Imagine how exciting it must have been to study medicine a hundred years ago.  Within a few years, the mediaeval dependence on purging, bleeding, cupping, sponging, the reliance on herbal remedies and the various charismatic cures was yielding to groundbreaking discoveries, based on scientific observation and experiment. Louis Pasteur had discovered the germ theory of disease with observations on anthrax, cholera, tuberculosis and smallpox and developed the use of immunisation.  Ronald  Ross had discovered the cause of malaria and a means to eradicate it.  Jean-Martin  Charcot had described the microscopic pathology of many common neurological illnesses.  Sigmund Freud was employing psychoanalysis to understand hysteria.  Wilhelm Roentgen had discovered X-rays and used them to generate images of the human body.  Marie Curie had identified radioactivity.  Ivan Pavlov’s work on the conditioned reflex heralded the science of psychology.   The herbal of the past was being refined and specific drugs were being manufactured.  Medicine was becoming scientific.  No longer would doctors sit beside the bedside of a patient with pneumonia administering sympathy and tepid sponging, He would soon be able to treat it.  Over the next fifty years, discovery built on discovery in every area of medicine.  Antibiotics were developed to treat infections.  Effective treatments were developed for ulcers, arthritis, high blood pressure, diabetes, colitis and depression.   The safe use of anaesthetics lead to surgical developments. Organs could be repaired, blood vessels dilated, tumours excised, cataracts removed and worn out joints replaced.  The discoveries occurred at such frequency and were so miraculous that by 1970 people looked forward to a time when all human illness would be vanquished and people would live, if not forever, for much longer.    


But that expectation was not realised.  Illness is still with us.  In fact, more people suffer from a long term illness now than did in the nineteen seventies.  The heady optimism in medical science has been replaced by a cynical and expensive realism.  Scientific medicine has lost its charm.  People are again reverting to charismatic treatments with little evidence to support them. There are few new groundbreaking discoveries. Much of the research that is done these days seems to repeat what is done in the past. More papers are published than ever before but the pace of real advance has slowed.  Why is this?    


Last week, I discussed this with my friend and colleague,  Professor David Thompson of Manchester University.   Our discourse ranged widely.  Ruminating with nostalgia on a gold age of academic freedoms, regretting the erosion of curiosity and the demise of the enthusiastic amateur, we concluded that regulation and control was stifling creativity.          


As a young lecturer in physiology I had established my academic reputation on a minimal budget by encouraging medical students to conduct simple experiments on themselves.  That would now be impossible. Low-budget blue-skies research no longer exists.  Ethics committees would frown.  Health and safety would forbid.  University finance officers would complain. 


Universities are businesses.  Government funding has declined.  They need to raise money from research and teaching.  For a young lecturer, advancement depends on more on grant income than the importance of the results, though it is to be hoped that the two are occasionally linked.  Research is highly competitive,  requiring complicated proposals and expensive funding.   


The great discoveries of the past often occurred as a result of painstaking observations.  Richard Ross dissected thousands of mosquitoes in his sweltering shack in Secunderabad before he found the one that contained the plasmodium larvae.  Charles Darwin took more than 20 years before he amassed sufficient evidence to write his theory of evolution.  Gregor Mendel meticulously pollinated 28,000 pea plants in the garden of the monastery at Brno.  Freud deduced his psychoanalytical theories from hour upon hour sitting behind his green leather couch, notebook in hand, listening to what his patients told him.  Each of them was free of the pressures of obtaining grants, justifying their existence.  Like artists and novelists, composers, they were compelled by curiosity.  This couldn’t occur now.  Universities, funding councils, biotech and pharmaceutical companies require gratification, if not immediate, pretty soon.         


Creativity, we agreed, requires an environment that is relaxed and free and supports curiosity.  But we live in a society under threat.  Global warming, terrorism, economic recession, unemployment, credit crunch, food contamination and depression affect us  us all.   Faced with threat, medical science like all other aspects of our society, has become controlled, restricted.  No longer can one make uncontrolled observations.  No longer can you have an open mind.  Scientists have to justify their activity all the time.  It is said that in order to obtain a grant, you already have to have done the experiments and shown they will work.  Otherwise, nobody would take the risk. 


