What If Penicillin Was Never Discovered?

The Actual History

In September 1928, Scottish bacteriologist Alexander Fleming returned to his laboratory at St. Mary's Hospital in London after a summer vacation. While examining some of his petri dishes containing Staphylococcus bacteria, he noticed something unusual: a mold had contaminated one of the culture plates, and the bacteria surrounding this mold had been destroyed. Fleming identified the mold as belonging to the Penicillium genus and named the antibacterial substance it produced "penicillin."

Despite this groundbreaking observation, Fleming's work on penicillin remained largely undeveloped for nearly a decade. He published his findings in 1929 in the British Journal of Experimental Pathology, but struggled with isolating and stabilizing the active compound. The clinical potential of penicillin might have remained unrealized if not for the efforts of a team at Oxford University led by Howard Florey, an Australian pathologist, and Ernst Chain, a German-Jewish refugee biochemist.

Beginning in 1938, Florey and Chain revived Fleming's work on penicillin. By 1941, they had developed methods to purify penicillin in quantities sufficient for clinical trials. The first human recipient was Albert Alexander, a policeman suffering from a severe infection. His dramatic improvement demonstrated penicillin's remarkable effectiveness, though limited supply meant his treatment couldn't be completed, and he ultimately succumbed to his infection.

World War II provided both the urgency and resources to scale up penicillin production. In 1941, the United States entered the war, and American pharmaceutical companies began mass-producing penicillin using deep-tank fermentation. By D-Day in June 1944, enough penicillin was available to treat all the wounded Allied forces. Penicillin dramatically reduced deaths from infected wounds and surgical complications, saving countless lives during the war.

In 1945, Fleming, Florey, and Chain shared the Nobel Prize in Physiology or Medicine for their roles in the discovery and development of penicillin. Fleming famously cautioned about the potential for bacteria to develop resistance to penicillin if used inappropriately or in insufficient doses.

Following the war, penicillin became widely available to the public, revolutionizing the treatment of previously deadly bacterial infections such as pneumonia, rheumatic fever, syphilis, and gonorrhea. Its success sparked the "antibiotic revolution," leading to the discovery and development of numerous other antibiotics over subsequent decades.

Penicillin and its derivatives remain among the most widely used antibiotics globally. The discovery fundamentally transformed medicine, drastically reducing mortality from bacterial infections, enabling more complex surgeries, supporting cancer treatments through infection prevention, and extending average human lifespans. It established the template for modern pharmaceutical research and development, cementing the role of laboratory science in medicine.

Today, while antimicrobial resistance represents a growing challenge, penicillin and other antibiotics continue to be cornerstones of modern healthcare, with billions of lives saved through their application over the past 80 years.

The Point of Divergence

What if Alexander Fleming had never discovered penicillin in 1928? In this alternate timeline, we explore a scenario where the serendipitous contamination of Fleming's petri dish never occurred, or perhaps where Fleming—known for his somewhat disorganized laboratory practices—simply discarded the contaminated plate without noticing its significance.

Several plausible variations could have led to this divergence:

First, the specific environmental conditions that allowed the Penicillium mold to grow and produce the antibiotic effect might not have aligned. Perhaps that summer in London had slightly different temperature or humidity patterns, preventing the specific strain of Penicillium notatum from growing effectively in Fleming's laboratory during his absence.

Alternatively, Fleming's workload might have been different upon his return from vacation. In our timeline, he took the time to methodically examine old culture plates before discarding them—a practice not universal among bacteriologists. If he had been called away to urgent clinical duties or been pressured to clear his backlog more quickly, he might have discarded the plate without the careful observation that led to his discovery.

A third possibility is that Fleming might have observed the effect but misinterpreted its significance. The antibacterial properties of certain molds had been noted occasionally by other scientists before Fleming, but these observations hadn't led to clinical development. Had Fleming been in a different frame of mind, he might have noted the observation but not pursued it with the same curiosity.

Finally, institutional factors could have played a role. If St. Mary's Hospital had different research priorities or funding constraints, Fleming might have been discouraged from pursuing what appeared to be a tangential finding unrelated to his primary research focus on lysozyme and other natural antibacterial substances.

