Oops! I have made a discovery

In many instances, original intent and subsequent benefit are unrelated


THERE is an expectation that, inevitably, new discoveries will lead to more drugs that will reduce the burden of illness.

But people must also come to terms with the fact that science and discovery is needful of discipline while being necessarily chaotic at the same time.

Investors and young people alike have come to believe that we can design a better future through science, and that this can be achieved on a timetable, if given sizeable investment. This seems true in the long term, but in the short term, unexpected surprises might disappoint.

Most important discoveries are driven by personal desires to answer questions that only serendipitously lead to useful applications.

In many instances, original intent and subsequent benefit are unrelated. Joseph Fourier, son of a tailor who became an administrator, historian and mathematician, developed a system combining sines and cosines to describe heat transfer in solid bodies.

Did he envisage that one day in the distant future, Fourier Transforms would be used in Magnetic Resonance Imaging (MRI) systems which have applications as diverse as structural biology and human imaging?

Legend has it that the industrial production of aspirin may have arisen because Felix Hoffmann wanted to help relieve his father's arthritis. By adding an acetyl moiety to salicylic acid, he not only helped his father, but also transformed Bayer into the world's first major pharmaceutical company.

On the other hand, Cisplatin, a very important drug in cancer chemotherapy, came about from studying how electric fields affect the growth of bacteria. It took awesome cleverness, masterful hiring and many years for Barnett Rosenberg, a physicist by training, to transform this chance discovery into a major drug.

Fortune favours the prepared mind

A GOOD number of major drug discoveries have come on the back of diligent follow-ups on apparent failures. Viagra started its life as a drug intended to dilate coronary arteries. Its intended use was based on the hypothesis that it inhibits an enzyme that contributes to the breakdown of nitric oxide, itself a potent vasodilator.

It failed as a heart drug but researchers noticed it had a prominent side effect: It caused erections. The rest, as they say, is history.

Minoxidil failed as an anti-hypertensive but found new life as a treatment for male pattern baldness. Gabapentin has rather modest success as a treatment for epileptic seizures but it may be better remembered for relieving discomfort in those suffering from diabetic neuropathy.

Iproniazid was meant to be an anti-tuberculosis drug but it was not particularly successful for that use. Clinicians using it noticed that it lifted mood and it became the first of a then new class of anti-depressants.

In the examples cited, an unexpected failure coupled with an unpredicted side effect was translated into a benefit. Louis Pasteur once said: 'Fortune favours the prepared mind.' How true.

But in addition to a keen eye, none of the discoveries would have seen the light of day had it not been for the web of people with different, specialised skills who brought the ideas to fruition.

Interdisciplinary cross-talk helps

EUROPEANS were well-positioned to lead in drug development in the early 20th century because they had a substantial base in organic chemistry developed in the previous century. In another illustration of how fortuitous occurrences opened new doors, the failed attempt to synthesise the anti-malarial quinine by William Perkins, led to the development of a purple substance that contributed to spawning a profitable dye industry.

Another dye, methylene blue, came to be used as an anti-malarial drug. This in turn led to the synthesis of quinacrine and formed the base of a molecule that later had a benefit on mental illness. Could anyone have predicted these developments a priori?

My personal favourite example of how skills from different disciplines can bring seemingly arcane science to life relates to the pretty MRI we view today.

This has come into being because of a confluence of mathematics, physics, engineering and medicine. It took over 30 years, the contributions of numerous scientists, including six Nobel laureates (Bloch, Purcell, Rabi, Ernst, Lauterbur, Mansfield), and industry to transform seminal observations of physical phenomena to a useful clinical tool that persons with neurological problems take for granted today.

David and Goliath: Does team size matter?

SIZE is important, because even if one were to take the position that truly significant discoveries occur in an unpredictable manner, it stands to reason that having more talented scientists at your disposal increases the likelihood of such a desirable event. Big teams attract investment and sometimes, the right talent.

However, sheer size alone is insufficient. There needs to be wider acceptance and appreciation of a great idea before it really takes off. Professor Arthur Kornberg, who won a Nobel prize for the discovery of mechanisms in the biological synthesis of DNA, once said: 'Great innovations whether in art, literature or science, seldom take the world by storm. They must be cultivated to be understood, understood before they can be properly appreciated.'

This calls for having a talent pool that has diverse skills and is willing to collaborate and promote one another, sometimes taking chances along the way. There may be security in numbers but big teams can be encumbered by layers of bureaucracy and risk-averse workers who can be a drag on innovation.

Having a good number of innovative people concentrated in small, reconfigurable clusters seems best. Small teams and individuals come through often enough to make them more than an interesting statistical anomaly. If I were to leave the reader with a single message, it is that any grand National Science Plan would do well to accommodate this point.

For instance, those coveting a new Blu-ray DVD recorder would do well to note that the enormous boost in storage capacity was made possible by the work of one Shuji Nakamura who toiled for years on making a blue light emitting diode (LED) with a team of about three people - sneaking ahead of the efforts from the likes of Sony, Hewlett-Packard, Xerox, Toshiba and Philips.

The small team which discovered Herceptin, a blockbuster anti-cancer drug, was actively discouraged from doing so because it did not fit into its company's agenda and because more experienced scientists felt that its chances for success were slim.

Professor Sydney Brenner, who made seminal contributions to molecular biology, recently recounted how the then doyennes of biology and chemistry felt that molecular biology was a dangerous area to get into. It is to his credit and our benefit that he chose to go against the tide of 'expert advice'.

Some years back, Prof Kornberg said: 'The lessons to be learnt from this history should be crystal clear. It is crucial for a society, a culture, a company to understand the nature of the creative process and to provide for its support. No matter how counter-intuitive it may seem, basic research is the lifeline of practical advances in medicine; Pioneering inventions are the source of industrial strength. The future is invented, not predicted.' These words still ring true today.