SCIENCE ADMINISTRATION FREDERICK BETZ PORTLAND STATE UNIVERSITY LECTURE 4

1. SCIENCE ADMINISTRATION FREDERICK BETZ PORTLAND STATE UNIVERSITY LECTURE 4 PROGRESS IN SCIENCE (CONTINUED) ILLUSTRATION: SCIENTIFIC DISCOVERY OF DNA

2. INFORMATION MODEL OF THE SCIENTIFIC METHOD UNIVERSITY S1 T1 NATURAL THING SCIENTIST OBSERVATION SCIENCE DEPARTMENTS DISCIPLINE THEORY T2 S2 NATURAL THING SCEINTIST PREDICTION SCIENCE INVENTS INSTRUMENTS FOR OBSERVATION AND EXPERIMENT. INSTRUMENTATION DEPENDS UPON SENSORY FOCUS AND UPON SENSITIVITY. EXPERIMENTS USE INSTRUMENTS TO OBSERVE AND ABSTRACT THE PROPERTIES OF NATURE THROUGH CONTROLLED EXPLORATION OF NATURE. THEORY IS THE GENERALIZATION OF THE ABSTRACTIONS OF NATURE AS PHENOMAL OBJECTS AND THEIR RELATIONSHIPS. PREDICTION IS A FORECAST BASED UPON A CAUSAL EXPLANATION OF THE THEORY.

3. In 1940, M. Delbruck, S. Luria, and A. Hershey, founders of the phage group, began collaborating on the study of viruses. One of their students was James Watson, who studied under Luria at the University of Illinois in the United States. Watson graduated in 1951 with a desire to discover the structure of DNA as this was the great goal of biology. He heard that the Rutherford Lab in Cambridge was strong in the x-ray study of organic molecules and an x-ray picture of DNA would be necessary. X-ray pictures could show the geometry of molecules. With a postdoc fellowship from the U.S. from the Ford Foundation, Watson asked Luria to arrange for him to do his postdoc at the Rutherford Lab.

4. The Rutherford Lab did have a researcher using x-rays to try to determine the structure of DNA. Her name was Rosalind Franklin, a young, bright scientist from Portugal. Franklin had come to Rutherford and begun a project in x-ray diffraction of crystallized DNA under the supervision of a senior scientist at the Rutherford Laboratory, Maurice Wilkins. X-ray crystallography is a technique for sending x-rays (high-energy photons) through crystals and inferring the structure of the crystals from the diffraction patterns the x-rays produced from the structure. (An analogy would be to have a line of pilings near the shore and watch a big wave come in and produce smaller waves from the pilings; and from watching the smaller waves, calculate backwards to measure the spacing between the pilings.) Scientific instrumentation and instrumental techniques are critical to the progress in science. Just as the microscope was essential to observe the cell and its structure, x-ray crystallography was essential to observe the structure of DNA.

5. Once at the Rutherford Lab, Watson found a collaborator in Francis Crick, then a graduate student working on a physics degree. Crick was a bit older than Watson because his graduate studies had been interrupted by service in the Second World War. Watson brought a knowledge of biology and organic chemistry to their collaboration, and Crick a knowledge of physics -- these were necessary for the job of constructing a molecular model of DNA. But a critical piece of information they needed was a first good x-ray diffraction picture of a crystal DNA. Franklin was working on this, and it was not easy. There were two crystalline forms of DNA, and only one of these would yield a good picture. Moreover, it had to be oriented just right to get a picture that would be interpretable as to structure. Franklin would finally get a good picture of the right form. She was an excellent scientist, (but would be badly treated by Watson, Crick, and Wilkins).

6. Meanwhile, Watson had learned of Linus Pauling’s and Robert Corey’s work on the structure of crystalline amino acids and small peptide proteins. Pauling published a structural description of a first example of a helical form of a protein – helixes are possible! Then Pauling was one of the most famous organic chemists in the world. And Watson feared that Pauling would soon model DNA structure -- robbing the young and ambitious scientist of fame and scientific immortality. Watson saw himself in a scientific race with Pauling to be the first to discover the structure of DNA. Then Pauling did not know the young Watson existed. New generations of scientists are key to scientific progress.

7. Reading Pauling’s paper, Watson then conjectured: what kind of x-ray diffraction picture would a helical molecule make? If DNA were helical, Watson wanted to be prepared to interpret it from an x-ray and asked another young expert in diffraction modeling for a tutorial. If the picture were taken ‛head-on’ down the axis of the helix, he learned how to measure the angle of the helix. Watson was thus equipped to interpret an x-ray picture of DNA -- if he could only get his hands on one. In science, both the prepared mind and the prepared eye are ready for the discovery. Appropriate theoretical background and appropriate instrumentation are essential to empirical discovery. Theory + instrumentation + observation = scientific progress.

