How John Gorman’s Anti-D Discovery Saved Millions of Babies — And Why Scientists Are Reinventing It

⏱ In 30 Seconds

✓ Australian physician Dr John Gorman helped develop anti-D immunoglobulin, transforming the prevention of Rh disease and helping save millions of babies.
✓ Before anti-D became available, Gorman recalled that around 10% of neonatal deaths in Melbourne were caused by Rh disease.
✓ Anti-D reveals an extraordinary paradox: the same type of antibody that can destroy an RhD-positive baby's red blood cells can also prevent the immune response that causes the disease.
✓ More than 60 years later, Professor Ian Wicks, Dr Behnaz Heydarchi and researchers at WEHI and Australian Red Cross Lifeblood are developing a recombinant anti-RhD antibody that could reduce dependence on rare human plasma donors.

The Story Hidden Inside a Routine Injection

For most pregnant women in Australia today, discovering that they are RhD negative is unlikely to cause much alarm.

There may be an extra blood test, an injection during pregnancy and, in some cases, another after delivery. What now appears routine hides one of the most remarkable stories in modern medicine.

Before anti-D immunoglobulin became available, incompatibility between a mother’s blood and that of her baby could have devastating consequences. A healthy woman could lose one baby after another. Some babies were born severely anaemic or jaundiced. Others suffered brain damage or died before or shortly after birth.

This was not a rare medical curiosity. John Gorman, who encountered Rh disease while training in Australia, later recalled a statistic that is difficult to imagine today: at one point, around 10% of neonatal deaths in Melbourne were caused by Rh disease.

The mother’s own immune system was making antibodies against her baby’s red blood cells.

Then, in the 1960s, an Australian doctor working in New York helped develop a solution that seemed almost counterintuitive: give the mother the very antibody involved in causing the disease.

The treatment became known as RhoGAM in the United States and anti-D immunoglobulin in Australia and many other countries. It transformed obstetric medicine and has been credited with saving millions of babies.

One of the scientists at the centre of that breakthrough was Australian physician Dr John Gorman.

For this work, Gorman would later share one of medicine’s most prestigious honours, the Albert Lasker Clinical Medical Research Award.

The medicine that emerged from the discovery developed an equally remarkable reputation. Gorman has described RhoGAM as possibly “the safest medicine in human history.”

Yet more than 60 years later, Gorman says the job is not finished.

The problem is no longer whether Rh disease can be prevented. It can. The problem is whether every mother who needs that protection can actually receive it.

At WEHI in Melbourne, Professor Ian Wicks, Dr Behnaz Heydarchi and their collaborators at Australian Red Cross Lifeblood are now trying to reinvent anti-D — replacing a medicine still dependent on the plasma of rare human donors with a recombinant antibody that could potentially be manufactured reliably and at scale.

Why reinvent one of medicine’s greatest success stories? Because knowing how to prevent a disease is not the same as making that prevention available to everyone who needs it.

When a Mother’s Immune System Turns Against Her Baby

Human red blood cells carry many different molecules on their surface. One of the most clinically important is the RhD antigen.

People whose red blood cells carry the D antigen are RhD positive. Those who do not are RhD negative.

Usually, this difference causes no problem. Pregnancy can change that.

For Rh disease, one combination matters above all: an RhD-negative mother carrying an RhD-positive baby.

Importantly, potential risk arises only when an RhD-negative mother carries an RhD-positive baby and fetal red blood cells enter her circulation.

Her immune system may recognise the RhD antigen as foreign and begin producing antibodies against it — a process known as RhD alloimmunisation, or sensitisation.

The first pregnancy may escape serious harm because the immune response often develops relatively late. But the immune system can remember the encounter.

During a later RhD-positive pregnancy, memory B cells can rapidly produce IgG anti-D antibodies. These antibodies can cross the placenta, bind fetal red blood cells and promote their destruction.

