Prof. John Crown, UCD Medicine Class of 1980, is one of Ireland’s leading medical oncologists, balancing a career as a consultant oncologist, researcher, professor, advocate, journalist and, from 2011-2016, an independent senator in Seanad Éireann.

Prof. Crown studied and trained in Ireland, the UK, and the USA at Mount Sinai Medical Centre in New York, working under the late, visionary founding figure of oncology Dr James Holland, and later at Memorial Sloan Kettering Cancer Centre (MSKCC), before returning to Dublin as Ireland’s 4th medical oncologist. Since his return, he has been a consultant oncologist at St Vincent’s University Hospital (SVUH) Dublin. We spoke to him about his career and the future of medicine.w

On activism and healthcare reform advocacy… 

It’s bizarre the way we run our health system. In general, in socialised health systems, there are 2 ways of doing it. One is called the Beveridge model, after Beveridge, the British civil servant of the 1940s. In this system, you take general taxation and the government provides healthcare. That’s a good way to do a subsistence healthcare system, but it doesn’t tend to lead towards excellence and it produces mediocre outcomes. For example, cancer survival in the UK is disappointing. Generally, it’s not the best way to run things.

The other socialised model is the Bismarck model, which was named after the Iron Chancellor himself. Introduced in Germany in the the 1880s, it survived world wars, German division and reunification, depression, and war-time national destruction. It’s a very good model, a model of social insurance where everybody must have cover, which is mostly provided by not-for-profit insurance, and the amount one pays depends on one's income. The money is then used to reimburse the activities of the hospitals, doctors etc. It’s a little more expensive but you tend not to have waiting lists and you get better access and less bureaucratic strangulation than you do with other systems.

Our system is full of paradoxes. We have the highest number of medical schools per head of population of any western country, while also having the smallest number of carer level medical posts. We have contrived to be simultaneously one of the leading exporters of doctors, while also being one of the leading importers of doctors. We have the longest waiting lists in the OECD. Only the UK NHS begins to approach us for wait times.

In the general election cycles in 2007 and 2011, both Fine Gael and Labour in opposition said that that they would push for the Bismarck model. I started advocating for it and endorsing their policies. I was elected to the Seanad in 2011 and continue the agitation for reform. Disappointingly, when they got into power in 2011, they quickly dropped the plan to reform the health service and to be quite honest with you I became very disillusioned. I’ve kind of opted out now of health care reform advocacy. I continued to highlight health deficiencies but knew there would be no reform. The fight has gone out of me at this stage. They’re never going to fix it, and the Sláintecare thing is patently absurd. Sláintecare is not going to counter the problems in the healthcare system, it’s finessing a little bit about the edges but not dealing with the fundamental problems. There is no will to do that. Maybe somebody else has the will to start advocating, but at this stage, I don’t. I decided not to run again in 2016.

On advice to a future generation of medics…

Go abroad. In my generation we always had to train away, and I think it was really good for Irish medicine that people spent a lot of their time training in big international centres of excellence. While we had, and have, very good nurses and nursing training here, we had consultants nearly to a woman and a man who had trained abroad in very good centres. That kept up standards at home. So, I’m a little concerned at the “you must train in Ireland” approach that we are developing. I was conceptually opposed to domesticating senior training in Ireland. I still am, and I’d like to see more people training abroad for more of it.

What I don’t like about the Irish system is that it has become a closed shop — if you don’t train in Ireland’s SpR system, you’re basically told you can’t get a consultant’s job, and I think that’s a mistake. Imagine you’ve trained somewhere like Harvard for 5 years, and you become a professor there. Are they really not going to give you a job in Ireland because you weren’t an Irish registrar? That’s the logic of the current system and I think that’s wrong. Part of it is a culturally small-minded attitude that we have. We like to “have a look at you” and see what you’re like before we give you a consultant job. We have incredibly good oncology trainees and I’m delighted that they do, by and large, get a chance to train abroad for now — the more time abroad the merrier. For the record, I don’t feel one bit upset by people who emigrate and decide not to come back. Until we fix the career and training structures in Ireland and stop using NCHDs as “paid staff” and start regarding them as trainees, deciding not to to work in the Irish system is a valid choice.

On becoming an oncologist…

Growing up in the States as a child in the ‘60s (I lived there ‘till I was ten), cancer was a big thing. The Americans at the time had a sense that American science was gradually fixing all the world’s technical problems. Maybe cancer was next. Very unusually in my class in medical school, from the time I went in in to pre-med I knew what I wanted to do, and that was to be a cancer specialist. I never deviated from that. I hate the tragedies I see every day, but I am endlessly fascinated by the potential of new treatments.

