Funding original ideas

The Nobel Prize in medicine and physiology was given to Barry Marshall and Robin Warren in 2005 (Sweet, M., “Smug as a bug.” Sydney Morning Herald, August 2 1997). They had discovered that a germ, helicobacter pylori, was the cause of gastritis and ulcers, when this went against conventional thinking. They had benefited humans with their discovery and rightly deserved the prize and the recognition.

Professor Marshall has been made a Fellow of the Royal Society and a Fellow of the Academy of Science in Australia, both very appropriate awards for any Nobel laureate.

But they were ridiculed by establishment scientists and doctors, certainly early on because their theories did not “fit” with mainstream thinking.

They applied for, and did not win, a project grant from the National Health and Medical Research Council (NHMRC) in 1983 for a project which embodied their views. They were funded the following year when the grant application went through their hospital.

The consensus view then (and I was one researcher in their field) was that acid was an essential component of ulcers and, since their infection theory did not mention acid, it was assumed that it must be mistaken. It was only when all of Koch’s postulates were satisfied that people came to accept the radical ideas which Marshall and Warren were promoting. The then current view correctly talked about the balance between acid and protection but did not realise that an infectious agent was the cause of diminished protection.

Had Marshall and Warren been totally dependent on peer review grants from the NHMRC, they would not have been able to do their work. A commentator has written: “There is no way that program funding would have been made available to a gastroenterology registrar and a hospital pathologist.” One wonders: why not? It is the idea and not the person who matters.

To be fair to the NHMRC they didn’t do nothing. In 2003, 20 years after the first rejection and just before Marshall and Warren got the Nobel Prize, the NHMRC again declined to fund Warren and Marshall. In 2006 Professor Marshall spoke to the new CEO of NHMRC soon after his appointment and consequently the NHMRC decided to establish special scholarships for those scientists awarded the Nobel Prize.

And so they should!

It seems that the system, careful as it is, failed in this instance. By the way, this treatment is in contrast to the treatment by the University of Western Australia and the Government of Western Australia which have been generous and quick with their support.

The error seems to have been one that statisticians call “confounders”. One can say that all rapists have eaten mashed potatoes, but one cannot then say that mashed potatoes cause rape. Similarly, one can observe that most people with duodenal ulcers have high levels of acid, but it does not follow logically that those acid levels cause duodenal ulcer. Yet that is the line of thinking that conventional research was pursuing.

It is not as if what happened in this instance was unique and was an accident. History is littered with examples that show similar failures to support ground breaking different ideas when those ideas have been heterodox.

First, we might consider the Great Plague in London in the 1600s. The consensus view at that time was that the fatal illness may have been caused by birds or miasmas and that long bird shaped facial masks with bunches of flowers or strong smelling herbs in the end were a protection against the birds and bad smells, and therefore against the plague. After all, those who wore the masks were not being attacked by birds, and were breathing the sweet smell of the flowers, not the bad smells of the environment. If someone at a consensus meeting then had stood and suggested that little bacteria, invisible to the naked eye, were the cause of bubonic plague, that person would have been laughed out of the meeting. The people responsible devised a logical - albeit an incorrect and ineffective - means of addressing the disease.

The conventional view of the time was wrong.

If a granting body of that time was giving money for medical research, it would have given money for projects about masks, shaped like a bird’s beak with flowers in the ends. It might have given money for projects looking at better shaped masks or the distance the flowers had to be away from the nose or whether some types of flowers or strong smelling substances were superior to others, and so on. It would have withheld money for anyone who dared to suggest a more modern cause of the plague.

Second, up to the time of Nicholas Copernicus everyone followed the cosmological theory of Ptolemy (Goldstein, Bernard R., “Saving the phenomena: The background to Ptolemy’s Planetary Theory: History of Astronomy, 28, 1997). It was Ptolemy who assumed that the earth was the centre of the universe - the so-called geocentric theory - and that all planets and stars rotated around the earth. Ptolemy’s theories were consistent with observations at that time and with religious beliefs and they had unquestioned acceptance for 1,400 years.

Followers of Thomas Kuhn will know that many theories are accepted initially if they fit with current observations, but that those theories develop flaws with continued observation, “scientific revolutions” then occur and that another paradigm is likely to emerge.

The flaws in Ptolemaic cosmology had become increasingly serious. There was a need to propose the existence of crystal spheres, invisible to humans to make the Ptolemaic theory work still - so that theory was ripe for revision.

Then along came Nicholas Copernicus (Hoyle F., The World of Nicolaus Copernicus, Proc. Roy. Soc. London, Ser A336, 1974). He published his learned book The Revolution of the Celestial Orbs in 1530. Had he been dependent on peer review then he would have got no money to do his work.

The historical story does not end there. Galilei Galileo was a mathematician and philosopher. He was arrested by the inquisition after he published his book Dialogue on the Ptolemaic and Copernican systems and he had to recant his views under threat of torture. The Church even had a special name - “the heliocentric heresy” (Brooks, G., People of the Book, Fourth Estate, 2008) - for what was being written and said by people like Galileo. It took the church 350 years to admit that Galileo had been on the right track all along (“Vatican admits Galileo was right” New Scientist, November 7, 1992). Galileo would have failed to get a project grant to support this work under a peer review system.