In this alternate timeline, the contaminated plate—if it ever existed—was discarded without notice, and Fleming continued his other bacteriological research without ever identifying or naming penicillin. The first naturally occurring antibiotic remained undiscovered in 1928, creating a vacuum in medical science that would dramatically alter the course of the 20th century and beyond.

The absence of Fleming's initial paper in 1929 means that Florey and Chain at Oxford never had the foundation to build upon when they began seeking antibacterial agents in the late 1930s. Without this critical starting point, the development of antibiotics would take a significantly different path.

Immediate Aftermath

World War II Medical Crisis

The most immediate and dramatic impact of penicillin's non-discovery would become apparent during World War II. In our timeline, penicillin was often described as the "miracle drug" that saved countless Allied soldiers:

Battlefield Medicine: Without penicillin, mortality rates from infected wounds would remain extremely high. Military surgeons would continue to rely primarily on wound debridement, antiseptics, and sulfanilamide (discovered in 1932) as their main weapons against infection. However, sulfanilamide's effectiveness was limited compared to penicillin, particularly against Staphylococcus infections common in traumatic wounds.
Surgical Outcomes: Surgical interventions would carry substantially higher risks. In our timeline, penicillin made previously hazardous surgical procedures much safer by preventing post-operative infections. Without this protection, military surgeons would need to be more conservative, potentially resulting in higher amputation rates and fewer attempted life-saving procedures.
Disease Outbreaks: Military encampments, with their crowded conditions, would face even greater challenges controlling outbreaks of bacterial diseases like pneumonia, meningitis, and scarlet fever. These conditions, readily treatable with penicillin in our timeline, would remain serious threats to military readiness and operations.

Wartime Research Priorities

The absence of penicillin would create a recognized gap that would almost certainly trigger concerted research efforts:

Allied Medical Research: Recognizing the desperate need for effective antibacterial agents, Allied nations would likely direct significant resources toward finding alternatives. The War Production Board in the United States might still have established special committees to tackle infectious disease control, but without penicillin as a model, their approaches would differ significantly.
Sulfonamide Focus: The sulfonamide drugs, discovered in the 1930s, would receive even greater research attention. Their limitations (narrower spectrum of activity, higher toxicity) would drive efforts to develop improved variants and entirely new synthetic antibacterial compounds.
Antiseptic Development: Research into improved antiseptics and wound management techniques would likely intensify. The work of Alexander Fleming himself might have continued to focus on antiseptics rather than antibiotics.

Medical Practice Evolution

The everyday practice of medicine would continue along pre-antibiotic lines well into the 1940s:

Sanatorium Culture: Isolation facilities for infectious diseases would remain a central feature of healthcare systems. Tuberculosis sanatoriums, in particular, would continue to be major institutions, as the first effective anti-tuberculosis antibiotics (streptomycin in 1943, followed by others) might be delayed in this timeline.
Chronic Infections: Common bacterial infections that became easily treatable in our timeline – strep throat, impetigo, otitis media, rheumatic fever, and many sexually transmitted infections – would continue to cause significant morbidity and mortality. Chronic infections would remain a much more common feature of life.
Maternal and Child Health: Puerperal fever (childbed fever) and neonatal infections would continue to claim many lives, maintaining higher maternal and infant mortality rates well into the mid-20th century.

Pharmaceutical Industry Development

The pharmaceutical landscape would evolve along markedly different lines:

Research Models: Without the penicillin model of natural product screening and fermentation-based production, pharmaceutical research might remain more chemistry-focused, emphasizing synthetic compounds like the sulfonamides.
Industry Structure: The wartime coordination between government, academic institutions, and pharmaceutical companies that characterized penicillin's development might not have occurred in the same way. The rapid expansion of pharmaceutical manufacturing capacity driven by penicillin production would likely have been delayed.
International Collaboration: The international scientific cooperation that developed around penicillin production during WWII (particularly between British and American scientists) might have taken different forms or been more limited in scope.

By the late 1940s, the absence of penicillin would create an increasingly recognized gap in medical capabilities. Public health authorities, confronting persistent infectious disease burdens that were rapidly declining in our timeline, would face mounting pressure to find alternatives. The stage would be set for a very different trajectory of medical development in the post-war era.

