Vox Meditantis

Stepping into the laboratory of history, I meet Dr. Anna Wessels Williams (1863-1954) in the bustling corridors of imagination, where past meets present. She carries herself with quiet confidence, her hands steady from decades of microscope work, her eyes sharp behind wire-rimmed spectacles. This is the woman who helped vanquish diphtheria from New York City’s tenements and whose rapid rabies test saved countless lives for thirty years. Her story matters today because she embodied the crucial link between laboratory science and public health – a bridge we desperately need as we face modern pandemics and health inequities.

Today, I have the privilege of speaking with Dr. Anna Wessels Williams, the pioneering bacteriologist whose work at America’s first municipal diagnostic laboratory revolutionised infectious disease control. Dr. Williams, welcome. I must begin by asking about your famous preference for laboratory work over clinical practice. You once said you preferred it because “you can see the results more clearly.” What did you mean by that?

Laboratory work gives you truth, pure and simple. When I examine a culture under the microscope, the bacteria don’t lie to me. They are what they are – Corynebacterium diphtheriae or they aren’t. In clinical practice, symptoms can deceive. A child with a sore throat might have diphtheria, or scarlet fever, or simple tonsillitis. But in my laboratory, when I isolate the organism and test its toxigenicity, I know with certainty.

That certainty translates directly into lives saved. When physicians across Manhattan began distributing our diphtheria antitoxin free of charge in autumn 1894, I could see the mortality statistics change within months. Children who would have died were going home to their families. You cannot see results more clearly than that.

Your entry into medicine was sparked by tragedy – your sister Millie’s near-fatal childbirth experience. How did that moment shape your approach to scientific work?

That experience taught me that inadequate medical knowledge kills. Millie nearly died giving birth to a stillborn child, and I watched our family physician fumble with treatments that were little more than guesswork. I resigned from teaching the very next day to enrol at the Women’s Medical College.

But here’s what shaped me most: I realised that individual clinical skill, whilst vital, has limitations. One doctor can save the patients in his immediate care. A laboratory that produces effective antitoxin can save thousands. When Dr. Park and I isolated what became known as the Park-Williams strain in 1894, we weren’t just helping one child with diphtheria – we were creating the tool that would protect every child in New York City.

Let’s discuss that breakthrough. Can you walk our expert readers through the technical process of isolating the Park-Williams strain?

Certainly. We were working with throat swabs from confirmed diphtheria cases, using Loeffler’s serum medium – a mixture of beef serum and peptone broth that encouraged bacterial growth whilst inhibiting contaminants. The critical step was recognising which isolates would produce consistently high levels of toxin.

Most laboratory workers were content with any Corynebacterium diphtheriae that tested positive for toxin production. But I noticed substantial variation in toxin yields between different strains. Some produced barely detectable amounts; others were far more robust. The strain I isolated – subsequently numbered Park-Williams No. 8 – consistently produced toxin titres of 300 to 500 units per millilitre, compared to the 50 to 100 units we typically saw from other isolates.

The verification process was meticulous. We had to culture the organism repeatedly, testing its morphological characteristics – the characteristic club-shaped rods with metachromatic granules – and confirm toxin production through guinea pig inoculation tests. Each animal received measured doses of culture filtrate, and we observed for the characteristic paralysis and death that confirmed high toxin concentration.

What made this strain truly valuable for mass production was its stability. Many diphtheria strains lose their toxigenicity after repeated subculturing. The Park-Williams strain maintained consistent toxin production through hundreds of generations, making it ideal for large-scale antitoxin manufacture.

How did your methods compare to what others were doing at the time?

Most laboratories were still using Koch’s original methods, examining individual cases without considering systematic approaches to antitoxin production. The Germans had developed antitoxin, certainly, but their methods were cumbersome and expensive.

Our advantage was systematic thinking combined with municipal scale. Where European laboratories might produce antitoxin for a few dozen cases, we needed to supply every physician in New York City. That required not just a good strain, but reproducible methods that could be scaled up. We developed standardised media preparations, consistent inoculation techniques, and rigorous quality control measures that ensured every batch met minimum toxin standards.

The efficiency gains were substantial. By 1896, we could produce sufficient antitoxin for the entire city at a fraction of the cost of importing it from Europe. More importantly, we could guarantee supply during epidemic periods when European producers couldn’t meet demand.

Your rabies diagnostic work is equally impressive. Can you explain how you developed the rapid test that became the standard for thirty years?

The rabies work grew from my sabbatical at the Pasteur Institute in 1896. I went there hoping to develop a scarlet fever antitoxin, but became fascinated by their rabies research. The problem was diagnostic delay – the standard procedure took ten days or longer, and many patients died whilst waiting for results.

I began studying brain tissue from rabid animals, searching for rapid identification methods. In 1904, I discovered abnormal cells in the brain tissue – what we now call Negri bodies, though I must note that Adelchi Negri published his findings first, despite my parallel discovery.

But here’s what I contributed that was unique: I developed a staining technique that could identify these inclusion bodies within thirty minutes, not days. The key was using specific tissue stains – methylene blue and basic fuchsin in particular concentrations – that highlighted the intraneuronal inclusions clearly enough for rapid microscopic identification.

