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The Scientific Method
Overview: I hope this lecture shows you that the scientific method is not as impersonal and dry as it sometimes appears. You will learn where scientific questions come from, and begin to appreciate the motivations of scientists who are interested in the biological bases of behaviour. Parkinson's disease is used as an example of a distressing human condition that may be amenable to a biologically based treatment. You will begin to appreciate the sheer number of people whose lives are devastated by psychiatric illness. Phrenology is used as an example of a theory which failed for several reasons: it was not supported by experimental evidence; and the technique was adopted by charlatans wanting to make 'a fast buck'. Nevertheless phrenology contains a grain of truth that has fuelled most of the work in psychobiology during this century - namely the notion of localization of function.

Learning objectives:
  • describe the steps involved in the design and execution of a scientific experiment
  • evaluate phrenology from a scientific perspective
  • describe the incidence of psychiatric illness within the general population
  • recognize the symptoms of Parkinson's disease
  • explain the rationale for Dunnet's experiment on the effects of dopamine-rich grafts on amphetamine-induced rotation
  • describe the results of Dunnet's experiment
  • evaluate the implications of Dunnet's experiment for the treatment of Parkinson's disease

The scientific method

Scientific journeys can start from the wish to test a theory, the need to find a solution to a problem , or just plain hunch. The next diagram manages to convey a rather dry and boring feeling about science. It really isn't like that at all. It can be the battleground for clashes between massive egos - you will meet plenty of those on your journey. But above all science is a public activity - with the communication of results at its heart. Curiously communication of results doesn't get a look in on this diagram. As I said in the lecture in my book it isn't science without public disclosure of methods and results. A full description of the method allows for replication in other labs by other scientists. It's there that your results will come under the sharpest scrutiny when the question is asked "Does this result replicate?" The Introduction and Discussion sections of a scientific paper are where you can detect the clash of scientists' egos.

Overview of scientific method

Point to ponder
Do you think everyday human thought relies on the scientific method, or does it need to be taught?

Darwin's theory of evolution in a nutshell

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It is agreed by scientists that species that now exist originate from very simple forms of life that existed millions of years ago.  Darwin gave us an important theory of how evolution occurs. It has been called "the single best idea anyone has ever had".
  • Darwin was struck by the fact that all organisms produce more offspring than are needed to replace the parents. For example, a pair of spawning salmon are estimated to produce 5,000 fertilized eggs, if all these eggs developed into adult salmon our rivers would be choked with salmon. Clearly there is massive mortality between egg and adult organism.
  • Despite this tendency to a progressive increase in numbers, the numbers of a given species remains more or less constant
  • From these two factors it follows that there is a 'struggle for existence' - some offspring survive, others perish
  • Offspring are not 'carbon-copies' of their parents; there is widespread heritable variation
  • Darwin suggested the novel idea that the fittest tend to survive, the unfit perish
  • Consequently this leads to adaptive improvement over the generations - evolution
Is Darwin's theory free of 'cultural values'? This section contains a set of optional readings, but it also contains details on how to spot a good scientific theory.

In recent years a 'Darwin industry' has developed involving historians attempting to understand, unravel, and interpret the cultural influences on Darwin, and Darwin's influence on culture. There is very clear coverage of the cultural context and impact of Darwinian theory in:

  • Bowler (2000) "Charles Darwin: The Man and his Influence", University of Cambridge, Cambridge, Chapter 1 "The Problem of Interpretation".
  • Ruse (1999). "Mystery of Mysteries: Is Evolution a Social Construct?". Harvard University Press, Cambridge, Mass. Chapter 3 "Charles Darwin"

When Darwin published his theory of evolution in 1859 it generated less controversy than we are sometimes led to believe. On the contrary, it was generally well accepted. Darwin's theory did not come as a 'bolt out of the blue' to an unsuspecting audience. In fact, Darwin was not alone in proposing a theory of evolution. There were already several accounts of evolution, but they were fundamentally different to Darwin's.

Pre-Darwinian theories postulated that evolution was the progressive unfolding of a purposeful plan involving a linear trend of increasingly complex species that culminated in the appearance of humans i.e. the natural world was considered to be a scala natura. These were evolutionary theories - in the sense that they rejected the picture of creation presented in the Book of Genesis - but they allowed space for God to operate as the master planner of a gradually improving world. But careful reading of Darwin's theory shows that it does not admit a purposive plan, and does not imply that humans as the highest rung on an evolutionary ladder. Instead it suggests that the mechanism underlying evolution feeds random variation between individual members of a species into a filtering mechanism composed of environmental pressures.

