Review: Kennedy D, Norman C (2005). What don't we know? Science, Special Supplement, 309: 75-102. DOI:10.1126/science.309.5731.75

Feature Paper: Kennedy D, Norman C (2005). What don't we know? Science, Special Supplement, 309: 75-102. DOI:10.1126/science.309.5731.75

Author Abstract: At Science, we tend to get excited about new discoveries that lift the veil a little on how things work, from cells to the universe. That puts our focus firmly on what has been added to our stock of knowledge. For this anniversary issue, we decided to shift our frame of reference, to look instead at what we don’t know: the scientific puzzles that are driving basic scientific research.

 
We began by asking Science’s Senior Editorial Board, our Board of Reviewing Editors, and our own editors and writers to suggest questions that point to critical knowledge gaps. The ground rules: Scientists should have a good shot at answering the questions over the next 25 years, or they should at least know how to go about answering them. We intended simply to choose 25 of these suggestions and turn them into a survey of the big questions facing science. But when a group of editors and writers sat down to select those big questions, we quickly realized that 25 simply wouldn’t convey the grand sweep of cutting-edge research that lies behind the responses we received. So we have ended up with 125 questions, a fitting number for Science’s 125th anniversary.
 
First, a note on what this special issue is not: It is not a survey of the big societal challenges that science can help solve, nor is it a forecast of what science might achieve. Think of it instead as a survey of our scientific ignorance, a broad swath of questions that scientists themselves are asking. As Tom Siegfried puts it in his introductory essay, they are “opportunities to be exploited.”


We selected 25 of the 125 questions to highlight based on several criteria: how fundamental they are, how broad-ranging, and whether their solutions will impact other scientific disciplines. Some have few immediate practical implications—the composition of the universe, for example. Others we chose because the answers will have enormous feasible, or how much the carbon dioxide we are pumping into the atmosphere will warm our planet, for example. Some, such as the nature of dark energy, have come to prominence only recently; others, such as the mechanism behind limb regeneration in amphibians, have intrigued scientists for more than a century. We listed the 25 highlighted questions in no special order, but we did group the 100 additional questions roughly by discipline.
 
Our sister online publications are also devoting special issues to Science’s 125th anniversary. The Science of Aging Knowledge Environment, SAGE KE (www.sageke.org), is surveying several big questions confronting researchers on aging. The Signal Transduction Knowledge Environment, STKE (www.stke.org), has selected classic Science articles that have had a high impact in the field of cell signaling and is highlighting them in an editorial guide. And Science’s Next Wave (www.nextwave.org) is looking at the careers of scientists grappling with some of the questions Science has identified.

 
We are acutely aware that even 125 un- knowns encompass only a partial answer to the question that heads this special section: What Don’t We Know? So we invite you to participate in a special forum on Science’s Web site (www.sciencemag.org/sciext/eletters/125th), in which you can comment on our 125 questions or nominate topics we missed—and we apol- ogize if they are the very questions you are working on.From the nature of the cosmos to the nature of societies, the following 100 questions span the sciences. Some are pieces of questions discussed above; others are big questions in their own right. Some will drive scientific inquiry for the next century; others may soon be answered. Many will undoubtedly spawn new questions.

Note to Readers: Follow links above for author email, full article text, or the publishing scientific journal. Author notes in my review are in quotes.

Review: The paper we'll review this week is a special supplement published by the eminent scientific journal "Science," which tries to outline 125 of the most important questions still remaining in science across a variety of fields. Since only the top questions have a dedicated single-page review written up for them (while remaining questions are only given a few sentences), I think the best way to approach a review this week is to merely list all of the questions mentioned and provide a copy of the special supplement so those interested can read further.

I would point out that the below list is not reflective of my personal views, but those of the Science journal staff, which seem predisposed to physics. Also remember that below is a list of scientific questions so questions such as "Does God exist?" will not be addressed since they can't be addressed scientific.

