Many important drugs were discovered by accident through serendipity. AZT, the first drug approved to treat HIV/AIDS, was originally developed in the 1960s as a cancer drug and abandoned until it was found to be effective against HIV in the 1980s. Warfarin was discovered when scientists investigated the unexplained bleeding in cattle grazing on moldy sweet clover hay. Lithium, now used to treat bipolar disorder, was first used in the 19th century for gout but its psychiatric benefits were rediscovered in the 1940s. Cortisone was identified while researchers searched for treatments for Addison's disease and its anti-inflammatory properties helped discover its effectiveness for rheumatoid arthritis. Over 24% of

1. SERENDIPITY

2. INTRODUCTION
 Serendipity means a “Pleasant Surprise”.
 This term was coined in the year 1754 by
Horace Walpole.
 It simply refers to “making discovery, by
accident and sagacity, of things which
are not in quest of”.

3. STATISTICSS
Almost 5.8%
(84/1437) of
the drugs in
the market are
serendipitous.
Of these, 2.2%
drugs were
discovered in
the
laboratories.
3.7% were
discovered in
clinical setting.
18.3%
pharmaceutical
s in clinical use
are derivatives
of drugs that
were
discovered with
the aid of
serendipity.
Total 24.1% of
drugs can be
addressed as
serendipitous.

4. Now, let us look at some drugs
which have been discovered
accidentally…

5. 1. AZT (Azidothaymidine)
Today, if someone is diagnosed from HIV, he / she can choose from
around 41 drugs that can treat the disease. But it wasn’t always the
case. It took seven years before the drug for HIV was approved by
US FDA. As it turned out, the first drug for HIV wasn't a new
compound made form scratch, but one which had already been made
and abandoned .
AZT was originally developed in 1960s by US researchers , for
prevention of cancer. The drug was supposed to enter into the DNA
of a cancer cell and mess with its ability to replicate or spread. But,
it didn’t work when tried on mice and was put aside.

6. Cont.…
Two decades later, when AIDS came as an infectious disease, the pharmaceutical
company Burroughs Wellcome, already known for its antiviral drugs, began their
search for a potential drug, hoping to find anything that might work against this
virus. Among the drugs tested, there was a Compound S , which was remade from
original AZT drug. When it was thrown in a dish having animal cells infected with
HIV, It seemed to block the virus’s activity.
The sample was sent to US FDA and National cancer institute ,where Dr. Samuel
Broder, head of the agency realized the importance of discovery. But, before
making it available to millions of people infected, researchers had to ensure the
safety of the drug and make sure that the drug would indeed stop the HIV in some
way, even if it didn’t cure the person entirely.

7. Cont.…
But patients couldn’t wait that long and thus, under enormous public
pressure, FDA’s review of AZT was fast tracked. Scientist quickly injected
AZT in subjects. The first goal was to check the safety of the drug.
Although it showed some side effects including severe intestinal problem,
damage to immune system , nausea, vomiting, it was overall considered
safe. The second goal was to check effectiveness. This was done by a
controversial trial in which a group of 300 infected people were given
either the drug or a sugar pill randomly and made to administer for six
months. Neither the doctor, nor the patient knew whether they were on
drug or not.
After 16 weeks , wellcome announced that they were stopping the trial as
there were strong evidences that the compound was working. The results
and AZT were publically announced as a breakthrough by the company .
FDA approved the first medicine for AIDS on March 19, 1987 in a recorded
20 months. But to this day, the study remains controversial.

8. 2. WARFARIN
Warfarin is one of the most widely used anticoagulant . It is estimated that
nearly 1% of population uses it regularly. But the story of discover of warfarin
begins from prairie of Canada % Northern Plains of America in the 1920s.
Previously, healthy cattle in these areas started to die due to internal
bleeding and the cause was unknown.
As there was no nutritional deficiency or pathogen responsible for the
hemorrhage, the diet of cattle was questioned. The cows and sheep had
grazed on Sweet clove hay and bleeding mostly occurred when the climate
and the hay were moist. Such damp hay became infected by molds such as
Penicillium nigricans and Penicillium jensi.

9. Cont.
Ten years after the original outbreak of the sweet clove disease, a young
Wisconsin farmer, Ed Carlson was perplexed from loosing so many of his
prized cattle. One winter, he travelled 200 miles with a dead cow in the
back of his truck, to the local agricultural experimental station, where
investigators Karl Link and his senior student Wilhelm were working.
Carlson entered Link’s office carrying a milk can full of unclotted blood.
Wilhelm experimented with the blood that evening and found out that the
cause of hemorrhagic sickness was in fact in the sweet clove. But the
active compound had yet to be identified or even isolated.

10. Cont.…
After around 6 years, Link’s laboratory was finally able to crystalize the
substance on June 29,1939. It proved to be 3,3’-methylene-bis[4-
hydroxycoumarin] . They found out that natural coumarin became oxidized in
damp moldy hay to form a substance better known as dicoumarol. Large scale
isolation was done which was funded by Wisconsin Alumni Research
Foundation (WARF) and patent rights were given to WARF in 1941.
It’s first approved use was as a rodenticide. But it wasn’t long before Endo
laboratories produced the first version of warfarin intended for human use
under the trade name Coumadin. In the 60 years since then, warfarin has
remained a staple drug in the treatment for clotting condition.