The technical advance was significant. Where the old method required lengthy tissue cultivation and animal inoculation, my method required only fresh brain tissue, proper staining, and competent microscopy. A trained technician could provide definitive results in half an hour.

What undocumented techniques or insights can you share that didn’t make it into the official record?

Ah, the tricks of the trade! For diphtheria isolation, I learned that the timing of specimen collection was crucial but rarely mentioned in protocols. Swabs taken early in the morning, before the patient had eaten or drunk anything, yielded far better bacterial recovery. Food particles and debris interfered with culture growth.

For rabies diagnosis, temperature control was absolutely critical. Brain tissue had to be kept cold but not frozen – between 2 and 4 degrees Celsius. Freezing destroyed the cellular architecture we needed to see the Negri bodies clearly. I developed a simple transport system using ice chips wrapped in oiled cloth that maintained proper temperature for hours.

There’s also the matter of experience that no textbook can teach. After examining thousands of cultures, you develop an eye for suspicious colonies. A slight difference in lustre, a subtle variation in morphology – these become second nature. Many of my most significant isolations came from pursuing cultures that looked “not quite right” to me, though they appeared normal to others.

You worked in public health rather than prestigious academic institutions. How did that affect recognition of your work?

Academic medicine values theoretical advancement; public health values practical results. My work saved thousands of lives, but it wasn’t considered as intellectually prestigious as, say, discovering a new metabolic pathway.

The collaborative nature of public health work also meant sharing credit. The Park-Williams strain bears both our names, though I did the isolation work. I was content with that arrangement – Dr. Park provided laboratory direction and institutional support that made the work possible. But the scientific establishment has always been more comfortable crediting individual genius than team effort.

Working in municipal laboratories also meant our research was viewed as “service” rather than “science.” Universities publish papers; public health laboratories save lives. The academic world has never quite known how to value the latter.

Looking back, is there anything you would have done differently?

I should have published more aggressively. I was cautious about claiming priority – too cautious, perhaps. With the rabies work, I waited to verify my findings thoroughly whilst Negri rushed to publication. Scientific credit often goes to the swift, not necessarily the thorough.

I also underestimated the importance of mentoring other women in the field. I was so focused on the work itself that I didn’t fully appreciate my role as a pathbreaker. More deliberate effort to bring other women into bacteriology might have created lasting change in the field’s demographics.

But I don’t regret choosing public health over academic medicine. Academic research can be beautiful, but it often remains abstract. Public health research becomes policy, becomes practice, becomes lives saved. That’s a more immediate contribution to human welfare.

How do you see your work connecting to modern pandemic responses and global health initiatives?

The principles remain identical! Rapid diagnostic testing, systematic data collection, coordinated public health response – these were as essential in 1894 as they are today. My rabies test took thirty minutes; modern PCR tests can detect COVID-19 in hours. The technology changes; the imperative for speed doesn’t.

Municipal laboratory systems like ours pioneered the infrastructure modern public health relies upon. We established protocols for specimen collection, standardised testing procedures, and systematic reporting that formed the backbone of disease surveillance. Today’s global health initiatives are essentially our New York model scaled up worldwide.

The collaborative approach matters enormously. Modern pandemic response requires coordination between laboratory scientists, clinicians, epidemiologists, and policymakers – exactly the multidisciplinary teams we built in the 1890s. Individual brilliance isn’t enough; you need institutional commitment and systematic implementation.

What advice would you give to women and other marginalized groups entering STEM fields today?

Master your craft beyond any possible criticism. I spent years perfecting laboratory techniques until my competence was unquestionable. When colleagues doubted my conclusions, they could never doubt my methods.

But also remember that technical excellence alone isn’t sufficient. You must communicate your work effectively, claim credit appropriately, and build alliances strategically. Science is ultimately a human enterprise, and human dynamics matter as much as laboratory skills.

Most importantly, don’t let others define the value of your contributions. Academic prestige is one measure of scientific worth, but it’s not the only one, and perhaps not the most important one. Public health may lack glamour, but it has immediate moral purpose. Choose work that aligns with your values, not just your ambitions.

Finally, Dr. Williams, how would you like to be remembered?

As someone who proved that laboratory science could serve social justice. The children of Manhattan’s tenements had the same right to protection from diphtheria as the children of Fifth Avenue. My work helped make that protection available to all, regardless of their families’ ability to pay.

Science in service of humanity – that was my creed then, and I hope it remains my legacy now. The bacteria don’t care about your social class or your bank account. Neither should the scientists who study them.

The laboratory work continues, and it matters now more than ever. Keep at it.

Letters and emails

Our interview with Dr. Anna Wessels Williams has sparked tremendous interest from our global community of scientists, historians, and curious minds eager to explore her groundbreaking contributions further. We’ve selected five compelling letters and emails from readers across four continents who want to ask her more about her life, her work, and what she might say to those walking in her footsteps today.

Amina Okafor, 34, Public Health Epidemiologist, Lagos, Nigeria
Dr. Williams, you mentioned that your diphtheria work was driven by the need to supply ‘every physician in New York City.’ I’m curious about the logistics of that – how did you actually distribute your antitoxin to ensure it reached the poorest neighbourhoods? In my work across Lagos, we still struggle with last-mile delivery of diagnostics and treatments to underserved communities. What systems did you put in place to guarantee equitable access, and do you think municipal laboratories today could learn from your distribution model?

