Blood beyond Earth: Inspiration4, Polaris Dawn and Fram2

Blood connects every organ to the body's supply of oxygen. It is also a revealing place to study what happens when humans leave Earth. Changes in red-cell survival, blood volume and gene expression offer different views of adaptation to flight—and of recovery after landing.

For the Borg Group, space haematology brings an established interest in haemoglobin regulation into a remarkable setting. Inspiration4, Polaris Dawn and Fram2 form an expanding sequence of opportunities to study human biology beyond Earth. Their scientific contributions are best understood alongside the longer-duration NASA and JAXA studies that helped establish the field.

Globin and regulatory-gene expression in plasma cell-free RNA from six JAXA astronauts, before, during and after flight. Figure 3 from Borg, Loy, Kim and colleagues, Nature Communications (2024), reproduced without alteration under CC BY 4.0. Colours represent the paper's RNA-expression analysis; they do not directly measure the percentage of fetal haemoglobin in blood.

First, what does “space anaemia” measure?

Haemoglobin concentration, red-cell production and red-cell destruction are related quantities, but they answer different questions. Fluid shifts can change a concentration; sustained loss of cells raises a question about the balance between their production and removal.

A 2022 Nature Medicine study by Trudel and colleagues followed 14 astronauts on approximately six-month ISS missions. Using carbon monoxide elimination as a measure of haem breakdown, alongside blood markers, the researchers reported an average 54% increase in haemolysis during flight relative to pre-flight measurements. Five of the 13 astronauts assessed for anaemia four days after landing were anaemic.

That study makes red-cell destruction central to the discussion. It also shows why a description of a group average should not become a claim that every astronaut has the same clinical response.

Inspiration4 · 2021: a short flight, a detailed molecular record

The Space Omics and Medical Atlas, or SOMA, brings together clinical and molecular measurements with an international astronaut biobank. Inspiration4's four-person, three-day mission helped demonstrate how much biological information a short commercial flight could contribute when sample collection was planned carefully.

Our Nature Communications study examined haemoglobin-related expression across the NASA Twins Study, JAXA and Inspiration4. In Inspiration4, the analysed blood samples were collected before and after flight; they did not provide an in-flight expression time series. Post-flight changes included increased HBG2 expression relative to pre-flight measurements. Across cohorts, the patterns varied by gene, sample and time point.

These findings make globin regulation an interesting route into space biology. They support investigation of developmental programmes, while an RNA signal alone cannot establish an increase in HbF protein or a completed reversal of the fetal-to-adult switch. The published Inspiration4 figure lets readers inspect that expression evidence directly.

Polaris Dawn · 2024: following the physiology

Polaris Dawn flew from 10 to 15 September 2024, with Jared Isaacman, Scott Poteet, Sarah Gillis and Anna Menon. Alongside its spacewalk and orbital objectives, the mission carried a substantial research programme.

The blood-research connection had been announced earlier through a University of Malta collaboration with the Ottawa Hospital Research Institute. NASA also described health measurements supported by TRISH, including biological sampling around the mission.

In its April 2025 report of initial findings, the Polaris programme reported increased markers of red-cell damage in work involving Ottawa and Université Paris-Est Créteil. This is a mission-reported preliminary finding, rather than a peer-reviewed demonstration of fetal haemoglobin induction. Its significance here is the opportunity to connect molecular observations with the physiology of red-cell survival.

Fram2 · 2025: blood research over the poles

Fram2's March–April 2025 mission extended human orbital flight over Earth's polar regions. Its official research programme listed 22 projects, including two associated with the University of Malta.

Space THAL focused on blood health, anaemia and red-cell production in the spaceflight setting. MELITE addressed skin and tissue microbiomes, including diabetic foot ulcers, linking the mission to questions developed through Maleth. The programme also included biospecimen collection and broader space-omics research.

These descriptions establish the questions the projects were designed to address. They should not be read as published findings that Fram2 increased HbF, changed a specific globin regulator or demonstrated a treatment benefit. For readers following the programme, distinguishing an experiment's objective from its results makes each subsequent publication more informative.

How the missions can inform one another

For an integrated interpretation, each observation needs its context: who was sampled, which biological material was measured, how long the mission lasted, and whether collection occurred before, during or after flight. A plasma RNA measurement, an immune-cell expression profile and a red-cell haemolysis marker describe different parts of the same person.

Our interpretation is that the strongest comparisons will connect those layers while retaining their distinctions. A recurring expression pattern across independent cohorts would strengthen a biological hypothesis; a mismatch might reveal differences in timing, cellular composition or exposure. Neither should be hidden to make the story simpler.

This is also why comparison with inherited globin disorders needs care. The Maltese KLF1 families offer a genetic setting for persistent fetal haemoglobin. Spaceflight offers a changing environmental setting. Similar signals can motivate comparison without establishing an identical cause.

The Globin Switch Atlas provides a place to explore those connections. The opportunity is to make the relationship between a gene, a cell and a physiological response increasingly precise—and to keep the underlying evidence visible as the story develops.

Evidence reviewed on 24 October 2026. Peer-reviewed studies, institutional mission accounts and preliminary programme reports are identified in the text.