Stored in an open-air warehouse in tropical Darwin, Australia, are dozens of trays containing cylindrical cores of rock. They are from drill holes bored hundreds of metres below the surface by mineral exploration companies decades ago.

Some of these cores at the Northern Territory Geological Survey are mudstone – a type of sedimentary rock formed from hardened seafloor mud. The companies that drilled these cores were largely unaware that within these mudstones were fossils of microscopic organisms buried on the seafloor of an ancient inland sea that covered much of northern Australia over 1.5 billion years ago.

As our new study, published today in Nature, shows, these fossils are crucial for addressing a longstanding puzzle about the major evolutionary leap that led to all complex life on Earth: the origin of eukaryotes.

Small but complex

All life on Earth can be placed into one of two types which are fundamentally different at the cellular level.

Prokaryotes (bacteria and archaea) have simple cellular organisation and are mostly single celled. Eukaryotes – including all animals, plants, algae and fungi – are very different. They have much more complicated cells featuring a nucleus and other specialised structures such as organelles which perform specific jobs.

The eukaryotic revolution transformed the planet. It led to the rise of animals and, eventually, to us. Based on observations from the genes of living organisms, it is now widely agreed that the last common ancestor of all living eukaryotes resulted from the symbiotic union of (at least) two prokaryotic microbes: an archaeon and a bacterium.

The first evidence for eukaryotic life comes in the form of these fossils of single-celled organisms. They show a level of cellular complexity not seen among prokaryotes, but common in eukaryotes.

Eukaryote fossils can be found around the world in rocks dating back at least 1.5 billion years. The fossils of the Northern Territory, the oldest of which date back to 1.75 billion years ago, are the oldest currently known eukaryote fossils globally.

But the ancient world in which early eukaryotes evolved remains shrouded in mystery. And so many fundamental aspects regarding their nature are unknown.

Oxygen – friend or foe?

Many types of bacteria can live and grow in places without oxygen. But nearly all eukaryotes alive today use oxygen for their survival. That’s because aerobic respiration – breaking down food using oxygen – provides the vast amounts of energy that complex life demands.

But the idea that oxygen has always been beneficial for all eukaryotes has come under fire in recent years. This follows the surprising discoveries of enigmatic eukaryotes that can thrive in conditions without oxygen.

There is also mounting evidence from the geological record that when eukaryotes were first evolving, oxygen was likely much scarcer. This means oxygen-free marine habitats would have been the norm. Collectively, these observations have called into question the assumption eukaryotes have depended on oxygen since their inception.

Genetic studies of living microbes belonging to groups considered closest to the ancestors of the first eukaryote can offer key insights into eukaryote ancestry. But only the fossil record can tell us about long-extinct lineages. And only geology can offer a window into the kind of world these organisms lived in.

More than 12,000 fossils

For our new study, we crushed up samples of the mudstone cores stored in Darwin, then dissolved them. We identified more than 12,000 fossils by analysing the organic residue left behind by this dissolution under a microscope.

We also studied the mudstones the fossils were preserved in to better understand what the environment was like when the sediments were deposited. This offered insight about the habitats in which these eukaryotes lived. And by analysing the chemistry of these mudstones, we could determine whether oxygen was present in the ancient seawater.

Our results show that eukaryote fossils were found in environments ranging from coastal mudflats to the open sea. But they were present only in samples deposited in oxygenated settings. Samples from oxygen-free environments contained only simple, prokaryotic forms.

This suggests that even the oldest known eukaryotes that lived on Earth 1.7 to 1.4 billion years ago were dependent on oxygen. These data lend support to a long-held hypothesis that oxygen played a key role in driving the evolution of early eukaryotes.

Resolving the drivers and context of the major evolutionary leap represented by early eukaryotes is one of the major outstanding questions in the life sciences. Ongoing studies of these enigmatic, ancient microfossils will no doubt tell us more about our own origins – and our place in the cosmos.

Maxwell Lechte received funding from the Moore–Simons Project on the Origin of the Eukaryotic Cell.

Leigh Anne Riedman receives funding from the NASA Exobiology program, and has received funding from the Moore–Simons Project on the Origin of the Eukaryotic Cell, the Palaeontological Association and the American Philosophical Society.

Some clinical trials aren’t designed to answer scientific questions. They’re designed to market drugs. In our recently published research, my team and I analyzed over 34,000 industry-funded trials and found that hundreds of studies across seven medical fields were likely designed to promote a drug to physicians rather than to generate scientific data. For some fields, nearly 1% of clinical trials were for marketing purposes.

Known as seeding trials, these studies prioritize marketing over science while disguising their commercial purpose as legitimate research. Pharmaceutical companies use them to familiarize physicians with new products under the guise of data collection. Participants sign consent forms, believing they are contributing to medical knowledge.

In reality, patients are absorbing risks that serve corporate interests rather than resolving genuine uncertainty about the therapeutic potential of a drug.

The term seeding trial first entered the medical literature in 1994, when then-commissioner of the Food and Drug Administration David Kessler and his colleagues described such studies as attempts to entice doctors to prescribe new drugs through trials that appear to serve little scientific purpose.

Three decades later, the problem of seeding trials persists.

How seeding trials work

While the structure of a seeding trial looks similar to legitimate clinical trials on the surface, the objectives are different.

In a typical clinical trial, researchers recruit patients across clinics and hospitals to test whether a treatment is safe and effective.

