with dementia”. I could not do this when I looked
into John’s eyes 43 years ago, but hopefully I will be able to do
so in future. This is why I became a chemist. Chemists invent
drugs and drugs save lives.
Acknowledgements
DFW acknowledges salary support from the Krembil Chair in
Drug Discovery Research for Alzheimer’s Disease.
© 2024 Wiley-VCH GmbH

Editorial
ChemMedChem doi.org/10.1002/cmdc.202400074
Conflict of Interests
The author declares no relevant conflicts of interest.
Keywords: dementia · Alzheimer’s disease · medicinal
chemistry · drug design · drug discovery
[1] S. Sassoon, Suicide in the Trenches, first published 23 February 1918 in
Cambridge Magazine (cited from: M. Copp, (ed). Cambridge Poets of the
Great War: An Anthology. Fairleigh Dickinson Univ. Press. 2001, pp. 60-
61).
[2] R. Kisilevsky, W. Szarek, D. F. Weaver, A method of treating amyloidosis.
U. S. Patent No. 5,728,375, issued March 17, 1998.
[3] C. Qiu, M. Kivipelto, E. von Strauss, Dialogues Clin. Neurosci. 2009, 11,
111–128.
[4] S. Page, T. Fletcher, Dementia. 2006, 5, 571–583.
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[5] R. A. Hansen, G. Gartlehner, A. P. Webb, L. C. Morgan, C. G. Moore, D. E.
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[6] C. H. van Dyck, C. J. Swanson, P. Aisen et al., N. Engl. J. Med. 2023, 388,
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[7] J. R. Sims, J. A. Zimmer, C. D. Evans, et al., Jama 2023, 330, 512–527.
[8] J. Hardy, D. J. Selkoe, Science. 2002, 297, 353–356.
[9] F. Leng, P. Edison, Nat. Rev. Neurol. 2021, 17, 157–172.
[10] T. C. Butler, Bull. Hist. Med. 1970, 44, 168–172.
[11] H. Dreser, Pfluegers Arch. 1899, 76, 306–318.
[12] A. Baeyer, Ber. Dtsch. Chem. Ges. 1885, 18, 2269–2281.
[13] T. Athar, K. Al Balushi, S. A. Khan, Mol. Biol. Rep. 2021, 48, 5629–5645.
[14] J. Cummings, Y. Zhou, G. Lee, K. Zhong, J. Fonseca, F. Cheng, Alzheimer’s
Dementia 2023, 9, e12385.
Manuscript received: January 24, 2024
Revised manuscript received: March 2, 2024
Version of record online: ■■■, ■■■■
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EDITORIAL
The fact that drug molecules are D. F. Weaver*
designed, created and invented by
1–6
chemists remains largely unknown by
the general public – an omission Chemists Invent Drugs and Drugs
which is merely one aspect of a wide- Save Lives
spread general underappreciation of
the role of chemistry in the health
and socioeconomic well-being of
humankind. Chemistry as a discipline
needs to change this narrative. We
need to have our stories heard.