Long-term Impact

The Delayed Antibiotic Revolution

Without Fleming's discovery to provide the initial breakthrough, the antibiotic era would likely still have dawned, but on a significantly altered timeline:

Alternative Discovery Pathways: Soil microbiologists like Selman Waksman, who discovered streptomycin in 1943, were already conducting systematic searches for antimicrobial substances produced by soil organisms. In this alternate timeline, streptomycin or another antibiotic might have become the first clinically important antibiotic, perhaps discovered in the late 1940s or early 1950s.
Synthetic Approaches: Without the natural product model provided by penicillin, research might have focused more intensively on fully synthetic antibacterial compounds. This could have accelerated the development of antibiotic classes like the quinolones (eventually discovered in the 1960s), but delayed the discovery of many natural antibiotics like the cephalosporins and tetracyclines.
Development Timeframes: The urgency and resources associated with WWII greatly accelerated penicillin's development in our timeline. Without this catalyst, the first effective antibiotics might have taken 5-10 years longer to reach widespread clinical use, remaining expensive and limited in availability until the late 1950s.

Demographics and Public Health

The delayed introduction of effective antibiotics would have profound demographic consequences extending through the latter half of the 20th century:

Mortality Patterns: Infectious diseases would remain among the leading causes of death well into the 1960s, particularly affecting children and young adults. Life expectancy gains that occurred from the 1940s through 1960s would be significantly reduced.
Population Growth: Global population growth might have been somewhat slower, with higher childhood mortality rates persisting longer in developing regions. The demographic transition in many nations would be delayed by a decade or more.
Public Health Infrastructure: The persistent threat of bacterial diseases would necessitate continued heavy investment in sanitation, quarantine facilities, and other public health measures. This might have diverted resources from other health priorities that gained prominence in our timeline.
Disease Eradication Efforts: Programs targeting diseases like tuberculosis, yaws, and trachoma would be significantly hampered without effective antibiotics, potentially delaying their control by decades in many regions.

Medical Practice and Specialization

The entire structure of modern medicine would have evolved differently without early access to effective antibiotics:

Surgical Development: The field of surgery would have progressed more cautiously without antibiotic prophylaxis. Complex procedures like organ transplantation, cardiac surgery, and joint replacements might have been delayed by 10-20 years. Surgical specialties would develop different techniques emphasizing infection prevention.
Cancer Treatment: Modern cancer chemotherapy, which often leaves patients vulnerable to infection, would face severe limitations. Cancer treatment protocols would likely have evolved with greater emphasis on surgery and radiation, with more conservative approaches to immunosuppressive therapies.
Infectious Disease Specialization: The specialty of infectious disease might have emerged earlier and with greater prominence, focused initially on complex management of infections without antibiotics before transitioning to antibiotic stewardship when drugs finally became available.
Chronic Disease Management: The transition of medical focus from acute infectious diseases to chronic conditions like heart disease, diabetes, and cancer might have been delayed by 15-20 years, altering research priorities and clinical training.

Pharmaceutical and Biotechnology Development

The absence of penicillin would fundamentally reshape the pharmaceutical industry and biomedical research:

Industry Formation: The modern pharmaceutical industry, which grew tremendously through antibiotic development in the 1940s-1960s, would have evolved along different lines. Companies that became industry giants through early antibiotic production might never have gained their dominant positions.
Drug Development Models: Without the penicillin precedent of natural product screening followed by synthetic modification, pharmaceutical research methodologies would likely have emphasized different approaches. This might have delayed some discoveries while accelerating others through alternative research paradigms.
Biotechnology Emergence: The techniques for large-scale microbial fermentation developed for penicillin production laid important groundwork for the biotechnology industry. Without this foundation, the biotech revolution might have been delayed or taken different forms.
Infectious Disease Research: Facing ongoing challenges from bacterial infections, more research resources might have been devoted to understanding host-pathogen interactions, potentially accelerating developments in immunology and vaccine technology as alternatives to absent antibiotics.

