by Michael Shermer
In the beginning — specifically on October 23, 4004 B.C., at noon — out of quantum foam fluctuation God created the Big Bang, followed by cosmological inflation and an expanding universe. And darkness was upon the face of the deep, so He commanded hydrogen atoms (which He created from Quarks) to fuse and become helium atoms and in the process release energy in the form of light. And the light maker he called the sun, and the process He called fusion. And He saw the light was good because now He could see what He was doing, so He created Earth. And the evening and the morning were the first day.
And God said, Let there be lots of fusion light makers in the sky. Some of these fusion makers He grouped into collections He called galaxies, and these appeared to be millions and even billions of light years from Earth, which would mean that they were created before the first creation in 4004 B.C. This was confusing, so God created tired light, and the creation story was preserved. And created He many wondrous splendors such as Red Giants, White Dwarfs, Quasars, Pulsars, Supernova, Worm Holes, and even Black Holes out of which nothing can escape. But since God cannot be constrained by nothing, He created Hawking radiation through which information can escape from Black Holes. This made God even more tired than tired light, and the evening and the morning were the second day.
And God said, Let the waters under the heavens be gathered together unto one place, and let the continents drift apart by plate tectonics. He decreed sea floor spreading would create zones of emergence, and He caused subduction zones to build mountains and cause earthquakes. In weak points in the crust God created volcanic islands, where the next day He would place organisms that were similar to but different from their relatives on the continents, so that still later created creatures called humans would mistake them for evolved descendants created by adaptive radiation. And the evening and the morning were the third day. And God saw that the land was barren, so He created animals bearing their own kind, declaring Thou shalt not evolve into new species, and thy equilibrium shall not be punctuated. And God placed into the rocks, fossils that appeared older than 4004 B.C. that were similar to but different from living creatures. And the sequence resembled descent with modification. And the evening and morning were the fourth day.
And God said, Let the waters bring forth abundantly the moving creatures that hath life, the fishes. And God created great whales whose skeletal structure and physiology were homologous with the land mammals he would create later that day. God then brought forth abundantly all creatures, great and small, declaring that microevolution was permitted, but not macroevolution. And God said, “Natura non facit saltum” — Nature shall not make leaps. And the evening and morning were the fifth day.
And God created the pongidids and hominids with 98 percent genetic similarity, naming two of them Adam and Eve. In the book in which God explained how He did all this, in one chapter He said he created Adam and Eve together out of the dust at the same time, but in another chapter He said He created Adam first, then later created Eve out of one of Adam’s ribs. This caused confusion in the valley of the shadow of doubt, so God created theologians to sort it out.
And in the ground placed He in abundance teeth, jaws, skulls, and pelvises of transitional fossils from pre-Adamite creatures. One chosen as his special creation He named Lucy, who could walk upright like a human but had a small brain like an ape. And God realized this too was confusing, so he created paleoanthropologists to figure it out.
Just as He was finishing up the loose ends of the creation God realized that Adam’s immediate descendants would not understand inflationary cosmology, global general relativity, quantum mechanics, astrophysics, biochemistry, paleontology, and evolutionary biology, so he created creation myths. But there were so many creation stories throughout the world God realized this too was confusing, so created He anthropologists and mythologists.
By now the valley of the shadow of doubt was overrunneth with skepticism, so God became angry, so angry that God lost His temper and cursed the first humans, telling them to go forth and multiply themselves (but not in those words). But the humans took God literally and now there are six billion of them. And the evening and morning were the sixth day.
By now God was tired, so He proclaimed, “Thank me its Friday,” and He made the weekend. It was a good idea.
Sunday, May 31, 2009
Friday, May 15, 2009
How RNA got started
Scientists may have figured out the chemistry that sparked the beginning of life on Earth.
The new findings map out a series of simple, efficient chemical reactions that could have formed molecules of RNA, a close cousin of DNA, from the basic materials available more than 3.85 billion years ago, researchers report online May 13 in Nature.
