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"A great deal of basic research has been done ... but I think the time has come to zero in on the targets — by trying to get our knowledge fully applied. ... We must make sure that no life-saving discovery is locked up in the laboratory."
—President Lyndon Baines Johnson, 1966

As director of the Montreal Neurological Institute and Hospital at McGill University, I spend much of my time discussing our research efforts with the public, and I am often struck by their perceptions about how breakthroughs are made in medical research. In this regard, not much has changed over the past 40 years.

Like LBJ, most people are of the opinion that scientists work in isolated laboratories, engaging in solitary studies whose results are jealously guarded. Most people are also frustrated with the pace and progress of research. If scientists would only focus on a specific disease target, collaborate more and communicate better with their colleagues, cures and therapies would tumble rapidly out of the lab and into the clinical arena. Why study irrelevant problems?

These notions reflect profound misconceptions about how discoveries are made and how scientists work. Contrary to popular belief, the vast majority of academic research scientists and clinicians are already quite focused, seek out collaborations with colleagues, and are eager to share their results. So why do the spectacular breakthroughs that we expect — vaccines against new infectious threats, cures for cancer, heart disease and neurological disorders — remain elusive? The answer is that they are not elusive, but only seem to be so; important discoveries are constantly in development. And what appears to be irrelevant today is often a crucial component of tomorrow's success.

We do not appreciate the colossal effort behind a truly revolutionary breakthrough. It takes the conjunction of many apparently unrelated observations and technologies to produce most breakthroughs, and they evolve over time — a long time, in most cases. Let me illustrate what I mean, using as a model an apparently sudden medical breakthrough, in vitro fertilization (IVF).

Today is the 28th birthday of the first "test tube" baby, Louise Joy Brown. Since her birth, about two million babies have been born worldwide whose mothers conceived by way of IVF. Today, "assisted reproduction" is routine, highly successful, and stunning in terms of what can be done for infertile couples.

The IVF story began with what seemed to be, according to the popular press, a well-planned, straightforward procedure carried out in Britain by gynecologist Patrick Steptoe and physiologist Robert Edwards in 1977. An egg was retrieved from Lesley Brown, fertilized in vitro, held in an incubator for a time, and then gently introduced into Ms. Brown's womb. On July 25, 1978, baby Louise was delivered by cesarean section. In some newspapers, it was noted in passing that, before her birth, the physician-scientists had carried out extensive, unsuccessful experiments for almost a decade.

By the late 1980s, IVF physicians and scientists established mastery over much of the reproductive process, and IVF birth rates were climbing. Multiple eggs in a woman's ovaries were pushed to maturation over a period of days using timed hormonal injections. As the eggs matured, they were monitored by ultrasound imaging, and the hormonal response measured by a highly sensitive technique called radioimmunoassay. Egg retrieval was also accomplished under ultrasound guidance, and the collected eggs fertilized in a lab dish. If necessary, eggs and/or sperm could be precisely "micromanipulated" to assist fertilization, and then introduced into the uterus.

It is instructive to see where these individual scientific components that are at the core of IVF clinical success came from. Until recently, when recombinant DNA technologies offered alternative sources, controlled ovarian stimulation could only be achieved through daily injections of hormones extracted from urine collected from post-menopausal women (e.g. nuns living in European convents). One problem was that, after collection, the hormones had to be concentrated and kept in their active state. In the early 1900s, L.F. Shackell had invented freeze-drying, a procedure that, over the next 30 years and under consumer pressure, was improved on by the coffee industry. Freeze-drying proved to be ideal for rendering hormones extracted from urine into a stable powder with a long shelf life. So the IVF industry owes at least some of its success to uncompromising coffee drinkers.

In the IVF patient, blood levels of response hormones are measured by radioimmunoassay, a technology invented by Rosalyn Yalow (who won a Nobel Prize in 1977) and Solomon Berson; they gradually perfected it — over a period of 15 years beginning in 1959 — to measure insulin levels in diabetics.

Ultrasound, the method used to monitor follicles, was not originally a medical procedure; it was developed for military applications to detect flaws in metals. In 1949, it was first suggested by George Ludwig, a U.S. Navy physician, that ultrasound might be used for medical purposes.

The micromanipulator used to capture and move eggs and sperm tiny distances in the lab dish is the 1941 invention of C.W. Rees, who designed the device to separate minuscule amoebic cysts from bacteria.

And finally, the sophisticated biochemistry of the IVF embryo laboratories, as well as the microscopes, airflow chambers, incubators and other devices that ensure a sterile environment, constant temperature and oxygen supply for the developing embryos, are the products of the accumulated knowledge from tens of thousands of cell-culture experiments carried out since 1885, when Wilhelm Roux first incubated chicken cells in a sterile, warmed broth, and kept them alive and healthy for several days.

This history, and there are thousands of science histories like this one, illustrates the extraordinarily broad foundation from totally different arenas of science that make for a "breakthrough" in medicine. The problem is that public misconceptions about how research is conducted have affected funding decisions — where to put dwindling research dollars — in the United States and Canada as well.

The demand for rapid "payoff science" so that we get "good value for our tax dollars" is great. And instead of educating the public about how research really works, well-meaning science and health administrators tend to opt for what appears to be the least complicated approach to attracting funds in the short term, and so endorse the idea that clinically useful, applicable results are to be expected within a time frame that, for those of us who are working scientists and clinicians, is impossibly short.

David R. Colman is Wilder Penfield Professor and director of the Montreal Neurological Institute and Hospital at McGill University.