Evolutionary theories were welcomed by some in the mid nineteenth century; they offered a progressive way forward for a society dominated by church and aristocracy. But they were treated with suspicion by others because they threatened to abolish the special place of Man in the natural world, and disrupt a relatively stable social structure that had seen fundamental political upheavals in nearby France. Perhaps Darwin's theory of evolution was better adapted than others to survive in the scientific and social environment that existed in England nearly 150 years ago.

Bowler suggests that in 1859 readers interpreted the main message of the Origin of Species in line with the cultural beliefs of their times:

  • They paid little attention to Darwin's theory that evolution relied on natural selection as the mechanism for change, and focussed instead on an evolution powered by Lamarkism, orthogenesis or a divine plan.
  • They held to the mistaken belief that evolution produced progress along a preordained path as a result of "the struggle for existence" and the "survival of the fittest", to attain the 'highest point' of evolution - mankind.

Darwin may have colluded with this misinterpretation to facilitate popular acceptance of his theory. Ruse (1999) argues that Darwin believed in social progress and this is increasingly evident in later revisions of the Origin of Species. For example, in the third edition published in 1861 he wrote that "natural selection clearly leads towards highness" (see Ruse 1999, p69-70).

Furthermore, Darwin seems influenced by the values of his social class, upbringing and circle of acquaintances. Ruse points out that in Darwin's book on human evolution - The Descent of Man - published in 1871, "Darwin brought in all of the cultural values of his sex, race and class. Not only do we learn that men are string and brave and brainy, whereas women are kind and gentle and sensitive; that whites are intelligent and hardworking whereas blacks are stupid and lazy; but that, on the whole, capitalism is no bad thing."

Darwin was highly respected during his lifetime - both before and after publication of the Origin of Species - and this is reflected in his resting place: He was buried next to that other national scientific hero, Sir Isaac Newton, in Westminster Abbey in 1882. And his fame lives on: In 2003 Darwin was voted the most important Briton of all time in a national survey organised by the BBC.

But you are now faced with a problem. Should you criticize Darwin's theory because it was tainted by cultural factors from an earlier period of our history? Or do you accept that Darwin, like all of us, is a product of our time and culture, but nevertheless he had an important insight into a reality that exists independently of time and culture?

Reading Ruse (1999) Chapter 1 "Karl Popper and Thomas Kuhn: Two Theories of Science" may help resolve this dilemma. The power of Ruse's (1999) evaluation of Darwin's influence comes from his analysis of:

  • the epistemic values of Darwin's theory together with a
  • consideration of non-epistemic factors surrounding evolutionary theory

Epistemic values or "scientific values" are a set of characteristics of a scientific theory that reveals a reality that - we assume - exists outside ourselves, and exists independently from us (i.e.' truth'). Ruse draws on work by McMullin to draw up a list of epistemic characteristics or "scientific values" which include:

  • predictive accuracy - the ability to forecast what we have not yet observed
  • internal coherence - the various parts of the theory should not contradict each other
  • external consistency - the theory should not contradict other accepted theories, or 'laws of nature'
  • unifying power - the theory should bring together and explain previously disparate areas of knowledge
  • fertility - the theory should generate novel hypotheses
  • falsifiability - it should be possible to construct hypotheses that could lead to the rejection of the theory - this is an especially important scientific value
  • simplicity and elegance - this is a value judgement i.e. it is a subjective judgement made by scientists. Consequently simplicity is a desired characteristic rather than a defining characteristic of a scientific theory.

Non-epistemic or "cultural values" factors refer to

  • factors in our culture that persuade us to construct a theory of reality based on our cultural experiences
  • the feedback-influence of scientific theories on our culture

Examination of the Darwin's life and times shows the influence of non-epistemic cultural values on the genesis of his theory, and particularly its development by his disciples. Furthermore, the epistemic qualities of evolutionary theory has had a powerful feedback effect on cultural values in the last century. For example, the use of metaphor such as Dawkin's 'selfish genes', and value-laden phrases such as 'survival of the fittest' (which was adopted by Darwin from Herbert Spencer), and "the struggle for existence" have entered the popular imagination.

When it was first published, Darwin's theory was not as epistemically strong as it is now. Ruse provides a convincing case that Darwin's theory contained several epistemic weaknesses:

  • The theory made few short-term predictions that could be objectively measured to enable falsifiability
  • Contemporary estimates of the earth's age did not allow enough time for evolution to have occurred
  • Darwin found it difficult to account for the evolution of sterile insects
  • Darwin did not provide a convincing explanation of how characteristics were passed from generation to generation
  • But Darwin's theory triumphed in its ability to unify information from separate areas of biology
  • And. We now know that the earth is older than first suspected. Mendel's work provided the 'missing' mechanism for heredity.