“This is a very impressive piece of work — a really excellent analysis,” comments chemist James Ferris of the Rensselaer Polytechnic Institute in Troy, N.Y.
The new research lends support to the idea that RNA-based life-forms were the first step toward the evolution of modern life. Called the RNA world hypothesis, the idea was first proposed some 40 years ago. But until now, scientists couldn’t figure out the chemical reactions that created the earliest RNA molecules.
Today, DNA encodes the genetic blueprint for life — excluding some viruses, for those who consider viruses living — and RNA acts as an intermediary in the process, making protein from DNA. But most scientists think it’s unlikely that DNA was the basis of the origin of life, says study coauthor John Sutherland of the University of Manchester in England.
Information-bearing DNA holds the code needed to put proteins together, but at the same time, proteins catalyze the reactions that produce DNA. It’s a chicken-or-egg problem. Scientists don’t think that DNA and proteins could have come about independently — regardless of which came first — and yet still work together in this way.
It’s more plausible that the first life-forms were based on a single molecule that could replicate itself and store genetic information — a molecule such as RNA (SN: 4/7/01, p. 212). RNA world proponents speculate modern DNA and proteins evolved from this RNA-dominated early life, and RNA in cells today is left over from this early time.
While reactions to make RNA from ancient precursors worked on paper, the chemistry didn’t work in the lab. And some scientists thought even RNA molecules were too complex to have spontaneously formed in the primordial soup. Sutherland and his colleagues have shown the reactions are possible.
RNA molecules are formed from three components: a sugar, a base and a phosphate group. In past research, chemists developed each of the components and then tried to put them together to make the complete molecule. “But the components are quite stable, and so they wouldn’t stick together,” Sutherland says. “After 40 years of trying, we decided there had to be a better way of doing this reaction.”
The team took a different approach, starting with a common precursor molecule that had a bit of the sugar and the base. “Basically, we took half a base, added that to half a sugar, added the other piece of base, and so on,” Sutherland says. “The key turned out to be the order that the ingredients are added and the way you put them together — like making a soufflé.”
Another difference is that Sutherland and his team added the phosphate to the mix earlier than in past experiments. Having the phosphate around so early helped the later stages of the reaction happen more quickly and efficiently, the scientists say.
The starting materials and the conditions of the reaction are consistent with models of the geochemistry of an early Earth, the team says.
“But while this is a step forward, it’s not the whole picture,” Ferris points out. “It’s not as simple as putting compounds in a beaker and mixing it up. It’s a series of steps. You still have to stop and purify and then do the next step, and that probably didn’t happen in the ancient world.”
Sutherland and his team can so far make RNA molecules with two different bases, and there are still another two bases to figure out. “It’s related chemistry,” Sutherland says. “That’s how it must have been in the very beginning — a series of fundamental reactions that could make all four types of RNA molecule.”
Once those RNA molecules formed, they would have had to string together to make multiple letters of the code, which could then make proteins. Proteins could then make all the components that make up a cell, and the process would continue from there.
Tuesday, May 12, 2009
What Seashells Tell
Starting from a slender, tapered shard, the shell of the Conus gloriamaris grows gradually outward in a lazy spiral, flaring out as it wraps itself in layer after layer of gleaming tan-and-white marbling. The meticulous design of a seashell has long been a source of fascination for mathematicians, but the biological process involved has remained mysterious. Equipped with a new understanding of how mollusks use an extensive network of nerve cells to coordinate precise deposits of shell material and pigment, researchers can now simulate the growth of almost any seashell on a computer. And while this may delight molluscophiles, the significance is broad: This advance marks a triumphant cross-pollination between mathematics and biology that is also yielding important insights into how complex neural networks interact and communicate.