8. Meanwhile, Watson and Crick had scoured the chemical literature about DNA and were trying to construct ’ball-and-wire-cutout’ models of DNA. At first they had tried a ‛triple helix’ model, and it didn’t work. Building a ‘model’ of a phenomenon is the first step toward constructing new scientific theory. Instrumentation, observation, experiment, modeling, theory.

9. Finally, Watson heard that Franklin had got a good picture, but he feared Franklin would not show it to him. Franklin was as fierce a competitor as Watson, and was not willing to show her picture before she had time to calculate its meaning. Watson sneaked a peak at the picture without Franklin’s permission. There it was! Clearly a helix, and a double helix! ----- the tutorial for Watson on crystallography had paid off for Watson. Watson measured the pattern and rushed to Crick with the information on the angle of the helix. Watson and Crick put their model together in the form of a double helix, two strands of amino acid chains, twisting about each other like intertwined spiral staircases. All the physical calculations and organic chemistry fit together in the model beautifully. Without a doubt! This was the holy grail of biology -- the double helix structure of DNA!

10. Moreover, the structure of DNA itself was informative about the process of DNA function. It clearly indicated the molecular action of DNA in the mitosis of cell reproduction. DNA was structured as a pair of twisted templates, complementary to one another. In reproduction, the two templates untwisted and separated from one another, providing two identical patterns for constructing proteins, that is, reproducing life. In this untwisting and chemical reproduction of proteins, life was biologically inherited. Structure and function (process) are two fundamental ideas in the scientific paradigm of biology. -- Also in technology – design as structure and function.

11. Now the bad part of the story – scientific prestige and human pride. Watson, Crick, and Wilkin published their paper on DNA structure and function – BUT WITHOUT FRANKLIN’S NAME AS A COLLABORATOR AND CO-AUTHOR. They had used her data. Wilkin was her nominal supervisor, but provided no substantive help. Watson and Crick did the model construction. Wilkin was on the paper because of the x-ray data. But Franklin did the work. BAD SCIENTIFIC ETHICS! BAD PROFESSIONAL CONDUCT! Watson next wrote a youthful, enthusiastic book on discovering the double helix, noted his theft and disparaged Franklin.

12. In 1995, Watson and Crick and Wilkins were awarded the Nobel Prize in Biology. The later excuse of the Nobel committee was that Rosalind Franklin had not been honored because of her untimely death before the prize was awarded. The Nobel committee could have clearly noted her contribution. This was not a nice story for science because she should have received appropriate recognition for her essential contribution. Watson will go down in scientific history as both a brilliant scientist and a text book example of bad professional conduct. And as an historical example of what once were ‘male chauvinist pigs in the scientific establishment. Wilkins will go down in scientific history as a poor scientific leader who didn’t take proper care of his professional colleagues and then stole proper credit from them. And Crick! No excuse for Crick! He was a physicist and should have known better and insisted upon Franklin’s name on the paper.

13. Roseland Franklin left Cambridge and went to France. There she continued her brilliant research on proteins. She had good friends and had a really good time living in Paris. Tragically, she died young of cancer. The moral of the story is that prizes aren’t everything. Doing good scientific work and living well -- for as long as the time one is given on this earth! SCIENCE ADMINISTRATION – SCIENTIFIC ETHICS IS AN IMPORTANT PART OF SCIENCE ADMINISTRATION: HONEST RESEARCH AND PROPER SCIENTIFIC CREDIT.

14. Genetic Coding Meanwhile, work on decoding the information process of DNA had begun. Proteins serve as structural elements of a cell and as catalysts and life. Proteins serve as structural elements of a cell and as catalysts (enzymes) for metabolic processes in a cell. DNA provides the structural template for protein manufacture, replicating proteins through the intermediary templates of RNA. DNA structure the synthesis of RNA, and RNA structures the synthesis of proteins. What had to be understood was how the information for protein manufacture was encoded in the DNA. In 1965, Marshall Nirenberg and Philip Neder deciphered the basic triplet coding of the DNA molecule. The amino acids that composed the DNA structure, acted in groups of three acids to code for a segment of protein construction.

15. It was about 100 years from the time that science discovered the chemical basis for heredity to understanding and modeling DNA’s molecular structure and mechanistic function in transmitting heredity information.