11. 3. Lithium
Lithium compounds, also known as lithium salts, are primarily used
as a psychiatric medication. It is primarily used to treat bipolar
disorder and treat major depressive disorder that does not improve
following the use of antidepressants. In these disorders, it reduces the
risk of suicide. Lithium is taken orally.
But Lithium was first used in the 19th century as treatment for gout.
Scientists discovered that the uric acid crystals isolated from the
kidney were dissolved by lithium. However, the level of lithium
required to dissolve the urates was toxic.

12. Because of prevalent theories linking excessive use of uric acid with mental
disorders, Carl Lange in Denmark and William Alexander in NY used
Lithium to treat mania from1870 onwards. But, by the turn of 20th century,
the use of this drug for psychiatric medicine was largely abandoned.
In the year 1943, the drug was rediscovered. During the WWII, John Cade
was interned at war camp in Singapore. There he noticed a link between
certain food deficiencies and diseases related to it in his fellow patients.
After the war, he started his investigation. He collected urine samples from
people with mania, depression, schizophrenia, aiming to discover some
secretions in the urine which might explain the symptoms.

13. Cont.…
He started injecting urine in the abdominal cavity of guinea pigs in increasing doses until they
died. These urine samples proved to be lethal in animals. In further experiments, he found that
lithium carbonate, which had been used to treat gout since 19th century reduced the toxicity of
urine. He also noticed that a large dose of medicine calmed the pigs. He wondered if this could
have the same tranquilizing effect on his patients and tried it on himself to check the safety of the
drug.
He soon succeeded in controlling mania in chronically hospitalized patients with them. This was
one of the first successful applications of a drug to treat mental illness, and it opened the door for
the development of medicines for other mental problems in the next decades. But Cade’s work
went largely unnoticed at that time . In 1950, he abandoned his experiment with lithium. Today
lithium helps to stabilize the moods of millions of people with this disorder, although the dose must
be carefully controlled.

14. 4: Cortisone
Cortisones are the drugs which are used to reduce inflammation, and
treat pain, allergic, and skin disorders, as well as autoimmune diseases
such as lupus and psoriasis. But its discovery is as controversial as it
could be.
The story began with search for treatment of Addison's disease.
Dr. Kendall worked for various years on thyroid gland and discovered
thyroxin. Then he moved towards research on adrenal gland. In 1929,
Hungarian scientist Albert Gyrogyi joined Mayo clinic after isolating
hexauronic acid from cow’s adrenal gland. At the same time, Joseph
Pfiffner, PHD joined Mayo clinic to visit Dr. Kendall bringing along his
extract from adrenal gland.

15. Cont.
They treated a person suffering from Addison's disease with this extract in a painful procedure that
led to the mans recovery in 36 hours. Then they treated 48 more patients before the supply ran out.
Considering pain of treatment and shortage In supply, a better alternative was needed. Now, Dr.
Kendall dedicated his time to find cortin. In 1931, he announced that had found his component but
later had to announce that he was wrong. In 1933 same thing happened. So Mayo Clinic Board of
governors decided to appoint another scientist for purifying and characterizing cortin.
By 1936, the race to find the compound was heating up. Dr. Kendall had discovered six compounds
named from ‘A’ to ‘E’ of which compound E became most promising candidate. The effort to find
cortin really ramped up in 1939, with US on brink of war with Germany. Rumors were that cortin
could be used as a steroid which will help military pilots for a better performance. So US National
Research Council made discovery of cortin their top priority. A committee of chemists, including Dr.
Kendall led the research but failed.

16. Eventually, funding stopped but the work continued. Dr. Lewis Sarette joined Dr. Kendall to speed up
the pursuit. Dr. Sarette finally succeeded in synthesizing cortin in 1944 using oxen bile. But a new
problem arose. Addison's disease was quite rare and also military's interest had faded. So cortin was
“A treatment in search of a disease”
When Philip Hench joined Mayo clinic, he shared his observation that a person having Rheumatoid
Arthritis showed reduction in symptoms during one of his jaundice attack. He reasoned that body
must be producing an anti-inflammatory chemical which is likely broken down by liver. He called it
factor X.
Later, he and Dr. Kendall suspected that the Factor X might be the compound E and resolved . Thus
they tested the factor on Rheumatoid Arthritis patients and this led to discovery of a potent drug.

17. Reference
 https://time.com/4705809/first-aids-drug-azt/
 https://en.wikipedia.org/wiki/Lithium_(medication)
 https://www.sciencefocus.com/science/six-drugs-discovered-by-accident/
 https://www.slideshare.net/jtkvkoh/serendipity-22046246
 https://pubmed.ncbi.nlm.nih.gov/18355382/
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712976/
 http://www.the-rheumatologist.org/article/the-tortured-path-to-the-cortisone-discovery/

18. THANK YOU