Image courtesy Alistair Boettiger
In the 80s, George Oster, a biophysicist at the University of California at Berkeley, and Bard Ermentrout, a mathematician at the University of Pittsburgh, developed a model for seashell growth and pigmentation based on the premise that a highly interconnected network of neurons controls the process. Unfortunately, Oster and Ermentrout lacked sufficient experimental evidence to confirm their theory. German researcher Hans Meinhardt found some success using an alternative model in which secreted chemicals that diffuse throughout the mollusk’s mantle — a tongue-like protrusion responsible for shell construction — govern these activities and turn pigment production on or off in different cells. But the results weren’t completely satisfactory. “Meinhardt could write these models that would produce beautiful pictures of shells,” says Oster. “The only problem is, he had to have a different model for every shell, and nobody has ever found these diffusing and reacting substances.”
More recent experimental findings have given new life to the neurosecretory model, however, including recent findings suggesting that the mantle uses pigment patterns in the shell as a “diary” of past shell-building activity. During shell construction, the mantle is always extended just a bit beyond the lip of the shell, inspecting its prior handiwork; Oster and Ermentrout hypothesized that pigment patterns from days past are scanned and interpreted by the mantle’s nerve network, triggering waves of excitation and inhibition that yield detailed instructions for the next round of construction. “What the mantle is doing is ‘tasting’ back in time,” says Oster, “so it can predict what it should do the next day and so that the pattern will be continuous.”
By charting these discrete patterns of neural excitation and inhibition, Oster and Ermentrout were able to build a mathematical model for shell formation that accounts for virtually any design observed in nature, from the zigzagging lines of Natica communis to the seemingly random patterns of mottled patches on a cone snail’s shell. “A single equation is sufficient to explain this tremendous diversity of patterns,” says Alistair Boettiger, a Berkeley graduate student who developed a computational modeling program for Oster and Ermentrout based on their findings. The team has modeled more than 30 shell types, and in each case the simulation bears a striking resemblance to the real thing. The program is even able to compensate for changes in growth and patterning caused by scratches and scrapes picked up in a mollusk’s tumultuous life at sea.
Just as pioneering experiments with oversize squid neurons in the 1940s and 50s established much of the foundation for modern neuroscience, Oster believes that modeling simple neural processes may have much broader implications for the field. For example, the primitive form of “memory” observed in mollusk neural networks might help researchers to decipher how far more sophisticated networks in the human brain enable us to use prior experience to build a picture of our world. To deepen their understanding, the team is now turning their attention to the cuttlefish, which rapidly changes colors and patterns.. “The patterns are very dynamic, and instead of taking months to form, they do it in a millisecond,” Oster says, “but it’s the same kind of nervous net, and it’s working in very much the same way.”
Monday, May 11, 2009
The Correlation Between Music and Math: A Neurobiology Perspective
Cindy Zhan
I remember the first time I heard the statement "Did you know that listening to classical music enhances your mathematical abilities?" I was both intrigued and excited, intrigued because I did not understand how music and math, two seemingly unrelated subject could possibly affect each other. I was also excited because I began to view classical music as some kind of magical potion that would transform my math skills from decent to extraordinary. When I had the opportunity to write this web paper, I immediately jumped into the topic of music and math. The questions that I wish to answer throughout this paper are; does listening to music really help you do better in math? If so, which part of the brain is controlling the correlation between math and music? In addition, how does music stimulate the brain in a way that enhances mathematical abilities?
It turns out that there is much evidence that supports the positive effects of music on one's ability to do math. Most research shows that when children are trained in music at a young age, they tend to improve in their math skills. The surprising thing in this research is not that music as a whole is enhancing math skills. It is certain aspects of music that are affecting mathematics ability in a big way. Studies done mostly in children of young age show that their academic performance increases after a certain period of music education and training. One particular study published in the journal 'Nature' showed that when groups of first graders were given music instruction that emphasized sequential skill development and musical games involving rhythmn and pitch, after six months, the students scored significantly better in math than students in groups that received traditional music instruction. (1)
The result of this study posed another important question. How does this type of music that emphasized sequential skills, rhythmn and pitch manage to improve children's ability to do math? It turned out that there are two distinguished types of reasoning, spatial temporal (ST) reasoning and Language analytical (LA) reasoning. LA reasoning would be involved in solving equations and obtaining a quantitative result. ST reasoning would be is utilized in activities like chess when one needs to think ahead several moves. The effect of music on math sometimes termed the Mozart effect. The Mozart effect gain its name after the discovery that listening to Mozart's compositions, which is very sequential, produces a short-termed enhancement of spatial-temporal reasoning. Some key reasoning features used in spatial temporal reasoning are