16. Recombinant DNA Techniques In 1965, several scientists began trying to cut and splice genes. In 1965, Paul Berg at Stanford planned to transfer DNA into Escherichia coli bacteria, using an animal virus (Svrp lambda phage). At this time, Peter Lobban, a Stanford graduate student, also was working on a similar idea for gene splicing. Lobban was studying under Dale Kaiser of the Stanford Medical School. When ideas are ripe, there often in science have been hotly competing scientists for the same scientific goal. Scientists compete for the fame of being the first to discover or to understand, second place gets no recognition

17. Berg obtained some EcoRI enzyme (which cleaves DNA) and gave the enzyme to one of his students, Janet Mertz. He told her to study the enzyme’s behavior in cutting DNA. Mertz noticed that when the EcoRI enzyme cleaved an SV40 DNA circlet, the free ends of the resulting cut re-formed by itself into a circle. Mertz asked a colleague at Stanford, to look at the action of the enzyme under an electron microscope. They learned that any two DNA molecules exposed to EcoRI could be ‛recombined’ to form hybrid DNA molecules. Nature had arranged DNA so that once cut, it re-spliced itself automatically.

18. Another professor in Stanford University’s Medical Department, learned of Janet Mertz’s results. Cohen then also thought of constructing a hybrid DNA molecule from plasmids using the EcoRI enzyme. Plasmids are the circles of DNA which float outside the nucleus in a cell and manufacture enzymes the cell needs for its metabolism (the DNA In the nucleus of the cell are principally used for reproduction). In November 1972, Cohen attended a biology conference in Hawaii. He was a colleague of Boyer and had given the EcoRI enzyme to Berg. At a dinner one evening, Cohen proposed to Boyer that they create a hybrid DNA molecule without the help of viruses. Another colleague at the that dinner, Stanley Falfkow of the University of Washington at Seattle offered them a plasmid, RSF1010, to use that confers resistance to antibiotics in bacteria so that they could see whether the recombined DNA worked in the new host. After returning from the Hawaii Conference, Boyer and Cohen began joint experiments. By the spring of 1973, Cohen and Boyer had completed three splicings of plasmid DNAs. Boyer presented the results of these experiments in June 1973 at the Gordon Research Conference on Nucleic Acids in the U.S. (With publication following in the Proceedings of the national Academy of Sciences, November 1973).

19. CONCLUSION After one hundred years of scientific research into the nature of heredity, humanity could now begin to deliberately manipulate genetic material at a molecular level -- and a new industry was born, biotechnology. Boyer and Cohen would win Nobel Prizes. Boyer would be involved in the first new biotechnology company (Genentech) to go public and would become a millionaire. The days for biologists to be industrial scientists had begun.

20. SCIENTIFIC PROGRESS AND SCIENCE BASES FOR TECHNOLOGY • Science has provided the knowledge bases for scientific technology: • Scientists pursue research that asks very basic and universal questions about what things exist and how things work. • To answer such questions, scientists require new instrumentation to discover and study things. • These studies are carried out by different disciplinary groups specializing in different instrumental and theoretical techniques: biologists, chemists, and physicists. • Major advances in science occur when sufficient parts of the puzzling object have been discovered and observed and someone imagines how to put it all together properly. A scientific model is conceptually powerful because it often shows both the structure and the dynamics of a process implied by the structure. • 5. Scientific progress takes much time, patience, continuity, and expense. Instruments need to be invented and developed. Phenomena need to be discovered and studied. Phenomenal processes are complex, subtle, multileveled, and microscopic in mechanistic detail.

21. 6. From an economic perspective, science can be viewed as a form of societal investment in possibilities of future technologies. Since time for scientific discovery is lengthy and science is complicated, science must be sponsored and performed as a kind of overhead function in society. Without the overhead of basic knowledge creation, technological innovation eventually stagnates for lack of new phenomenal knowledge for its inventive ideas. 7. Once science has created a new phenomenal knowledge base, inventions for a new technology may be made by either scientists or by technologists (for example, scientists invented the recombinant DNA techniques). These radical technological inventions start a new technology S-curve. This is the time to begin investment in a technological revolution and to begin new industries based upon it.

22. When the new technology is pervasive across several industries (as genetic engineering is across medicine, agriculture, forestry, marine biology, materials, etc), the technological revolution may fuel a new economic expansion. The long-waves of economy history are grounded in scientific advances that create basic new industrial technologies. • 9. These are general implications for businesses. Businesses should be supportive university research which focuses on fundamental questions underlying core-technologies of the business. Businesses need to belong to university centers which focus upon the science bases of their core-technologies -- to maintain a ‛window-on-science’ for technological forecasting.