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First Base: Questions of Science and Progress

By Kevin Davies
Sept 15, 2005 | This month marks the centenary of the publication of the third of Albert Einstein's Annus Mirabilis papers, transforming physics with his theory of special relativity, which of course inspired that equation - E=mc2.

Nowadays, such individual genius is submerged or lost. Most major papers feature small armies of authors, as the importance of technological development frequently overshadows intellectual ingenuity. "Innovation is less the achievement of a lone scientist, more the result of collaboration between fertile minds sharing ideas," says Harlan Weissman, executive vice president, R&D, Johnson & Johnson.

There are exceptions, however. At the recent Pharma Achievement Awards, Judah Folkman received the Lifetime Achievement award. In the early '70s, Folkman pioneered the field of angiogenesis, a conceptually novel approach to cancer therapy that has, after three decades, finally delivered drug candidates into the clinic. He recalled with a smile one of his favorite reviews, which said: "The idea of an angiogenesis inhibitor in the body exists only in the mind of the principal investigator."

Modern high-throughput, multidisciplinary science may not be the ideal breeding ground for genius scientists, but whether the province of a lone individual or an international consortium, there are copious scientific challenges yet to be solved. Recently, Science magazine* marked its 125th anniversary by posing 125 outstanding questions on the theme: What don't we know?

Some questions ranged from the childlike wonder - Why do we dream? How much can human life span be extended? - to the medically urgent - What causes schizophrenia? To what extent can we stave off Alzheimer's? Others were delightfully arcane, including my own favorite: Do mathematically interesting zero-value solutions of the Riemann zeta function all have the form a + bi?

As tempting as it is to devote the rest of this column to pondering that question, I choose instead to highlight a few examples, which Science viewed as more "a survey of scientific ignorance" than a declaration of major societal challenges, which should strike a chord among Bio-IT World readers:

To What Extent Are Genetic Variation and Personal Health Linked?

Advances in microarray technology, software analysis, and computing power are lending belated credence to the concept of personalized medicine. "Ultimately, comprehensive personalized medicine will come only if pharmaceutical companies want it too," says Science. Whether motivated by more efficient clinical trials or reduced risk of adverse events, Big Pharma is beginning to think beyond the blockbuster.

How Will Big Pictures Emerge from a Sea of Biological Data?

As fields from biomechanics to ecology "have gone digital...a central question confronting virtually all fields of biology is whether scientists can deduce from this torrent of molecular data how systems and whole organisms work." Systems biology has claimed only modest successes so far, but new multidisciplinary teams such as that being assembled at the Howard Hughes Medical Institute's Janelia Farm should pay dividends.

What Are the Limits of Conventional Computing?

The persistence of Moore's Law notwithstanding, computer scientists are enamored of the possibilities of quantum computing. By transcending the limits of the binary code (1 and 0), the prospect of new thresholds of computing power are perhaps within reach.

Is an Effective HIV Vaccine Feasible?

Two decades since the discovery of HIV, we still lack an HIV vaccine despite billions of dollars spent in research. This summer, the Bill and Melinda Gates Foundation spurred new initiatives in vaccine research as part of its $436-million Grand Challenges in Global Health program.

How Much Will New Technologies Lower the Cost of Sequencing?

Recent breakthroughs in sequencing approach and technology (see page 1) mark a new low point in the cost of genome sequencing. The goal of $100,000 is attainable in the next few years.

Can We Predict How Proteins Will Fold?

A three-dimensional process that occurs in microseconds consumes about 30 years of computer time to model. This remains one of the biggest challenges in biology.

While teamwork and technology will likely provide most of the answers, I trust there is still a place for a spark of individual brilliance in pulling the biggest puzzles apart...

"125 questions: what don't we know?" Science 309 (5731), 75-102; 2005.

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