1. The transformation and relating of mental images in space and time
2. Symmetries of the inherent cortical firing patterns used to compare physical and mental images and
3. Natural temporal sequences of those inherent cortical patterns (3).
The same people who conducted the Mozart effect experiment also suggested that spatial-temporal reasoning is crucial in math. The areas of math that require ST reasoning are geometry and certain aspects of calculus, which require transformations of images in space and time. In higher mathematics, the ability to write mathematical proofs is also associated with ST reasoning because proof writing is a task that requires intuitive sense of natural sequences and the ability to think ahead several steps.
As to the question, what part of the brain controls the correlation between math and music, there are also many resources that provide answers. Dr. Gottfried Schlaug, found that certain regions of the brain such as the corpus callosum and the right motor cortex, were larger in musician who started their musical training before the age of 7 (2). As to what happens in that area of the brain when one listens to music, we turn to the experiment performed by Xiaodeng Leng and Gordon Shaw. Gordon and Leng developed a model of higher brain function, which is based on the trion model. The trion model is a highly structured mathematical realization of the Mountcastle organization principle, with the column as the basic neuronal network in mammalian cortex. The column comprises minicolumns called trions. One particular columnar network of trions has a large repertoire of spatial-temporal firing patterns, which can be excited and used in memory and higher brain functions (3). Shaw and Leng performed an experiment in which they mapped the trion model of firing patterns in that particular column onto various pitches and instruments producing recognizable styles of music. This mapping of the trions gaves insight to relate the neuronal processes involved in music and abstract spatial-temporal reasoning (3). It shows that the part of the cortex, which contains the repertoire of spatial-temporal firing patterns, can be excited by music and is utilized in higher brain functions such as spatial-temporal thinking in mathematics.
In conclusion, my research into math and music does seem to suggest that music enhances mathematics skills. Music targets one specific area of the brain to stimulate the use of spatial-temporal reasoning, which is useful in mathematical thinking. However, as to the question of whether or not music is the magical portion that will elevate anyone's ability to do math, the answer unfortunately . . .would be no. Just because most mathematicians are fond of music, dosen't mean that all musicians are fond of mathematics. I found a letter posted on the web written by a fourteen-year-old overachiever to a mathematics professor. The student expresses his fraustration that even though he is an excellent musician, math is one of his weakest subjects. In math, he is not making the grades that he needs to stay in a certain prestigious academic program (4).
This letter seems to suggest that listening to music, or being able to master a musical instrument does not automatically guarantee that one can perform well in math. In other words, there are many musicians who are good in music but not in math. Music is a lot more than notes conforming to mathematical patterns and formulas. Music is exhilarating because of the intricacies of the patterns that occurs. Whether or not these patterns resemble math has no relevance to many musicians. More often than not, musicians are inclined to practice music because of the wonders and awe that they feel for music even if they are not aware of the math that is in music.
I remember the first time I heard the statement "Did you know that listening to classical music enhances your mathematical abilities?" I was both intrigued and excited, intrigued because I did not understand how music and math, two seemingly unrelated subject could possibly affect each other. I was also excited because I began to view classical music as some kind of magical potion that would transform my math skills from decent to extraordinary. When I had the opportunity to write this web paper, I immediately jumped into the topic of music and math. The questions that I wish to answer throughout this paper are; does listening to music really help you do better in math? If so, which part of the brain is controlling the correlation between math and music? In addition, how does music stimulate the brain in a way that enhances mathematical abilities?
