The man who saved 2.4 million babies, and the lab replicating his remarkable blood

A tall and good-looking man was waiting for Robyn Barlow in a bed bay on the ground floor of the Australian Red Cross Blood Transfusion Service at 1 York Street one afternoon in 1967.

James Harrison had a deep voice and a lovely smile, and cut a fine figure in his suit. Barlow sat at the end of the bed, and the pair talked as Harrison’s blood was slowly siphoned from his right arm. It was a ritual they would repeat with increasing frequency: every three months, then monthly and finally fortnightly.

“He is my hero,” Barlow says 58 years later.

A regular blood donation can save three lives. A plasma donation can save up to 18. Harrison was no ordinary donor. His remarkable blood helped save the lives of 2.4 million babies.

Known as the man with the golden arm, Harrison had blood that contained high concentrations of a potent antibody used to make the anti-D injections that protect unborn babies from a deadly and devastating condition called rhesus D haemolytic disease of the fetus and newborn (HDFN).

“Every ampoule of anti-D ever made in Australia had James in it until he retired [in 2018],” Barlow said.

Harrison died on Monday, February 17. He was 88.

His legacy is at the heart of a wild story about canny science, boundless goodwill, an errant blood transfusion, rhesus monkeys and rabbits vanquishing a devastating and deadly disease. It’s also a story of the search for the holy grail of anti-D research: reproducing what made Harrison’s donations so special in the form of laboratory-made anti-D serum, or “James in a jar”.

An exceptionally cruel disease

Before anti-D was discovered, HDFN killed more infants than almost any other disease and caused lifelong disability. Up to one in six newborns were at risk, amounting to 40,000 babies every year in Australia.

HDFN manifests when a pregnant woman with rhesus-negative blood (O-, A-, B- or AB-) is carrying a baby that has inherited their father’s positive blood type.

If that baby’s blood cells cross the placenta to the mother – which happens in almost every pregnancy – the mother’s immune system mistakes them for a foreign invader and produces antibodies that can cross back through the placenta to seek out and destroy the threat.

This defence system can have catastrophic consequences. HDFN causes miscarriage and stillbirth. Newborns who survive are born bloated, with brain damage or severe anaemia (a condition caused by a lack of healthy oxygen-rich red blood cells).

A woman’s first baby is usually spared, but her immune system is now “sensitised” and primed to fight off the next invaders: her child’s younger siblings.

The mother’s antibodies multiply, intensifying the reaction to her babies’ red blood cells with the potential to inflict increasingly severe damage with every subsequent pregnancy.

The Rhesus monkey and the rabbit

No one knew what caused HDN before the Rhesus factor was discovered in 1940. Scientists Austrian-American Karl Landsteiner and American Alexander Weiner injected the red blood cells of rhesus monkeys into rabbits. The monkey’s blood raised antibodies in the rabbits, but Landsteiner and Weiner also found these rabbit antibodies also reacted to the red blood cells of roughly 85 per cent of caucasian humans.

This 85 per cent had rhesus factor: the Rh-D protein in their red blood cells (Rhesus positive). The other 15 per cent who don’t have the Rh-D protein are rhesus-negative.

The ‘unvaccine’

In the late 1950s, a young doctor from Bendigo, John Gorman, hit upon a mad idea: what if the cause of HDFN was also the solution?

With his colleagues, American obstetrician Vincent Freda and immunologist William Pollack, Gorman theorised that injecting Rh-negative pregnant women with lower doses of the antibodies would “mop up” her baby’s Rh-positive blood cells before the mother’s immune system could detect them and mobilise its own antibodies.

It was an “unvaccine”, Gorman quipped. Vaccines trigger an immune response to protect against viruses. Anti-D, he theorised, would stop the immune response that caused HDFN.

Vincent Freda (left) and John Gorman.

After preliminary trials among male volunteers in Sing Sing prison, Gorman’s sister-in-law and nurse, Kath Gorman, was the first woman injected with anti-D (she went on to have seven children). Gorman announced the breakthrough at the International Blood Transfusion Congress in Sydney in 1966.

“It was a sensation,” Barlow said. “It was absolutely captivating.”

At the time, eminent Australian immunologist Gustav Nossal called the defeat of HDFN a revolution in medicine.

Within months, the Australian Red Cross Blood Service (now Lifeblood) was scouring its records for people whose blood contained pre-formed anti-D to establish the world’s first anti-D donor program.

Some of the first donors were mothers whose babies died of HDFN. Men soon followed, and Harrison was among them.

James’ marvellous immunoglobulin

It’s unclear why exactly Harrison’s blood came to be so rich in anti-D and sustained its potency for years, but it probably has a lot to do with a massive blood transfusion he received when he was 14 years old.

Harrison reckoned he needed 13 units (7.4 litres) of blood to survive the risky operation to remove most of his left lung. But he could not be sure because he was just happy to be alive. He swore to become a blood donor when he turned 18. Some of those units must have been Rh+ blood.

The first anti-D donors were given 20 millilitres of positive blood to maintain their antibody levels. Harrison’s body was flooded with the stuff.

“Who knows how many units were positive blood, but it was a jolly good thing that they were,” Barlow said.

Harrison, then an administrator at NSW’s railway authority, did not hesitate when the Red Cross asked him to join their anti-D program in 1967. In 2016, Harrison said: “They asked me to be a guinea pig, and I’ve been donating ever since.”