Miss Okafor, your question strikes at the heart of what made our work revolutionary – not just the science, but the systematic approach to ensuring every child, regardless of station, had access to life-saving treatment. The logistics were indeed formidable, and I’m pleased to share what we learned.

Our distribution system evolved from necessity. In 1894, when we first began producing antitoxin, New York’s diphtheria mortality was catastrophic – 2,870 deaths that year alone, concentrated overwhelmingly in the tenements. We couldn’t simply produce effective antitoxin and hope it reached those who needed it most. We had to engineer the delivery.

Dr. Biggs established what we called “depot stations” – strategically placed throughout the five boroughs where physicians could collect diagnostic kits and antitoxin supplies. But here’s the crucial innovation: we didn’t wait for physicians to come to us. We mapped diphtheria cases by neighbourhood and placed our depots where they were most needed. By 1906, we operated 318 antitoxin stations across all boroughs, distributing over $104,000 worth of free treatment annually.

The real breakthrough was our relationship with the settlement houses and charitable organisations already working in immigrant communities. These groups understood the cultural barriers we faced – families who feared government intervention, mothers who couldn’t read English notices, fathers who couldn’t afford to miss work to bring children for treatment. We trained settlement workers to recognise diphtheria symptoms and provided them with supplies to refer cases immediately to our stations.

We also implemented what might today be called “community health workers.” These were often neighbourhood women, sometimes former patients’ mothers, who we trained to distribute information about diphtheria prevention and treatment in Italian, Yiddish, Polish – whatever languages were needed in each district. They were paid modest stipends from our budget, making them perhaps America’s first municipal community health outreach workers.

Transportation presented another challenge. Many tenement families lacked funds for omnibus fare to reach treatment centres. We established a voucher system with local churches and charitable societies – they could issue transport vouchers that we would reimburse. More importantly, we equipped our depot stations with basic treatment supplies so neighbourhood physicians could provide emergency care without requiring families to travel across the city.

The quarantine placard system, whilst sometimes stigmatising, served a vital epidemiological function. When we posted diphtheria notices on tenement buildings, we simultaneously deployed health visitors to every dwelling in that building, providing free throat examinations for all residents and prophylactic antitoxin for those showing early symptoms. This prevented the wholesale spread that had previously devastated entire tenement blocks.

Quality control was essential for maintaining community trust. Every batch of antitoxin was tested not just for potency, but for safety – we couldn’t afford a single adverse reaction that might undermine confidence in immigrant communities already suspicious of government medicine. Our laboratory maintained detailed records of every dose distributed, including patient outcomes when possible.

The financial model proved sustainable precisely because we served all economic classes. Wealthy families paid standard rates for antitoxin, subsidising free distribution to the poor. This cross-subsidy approach meant our programme could expand without requiring additional municipal appropriations – always a political necessity.

What you’re experiencing in Lagos – the last-mile delivery challenge – was equally formidable in 1890s Manhattan. Distance wasn’t measured in kilometres but in economic barriers, cultural mistrust, and linguistic isolation. Our success came from recognising that effective distribution requires understanding community structures, not just transportation logistics.

For modern municipal laboratories, I’d emphasise three principles: first, map your need, don’t guess at it. We tracked every case by ward and building, identifying precisely where interventions were most needed. Second, work with existing community networks rather than creating parallel systems. The settlement houses were our greatest allies because they already held community trust. Third, design your financing to be politically sustainable – cross-subsidisation from paying patients ensured we never depended solely on municipal appropriations, which could be cut during budget crises.

The results vindicated our approach. By 1900, diphtheria deaths had fallen by more than half despite continued population growth. More importantly, mortality rates equalised across economic classes – children in the tenements had nearly the same survival chances as children on Fifth Avenue. That was social justice through systematic public health practice.

Your work in Lagos faces similar challenges but with far better tools – mobile technology, improved transportation, global health funding mechanisms. The principles remain: systematic mapping, community partnership, sustainable financing, and absolute commitment to reaching those who need help most. The bacteria don’t discriminate by social class, and neither should our systems for combating them.

Daniel Rodriguez, 29, Biomedical Engineer, Barcelona, Spain
I’m fascinated by your rapid rabies test using methylene blue and basic fuchsin stains. The thirty-minute turnaround was revolutionary for 1904, but I’m wondering about the technical trade-offs. What was your false positive and false negative rate compared to the ten-day gold standard? And given that you were working without modern quality control measures, how did you validate the reliability of your staining technique across different technicians and laboratory conditions?

Mr. Rodriguez, you’ve posed exactly the sort of rigorous question that drove my work – the eternal tension between speed and accuracy in diagnostic medicine. The technical trade-offs of my rapid rabies test were considerable, and I’m pleased you’ve asked for the specific performance data that few bothered to document thoroughly at the time.

Regarding accuracy rates, my thirty-minute test achieved approximately 85-90% sensitivity compared to the ten-day animal inoculation standard. This meant I was correctly identifying roughly nine out of ten true rabies cases rapidly, missing perhaps one case that would have been caught by the longer method. The specificity was higher – around 95-98% – meaning false positives were relatively rare.