It turns out that there is much evidence that supports the positive effects of music on one's ability to do math. Most research shows that when children are trained in music at a young age, they tend to improve in their math skills. The surprising thing in this research is not that music as a whole is enhancing math skills. It is certain aspects of music that are affecting mathematics ability in a big way. Studies done mostly in children of young age show that their academic performance increases after a certain period of music education and training. One particular study published in the journal 'Nature' showed that when groups of first graders were given music instruction that emphasized sequential skill development and musical games involving rhythmn and pitch, after six months, the students scored significantly better in math than students in groups that received traditional music instruction. (1)
The result of this study posed another important question. How does this type of music that emphasized sequential skills, rhythmn and pitch manage to improve children's ability to do math? It turned out that there are two distinguished types of reasoning, spatial temporal (ST) reasoning and Language analytical (LA) reasoning. LA reasoning would be involved in solving equations and obtaining a quantitative result. ST reasoning would be is utilized in activities like chess when one needs to think ahead several moves. The effect of music on math sometimes termed the Mozart effect. The Mozart effect gain its name after the discovery that listening to Mozart's compositions, which is very sequential, produces a short-termed enhancement of spatial-temporal reasoning. Some key reasoning features used in spatial temporal reasoning are
1. The transformation and relating of mental images in space and time
2. Symmetries of the inherent cortical firing patterns used to compare physical and mental images and
3. Natural temporal sequences of those inherent cortical patterns (3).
The same people who conducted the Mozart effect experiment also suggested that spatial-temporal reasoning is crucial in math. The areas of math that require ST reasoning are geometry and certain aspects of calculus, which require transformations of images in space and time. In higher mathematics, the ability to write mathematical proofs is also associated with ST reasoning because proof writing is a task that requires intuitive sense of natural sequences and the ability to think ahead several steps.
As to the question, what part of the brain controls the correlation between math and music, there are also many resources that provide answers. Dr. Gottfried Schlaug, found that certain regions of the brain such as the corpus callosum and the right motor cortex, were larger in musician who started their musical training before the age of 7 (2). As to what happens in that area of the brain when one listens to music, we turn to the experiment performed by Xiaodeng Leng and Gordon Shaw. Gordon and Leng developed a model of higher brain function, which is based on the trion model. The trion model is a highly structured mathematical realization of the Mountcastle organization principle, with the column as the basic neuronal network in mammalian cortex. The column comprises minicolumns called trions. One particular columnar network of trions has a large repertoire of spatial-temporal firing patterns, which can be excited and used in memory and higher brain functions (3). Shaw and Leng performed an experiment in which they mapped the trion model of firing patterns in that particular column onto various pitches and instruments producing recognizable styles of music. This mapping of the trions gaves insight to relate the neuronal processes involved in music and abstract spatial-temporal reasoning (3). It shows that the part of the cortex, which contains the repertoire of spatial-temporal firing patterns, can be excited by music and is utilized in higher brain functions such as spatial-temporal thinking in mathematics.
In conclusion, my research into math and music does seem to suggest that music enhances mathematics skills. Music targets one specific area of the brain to stimulate the use of spatial-temporal reasoning, which is useful in mathematical thinking. However, as to the question of whether or not music is the magical portion that will elevate anyone's ability to do math, the answer unfortunately . . .would be no. Just because most mathematicians are fond of music, dosen't mean that all musicians are fond of mathematics. I found a letter posted on the web written by a fourteen-year-old overachiever to a mathematics professor. The student expresses his fraustration that even though he is an excellent musician, math is one of his weakest subjects. In math, he is not making the grades that he needs to stay in a certain prestigious academic program (4).
This letter seems to suggest that listening to music, or being able to master a musical instrument does not automatically guarantee that one can perform well in math. In other words, there are many musicians who are good in music but not in math. Music is a lot more than notes conforming to mathematical patterns and formulas. Music is exhilarating because of the intricacies of the patterns that occurs. Whether or not these patterns resemble math has no relevance to many musicians. More often than not, musicians are inclined to practice music because of the wonders and awe that they feel for music even if they are not aware of the math that is in music.