Fifteen years after the transfusion, Harrison still had sky-high antibody levels.

“Very few people have these antibodies in such strong concentrations,” said Jemma Falkenmire from Lifeblood. “His body produces a lot of them, and when he donates, it produces more.”

Barlow has no memory of the day she met Harrison.

“James talked about it all the time, but it was nothing special for me,” she said. As the Rh program co-ordinator, Barlow had 200 donors to look after. “He was a favourite, but I had many favourites.”

From left: Australian Red Cross Rh donor program nurse Liz Thynne, James Harrison and Robyn Barlow.

Harrison would emerge as the exemplar.

“He was almost too eager,” Barlow said. “Rules are rules, but we broke them for James. He’d come back 11 or 12 days after his last donation instead of waiting the [mandatory] two weeks. I’d call the director and say, ‘James is here. Can I bleed him, please?’”

The last donation

Harrison’s final tally was 1173 donations: 1163 from his right arm and 10 from his left (“It didn’t hurt in the right arm,” he would say). He never watched the needle go in.

Today, the number of Australian children who die from HDFN has fallen over a hundred-fold to about 0.01 deaths per 1000 – about four babies a year.

Every Rh-negative pregnant woman in Australia (about 17 per cent of all pregnant women) receives the booster at 28 and 34 weeks gestation and after birth.

Harrison’s daughter, Tracey Mellowship, was one of them.

“When I had our second son, Scott [in 1995], they’d run out of anti-D in Australia. They kept a vial for me because they knew I’d need it and shipped it out. His last vial. That was pretty special,” Mellowship said.

“He has left behind a legacy of so many families – including his own – that may not have existed without his unwavering kindness.”

Harrison would take Scott and his older brother, Jarrod, to the donor centre at Town Hall on school holidays. The cafe there is named in Harrison’s honour.

“We just loved the milkshakes we got afterwards,” Jarrod Mellowship said. “We didn’t realise what it was all about until he started getting Guinness World Records [for donating more times than anyone on the planet] and a Medal of Australia. But to us, he was just Grandad.”

Jarrod Mellowship’s partner, Rebecca, needed anti-D injections during her pregnancies.

“It’s pretty cool that part of him went into mum and got me a brother, then protected my kids, his great-grandkids,” Jarrod Mellowship said.

James Harrison’s grandsons Scott (left) and Jarrod (far right) with Jarrod’s wife Rebecca and the couple’s children (Daisy, 9, Jaycee, 2, Trey, 2, and Addison, 3 months).Credit: Edwina Pickles

James in a jar

In the 58 years since Gorman presented his anti-D therapy, the product has not changed. It is still wholly dependent on volunteer donors.

“Their blood is the only way we can prevent this disease,” said Professor David Irving, director of research at Lifeblood.

Australia has fewer than 200 anti-D donors. The program is labour-intensive and an enormous commitment for these volunteers, Irving said. All this requires world-first healthcare infrastructure, something many parts of the world do not have.

Creating a new therapy has long been a “holy grail”, Irving said. This dream of a lab-made anti-D is affectionately known among Lifeblood staff as “James in a jar”.

Professor Ian Wicks first came across the concept in a Good Weekend article in 2016.

Postdoctoral researcher Dr Behnaz Heydarchi (left) and Professor Ian Wicks.Credit: Simon Schluter

“That was the catalyst,” the rheumatologist and clinician-scientist at the Walter Eliza Hall Institute of Medical Research (WEHI) said.

“I thought: perhaps we could apply WEHI’s advanced technologies to try and capture this magic ingredient in naturally occurring antibodies found in the blood of donors like James Harrison.”

From blood samples donated by Harrison and about 30 other anti-D donors, Wicks and senior post-doctoral researcher Dr Behnaz Heydarchi isolated and sequenced fragments of the antibody proteins (a process known as proteomics).

“We also took the antibody-producing cells (called B cells) and performed next-generation DNA sequencing of the antibody genes,” Wicks said. “Then we matched the two pieces of data together to [find] what we predicted to be the anti-D antibodies from these men.”

They discovered several hundred individual anti-D antibodies that had to be produced in the lab and tested on red blood cells.

James Harrison, aged 20.

“We’re optimistic that we now have antibodies that compare favourably to the polyclonal mixture [the donor-derived anti-D],” he said.

Wicks’ team is now considering clinical trials, which will probably start with male participants before moving to trials in pregnancy.

“It will be really important for women to be front and centre in the design of these clinical trials and what they think would be ethically acceptable,” Wicks said.

He has begun engaging with women whose pregnancies and children have been affected by HDFN.

“It has been fascinating for us as researchers to see what is hopefully the next chapter unfold in this story, which all started with an idea from an Australian GP from Bendigo [Dr John Gorman], and involved such generous and altruistic people like James Harrison along the way, donating thousands of times to protect millions of women and babies,” Wicks said.

As for Harrison, he did not want anything in return for his gift, not even attention. “He was always very humble,” daughter Tracey said. “But I’m sure he secretly loved it.”

Barlow, who remained Harrison’s friend to the end of his life, said: “We have no way of adequately thanking him. James’ contribution to babies’ lives saved, and tragedies averted represents all that is good and enduring in our society.”

And he always wanted someone, one day, to beat his record.

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