These numbers might seem disappointing by today’s molecular standards, but consider the context. The ten-day gold standard itself was hardly perfect – animal inoculation required healthy laboratory animals, sterile technique, and considerable expense. More critically, patients often died whilst waiting for results. My test provided actionable information within the same day, when post-exposure prophylaxis could still be administered effectively.

The technical limitations were significant and worth discussing candidly. Negri bodies – those intracytoplasmic inclusion structures I was detecting – are not present in all rabies cases. Modern studies show they occur in only 40-80% of infections, which explains my sensitivity limitations. Some rabies cases, particularly those caused by certain viral strains or caught in early stages, simply don’t produce sufficient Negri body formation for microscopic detection.

My staining protocol used very specific concentrations – 1% basic fuchsin followed by methylene blue counterstain, each applied for precisely 2-5 seconds. The timing was crucial. Too brief, and the Negri bodies wouldn’t take the magenta stain sufficiently; too long, and background tissue would obscure the diagnostic structures. I developed this timing through hundreds of trials, but it required considerable skill to execute consistently.

Quality control presented enormous challenges without modern standardisation protocols. I addressed this by developing what you might call a “buddy system” – every positive identification had to be confirmed by a second technician examining the same slide independently. For negative results, we would prepare multiple slides from different brain regions, as Negri bodies aren’t uniformly distributed throughout infected tissue.

The reliability across different technicians was indeed problematic. I observed that experienced microscopists could achieve results approaching my own accuracy, but novice technicians often struggled with distinguishing true Negri bodies from what we now call “pseudo-Negri bodies” – non-specific protein inclusions that can appear in perfectly healthy brain tissue. This required extensive training programs, something I hadn’t initially anticipated.

Interestingly, I discovered that specimen quality dramatically affected results. Fresh brain tissue examined within hours of death yielded far better results than material that had begun to decompose. Temperature control was essential – specimens kept too warm developed artefacts that mimicked pathological changes, whilst frozen tissue lost the cellular architecture necessary for proper staining.

The methylene blue and basic fuchsin combination worked because Negri bodies have a unique affinity for acidophilic stains whilst the surrounding neural tissue preferentially takes up basic dyes. This differential staining relies on the protein composition of the viral inclusions – they’re rich in viral nucleoprotein complexed with host cell ribosomes, creating structures with distinct staining properties.

Modern validation would have been invaluable. I had no statistical framework for calculating confidence intervals or systematic methods for bias detection. My “validation” consisted of comparing results with animal inoculation when possible, but this was expensive and time-consuming. I estimated my accuracy through clinical follow-up – tracking whether patients who tested negative subsequently developed rabies symptoms – but this was hardly systematic epidemiological surveillance.

Comparing to today’s molecular methods is humbling. Modern RT-PCR techniques achieve 95-99% sensitivity and specificity whilst providing results in 2-4 hours. Your contemporary rapid immunochromatographic tests perform better than my method did – around 92-100% sensitivity depending on the specific platform.

But here’s what I think remains relevant: the principle of rapid, field-deployable diagnostics. Modern molecular tests require sophisticated equipment and trained technicians. My test could be performed anywhere with a microscope and basic staining supplies. In resource-limited settings – much like those you encounter in biotech startups facing infrastructure constraints – simple, robust methods still have value.

The false negative rate of 10-15% was clinically acceptable given the alternative. Before my test, physicians had to decide on prophylaxis based entirely on clinical suspicion, often treating patients unnecessarily whilst missing others who truly needed intervention. My test provided an evidence-based decision point, even if imperfect.

For quality control, I would now implement systematic blind testing – having technicians examine slides without knowing the clinical history or preliminary diagnosis. I would also insist on standardised training protocols with certification requirements before technicians could interpret results independently. Statistical tracking of inter-observer agreement would have identified systematic biases in our interpretation methods.

The lesson for modern diagnostics is that perfect accuracy isn’t always the primary goal – clinical utility is. A rapid test with 85% sensitivity that enables immediate treatment decisions may save more lives than a 99% sensitive test that takes too long to influence patient care. The key is understanding the limitations and building clinical protocols that account for them appropriately.

Your biotechnology work faces similar trade-offs, I imagine. Speed versus accuracy, simplicity versus precision, cost versus performance. The principles of rigorous validation, systematic quality control, and honest assessment of limitations remain as relevant today as they were in my laboratory more than a century ago.

Haruka Tanaka, 42, Science Policy Researcher, Tokyo, Japan
Dr. Williams, you chose collaborative work over individual recognition, yet you also acknowledged being ‘too cautious’ about claiming priority. This tension between collaboration and self-advocacy still challenges women in science today. If you could mentor your younger self through that decision with the rabies diagnostic work – knowing that Negri would publish first – what specific strategies would you recommend for claiming appropriate credit while maintaining productive partnerships? How do we balance generosity with professional survival?

Miss Tanaka, your question strikes at perhaps the most painful lesson of my career – and one that remains acutely relevant for women in science today. The tension between collaboration and self-advocacy is indeed a tightrope walk, and I fear I didn’t always balance it well.

Looking back on the rabies diagnostic work, I see now that my excessive caution about claiming priority stemmed from a deeply ingrained belief that good science spoke for itself, and that persistent self-promotion was somehow unseemly. This was naive, particularly in a field where professional recognition often determined access to resources, laboratory space, and future research opportunities.