Thursday, May 7, 2009
Our genes, ourselves?
Ari Berkowitz Division of Biology, California Institute of Technology
"Now we know, in large measure, our fate is in our genes." So said James Watson (Jaroff 1989), Nobel laureate, co-discoverer of the structure of DNA, and first leader of the Human Genome Project.
Is he right? We in the United States seem to be of two minds. Most of us have an intuition that, although our genes provide advantages and constraints, we retain great control over our lives. But we are developing a second, competing intuition that, like it or not, our genes determine our abilities, our preferences, and our emotions. Perhaps this second intuition is what induced Rutgers University President Francis Lawrence, a man who has spent years trying to increase opportunities for minorities, to say that blacks do not have "the genetic, hereditary background" to do as well as whites on college admissions tests, a statement which caused an uproar across the country (Olen 1995). We would like to think we are much more than the sum of our genes, but scientists have apparently demonstrated that our genes determine some of our most complex behavioral and cognitive characteristics.
Science is not an unblemished source of objectivity. Science is done by scientists. Scientists both influence contemporary culture and are influenced by the culture. Research questions are chosen and framed partly in response to current medical, social, and political concerns. The process of obtaining research funding requires scientists to write proposals to compete for grants and encourages them to present flashy results on issues of immediate public interest. The development of powerful new methods for studying DNA in the past three decades has led to a proliferation of explanations of all sorts of human characteristics in terms of genes.
The focus on genes as the primary mode of biological explanation has been especially clear in the marketing of the Human Genome Project. In support of this project, some respected biologists have expressed views that are surprisingly similar to those once held by the leaders of the American eugenics movement, which brought us racially-based immigration quotas and laws for forced sterilization of the "feeble-minded".
Charles B. Davenport, the biologist who led the American eugenics movement as founder and director of the Eugenics Record Office at Cold Spring Harbor, New York , wrote in 1928:
[T]he widespread existence of crime enforces the lessons of eugenics. We are breeding too many people with feeble inhibitions and without proper social instincts; persons who have a tendency toward periodic outbreaks of temper and to assaults; persons who are liable to periodic bad behavior, including the kind that is associated with the epileptic state; persons who are introverts, selfish and non-social. Satisfactory progress will be made only when we understand how those with congenital criminalistic make- up are bred and try to prevent such breeding. If we permit them to be born, then we must apply such special treatment as will prevent their behavior from disorganizing society.
Daniel E. Koshland, Jr., a contemporary molecular biologist and then Editor-in-Chief of the journal Science, wrote in Science in 1990:
Last week a crazed gunman terrorized hostages in a bar in Berkeley, killing one and wounding many others.... Schizophrenia (the disease from which the Berkeley gunman is thought to have suffered) and other major mental illnesses can have a multigenic origin. A sequenced human genome will be a very important tool for understanding this precise category of diseases....The combination of new tools may not only let us help in reducing crime, but also aid some of our most disadvantaged citizens, the mentally ill. Although increased funding of mental health centers, stricter gun control, increased supervision of the mentally unbalanced, or higher standards for probation officers may be desirable, they are Band-Aid remedies. In the long run, the solution will be found in the knowledge required to produce accurate diagnoses and cures. The research to provide that knowledge will be far cheaper, and the results much fairer, than Draconian law enforcement.
Robert L. Sinsheimer, biologist and former chancellor at the University of California, Santa Cruz and an architect of the Human Genome Project, wrote in 1969:
The new genetics would permit in principle the conversion of all of the unfit to the highest genetic level.... I know there are those who find this concept and this prospect repugnant.... They are not among the losers in that chromosomal lottery that so firmly channels our human destinies... [such as] the 50,000,000 "normal" Americans with an IQ of less than 90.... Equality of opportunity is a noble aim given the currently inescapable genetic diversity of man. But what does equality of opportunity mean to the child born with an IQ of 50?
In 1991, in support of the Human Genome Project, Sinsheimer affirmed, "[i]n the deepest sense we are who we are because of our genes."