1. What is the universe made of?
2. Is ours the only universe?
3. What drove cosmic inflation?
4. What is the biological basis of consciousness?
5. When and how did the first stars and galaxies form?
6. Where do ultra-high-energy cosmic rays come from?
7. What powers quasars?
8. What is the nature of black holes?
9. Why do humans have so few genes?
10. Why is there more matter than antimatter?
11. Does the proton decay?
12. What is the nature of gravity?
13. Why is time different from other dimensions?
14. To what extent are genetic variation and personal health linked?
15. Are there smaller building blocks than quarks?
16. Are neutrinos their own antiparticles?
17. Is there a unified theory explaining all correlated electron systems?
18. What is the most powerful laser researchers can build?
19. Can the laws of physics be unified?
20. Can researchers make a perfect optical lens?
21. Is it possible to create magnetic semiconductors that work at room temperature?
22. What is the pairing mechanism behind high-temperature superconductivity?
23. Can we develop a general theory of the dynamics of turbulent flows and the motion of granular materials?
24. How much can human life span be extended?
25. Are there stable high-atomic-number elements?
26. Is superfluidity possible in a solid? If so, how?
27. What is the structure of water?
28. What is the nature of the glassy state?
29. Are there limits to rational chemical synthesis?
30. What controls organ regeneration?
31. What is the ultimate efficiency of photovoltaic cells?
32. Will fusion always be the energy source of the future?
33. What drives the solar magnetic cycle?
34. How do planets form?
35. How can a skin cell become a nerve cell?
36. What causes ice ages?
37. What causes reversals in Earth's magnetic field?
38. Are there earthquake precursors that can lead to useful predictions?
39. Is there -- or was there -- life elsewhere in the solar system?
40. How does a single somatic cell become a whole plant?
41. What is the origin of homochirality in nature?
42. Can we predict how proteins will fold?
43. How many proteins are there in humans?
44. How do proteins find their partners?
45. How does Earth's interior work?
46. How many forms of cell death are there?
47. What keeps intracellular traffic running smoothly?
48. What enables cellular components to copy themselves independent of DNA?
49. What roles to different forms of RNA play in genome function?
50. Are we alone in the universe?
51. What role do telomeres and centromeres play in genome function?
52. Why are some genomes really big and others quite compact?
53. What is all that "junk" doing in our genomes?
54. How much will new technologies lower the cost of sequencing?
55. How and where did life on Earth arise?
56. How do organs and whole organisms know when to stop growing?
57. How can genome changes other than mutations be inherited?
58. How is asymmetry determined in the embryo?
59. How do limbs, fins, and faces develop and evolve?
60. What determines species diversity?
61. What triggers puberty?
62. Are stem cells at the heart of all cancers?
63. Is cancer susceptible to immune control?
64. Can cancers be controlled rather than cured?
65. What genetic changes made us uniquely human?
66. Is inflammation a major factor in all chronic diseases?
67. How do prion diseases work?
68. How much do vertebrates depend on the innate immune system to fight infection?
69. Does immunologic memory require chronic exposure to antigens?
70. How are memories stored and retrieved?
71. Why doesn't a pregnant woman reject her fetus?
72. What synchronizes an organism's circadian clocks?
73. How do migrating organisms find their way?
74. Why do we sleep?
75. How did cooperative behavior evolve?
76. Why do we dream?
77. Why are there critical periods for language learning?
78. Do pheromones influence human behavior?
79. How do general anesthetics work?
80. How will big pictures emerge from a sea of biological data?
81. What causes schizophrenia?
82. What causes autism?
83. To what extent can we stave off Alzheimer's?
84. What is the biological basis of addiction?
85. How far can we push chemical self-assembly?
86. Is morality hard-wired into the brain?
87. What are the limits of learning by machines?
88. How much of personality is genetic?
89. What is the biological root of sexual orientation?
90. What are the limits of conventional computing?
91. Will there ever be a tree of life that systematists can agree on?
92. How many species are there on Earth?
93. What is a species?
94. Why does lateral transfer occur in so many species and how?
95. Who was LUCA (the last universal common ancestor)?
96. Can we selectively shut off immune responses?
97. How did flowers evolve?
98. How do plants make cell walls?
99. How is plant growth controlled?
100. Why aren't all plants immune to all diseases?
101. What is the basis of variation in stress tolerance in plants?
102. Do deeper principles underlie quantum uncertainty and nonlocality?
103. What caused mass extinctions?
104. Can we prevent extinction?
105. Why were some dinosaurs so large?
106. How will ecosystems respond to global warming?
107. Is an effective HIV vaccine feasible?
108. How many kinds of humans coexisted in the recent past, and how did they relate?
109. What gave rise to modern human behavior?
110. What are the roots of human culture?
111. What are the evolutionary roots of language and music?
112. How hot will the Greenhouse World be?
113. What are human races, and how did they develop?
114. Why do some countries grow and others stagnate?
115. What impact do large government deficits have on a country's interest rates and economic growth rate?
116. Are political and economic freedom closely tied?
117. Why has poverty increased and life expectancy declined in sub-Saharan Africa?
118. What can replace cheap oil -- and when?
119. Is there a simple test for determining whether an elliptic curve has an infinite number of rational solutions?
120. Can a Hodge cycle be written as a sum of algebraic cycles?
121. Will Malthus continue to be wrong?
122. Will mathematicians unleash the power of the Navier-Stokes equations?
123. Does Poincaré's test identify spheres in four-dimensional space?
124. Do mathematically interesting zero-value solutions of the Riemann zeta function all have the form of a + bi?
125. Does the Standard Model of particle physics rest on solid mathematical foundations?