Medical science, like other aspects of society has become risk aversive.  Perhaps the catastrophes of the past,  Thalidomide, the Alder Hey organ scandal, the Summerlin affair at Sloan Kettering, where Bo Summerlin faked his results,  have made scientists over cautious.  But while science must conform to high ethical standards,  it has also to embrace risk. 


Discovery favours the prepared mind, but the prepared mind also needs to be an open mind.  Medical scientists need to take intellectual risks, dare to be mavericks, stand up against the crowd for what they suspect to be true. 


This is more and more difficult to do.  Medical science is so bound by diagnostic criteria, accepted protocols, statistical method, peer review that it is impossible for its exponents to think out of the box.  The maverick is seen as dangerous and excluded.         


For example, common human ailments like Irritable Bowel Syndrome, Chronic Fatigue Syndrome, Fibromyalgia and Functional Dyspepsia that have no basis in pathology and no well defined cause, are defined by sets of rigid symptomatic criteria, determined by committee. To be published, all studies on unexplained illness  have to conform to this medical encyclical.  If a scientist ignores that, his work will not be published and his career will be stillborn.  The medical sociologist, David Armstrong, commented that such illnesses are representative of the medical textbook, as arbiter of the political belief system.  In other words, doctors determine what an illness will be like and the patients conform, just as they did when Jean-Martin Charcot defined La Grande Hysterie.  Yet, people with Irritable Bowels, for example often have a myriad of symptoms affecting other parts of the body.  They also have emotional disturbance.  Talk to them for a few minutes, it soon becomes clear that they are suffering from a state of dysphoria involving mind and body.  Many suffer from unresolved guilt or shame, others from fear, from despair and nearly all from loneliness.  But there no medical definition of guilt.  And no government agency would ever wish to acknowledge loneliness as the common ailment in western societies.  As Professor Bryan Tucker once declared, ‘Illness is a language, the body is representation and medicine is political practice.’ 


Clinical scientists are exponents of evidence-based medicine.  This means that their hypotheses are tested by randomised, placebo-controlled, double- blind clinical trials.  In other words a homogeneous population with the same illness is treated randomly with either a drug or an identical placebo, but both the patient and the clinical investigator is unaware of the identity of the treatment.  Such studies may assume a methodological rigour, but the reality is otherwise.  People are individuals, they may not have the same illness, and their reaction to the same treatment varies not only between individuals but within the same individual at different times.  Take any physiological measurement, blood pressure, pulse rate, blood levels of hormones, gastrointestinal absorption,  liver function, mood;  they all show continuous fluctuations.  Yet measurements of often just taken once and treated as if they are representative. 


There is considerable noise in any biological system, so much variation that it is difficult to come to any definitive conclusion.  In the past, scientists would often study the same system repeatedly until they were sure.  Professor James Hunt measured how his own stomach emptied hundreds of times repeatedly until he understood its variations.  In the past, family doctors knew their patients really well, they knew how their ailments fluctuated according to the vicissitudes of their lives and were therefore acutely aware when something happened that didn’t fit the pattern.  Yann Maertal makes the same point in his book,  ‘The Life of Pi.’  Talking about zoo-keeping, he writes that animals are creatures of  habit – so that if a stork for example is not standing at his usual place at a certain time of day, then you know something is wrong.  Few scientists have the time to get to know their subjects or even the system they are studying that well any more.  Dr Ronald Ross had dissected thousands of mosquitoes.  He knew what he was looking for.  He only needed to see plasmodia in the gastric wall in one Anopheles to realise the cause of malaria.  But it is more expedient to study a large number of subjects briefly and let the stats sort it out.  The difficulty with that approach is that statistics are only as good as the population studied and the quality of the data.  Ronald Fisher developed his statistical methods from a study of genetics and crop variation, where the data is homogeneous.  If the population is heterogeneous and the measurements variable,  any amount of statistical analysis cannot make the conclusions right.  I would suspect that too many otherwise important results are obtained by hurried experiments and the lazy use of statistics. 