In contrast, the pharmaceutical company behind a seeding trial enrolls large numbers of physicians at many sites, each seeing only a few patients. The goal is exposure: getting doctors to prescribe the drug, not generating robust data. Doctors may be selected based on their prescribing volume rather than their research credentials.

In a legitimate trial, the number of study sites reflects the number of patients needed to answer a scientific question. In a seeding trial, the number of sites reflects the number of doctors the company wants to reach.

Seeding trials often target drugs already on the market and operate as Phase 4, or postmarketing, studies. These types of studies are typically conducted after a drug has been approved to monitor its long-term safety or effectiveness. This trial stage receives less regulatory scrutiny than trials for initial drug approval, and the aims of the study may have limited relevance to actual patient care. For example, a seeding trial might measure whether patients prefer the taste of a new formulation or how quickly a drug dissolves in the stomach, rather than whether it actually improves health outcomes.

Legitimate trials also have independent oversight, with committees of scientists and ethicists who monitor the study’s progress and can halt it if patients are being harmed.

In a seeding trial, this oversight is often minimal. The sponsor of the study – typically the pharmaceutical company funding the research – maintains heavy control over the trial’s design and conduct.

Cases that exposed seeding trials

Seeding trials had attracted little public attention until litigation in the 1990s forced open the internal files of two major pharmaceutical companies, revealing that studies presented as science had been designed as marketing campaigns.

The most notorious example is Merck’s ADVANTAGE trial for the painkiller Vioxx (rofecoxib), which was first approved in 1999. The company presented the study, which ran from 1999 to 2001, as scientific research, but internal documents revealed that its primary purpose was to encourage physicians to prescribe Vioxx to their patients.

Meanwhile, Merck was accused of downplaying the significant cardiovascular risks associated with the drug. The consequences were severe: Approximately 30,000 lawsuits and nearly $5 billion in compensation followed Vioxx’s withdrawal from the market.

Parke-Davis’ STEPS trial for the painkiller Neurontin (gabapentin) – first approved in 1993 for epilepsy – followed a similar pattern of disguising marketing as research. Internal documents showed that the trial, which ran from 1996 to 1998, aimed to disseminate marketing messages through the medical literature and encourage clinicians to prescribe the drug off-label for conditions it was not approved for, such as neuropathic pain and bipolar disorder.

Unlike Vioxx, gabapentin was never withdrawn. The trial’s commercial legacy outlasted its scientific one.

These cases came to light only because litigation forced the release of internal company documents. Without that exposure, they would have remained indistinguishable from ordinary research.

How common are seeding trials?

My team and I study how pharmaceutical firms innovate and respond to regulations. To estimate the prevalence of seeding trials, we analyzed nearly 34,400 industry-funded Phase 3 and Phase 4 studies that posted results on ClinicalTrials.gov between 1998 and 2024. The trials covered seven therapeutic areas where researchers had previously documented seeding trials, including major depressive disorder, epilepsy, Type 2 diabetes and rheumatoid arthritis.

We screened these trials for criteria that prior research has identified as hallmarks of a seeded trial, such as low patient-to-site ratios and limited independent oversight.

Ultimately, we identified 204 trials – 0.59% – that had characteristics consistent with marketing-driven study design. The prevalence of these probable seeding trials in different disciplines ranged from 0.15% in osteoarthritis to 0.98% in rheumatoid arthritis.

These figures might understate the true scope of marketing-driven research. The criteria we used capture only the most identifiable cases of studies driven by marketing purposes. Definitively identifying seeding trials requires access to internal sponsor documents revealing the intent of the study, and those documents surface only through litigation or whistleblowers.

Many trials occupy an ambiguous middle ground, generating useful data while simultaneously serving promotional objectives. Without systematic surveillance, the full extent of marketing-driven studies remains unknown.

The criteria to identify seeding trials also require careful interpretation. A low patient-to-site ratio, for instance, can reflect the practical difficulties of enrolling patients in studies of drugs already on the market, such as trials testing new drug combinations or new uses for an existing treatment. These markers are best understood as signals of possible marketing intent warranting closer scrutiny, not proof of marketing intent.

Whether the prevalence of seeding trials has shifted with the expansion of transparency requirements over the past decade cannot be determined from existing registry data.

What can be done

Seeding trials may be uncommon, but they are not accidental. They reflect structural incentives in a system where the companies that fund research also stand to gain from its results. Strengthening transparency in clinical trial registration, funding disclosure and oversight would help ensure that clinical research serves patients first.

Along with other researchers, we’ve proposed reforms that cluster around two areas. The first is standardized reporting that discloses trial funding, investigator payments, enrollment criteria and the rationale for site selection. The second is independent oversight, such as committees funded through pooled industry levies, which are fees collected from pharmaceutical companies to finance independent monitoring. Random audits with publicly available results are one form of such oversight.

Some infrastructure for tracking financial relationships between industry and physicians is already in place. In the U.S., the Open Payments database allows public tracking of industry payments to physicians. But regulatory variability across countries creates openings for companies to conduct marketing-driven trials in jurisdictions with weaker oversight, particularly in low- and middle-income countries.

Clinicians can protect themselves and their patients by screening for a set of red flags before agreeing to participate in or cite a trial in their research. These include unusually low patient-to-site ratios, selecting investigators based on prescribing volume, sponsor-dominated oversight and study endpoints of limited clinical relevance. Consent forms are among the few documents patients see before enrolling, and clearer disclosure of the commercial and scientific purpose of a study is among the reforms we have called for.

For patients, clinicians and regulators alike, the question to ask of any trial is the same: Whom does it really serve?

Sukhun Kang does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.