If you want a bit more history consider the story of Ignaz Phillip Semmelweiss. This Hungarian physician believed that hand washing, particularly after autopsies, cut the incidence of puerperal fever from about 10 per cent to 2 per cent. He had evidence to support his claim which ran counter to contemporary continental theories which were based on innate individual factors being the cause of puerperal sepsis. He was ridiculed because it was “known” that childbed fever was spread by the hysteria of the birthing mothers and couldn't possibly be attributed to doctors who wiped their hands on their frock coats. He was derided and ridiculed by his colleagues, was forced to resign his post in Vienna, move to Budapest, and was eventually committed to a mental institution where he quickly died.

He was proven right eventually about the cause of puerperal infection. It was just that microbiology was not a science then and germs, as a cause of disease, were not understood.

Under a peer review system he would have done even worse than he did in real life.

Peer review of project applications rewards orthodoxy and conventional thinking, the use of accepted paradigms, and the placing of more bricks in walls that others have imagined and built.

When assessing projects for the NHMRC, for possible funding, one is asked to consider “track record” among other factors (e.g. Nicol, M. B., Heradeera, K., Butler, L, NHMRC grant applications: a comparison of “track record” scores allocated by grant assessors with bibliometric analysis of publications. Med. J. Aust., 2007, 187). This gives marks to established players in any field and mitigates against new entrants, particularly any not associated with an established laboratory or those espousing heterodox ideas. Using that criterion it is easy to understand why Warren and Marshall failed to get project funding. They got the Nobel Prize instead. And the NHMRC seems to have taken a Panglossian view of the whole awful event.

On the other hand, under a peer review system, we do get critical examination of what people want funding for (and often projects need critical examination) and then projects are “graded” to fit the available money. But remember, peer review funding would have supported long masks for preventing plague; Ptolemaic cosmology, however flawed it was; conventional theory about the causes of fatal puerperal fever; acid and not infection as the cause of peptic ulcers.

Official bodies give people project money for not challenging existing paradigms. The people who are asked to act as peer reviewers are themselves the “experts” in any area, the very people who might have invented prevailing theories or the people whose own work is based on prevailing theories.

Spinoza was excommunicated by the Jewish community of Amsterdam for having heterodox ideas (Russell, B., A History of Western Philisophy, George Allen and Unwin Ltd, London, 1948) and many others have suffered rejection and ridicule because their ideas were too radical. Authorities have generally not been comfortable with new and different ideas.

People who get project funding do make advances, but they are often incremental advances only. New bricks in old walls are worth having. It is a safe way of proceeding. It is risk averse but it is not world altering.

The opposite of peer-reviewed project funding might be called block funding where money is given to an institution, or a laboratory, or even to one person, and they are told to go away and think. Whenever one is given “tenure” at any institution of higher learning, one’s salary is guaranteed and one is expected to do some teaching and research and thinking in return.

The advantage of this system is that people are more willing to think in unorthodox ways, to develop new paradigms, to come from “left field” and to make some real progress. New walls are built for others to work on. Salaries are not at risk and it is “safe” to think in different ways.

The weaknesses of this system of block funding relate especially to how you pick institutions, or laboratories, or people, to support, and the means that institutions use to recruit new employees. Nepotism, or favouritism, or group attitudes (especially to the “other”) are potential problems; as is the possibility that selected people might not deliver the outcomes you hope for.

In the peer reviewed model there is less suggestion of partiality, or nepotism, or favouritism, or risk of ineffective appointments, (but not “no” - there are sometimes limited numbers of people in an area and all are known to all) all dangers with block funding.

One potential negative of the block funding model is that people might spend too much time down at the local pub and not enough time thinking. But, on balance, if only one was available, the block funding model seems better because it is essential for making the big advances. Luckily, both kinds of funding are available.

Some of my own academic colleagues were doing meaningless research. It was possible to challenge them with questions like: “How will the world be different if your work succeeds?” and “When you finish your research life, which part of your work will be remembered?” And they, too frequently, could not answer either question, partly because they had never considered either question.

There is no point counting the numbers of grains of sand on any beach. Such work would be original - but worthless.

The NHMRC disburses funds made available for biomedical research by the government of the day. It has processes which are transparent and thorough. But it did not give project funding to two people who went on to get the Nobel Prize. This should have led to a public, open and critical self examination of its methods - their validity and their robustness. One wonders did such an examination occur or whether the response was to apply a band-aid and hope the problem would not recur. You see, it is not that the NHMRC did nothing. What it did was the minimum and it did nothing to address the underlying problem. The belief seems to have been that the system is satisfactory, when, clearly, it is not.

Governments have been giving more and more support for project funding and have moved away from block funding. Project funding, alone, is a recipe for mediocrity and conformity.

If we want a nation that develops original ideas then we need to support people over projects.