When I discovered those intraneuronal inclusion bodies in 1904, I spent months confirming my findings, repeating experiments, ensuring that what I was seeing was genuine and reproducible. Meanwhile, Adelchi Negri was working on similar observations in Italy. He published first in April 1903, whilst I was still perfecting my staining techniques and validation methods. The bodies became known as “Negri bodies,” though my rapid diagnostic method based on detecting them proved more clinically useful than his initial description.

The specific strategies I would counsel my younger self – and contemporary women facing similar dilemmas – centre on what I now understand as “strategic visibility.” First, publish preliminary findings early, even if incomplete. The scientific record favours priority of publication over thoroughness of initial investigation. I could have published a brief communication about the inclusion bodies whilst continuing refinement work. This establishes priority whilst allowing for subsequent detailed papers.

Second, maintain meticulous documentation of all experimental work with dated laboratory notebooks witnessed by colleagues. I kept excellent records, but didn’t ensure they were formally witnessed or deposited where they could establish priority if needed. Modern scientists understand this better – timestamp everything, share preliminary data at conferences, establish digital traces of discovery.

Third, develop what we might call “collaborative self-advocacy.” Rather than choosing between individual recognition and team credit, frame contributions explicitly within collaborative work. When Dr. Park and I published on the diphtheria strain, I could have insisted that individual contributions be specified in the methodology sections. Sharing credit needn’t mean obscuring individual expertise.

The gender dynamics were particularly treacherous. Women who promoted their work too aggressively were labelled as unfeminine or difficult, whilst those who remained modestly collaborative often found their contributions subsumed into their male colleagues’ reputations. This double bind required extraordinarily delicate navigation.

My approach with Dr. Park worked because he genuinely valued collaborative science and ensured I received appropriate recognition. But this depended entirely on his personal integrity – a risky foundation for career advancement. I should have simultaneously built independent professional networks, perhaps through the women’s medical societies that were emerging during my career.

The institutional context matters enormously. Working in municipal public health rather than prestigious academic institutions meant my work was inherently collaborative and service-oriented. Academic medicine rewards individual achievement more explicitly. Understanding these different professional cultures and adapting strategies accordingly is crucial.

For contemporary women, I would emphasise creating documentation trails that establish individual contributions within collaborative projects. Email chains, grant applications listing specific roles, conference presentations by individual team members – these create records of who contributed what. Modern digital tools make this easier than it was in my era.

I would also recommend what we might call “generous but visible” collaboration. Share credit freely, but ensure your specific contributions are clearly articulated. When I developed the rapid rabies test, I could have written papers that acknowledged the foundational work of others whilst explicitly describing my methodological innovations and clinical applications.

The emotional dimension shouldn’t be underestimated. Watching Negri receive credit for “my” discovery was genuinely painful, though I tried not to show it. Women often absorb these disappointments silently, which compounds the professional damage. Building support networks with other women facing similar challenges provides both practical advice and emotional sustenance.

Professional partnerships require constant negotiation. With Dr. Park, we developed mutual respect through years of successful collaboration, but I should have been more explicit about ensuring balanced recognition from the beginning. Establishing clear agreements about publication order, conference presentations, and public recognition prevents misunderstandings later.

The broader lesson is that scientific merit alone is insufficient for professional advancement. This remains as true today as it was in 1904. Women must master both the science and the professional dynamics, whilst often having less margin for error than male colleagues.

Would different choices have dramatically altered my career trajectory? Perhaps. Academic recognition might have led to university positions, larger laboratories, more prestigious research opportunities. But I also found deep satisfaction in public health work that directly improved human welfare. The key is making conscious choices about trade-offs rather than defaulting to modesty and hoping for the best.

For women today, I would say: document everything, publish early and often, build diverse professional networks, and remember that advocating for appropriate recognition serves not just your career but all women in science. When we allow our contributions to be diminished, we perpetuate the very systems that constrain future generations.

The collaborative skills that often come naturally to women are genuine assets in modern science, where most breakthrough work requires interdisciplinary teams. The challenge is ensuring that collaborative excellence translates into individual recognition and career advancement. This requires active professional strategy, not just outstanding scientific work.

Science is ultimately a human enterprise, shaped by human relationships and social dynamics. Understanding and navigating these realities doesn’t compromise scientific integrity – it ensures that the best scientific work reaches its full impact through appropriate recognition and continued funding.

Thiago Silva, 31, Biotechnology Startup Founder, São Paulo, Brazil
What if your Park-Williams strain had failed to maintain its toxin production after the first few generations? You mentioned this stability was crucial, but it seems like a tremendous risk to base an entire city’s diphtheria response on one bacterial strain. Did you have contingency plans, and how would you have scaled up alternative approaches? I’m thinking about this because we face similar ‘single point of failure’ risks in biotechnology today – how do you balance the efficiency of standardisation with the resilience of redundancy?

Mr. Silva, your question cuts to the heart of what kept me awake many nights in 1894 – the terrifying prospect of our entire diphtheria response collapsing due to bacterial failure. You’re absolutely right to identify this as a single point of failure, and I’m pleased to share both our contingency plans and the lessons learned that remain relevant for modern biotechnology.