The result is haemolytic disease of the fetus and newborn, or HDFN.

In severe cases, the baby can develop profound anaemia, hydrops fetalis and dangerous levels of bilirubin after birth, potentially causing neurological injury or death.

Before effective prophylaxis, it was one of the great unresolved problems of obstetric medicine.

For the young John Gorman in Melbourne, it was not something hidden in a medical textbook. He saw what it could do.

From Melbourne to New York

John Gorman graduated in medicine from the University of Melbourne in 1953 and later moved to the United States, where he worked at Columbia Presbyterian Medical Center in New York.

There he joined obstetrician Vincent Freda and protein chemist William Pollack in trying to solve the Rh disease problem.

Scientists already understood the basic sequence: an RhD-negative mother encounters RhD-positive fetal red cells, becomes sensitised, and may later produce antibodies capable of threatening another RhD-positive baby.

The question was how to stop sensitisation.

Gorman and his colleagues began thinking in almost the opposite direction: what if they deliberately gave the mother anti-D?

It seemed counterintuitive because anti-D was the very antibody involved in the disease. But they reasoned that passively administered anti-D might prevent the mother’s immune system from developing its own long-lasting anti-D response.

That idea led to one of the great paradoxes in immunology.

The Antibody That Can Kill a Baby — And Save One

The antibody that can help cause Rh disease is also the antibody used to prevent it.

In an already sensitised mother, her own IgG anti-D can cross the placenta, bind her baby’s RhD-positive red cells and promote their destruction.

Yet when anti-D immunoglobulin is given to an unsensitised RhD-negative woman at the appropriate time, it can have the opposite effect.

The administered antibodies bind RhD-positive fetal red cells that have entered the maternal circulation and help clear them before the mother develops a strong immune response.

She therefore does not establish the dangerous immune memory that could threaten a later pregnancy.

The same antigen. The same type of antibody. A completely different outcome.

Remarkably, even after more than half a century of successful clinical use, the complete mechanism of anti-D immune suppression is still not fully understood. Rapid clearance of fetal red cells is considered important, but Fc-receptor interactions and other immune mechanisms may also contribute.

That unanswered biology would become important again decades later. First, however, Gorman and his colleagues had to prove that their extraordinary idea worked.

An Experiment From Another Era

Gorman and Freda initially tested the concept using RhD-negative male volunteers at Sing Sing prison in New York.

The volunteers were exposed to RhD-positive red blood cells, while some also received passive anti-D.

The experiments indicated that administered anti-D could suppress active RhD sensitisation.

But demonstrating the principle in male volunteers was one thing. Preventing Rh disease meant showing that it could work in pregnancy.

For Gorman, that next step became remarkably personal.

The Volunteer Was His Sister-in-Law

John Gorman’s younger brother Frank was a doctor, and Frank’s wife, Kath, was a nurse.

Kath was RhD negative, Frank was RhD positive, and in 1964 Kath was pregnant. She was exactly the kind of woman the experimental treatment was intended to protect.

Kath and Frank understood both the risk of Rh disease and the experimental nature of the treatment, and they agreed to try it.

The anti-D preparation travelled from New York to Britain, where the couple were living. Kath later recalled that it arrived at Heathrow Airport in an ordinary foam container sealed with tape.

It was an unremarkable package carrying an extraordinary idea.

Kath received the anti-D. After giving birth to an RhD-positive baby, she did not become sensitised and later gave birth to another healthy son.

For the Gorman family, the result was deeply personal. For medicine, it provided further evidence that an idea that seemed almost backwards could actually work.

From Experimental Antibody to Routine Medicine

By the late 1960s, anti-D immunoglobulin was entering clinical practice.

RhoGAM was introduced in the United States in 1968. Australia also moved rapidly, establishing a national Rh program and making anti-D available to pregnant women who needed it.

With appropriate prophylaxis, the risk of RhD sensitisation can be reduced to well below 1%.