Evolutionary theory now forms the paradigm for the biological sciences. A paradigm is a body of theory, results, methods, and set of acceptable questions that are embraced by the vast majority of people working in a particular discipline. It is a generally accepted way of doing science (see Ruse 1999, p19). You may be wondering what paradigm binds together all psychologists. I can't give you the answer.

I started my undergraduate studies in Zoology, Physiology and Botany so was immersed in the evolutionary paradigm from a tender age. But then I switched to psychology where a favourite student-discussion question used to be "Is psychology a science". I used to thoroughly enjoy arguing with friends that 'psychology is a pre-paradigmatic junk yard full of cognitive scrap metal'. Read about Thomas Kuhn's views on scientific paradigms in Ruse Chapter 1 if you want to continue this time-honoured student drinking game.

 

 

Here is an example of  theory construction and the scientific method applied to a current problem.

Phrenology: The beginnings of Localization of Function


Faculties shown on phrenologist's model Franz Joseph Gall

The Austrian physician Franz Joseph Gall (1758-1828) suggested that the brain was the location of all mental activities. He collected the skulls of criminals and busts of famous men. Gall postulated that the surface of the skull would mirror the exaggeration of functional areas in the cortex so that he could correlate bumps in the skull with faculties prominent in certain individuals and created a map locating particular mental functions in particular areas of the cortex. This became Phrenology, which claimed that mapping the bumps on a person's head would give indications of the capabilities and personality of the individual. Adapted from The Brain Project by Stephen Jones.

Although today phrenology is not regarded seriously, Gall did express important insights. For example he wrote: "that the cerebral cortex represented the highest level of the brain and that the development of this area characterized mammals and man."

"In the early 19th century, Phrenology gained a rapidly growing interest. Some unscrupulous people did however abuse the science for commercial purposes, and the Victorian period saw the emergence of Phrenological parlours which were closer to astrology, chiromancy, and the like, than to real scientific characterology. Unfortunately, those con-men have done a lot to stain the image of Phrenology as a real science, and their bad influence lives up to today." Quotation from Phrenology by Peter Van den Bossche

The most serious challenge to phrenology came from Paul Flourens, (French), who developed the 'ablation' (or surgical removal) experiment. He removed areas of the cerebral cortex of animals but did not observe clear-cut specific changes in behavior. Flourens wrote: "a large section of the cerebral lobes can be removed without loss of function. As more is removed all functions weaken and gradually disappear. Thus the cerebral lobes operate in unison for the full exercise of their functions."

There are still some people who advocate Phrenology and its modern manifestation physiognomy/personology which claims to be able to assess human ability, potential, character and future prospects through the study of a person's facial characteristics.

Phrenology and Race in Nineteenth-Century England This site shows how phrenology/physiognomy was used to support racial stereotypes

The History of Phrenology on the Web By John van Wyhe, Ph.D. "...the most comprehensive website for the history of phrenology- the most popular Victorian science. This site provides an accurate overview of phrenology, the largest collection of phrenological images, and many digitized primary sources relevant not only to the history of phrenology, but also to the history of naturalism and evolutionary thought. "

It is now known that damage to specific parts of the brain can lead to behavioural changes. In 1861, Paul Broca described the case of a man who - when he was alive - appeared normal except that he was unable to speak. When he died, Broca autopsied the man's brain and found a lesion of the left frontal lobe of the left hemisphere. This loss of the language faculty is known as `aphasia'. Broca's observation marks the beginning of an idea known as localization of function.

Stephen Jones' site has a very good description of the development of early Neuro-anatomy and Neuro-physiology with special reference to the localization of function

 

Point to ponder
Why do you think phrenology is dismissed as pseudo-science?

Incidence of psychiatric disorders

There is a grain of truth in the phrenologists claim that ' faculties are organized within the brain '. Nowadays this insight is referred to as Localization of Function . Put simply localization of function holds that parts of the brain are specialized to carry out particular functions. Localization of function is the bedrock of contemporary research into the relationship between brain and behaviour. It is the belief that we can ultimately understand how the brain controls our behaviour. Why would we want this knowledge? One very good reason is that it may help us understand what happens when behaviour becomes disturbed. For example, the next section of the lecture gives you some idea the enormous number of people who suffer because of brain abnormality.
Please don't get the idea that I, or any other neuroscientist for that matter, believes that psychiatric illness is simply the result of abnormal brain chemistry. It isn't. Clearly an individual's external environment may play an important role in the development of these very distressing conditions. But there is a complex interaction between a person's internal and external environment.
Put simply: The brain affects behaviour and behaviour affects the brain.