The risk was indeed enormous. By autumn 1894, we were distributing antitoxin to every practicing physician in New York City – over 2,000 doctors serving nearly two million people. If the Park-Williams strain had lost its toxigenicity, children would have died whilst we scrambled to develop alternatives. The political and professional consequences would have been catastrophic, potentially setting back public health bacteriology by decades.

Our primary contingency was maintaining parallel bacterial archives. I preserved the original Park-Williams isolate using three different methods – dried on sterile silk threads, suspended in glycerol solutions, and maintained as continuous cultures on fresh media. Each method had different failure modes, providing redundancy against bacterial degradation. The silk thread method, borrowed from Koch’s laboratory, could preserve viable bacteria for months even without refrigeration.

More importantly, I simultaneously maintained seven other high-toxin-producing diphtheria strains isolated from different patients. These weren’t mere laboratory curiosities – each was fully characterised for toxin production, growth characteristics, and stability. If Park-Williams No. 8 had failed, we could have switched to Park-Williams No. 3 or No. 12 within days rather than weeks.

The backup production system was equally crucial. We established satellite laboratories in Brooklyn and the Bronx, each maintaining independent bacterial stocks and production capabilities. This geographical distribution protected against laboratory fires, contamination events, or equipment failures that could have disrupted central production. Each satellite could produce 500 doses of antitoxin weekly – sufficient for emergency coverage whilst we rebuilt primary production.

Quality control protocols provided early warning of bacterial degradation. We tested every tenth batch for toxin potency using standardised guinea pig assays. Declining toxin levels would have triggered immediate investigation and potential strain replacement before clinical efficacy was compromised. This systematic monitoring caught several instances of bacterial contamination that could have compromised entire production runs.

The financial contingencies were perhaps most critical. We negotiated standing agreements with European suppliers – primarily Behring’s laboratory in Germany – to provide emergency antitoxin shipments within 10 days of telegraph notification. This was expensive but essential insurance against production failures during epidemic periods. Municipal authorities understood that antitoxin shortage during an outbreak would cost far more in mortality and economic disruption than emergency importation expenses.

Personnel redundancy was equally vital. I trained three laboratory technicians in the complete isolation and characterisation process, ensuring that bacterial work could continue even if I became ill or unavailable. Each technician maintained their own set of working cultures, preventing total loss from individual errors or contamination events.

The specific technical failures we prepared for included: bacterial mutation leading to toxin loss, contamination with non-toxigenic strains, laboratory accidents destroying culture collections, and equipment failures preventing proper incubation or media preparation. Each scenario had documented response protocols and designated responsible personnel.

Regarding alternatives to our standardised approach, we explored several parallel strategies. One involved maintaining multiple diphtheria strains from different geographical regions, reasoning that evolutionary pressures might affect bacterial stability differently. We also experimented with what we now recognise as bacterial preservation techniques – storing cultures in various media compositions and temperatures to identify optimal long-term storage conditions.

The efficiency versus resilience trade-off was constant. Standardising on Park-Williams No. 8 allowed us to optimise media composition, production timing, and quality control procedures for maximum efficiency. But this specialisation created vulnerability. Maintaining backup strains required additional laboratory space, personnel time, and materials – reducing overall efficiency but providing essential resilience.

Modern biotechnology faces identical challenges, though with superior tools. Your industry benefits from cryogenic storage, molecular characterisation, and rapid genetic sequencing that can detect bacterial changes before they affect product quality. But the fundamental principles remain: maintain multiple backup systems, test systematically for degradation, prepare for rapid alternative deployment, and balance efficiency with resilience based on risk tolerance.

The lessons for startup biotechnology are particularly relevant. Early-stage companies often operate with minimal redundancy due to resource constraints, but this creates enormous vulnerability. One contamination event or bacterial failure can destroy months of work and investor confidence. Building systematic backup systems from the beginning – even if expensive – provides essential insurance against catastrophic loss.

Modern molecular methods would have revolutionised our approach. Genetic sequencing could have identified the specific genes responsible for toxin production in Park-Williams No. 8, allowing us to monitor for mutations that might affect stability. Plasmid-based toxin production could have provided more stable alternatives to chromosomal integration. Frozen bacterial stocks at -80°C could have preserved original strains indefinitely.

But the strategic thinking remains unchanged: identify critical failure points, develop multiple independent backup systems, test systematically for early warning signs, and prepare rapid response protocols for when failures occur. The Park-Williams strain did remain stable for decades, validating our choice, but having comprehensive contingencies allowed us to take that calculated risk responsibly.

Your biotechnology work likely involves similar single-point-of-failure risks – key bacterial strains, essential equipment, critical personnel, or regulatory approvals. The principles I learned apply directly: redundancy costs less than failure, systematic monitoring prevents catastrophic surprises, and robust contingency planning enables bold innovation whilst managing existential risks.

The children of New York depended on our bacterial strain remaining stable. That responsibility demanded not just excellent science, but careful risk management and comprehensive backup planning. Modern biotechnology faces the same imperative – breakthrough innovation coupled with systematic resilience planning.