The philosopher Karl Popper influenced the conduct of research by insisting that the role of the scientist was not just to establish a hypothesis by painstaking observation, but to ensure that it is presented in a way that can be disproved.  While Popper’s condition of falsifiability upholds standards of intellectual rigour, it seems at the same time to stifle curiosity and imagination.  Instead of saying,  ‘I wonder if’, it seems to declare ‘don’t believe anything you can’t prove’.  How would William Harvey have fared if he had spent his time trying to prove that the blood didn’t circulate?  It might be argued that Popper’s influence has led to a whole raft of research that attempts to disprove the obvious or to contradict the accepted wisdom of previous studies.  For example,  the government recently spent 20 million pounds to attempt to disprove that providing children with a one piece of fruit a day would not lead to a fructarian habit and better health.  They succeeded!


Publish or perish is truer now than ever before.  No medical scientist can ever hope to succeed without publishing their results.  To meet the demand, the number of medical journals has multiplied exponentially.  There is a journal for everything.  No editor can possibly hope to keep pace with the sheer complexity of the area covered by their journal.  They all operate a peer review system to assure studies are conducted according to rigidly controlled protocols and the results valid.  But papers on a certain topic tend to be reviewed by the same magic circle.  This forms a cosy club; a case of you scratch my back and I’ll scratch yours.  Some journals even ask authors to suggest reviewers.  Nobody wants to rocks the boat.  So the research tends to confirm the status quo, conform to an agreed philosophy and everybody feels happy.  Nobody, not even scientists, like change.   The same system operates when research grants, of course, are reviewed. 


In the film industry, the same small group of celebrity actors get the best parts.  Presently it is Keira Knightly.  A year or so ago, it was Kate Winslet.  In the nineties, Meryl Streep. To them that have shall be given more, while those that have not shall be denied.  The same occurs in science.  The same people get the grants and get their papers published.  It can be hard to break into the magic circle but also you have to do something very wrong to be evicted.


Medical science has become big business, but the purse strings are controlled, not by fellow scientists, but by powerful organisations,  national governments,  multinational industries, world banks.  Although lip service is given to the opportunity for individual scientists to gain funding for their own original ideas, the reality is more that these organisations set their research priorities and invite key scientists to come up with proposals to investigate them.  There is little scope for curiosity. 


The Pharmaceutical industry is the biggest player.  Multinationals exist to sell drugs.  So they manipulate medical research by funding key scientists, sponsoring new medical journals, supporting academic appointments and laboratories and underwriting conferences as well as withholding negative negative results and publicising favourable studies.  There is little medical research that is carried out that does not have the dead hand of the pharmaceutical industry on it.  Money is power.   So if a drug company is developing a new drug to treat – say the symptoms of burning mouth,  first they will co-opt all the scientists who have ever written about this symptom to conduct research on it, next they will organise conferences on it, they will implant the idea that perhaps burning mouth is distinct disease – oralgia syndrome,  they will sponsor a meeting to define criteria and devise priorities for research, they will underwrite ‘The International Journal for Oralgia.’   By all these methods, they establish a condition, which only they can cure.       


In a political climate of nepotism, institutional pressure, governmental control and pharmaceutical manipulation, is it any wonder that the well of knowledge seems to have dried up.  Even the most honest and well intentioned scientists are compromised  by political forces from thinking out of the box.  The cost is control is creativity. Free thinking is dangerous and discouraged.  So how can scientists ever make truly groundbreaking observations any more.  It is not surprising that medical science appears to discover more and more about less and less. 


Any scientist worth their salt has to liberate the imagination from external control.  They have to be able to day dream; their head in the clouds while their feet are firmly anchored to the earth.  Discovery thrives in a free environment.   You can’t regulate creativity.  You can’t contain inspiration.  This would be like trying to bottle moonshine.   Discovery needs space to think and time to reflect.  So instead of expending efforts trying to establish rigorous definitions and rigid experimental protocols, medical scientists would do better to learn the lessons of the past, try to encourage curiosity and emulate as far as is possible the conditions in which the  breakthroughs were achieved.  There is little that is more fun, more exhiliarating than the thrill of discovery, recording something that nobody has seen before.  Unless medical science can inspire its acolytes to find that sense of excitement that comes from intellectual activity, it is lost. 


(Comments, critiques of this article would be very welcome)