Incidence of psychiatric disorders


Parkinson's disease

Parkinson's disease provides a very clear example of the application of the scientific method to the alleviation of human suffering. Over one million Americans suffer from this disease which usually strikes the over 40's. This section begins by describing the symptoms of Parkinson's disease and its progression. Although drugs can be used to treat the symptoms, not all patients respond well to these medicines, and they do not offer a cure for Parkinson's, only relief from its symptoms. Therefore we will examine an example of a ground breaking series of experiments involving an animal model of Parkinson's disease which offer the hope for a new form of treatment involving tissue transplantation into a part of the patient's brain that is affected by the disease.

Early symptoms of Parkinson's disease

Tremor of one hand is a frequent early manifestation of parkinsonism
Tremor of one hand is a frequent early manifestation of parkinsonism
Tremor often improves or disappears with purposeful function
Tremor often improves or disappears with purposeful function
Difficulty in performing simple manual functions ( e.g. doing up a shirt button ) may be initial symptom
Difficulty in performing simple manual functions

Writing shows 'micrographia' (small size) and effects of tremor Writing shows 'micrographia' (small size)

Improvement after L-DOPA therapy Improvement after L-DOPA therapy


Five stages of Parkinson's disease


Stages in the development of parkinsonian symptoms .
(a) Stage 1 : unilateral involvement; blank faces; affected arm in semiflexed position with tremor; patient lean to unaffected side.
(b) Stage 2: bilateral involvement with early postural changes; slow, shuffling gait with decreased excursion of legs.
(c) Stage 3: pronounced gait disturbances; moderate generalized disability; postural instability with tendency to fall .

Last stages in the development of parkinsonian symptoms.
(d) Stage 4; significant disability; limited ambulation with assistance.
(e) Stage 5; complete invalidism; patient confined to bed or chair; cannot stand or walk even with assistance.


Brain chemistry and Parkinson's disease

Parkinson's disease is thought to be caused by a breakdown in communication between two areas of the brain: the substantia nigra and the striatum (the striatum consists of two structures: the caudate nucleus and the putamen). The striatum controls movement, balance, and walking. Cells in the substantia nigra synapse with cells in the striatum. Dopamine is the chemical messenger released at these synapses. Patients with Parkinson's disease are missing about 80% of the cells in the substantia nigra, and there is a corresponding loss of about 80% of dopamine in the striatum. Treatments for the disease involve replacing this lost dopaminergic function. The most common treatment involves giving the patient the drug L-DOPA which is converted into dopamine in the brain.
Results of L-DOPA therapy

Moreover in the long term:

Therefore there is still a need for research into causes and treatments for this debilitating condition.
One avenue of research is attempting to develop a Tissue Transplantation Therapy . This involves replacing damaged cells in the patient's brain with new cells that synthesize the chemical dopamine. This therapy has its roots in groundbreaking basic research in animals such as that carried out by Dunnet in Cambridge, UK.
Introduction to Dunnet's experiments


Rotometer

Here is a picture of the Rotometer Dunnet used in his experiment A wire connected to the recorder extends from a harness fitted around the rat's chest. This device records circling behaviour in rats. The hemisphere-shaped bowl tends to encourage circling behaviour in amphetamine treated rats.

rotometer a device to record circling behaviour in rats


This figure shows the results of Dunnet's experiment on the effects of dopamine-rich grafts on amphetamine-induced rotation.
Rotation in intact control rats (the bottom line), rats with unilateral nigrostriatal lesions, and rats with unilateral nigrostriatal lesions + dopamine-rich ( DA graft ), serotonin-rich (5-HT graft ), or striatal (CPu graft ) cell suspension grafts into the denervated host neostriatum. The lesions induce a marked turning asymmetry, which is alleviated only in the group receiving DA-rich grafts.

the effects of dopamine-rich grafts on amphetamine-induced rotation


In one subgroup of rats with DA-rich grafts, the grafts were lesioned by an injection of the neurotoxin 6-hydroxydopamine (6-OHDA) (indicated by the arrow above the line representing the DA graft removed group). Destruction of the DA cells in the graft reinstated the initial rotation asymmetry.