Sofia Petrova, 38, Medical Historian, Prague, Czech Republic
You worked during the transition from miasma theory to germ theory, when many physicians still doubted bacterial causation of disease. I’m curious about the resistance you encountered – not just as a woman, but as someone advocating for laboratory-based medicine over clinical intuition. What was your most memorable encounter with a sceptical physician, and how did you handle the tension between respecting clinical experience and insisting on laboratory evidence? How did you manage those delicate professional relationships?

Miss Petrova, your question brings back memories of battles that were as much about professional pride as scientific truth. The transition from miasma to germ theory wasn’t merely an intellectual shift – it threatened the very foundation of clinical authority that physicians had built their careers upon.

My most memorable encounter involved Dr. Harrison Blackwood, a prominent Manhattan internist with forty years’ clinical experience treating diphtheria. This was autumn 1895, just after we’d published our initial findings on the Park-Williams strain and begun distributing free antitoxin. Dr. Blackwood arrived at our laboratory, demanded to speak with Dr. Park, and when informed he was in consultation with me, reluctantly agreed to meet with “the lady bacteriologist.”

His opening words were unforgettable: “Miss Williams, I have been treating throat distempers since before you were born. I can distinguish true diphtheria from false by the smell of the child’s breath, the particular quality of the membrane, and the family’s constitution. Your microscopic amusements may be interesting, but they cannot replace a physician’s trained eye.”

I responded by showing him two throat cultures on microscope slides – both from children with identical clinical presentations that he would have diagnosed as diphtheria. One showed the characteristic club-shaped Corynebacterium diphtheriae with metachromatic granules; the other revealed only streptococci. “Doctor,” I said, “your clinical eye sees the same symptoms, but these organisms require entirely different treatments. The diphtheria case needs antitoxin; the streptococcal case could be harmed by it. Without laboratory confirmation, how do you distinguish them?”

His reply revealed the fundamental tension: “Young lady, medicine is an art built on experience and clinical judgement. These laboratory procedures reduce the complexity of human illness to simple microscopic observations. A true physician treats the patient, not the bacteria.” This wasn’t mere stubbornness – it represented a genuine epistemological conflict about how medical knowledge should be generated and validated.

The professional dynamics were particularly fraught because germ theory threatened established hierarchies. Senior physicians had built their reputations on clinical acumen – their ability to diagnose and treat based on careful observation and accumulated experience. Laboratory medicine suggested that a young woman with a microscope could provide more definitive diagnostic information than a distinguished physician with decades of practice.

I learned to address these confrontations by respecting clinical expertise whilst demonstrating laboratory value. Rather than dismissing Dr. Blackwood’s experience, I acknowledged it: “Your clinical observations are absolutely correct – these children do present with similar symptoms. Laboratory testing doesn’t replace clinical judgement; it provides additional information to guide treatment decisions more precisely.”

The resistance had multiple layers. Miasma theory wasn’t simply wrong – it had logical foundations given available knowledge. Bad air did correlate with disease outbreaks, particularly in crowded, unsanitary conditions. The connection seemed obvious: filth produced noxious vapours, vapours caused illness. Our bacterial theory seemed unnecessarily complex and required expensive laboratory infrastructure.

More fundamentally, miasma theory supported existing medical practice patterns. Physicians could diagnose and treat based on clinical observation without requiring laboratory confirmation. Germ theory demanded systematic specimen collection, bacterial isolation, and microscopic identification – procedures that many practitioners found burdensome and unnecessary.

The economic implications were equally challenging. Laboratory medicine required significant investment in equipment, trained personnel, and reagents. Many physicians saw this as an expensive complication rather than a valuable improvement. Why spend money on bacterial cultures when clinical diagnosis had served adequately for generations?

My strategy evolved through repeated confrontations. First, I always brought concrete evidence – actual bacterial cultures, patient outcome data, comparative statistics. Abstract theoretical arguments proved less persuasive than visible demonstrations of diagnostic accuracy. Second, I framed laboratory testing as enhancing rather than replacing clinical skills. This preserved physician authority whilst introducing scientific validation.

The gender dimension added particular complexity. Male physicians often felt their professional competence was being questioned by a woman, which triggered defensiveness beyond normal scientific scepticism. I learned to present findings collaboratively: “Dr. Park and I have observed…” rather than claiming individual credit. This reduced perceived threat whilst ensuring scientific accuracy.

Time proved our most powerful ally. As antitoxin distribution expanded, mortality statistics became undeniable. Children treated with laboratory-confirmed diphtheria cases and appropriate antitoxin had dramatically better survival rates than those treated based solely on clinical diagnosis. Results spoke louder than arguments.

Some physicians adapted more readily than others. Younger practitioners, particularly those with hospital training, embraced laboratory methods more quickly. They had less invested in traditional approaches and saw technological advancement as professional opportunity rather than threat.

The institutional context mattered enormously. Hospital-based physicians encountered laboratory medicine through daily practice, making adoption more natural. Private practitioners, particularly those serving wealthy patients, faced different pressures. Their patients expected personalised attention from distinguished physicians, not impersonal laboratory reports.

Educational initiatives proved crucial for long-term acceptance. We began offering courses for practicing physicians on bacterial identification and culture techniques. This transformed laboratory medicine from mysterious black box to understandable tool. Physicians who understood the methods were more likely to trust the results.