On breast cancer research…

Breast cancer remains a huge tragic problem around the world. It has however been one of the most successful areas of cancer research, with many scientific advances being translated into improved patient outcomes. I have been lucky enough to have a bit part in some of them. A very important influence in my life was Dr Larry Norton, who nudged me in the direction of breast cancer. When he became the head of the breast cancer service in MSKCC I was his first recruit and I helped him build up that service over the next few years. MSKCC is like Disneyland for oncologists. It was very inspiring to work in a place where everyone wanted to cure cancer, and where everyone thought that doing so was the right thing. When I came back to Ireland in 1993 on the other hand, oncology was often just seen as another drain on resources. You were made to feel that you were just contributing to the problems of waiting lists for other things if you were trying to spend money on cancer. It was very difficult.

When I left New York, I was involved in a field of research trying to cure advanced, incurable secondary breast cancer by giving very big doses of chemotherapy. The theory was that since secondary breast cancer was sort of chemotherapy sensitive, but sadly not curable by chemotherapy, maybe if you give a bigger dose you could finish the job off. Of course, the problems with bigger doses, due to the lack of specificity with chemotherapy, is that you also get higher toxicity. The principle dose-limiting toxicity was myelosuppression. The practice of giving very large doses of chemotherapy in treating other cancers, supported by infusions of the patient’s own hematopoietic stem cells, had evolved to make it a very standard treatment in many blood cancers - lymphoma, myeloma, and some leukaemias. So we thought we should study it in metastatic breast cancer.

I got involved very early on, in fact I was running the programme for it in MSKCC by the time I left. It would be hard to think of a enterprise that would have been harder to do in a very underdeveloped cancer service such as I found in Ireland in 1993, but we actually did it. We ran two big international trials from SVUH, one in high-risk early stage and another in secondary breast cancer. In 1998, the first 4 randomised trials were published — 3 negative, 1 positive — and it transpired that one of the leaders in the field, who was working in South Africa and published the positive trial, published fraudulent research. The field quickly died. This was disappointing as one of our studies actually showed some benefit. This was terribly disappointing for the women who faced this dreaded diagnosis and especially for the brave women who joined the studies. On a personal level, I thought this was going be an improved treatment and was going to cure some patients with secondary breast cancer. It all came crashing to the ground very disappointingly.

I had already got St Vincent’s involved in the original Herceptin randomised trial, one of the first studies we opened here. We succeeded in getting one patient involved in what became one of the most widely-cited trials in medicine. By the time the next Herceptin trial came around, I was a co-author and by the one after that I was co-principal investigator with Dr Slamon. This was published in the New England Journal of Medicine. It studied Herceptin in patients with early stage HER2+ disease, meaning with no distant secondary disease. In this setting, treatment with chemotherapy plus herceptin has made a colossal difference to the risk of the cancer coming back.

The difference is even bigger than we thought because, the difference between the chemotherapy alone arm and chemotherapy plus herceptin arm is big but it doesn’t look like it was completely different. However, what people forget is that the chemotherapy alone arm was already very good, because chemotherapy was most active in HER2+ breast cancer. Chemotherapy plus herceptin have made relapse with secondary disease a distinctly uncommon event. It is probably somewhere under 20% and in some studies, it’s even lower.

Before I left New York, I had also been exposed to some of the newer beginnings of molecular oncology. Around 1997, we had a visit to St Vincent’s from a California cancer researcher called Dr Dennis Slamon. Dennis had been working for many years on a type of breast cancer that had a very specific abmnormality called the HER2 alteration, which made it more dangerous. He helped develop a drug called Herceptin, which revolutionised the treatment for this disease. His initial work was greeted with scepticism, but he persevered and was proven correct.

In about 1999, I fortuitously found myself seated next to Dr Slamon for a long flight. I got a one-to-one four-hour private mid-air tutorial on the new field of molecular oncology. It was “my road to Damascus moment”. lt was transformative for me and I came away from it thinking, “Well, we tried the chemo, let’s try something else”. So I got reformatted towards molecular oncology from 1999 onwards and I must say, I’ve done rather little chemotherapy research since then. It's been all molecular.