Antibiotic Resistance Patterns

The later introduction of antibiotics would create a very different landscape of antibiotic resistance:

Resistance Timeline: When antibiotics finally entered widespread use in this alternate timeline, they would encounter bacterial populations that hadn't previously been exposed to these selective pressures. Initial effectiveness might have been higher, with resistance developing along different patterns.
Antibiotic Stewardship: Having witnessed decades of uncontrolled infectious diseases, medical authorities might have implemented stricter controls on antibiotic use from the beginning, potentially slowing the development of resistance.
Resistant Organism Profile: The specific organisms developing problematic resistance patterns would likely differ. In our timeline, early and widespread penicillin use drove the evolution of resistant Staphylococcus strains by the 1950s. In this alternate timeline, different pathogens might have emerged as the primary resistance concerns.

Present Day (2025) Scenario

By 2025 in this alternate timeline, antibiotics would certainly be an established part of medicine, but the world would look noticeably different:

Disease Burden: Bacterial infectious diseases would likely maintain a higher position among causes of morbidity and mortality, perhaps similar to our 1970s-1980s. Certain infections might remain more common and more feared.
Medical Technology: Advanced medical interventions might be more limited or carry higher risks, with procedures requiring significant immunosuppression being less routine than in our timeline.
Public Health Systems: Stronger infrastructure for managing infectious disease outbreaks might exist, with greater experience in non-antibiotic control measures potentially offering advantages during viral epidemics like COVID-19.
Antibiotic Pipeline: With a shorter history of antibiotic use, the current antibiotic development pipeline might be more robust, facing less severe resistance challenges than in our timeline.
Global Health Disparities: The gap in infectious disease control between wealthy and poor nations might be even more pronounced, with effective antibiotics remaining less accessible in resource-limited settings.

This alternate 2025 would be recognizable but distinctly different—a world where infectious disease control came later and progressed along different technological paths, reshaping medicine, public health, and countless individual lives along the way.

Expert Opinions

Dr. Marisa Fernandez, Professor of Medical History at Columbia University, offers this perspective: "Fleming's discovery of penicillin was one of history's great serendipitous moments—the kind that can't be scheduled or planned. In a timeline where that moment never occurred, I believe we would have eventually discovered antibiotics through more systematic approaches, like Waksman's soil screening program that found streptomycin. But that systematic discovery might have come a decade or more later, and without the wartime imperative to develop penicillin. The human cost would have been enormous—millions of additional deaths from bacterial infections throughout the 1940s and 50s, and a medical profession forced to continue working with frequently futile treatments for common infections. It's fascinating but sobering to consider how much of modern medicine's success rested on that initial chance observation."

Professor James Liu, Chair of Pharmaceutical Sciences at Stanford University, suggests: "The non-discovery of penicillin would have significantly altered the trajectory of pharmaceutical development. The fermentation methods developed for penicillin production became the foundation for many other biotech products. Without that model, I believe the pharmaceutical industry would have continued its focus on synthetic chemistry for much longer. We might have seen earlier development of certain synthetic antibacterials, but the entire class of beta-lactam antibiotics—penicillins, cephalosporins, carbapenems—might have been significantly delayed. The interesting question is whether this alternate pathway would have ultimately produced more or less effective treatments for resistant infections by the 21st century. A different development sequence might have led to more novel mechanisms of action rather than the incremental modifications to existing antibiotic classes that characterized much of our actual antibiotic development."

Dr. Eleanor Mbeki, Global Health Policy Advisor and former WHO Director of Infectious Disease Programs, provides this assessment: "When we consider the absence of penicillin, we must think globally. In high-income countries, the delay of effective antibiotics would have been devastating but eventually overcome. In the developing world, however, the consequences would have been catastrophic and persistent. The control of endemic bacterial diseases like yaws, trachoma, and rheumatic fever—which were dramatically reduced by mass antibiotic campaigns in the 1950s and 60s—might still be major public health challenges today. The demographic transition in many countries, with its associated economic development, might have been delayed by decades. I believe this alternate timeline would have seen even greater global health disparities than we observe in our world, with infectious disease control remaining a luxury of the wealthiest nations well into the 21st century."