A disease that Gorman remembered accounting for around one in ten neonatal deaths in Melbourne became increasingly uncommon in countries with reliable screening and anti-D prophylaxis.

Children who might once have died were born healthy. Women who might have lost successive pregnancies could have healthy families.

Anti-D became one of the great success stories of preventive medicine.

Recognition

In 1980, John Gorman shared the Albert Lasker Clinical Medical Research Award with Vincent Freda, William Pollack, Cyril Clarke and Ronald Finn for their contributions to the development of Rh immune globulin and the prevention of Rh haemolytic disease.

The Lasker Awards are among the most prestigious honours in biomedical research and medicine.

Gorman’s story also connects with a broader history of Australian biomedical scientists recognised by the Lasker Awards, including scientists associated with Melbourne’s WEHI. You can read more in WEHI's Three Lasker Award Winners: Burnet, Metcalf & Miller.

More than four decades later, in 2024, Gorman was appointed an Honorary Companion of the Order of Australia for his contribution to the prevention of Rh disease.

“The Safest Medicine in Human History”

John Gorman has described RhoGAM as possibly “the safest medicine in human history.”

It is an extraordinary claim, but its safety record is remarkable.

Current U.S. prescribing information for RhoGAM states that no fatalities have been reported from anaphylaxis or any other cause related to its administration.

After more than half a century of use in millions of women, that is an exceptional record for a biological medicine.

There is an important qualification: this statement refers specifically to RhoGAM used for RhD prophylaxis. Other anti-D products administered intravenously for unrelated conditions such as immune thrombocytopenia have rarely been associated with severe haemolysis and fatal complications.

For preventing RhD sensitisation in pregnancy, however, the record is extraordinary.

So why are scientists trying to reinvent it?

The problem is not that anti-D is unsafe. The problem is that too many women still cannot get it.

The Medicine Still Comes From People

Many modern biological medicines can be manufactured using recombinant technology. Anti-D remains different.

The anti-D immunoglobulin used in Australia is still derived from human plasma, and the donors need sufficiently high levels of anti-D antibodies.

That makes them exceptionally rare.

Australian Red Cross Lifeblood reports that most of Australia’s anti-D plasma comes from a regular donor pool of only about 115 people.

A medicine used to protect pregnancies across an entire country therefore depends heavily on a group of donors small enough to fit inside a lecture theatre.

Their plasma is collected and processed to manufacture anti-D immunoglobulin. The system works remarkably well, but it is difficult to scale.

Internationally, the problem is much greater.

A Medical Triumph That Has Not Reached Everyone

WEHI researchers working on the next generation of anti-RhD therapy estimate that around half of pregnant women who need plasma-derived anti-RhD prophylaxis worldwide do not have adequate access to it.

HDFN remains dramatically more common in lower-resource countries.

This creates an uncomfortable contradiction. Medicine solved the fundamental scientific problem of preventing RhD alloimmunisation more than half a century ago, yet babies still suffer from a largely preventable disease because the prevention does not reach everyone.

The World Health Organization includes anti-D immunoglobulin on its Model List of Essential Medicines.

It is not an experimental treatment or a luxury medicine. It is an established preventive intervention considered part of essential healthcare.

Yet access remains profoundly unequal.

A Personal Note

What strikes me most about the anti-D story is that the fundamental scientific problem was solved more than half a century ago. We know how to prevent Rh disease, and anti-D is included on the WHO Model List of Essential Medicines. Yet many women around the world still cannot reliably access it.

To me, that is a powerful reminder that a medical discovery is not truly finished simply because the science works. It also has to reach the people who need it.

There is also a personal connection for me. Professor Ian Wicks, a rheumatologist who leads this work at WEHI, was the senior author of our research on the IL-1β–GM-CSF pathway in acute rheumatic fever and is a clinician-scientist I have long respected. As I prepare to leave WEHI, I will be following this project with particular interest. I sincerely hope that Ian, Behnaz and the rest of the team succeed in bringing it all the way to the clinic — and ultimately to the mothers and babies who need it.