We also did research, led by my ex-SVH colleagues, Professor Giuseppe Gullo, which was published in the British Journal of Cancer last year, which showed that patients who got chemotherapy and herceptin and then had surgery had a better result than those who had the surgery first. Surgery first was the usual way of doing it. In that trial, about half of the patients who went for surgery had virtually no cancer left when they went for the operation.

We then got involved in the Katherine study, in which patients who had residual cancer following preoperative chemotherapy plus herceptin were randomly assigned to get a new drug called TDM1 or more herceptin. The TDM1 drug is a stunning bit of biotechnology. It’s a Herceptin molecule with chemotherapy stuck onto it. That trial was strongly positive. We were co-authors on that paper, published that in the NEJM in December gone by. So, we’ve had a good run at HER2+. In reality, we’ve shown that some patients in our database with HER2+, metastatic disease, get cured — people getting 8-year or 10- year remissions from secondary breast cancer. We’re starting a new study here soon called the Caroline-1 trial which we hope will make that even better by adding another drug in with the current standard drugs. Caroline Hickey Dwyer was a young lady who died in her 30s from breast cancer and her family have done tremendous fundraising for us through an organisation called the Caroline Foundation which sponsors some of our researchers. Our new generation of trials will all be named after her. We will be starting that, I hope, as soon as next week.

I’m now on the advisory board for Dr Slamon’s international group and we’re just about to open up a new study in Ireland that he’ll be leading internationally but I’ll be leading in Ireland looking at a new molecular drug in early stage breast cancer.

On his current research efforts and the future of breast cancer treatment…

There is a drug called palbociclib, which has a really interesting story. A man called David Fry was working with a company called Warner Lambert many years ago. He is a chemist, and they developed palbociclib an anti-cancer drug that is active on the cell cycle. Dr Slamon’s group then showed that the drug was quite active in in-vitro. Contrary to expectations that the drug would work best in the most aggressive cancers, i.e. those with altered HER2, in fact, it had a very big effect on estrogenreceptor positive cells. So they started a trial and they were seeing some evidence of activity but they were having real trouble with recruitment. He contacted me asking for help, so we put a large number of Irish patients on the study and we saw some stunning results. That first study which became known as Paloma-1. St Vincent’s really had a big role in putting that drug on the map. By the time the second study, the confirmatory trial, came around there were Irish patients on that trial, too, and Dr Janice Walshe of St Vincent’s led the Irish effort.

On where other cancer treatment will go in the next 10 years…

While cancer biology is the biggest target, we also had a great big piece of unanticipated good luck the last few years with respect to immunotherapy. We thought old immune therapies weren’t very good because the immune system wasn’t good at recognising cancer as foreign. Cancer is after all our own tissue gone rogue. To quote Pogo “We have met the enemy and he is us” That’s what cancer is. It is us. We thought the immune system just can’t do it and we were wrong. The immune system was actually much better at recognising many cancers as foreign than we realised. There are however natural checkpoints in the immune system that stop it from giving us all auto-immune disease, like rheumatoid arthritis or ulcerative colitis. Cancer is relatively protected by those checkpoints. It was a discovery by Jim Allison and Tasuku Honjo (joint winners of the 2018 Nobel Prize in Physiology and Medicine) that found these checkpoints and showed that the checkpoints can be turned off. It has absolutely revolutionised cancer therapy.

So, I think we are going to see colossal improvements in the immune treatments. The cancer burden will continue to be very big, however, because we are living longer. In lung cancer, immune treatment has been transformative, and in melanoma it is really unbelievable. Melanoma is an increasingly big problem in Ireland — we may have the biggest melanoma incidence in the world. Immune therapy also work somewhat on cancers such as oesophageal, gastric, renal similarly on cervical, a subset of patients with colon cancer. Even some rarities like merkel cell cancer have proven to be really sensitive to immune treatment.

The first really good news story we’ve seen in triplenegative breast cancer, which historically has not had good treatment, was a recent trial that saw benefit in patients treated with immune therapy.

I think we will also see huge movements in early detection. The first confirmatory data that showed a big improvement in lung screening has, for cigarette smokers and former cigarette smokers screened with CT scans, colossally reduced their chances of dying with lung cancer. Mammographic screening is crude, it works but we need better technologies. Cervical screening is going to improve dramatically now with the introduction of HPV screening — everybody needs to get their vaccine. It will make cervical cancer deaths a rarity. We need smoking control. Put an extra €5 on every packet of cigarettes and ring fence the money for lung cancer screening, cardiac disease, COPD, and new cancer drugs. Stop whingeing about it, and just do it!