Destruction of the DA cells in the graft reinstated the initial rotation asymmetry
Main points:



Source of DA neurones [from Antiparkinsons Pravin K. Mishra, Ph.D. ]

Point to ponder
Do you think Parkinson's disease is a psychiatric illness?

Supplementary Internet Resources

Medications for Parkinson's disease can be effective, but they sometimes wear off too soon. Discover what's being done to allow patients to get longer responses to their treatment. 

Video here:

  • Treatment for Parkinson's : What should you take
  • When Parkinson's  meds wear off: A personal look
  • Current treatments for Parkinson's disease

The Bachmann-Strauss Dystonia & Parkinson Foundation

Parkinson's disease generally affects people in later life, but there are inherited forms of the disease (e.g. autosomal recessive juvenile parkinsonism) that affect younger people. In the 9 April 1998 issue of Nature, a group of Japanese scientists report that they have identified the gene for one of these early-onset forms of parkinsonism.


Here is a link to a recent Behavioral & Brain Sciences article which covers transplantation in great detail
FETAL BRAIN TISSUE GRAFTS AS THERAPY FOR BRAIN DYSFUNCTIONS: SOME PRACTICAL AND THEORETICAL ISSUES
Abstract "Grafting embryonic neural tissue into the brains of adult patients is currently being used to treat Parkinson's disease and is being given serious consideration as therapy for a variety of other degenerative and traumatic disorders. This target article evaluates the use of transplants to promote recovery from brain injury and highlights the kinds of questions and problems that must be addressed before this form of therapy is routinely applied. It has been argued that neural transplantation can promote functional recovery through the replacement of damaged nerve cells, the reestablishment of specific nerve pathways lost as a result of injury, the release of specific neurotransmitters, or the production of factors that promote neuronal growth. The latter two mechanisms, which need not rely on anatomical connections to the host brain, are open to examination through nonsurgical, less intrusive therapy. Subjective judgments in selecting which patients will receive grafts and in assessing the outcome of graft therapy make evaluation of the procedure methodologically difficult. In addition, little long-term assessment of transplant efficacy and effect has been done in nonhuman primates. Carefully controlled human studies, with multiple testing paradigms, are also needed to establish the efficacy of transplant therapy. "


VICTORY OVER PARKINSON'S DISEASE IN SIGHT!
Introduction
"The ailment now called Parkinson's disease (PD) has devastated the lives of many millions of people over the centuries. Until the middle l900s, there was little basis for hope that the lives of those afflicted could ever be salvaged. Since the cause of PD is unknown, the treatment is to minimize the symptoms. We owe much to the researchers who discovered the detailed structure and processes of the human nervous system, so that building on their work, we find ourselves on the new threshold of triumph over PD. We can't yet pinpoint the cause or the cure, but we have the very next best thing to a cure; we have found a way to control and reverse the course of the symptoms for most PD patients. Robert P. Iacono, M.D., F.A.C.S., Associate Professor of Neurosurgery at Loma Linda University, is the leader of a specialized Clinical Neurosurgical Group, a "Tiger Team" that has made clinical breakthroughs in treatment of PD. Progress is continuing with ever increasing swiftness."


From The Harvard Mahoney Neuroscience Institute Letter FETAL NERVE CELL TRANSPLANTATION: ADVANCES IN THE TREATMENT OF PARKINSON'S DISEASE
Introduction
"There are billions of nerve cells in a human brain. In neurodegenerative disorders, such as Parkinson's and Huntington's disease, selective loss of some 500,000 cells in critical brain regions can lead to devastating symptoms. Nerve cell death in these diseases occurs over years or decades and results in specific signs and symptoms, such as lack of movements (in Parkinson's) or excess movements (in Huntington's disease). Although several theories have been presented for the causes of neurodegenerative disease, the exact pathological mechanisms involved are not known. Treatment alternatives are few and limited in effect and duration. Neuroscientists and neurologists working in this field have attempted to replace neurotransmitters lost in the disease process by pharmacological treatments. L-dopa or related agents bring relief to many Parkinsonian patients, but L-dopa becomes ineffective over time and debilitating side-effects develop with prolonged use. No equivalent drug alternative exists for patients with Huntington's disease. Because standard therapies for these patients are largely ineffective, alternative strategies are being developed. Intense research efforts are directed towards drugs that may block nerve cell death and novel cell-based therapies, which replace defective nerve cells. "


Eric Chudler's pages provide easy to follow background information on a number of topics:

Parkinsons Disease: Sources of information and support groups on the Internet

Copyright Dr. C.A.P. Kenyon 1994-2006