“The Job Is Not Finished”

More than half a century after helping develop anti-D prophylaxis, John Gorman has continued to advocate for the global elimination of Rh disease through the World Initiative for Rh Disease Eradication.

He has lived long enough to see a disease that once killed large numbers of babies become uncommon in countries such as Australia and the United States.

But that success is not universal.

His assessment is simple: The job is not finished.

Remarkably, the next chapter takes the story back to Melbourne, where Gorman’s own medical career began.

Back to Melbourne: The WEHI Team Reinventing Anti-D

At WEHI, Professor Ian Wicks, Dr Behnaz Heydarchi and collaborators at Australian Red Cross Lifeblood are working to develop a recombinant anti-RhD antibody.

Their goal is not to replace Gorman’s discovery, but to overcome one of its remaining limitations by developing an anti-RhD antibody that can be manufactured using recombinant technology.

If successful, such a medicine could be standardised and manufactured at scale, potentially making anti-D easier to supply in parts of the world where plasma-derived prophylaxis remains difficult to obtain.

But scientists cannot simply manufacture any antibody that binds RhD. It also has to behave correctly in the immune system.

That brings the story back to the immunological mystery Gorman exploited more than 60 years ago.

Why the Fc Region Matters

An antibody has two broad functional components.

Its antigen-binding regions recognise a target — in this case, RhD — while the Fc region communicates with the immune system, interacting with receptors on immune cells and influencing what happens to an antibody-coated cell.

For anti-D prophylaxis, that function may be critical.

Professor Wicks and colleagues have therefore investigated whether engineering the Fc region of anti-RhD monoclonal antibodies can improve their activity.

In research published in Blood Advances, selected Fc-engineered antibodies showed substantially improved functional activity while maintaining recognition of RhD, approaching the activity of plasma-derived polyclonal anti-D in laboratory assays.

That provided an important proof of principle, but the researchers have also taken another approach: instead of trying only to invent the ideal antibody, why not examine what the human immune system has already produced?

180 Antibodies, One Lead Candidate

Anti-D plasma donors provide a natural library of antibodies against RhD.

Using approaches including next-generation sequencing, proteomics, antigen-binding studies, functional assays and epitope mapping, the WEHI–Lifeblood team has examined approximately 180 human anti-RhD antibodies.

From them, the researchers have identified one lead monoclonal antibody clone.

According to WEHI’s 2026 development program, that candidate is undergoing further optimisation and evaluation, including studies of its function and recognition of different RhD variants.

The ultimate aim is a safe, standardised and scalable recombinant anti-RhD antibody that could reduce dependence on plasma-derived anti-D.

It is still research, and there is no guarantee that a successful laboratory antibody will ultimately become an approved medicine.

That uncertainty is precisely why the research continues.

From Melbourne to the World — And Back Again

As a young doctor in Melbourne, John Gorman encountered a disease responsible for an astonishing proportion of neonatal deaths.

He travelled to New York and, with Freda, Pollack and others, helped turn one of immunology’s strangest paradoxes into a medicine.

The antibody that could destroy a baby’s red blood cells became the antibody used to protect babies from that destruction.

Anti-D went on to protect millions of babies and made Rh disease increasingly uncommon in countries with reliable access to prophylaxis.

More than 60 years later, part of the next chapter is being written back in Melbourne. Ian Wicks, Behnaz Heydarchi and their colleagues are not trying to rewrite John Gorman’s discovery. They are trying to extend its reach.

In the 1960s, the question was: Can we prevent Rh disease?

Today, the question is: Can we make that prevention available to every mother who needs it?

John Gorman helped answer the first question. The answer to the second is still being written.

The job is not finished.

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This article is intended for general educational purposes. Readers seeking a more technical account should consult the original scientific publications and specialist sources.

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