Looking back, I realise that successful professional transitions require both scientific validity and careful attention to human dynamics. The evidence supporting germ theory was overwhelming, but evidence alone wasn’t sufficient. Change required respecting existing professional expertise whilst demonstrating clear practical advantages of new approaches.

The lesson remains relevant for contemporary medical innovations. New technologies, whether genetic testing, artificial intelligence diagnostics, or personalised medicine, face similar resistance from practitioners comfortable with established methods. Success requires not just scientific proof but thoughtful implementation that preserves professional dignity whilst improving patient care.

Dr. Blackwood, incidentally, eventually became one of our strongest supporters. By 1900, he was routinely sending throat swabs for bacterial confirmation and crediting laboratory results with improving his diagnostic accuracy. Personal relationships and demonstrated results ultimately proved more persuasive than theoretical arguments.

Reflection

As our conversation with Dr. Anna Wessels Williams draws to a close, I’m struck by the profound relevance of her experiences to the challenges facing modern science. Her story illuminates persistent tensions that continue to shape scientific careers today – the balance between collaboration and individual recognition, the struggle for women to claim appropriate credit whilst maintaining productive partnerships, and the eternal conflict between institutional prestige and practical impact.

What emerges most powerfully from Williams’ account is her unflinching commitment to “science in service of humanity” – a philosophy that led her to choose municipal public health over academic glory. Her detailed descriptions of the antitoxin distribution system reveal a sophisticated understanding of health equity that anticipated modern global health initiatives by over a century. The depot stations, community health workers, and cross-subsidisation models she helped develop remain remarkably relevant templates for addressing healthcare disparities in today’s world.

Her technical insights offer fascinating glimpses into the methodical precision that characterised early bacteriology. The specific staining concentrations, timing protocols, and quality control measures she described suggest a level of systematic rigour often absent from sanitised historical accounts. Her candid acknowledgment of the 10-15% false negative rate in her rabies test, whilst disappointing by contemporary standards, reflects an intellectual honesty about diagnostic limitations that modern medicine could emulate.

Perhaps most striking is Williams’ nuanced analysis of the gender dynamics that shaped her career. Her confession about being “too cautious” in claiming priority for the rabies diagnostic work differs markedly from historical accounts that typically present her as simply modest or collaborative. Her strategic recommendations for contemporary women scientists – document everything, publish early, build diverse networks – reveal a hard-won understanding of professional survival that transcends her era.

The historical record remains frustratingly incomplete about Williams’ personal struggles and professional disappointments. Standard biographies emphasise her achievements whilst glossing over the emotional toll of watching male colleagues receive disproportionate credit for collaborative work. Her frank discussion of the pain surrounding Negri’s priority in publishing rabies findings provides a more human dimension often missing from scientific hagiography.

Some aspects of her account challenge conventional interpretations. Her emphasis on systematic contingency planning for potential bacterial strain failure suggests a level of risk management sophistication rarely attributed to early public health laboratories. Her detailed description of physician resistance to germ theory reveals the deeply personal and professional stakes involved in paradigm shifts – dynamics that contemporary accounts often reduce to simple scientific progress narratives.

The parallels between Williams’ era and our own are both encouraging and sobering. Her pioneering work in rapid diagnostics and municipal health systems anticipated modern pandemic response infrastructure, yet many of the barriers she faced – institutional bias, gender discrimination, the tension between pure and applied research – persist today. Her success in implementing systematic public health interventions offers hope for addressing contemporary global health challenges, whilst her struggles with professional recognition serve as a reminder of how far we still have to travel.

What lingers most powerfully is Williams’ voice itself – authoritative yet reflective, passionate about scientific rigour whilst deeply concerned with human welfare. Her insistence that the greatest scientific achievements are measured not in prizes won but in lives saved challenges our contemporary obsession with individual accolades and institutional rankings. In an age of increasing scientific specialisation and academic competition, her example suggests that the most meaningful innovations emerge from work that bridges laboratory and community, theory and practice.

Dr. Anna Wessels Williams conquered diphtheria not through isolated genius but through systematic collaboration, methodical precision, and unwavering commitment to public service. Her legacy reminds us that science at its best serves not the scientific establishment but humanity itself – a lesson as urgent today as it was in the laboratories of 1890s New York.

Who have we missed?

This series is all about recovering the voices history left behind – and I’d love your help finding the next one. If there’s a woman in STEM you think deserves to be interviewed in this way – whether a forgotten inventor, unsung technician, or overlooked researcher – please share her story.

Email me at voxmeditantis@gmail.com or leave a comment below with your suggestion – even just a name is a great start. Let’s keep uncovering the women who shaped science and innovation, one conversation at a time.

Editorial Note: This interview is a dramatised reconstruction based on historical sources and records of Dr. Anna Wessels Williams’ life and work. Whilst grounded in documented facts about her scientific achievements, laboratory methods, and professional experiences, the dialogue, personal reflections, and specific anecdotes represent creative interpretation of the historical record. Some technical details and personal insights are extrapolated from available evidence about her era and field of work. This fictional interview aims to illuminate Williams’ contributions to bacteriology and public health whilst acknowledging the limitations and gaps in historical documentation about her lived experience.

Bob Lynn | © 2025 Vox Meditantis. All rights reserved. | 🌐 Translate