Leaps and bounds: a new way to do science

The way we fund and do science needs to change if we are to address the big issues facing humanity with the urgency they demand. We are faced with multiple and massive challenges, including climate, hunger, population, aging, water, biodiversity, inequalities and health crises. Current research funding models produce ‘too little, too late’ and are not bringing the breakthroughs, innovation, implementation or impact at the pace that is needed. 

Wellcome Leap, a US-based non-profit ogranisation, was established by the Wellcome Trust (UK) in 2020 to accelerate and increase the number of breakthroughs in human health. The organisation, which operates globally, is a re-tooling of the DARPA model (Defense Advanced Research Projects Agency), which has played a major role in many breakthrough advances since its launch in 1957 by President Eisenhower1[1].  These include miniaturised GPS, mRNA vaccines, stealth technology, the internet, night vision, and autonomous vehicles.  

As outlined in “Changing the Business of Breakthroughs” (Issues, Summer 2022), Wellcome Leap sets clear, ambitious and measurable goals that are laser focused on global problems. They are mission-driven, or what has been called ‘use-inspired’ research, designed to create new capabilitities or solve specific problems. They use a pre-signed master agreement with organisations to remove common barriers and institutional delays. Philanthropy funding allows them to act quickly, without concern for elections cycles, re-alignment of political will or the need to create new incentive structures. Wellcome Leap has other distinctive and disruptive attributes that stack the odds in favour of success. 

Project areas are not selected by a consensus-based peer-review process. There is no necessity for preliminary evidence or proof that something will work before funding. There is a greater risk tolerance and a willingness to make anticipatory decisions and investments. This risk is somewhat mitigated by an activities-based funding approach which means that funding can be reallocated in the face of unsatisfactory progress, a ‘fast-fail’ approach. The investigators are called ‘performers’ and must meet robust milestones within tight timelines. There is an agility such that the team that is funded may not be the team that finally makes the breakthrough. Diverse teams are brought together and synergies created rapidly with a programme director at the helm, synchronising, directing the network and removing obstacles.

The latest Wellcome Leap ‘SAVE program’ (USD50m) has just been launched. SAVE stands for “Surgery: Assess/Validate/Expand” and targets the global surgery crisis. The WHO estimates that there are more than 5 billion people in the world that do not have access to safe surgery and anaesthesia and that an additional 143 million surgical operations are needed each year to meet basic health needs. The ‘failure to rescue’ patients from postoperative complications is a leading cause of death, which is also the third most common cause of death globally.  Of these postoperative deaths, 1.5 million per year could be prevented through access to safe surgery.  In addition to the massive human toll, this lack of access to safe surgery during the next decade is projected to cost $10 trillion in lost global GDP. 

Two of the major barriers to delivering safe surgery are lack of surgeons and inadequate early detection of postoperative complications.  These barriers are starkly evident in low and middle income countries.

True to form, the SAVE programme is stunningly ambitious. They have contracted 13 ‘performers’ (principle investigators), 43 co-investigators and 26 organisations to deliver safer surgery and improved outcomes, particularly in resource-limited settings.  The specific goals are:

• to demonstrate the capability to train practitioners who are not medical doctors to deliver routine laparoscopic (‘key-hole’) surgery using next-generation training methods
• to shorten the time-line to train surgeons by a full year, and
• to reduce postoperative complications and mortality by >50% through advanced sensing, monitoring and pattern recognition strategies.

Aoteroa New Zealand is part of the SAVE programme through the Surgical and Translational Research (StaR) Centre, led by Professor John Windsor FRSNZ at the University of Auckland.  A technology innovation pioneered with Professors Paul Kilmartin (Chemistry) and Anthony Phillips (Biological Sciences) has significantly transformed voltammetry (an electrochemical test) to a clinical point-of-care repeatable measurement of oxidative stress.  It takes less than 5 minutes, uses no reagents and not much more than a drop of blood.

Patients are currently monitored after surgery using the familiar measures of heart rate, blood pressure, urine output, oxygenation and temperature. Accurate monitoring is very dependent on well-trained nurses. As whole body measures, they do not indicate what is happening at the cellular level. Voltammetry allows monitoring at this more fundamental level. Oxygen free radicals are generated by stressed mitochondria in cells (and inflammatory cells) and these increase with surgery, complications and many other diseases. Rampant free radicals result in depletion of our body’s antioxidant defenses. This imbalance, or oxidative stress, has serious consequences because unquenched oxygen free radicals cause widespread damage to lipid cell membranes, DNA and proteins. Voltammetry provides a quantitative measure of the most important low molecular weight antioxidants and a measure of total anti-oxidant capacity.

The 3-year SAVE programme provides the opportunity to refine and validate this technology for use in patients, prepare it for commercialisation and to validate the early detection of postoperative complications.  It also provides the opportunity to work with the other performers to integrate this technology with other approaches to patient monitoring to accurately predict patient deterioration (to allow early intervention) or recovery (to allow early discharge).

The urgency implicit in the research model used by Wellcome Leap is shaping the way science is done and funded. They take greater risk, create synergistic networks and fund on progressive milestones. It gives hope for solutions that will make a global difference.

[1] Dugan and Gabriel.  Changing the business of breakthroughs.  Issues in Science and Technology.  2022; 70-74.