Across the world, an estimated 300 to 400 million people live with a rare disease. Yet for most of the twentieth century, these individuals lived in near-total isolation – medically, scientifically, and politically. No treatments, no dedicated research programmes, and no networks to connect the at times handful of patients and clinicians who shared the same obscure diagnosis.
At LDA Research, we have spent nearly twenty years working in the rare disease space, and the transformation we have witnessed in that time has been remarkable. The story of how that change came about is one of grassroots advocacy, legislative courage, and an increasingly global realisation that rare diseases, precisely because they are rare, demand collective action.
Japan: The First to Act (1972)
The earliest formal national response to rare diseases did not come from the United States or Western Europe, as many assume. It came from Japan. In 1972, the Japanese government issued its Outline of Measures to Combat Intractable Diseases, establishing what became known as the Nanbyo framework, with “Nanbyo” roughly translating as “difficult illness.” This was not merely a research programme; it was a government commitment to recognise that certain diseases, by their very nature, demanded dedicated infrastructure, specialist networks, and sustained public funding.
The Nanbyo programme established research groups, designated specialist hospitals, and began building the kind of systematic clinical data collection that remains the backbone of any rare disease network today. Japan’s orphan drug legislation followed in 1993, providing commercial incentives to match the clinical infrastructure that had been taking shape for two decades. This early start gave Japan a substantial advantage in specialist expertise, and it is no coincidence that Japan remains one of the world’s most active players in rare disease research – though, as later blogs in this series will explore, challenges around drug access have grown in recent years.
The United States: Advocacy Meets Legislation (1983)
In the United States, the catalyst was different. It was not government initiative but patient and family advocacy – loud, persistent, and ultimately impossible to ignore – that drove change. By the early 1980s, fewer than forty drugs had ever been approved specifically for rare diseases. Pharmaceutical companies had little incentive to develop treatments for small patient populations; the economics simply did not add up.
The turning point came on 4 January 1983, when President Ronald Reagan signed the Orphan Drug Act into law. The legislation was championed in Congress by Representative Henry Waxman, who made the moral case with characteristic directness during hearings in 1982: “For those with rare diseases, this is a tragic, and sometimes hopeless, situation. For the rest of us who believe that people with rare diseases suffer no less and are no less deserving because they are so few, this situation is intolerable. It must be changed.”
The Act’s passage was also given unexpected momentum when actor Jack Klugman testified before Congress, having used his television series Quincy M.E. to dramatise the plight of patients with rare diseases. The legislation created a suite of financial incentives for companies willing to develop treatments for diseases affecting fewer than 200,000 Americans – tax credits, extended market exclusivity, and expedited regulatory review changed the calculus of orphan drug development overnight.
Equally important was the founding of the National Organization for Rare Disorders (NORD) in the same year. NORD became the first umbrella organisation specifically designed to unite the voices of multiple rare disease patient groups – an acknowledgement that no single disease community had the numbers or resources to lobby effectively on its own, but that together they could. The Rare Diseases Clinical Research Network (RDCRN), established by the NIH in the early 2000s, built on that foundation by creating a formal infrastructure of disease-specific consortia, registries, and collaborative clinical trials.
Europe and the UK: Regulation, Networks, and Patient Power (1990s–2000s)
Europe’s engagement with rare diseases developed more gradually, but ultimately produced some of the most sophisticated collaborative infrastructure in the world. The European Organisation for Rare Diseases (EURORDIS) was founded in 1997, drawing direct inspiration from NORD’s model in the United States. Indeed, NORD’s leadership actively advised those establishing EURORDIS, reflecting an early instinct toward cross-border learning that would come to define the field.
The European Union’s Regulation on Orphan Medicinal Products followed in 2000, establishing the Committee for Orphan Medicinal Products within the European Medicines Agency and bringing a regulatory framework that would eventually cover the diverse health systems of EU member states. In parallel, national networks were emerging across the continent. France launched its National Plan for Rare Diseases in 2004, widely regarded as a model for structured government commitment. The European Reference Networks (ERNs) – virtual clinical networks linking specialist centres across member states – became fully operational by 2017, connecting expertise in dozens of disease areas without requiring patients to leave their home countries.
In the United Kingdom, Genetic Alliance UK (originally the Genetic Interest Group, founded in 1989) had been building a patient-led network for genetic and rare conditions for years before European-level structures fell into place. The UK’s own Rare Diseases Framework, and its constituent national action plans for England, Scotland, Wales, and Northern Ireland, reflected a recognition that coordination – and not just funding – was the central challenge.
Going Global: IRDiRC and the Drive for International Coordination (2011–present)
By 2011, it was clear that even the most sophisticated national and regional networks were insufficient. Rare diseases, distributed across small patient populations worldwide, could only be fully understood – and treatments only efficiently developed – through genuinely international collaboration. The International Rare Diseases Research Consortium (IRDiRC) was launched that year under the joint leadership of the US National Institutes of Health and the European Commission, with an initial membership of twenty-one organisations and an ambitious goal: contribute to 200 new rare disease therapies and the means to diagnose most rare diseases by 2020.
Remarkably, that target was achieved three years ahead of schedule. By 2017, IRDiRC had grown to nearly fifty member organisations spanning six continents, setting new goals for the decade to 2027. Its work on data standards, patient registries, clinical trial methodology, and regulatory harmonisation provided a framework that national networks could plug into rather than duplicate.
The most visible symbol of this global movement came in May 2024, when the 12th European Conference on Rare Diseases and Orphan Products (ECRD) convened in Brussels, bringing together over 1,500 stakeholders – including patients, researchers, clinicians, regulators, and industry representatives – from across the world. It marked a moment when what had begun as isolated national efforts had unmistakably become a worldwide endeavour.
A Foundation for Everything That Follows
The history of rare disease networks is, at its core, a story about recognising that vulnerability shared across borders is still vulnerability shared. Japan’s pioneering Nanbyo programme, the US Orphan Drug Act, the patient-led energy of NORD and EURORDIS, and the international architecture of IRDiRC each represent a stage in an evolution from isolation toward connection.
The subsequent blogs in this series will examine how that evolution looks from the perspectives of those most invested in its outcome – pharmaceutical companies weighing commercial risk, regulators balancing speed and safety, and patients navigating a system only incrementally built around their true needs. Each perspective illuminates something the others miss. Together, they explain why rare disease networks matter, and why the work of building and sustaining them remains far from finished.
Next in the series: How the pharmaceutical industry’s relationship with rare diseases evolved from studied indifference to strategic commitment — and where the limits of that commitment still lie.