Does the available scientific evidence actually tell us that our genes determine our behavioral, emotional, and cognitive characteristics? Do single genes specify particular behavioral traits? To answer these questions, most non-specialists depend upon the cursory reports of new research findings that appear regularly in the lay press. These reports are often oversimplified and may be shaped by the desire of both journalists and scientists to create an exciting story. Sober-minded assessments with broader perspectives seldom attract as much interest, either in the lay press or in scientific journals. As a result, our perceptions of the scientific evidence may be skewed by a few dramatic findings, some of which may be wrong.
Nowhere has this been more clear than in the representation of the roles of genes in determining uniquely human characteristics, involving our thoughts, emotions, and behaviors. Within the past decade, there have been highly visible reports localizing genes for schizophrenia (Sherrington et al. 1988), manic-depression (Baron et al. 1987, Egeland et al. 1987), alcoholism (Blum et al. 1990), and homosexuality (Hamer et al. 1993). Recently, there was even a report of a "gene site for bed-wetting" (Goleman 1995). Other groups of scientists have generally been unable to reproduce the findings for schizophrenia (Kennedy et al. 1988), manic-depression (Detera-Wadleigh et al. 1987, Hodgkinson et al. 1987), and alcoholism (Gelernter et al. 1991, 1993). Authors of two studies claiming to have found a gene for manic-depression (in two different places), have both published retractions of their conclusions (Baron et al. 1993, Kelsoe et al. 1989), unusual and embarrassing events among scientists. These reversals have led to much methodological soul-searching within the pages of scientific journals and books, but have been described cursorily in newspapers and less, if at all, on television. Research linking genes to complex human mental and behavioral characteristics has been tremendously successful in molding public opinion, in the absence of much lasting scientific evidence.
There is only one antidote for the effects of skewed research reporting: non-specialists must learn more about experiments and interpretations used in this branch of science. Examining the types of methods and experiments that are used to support simple genetic explanations of human behavior allows one to see how ambiguities and biases can lead to misinterpretations. The relationship between a gene and a human behavior is rarely, if ever, a one-to-one correspondence, even though disruption of a single gene occasionally has a dramatic effect on behavior. Nor can one quantify the contribution of genes as a whole to any particular behavior or cognitive ability. Instead, each gene is a single player in a wonderfully intricate story, involving non-additive interactions of genes, proteins, hormones, food, and life experiences, and leading to effects on a variety of cognitive and behavioral functions. Our thoughts, emotions, and behaviors certainly have biological mechanisms, but this does not mean we can separate and quantify the genetic contributions to these processes.
Linkage Studies
It has long been observed that certain human behavioral characteristics tend to "run in families," but these characteristics might be caused by either genes or environments, or some combinations of the two. For much of this century, some investigators have attempted to demonstrate and quantify genetic contributions to human cognition and behavior, most notably IQ., by examining identical twins and applying questionable interpretations (see Kamin 1974, Lewontin et al. 1984, and below). More recently, some researchers have taken advantage of new techniques for manipulation of DNA to attempt to locate individual genes that either determine or convey a propensity to behavioral characteristics. Such studies are much easier to conduct with non- human animals, in laboratory settings where environmental effects and mating pairs can be controlled, than with human beings, but it is eventually necessary to examine human DNA if one wishes to find genes that cause, for example, human psychiatric conditions.
Experiments linking a gene to a complex human characteristic can be informative, but they also can produce misconceptions if they are not interpreted with care. Such experiments generally rely on a statistical argument that a segment of DNA and a complex characteristic tend to co-occur in individuals more often than one would expect at random. In particular, the statistical argument relies on the natural process of "crossing over," in which the matching chromosomes of each parent pair up and sometimes exchange pieces of DNA. Thus, two genes that had begun on the same chromosome can end up on different chromosomes. The probability that two stretches of DNA will end up in the same gamete (and thus the same person), despite crossing over, is related to their proximity on the chromosome: the closer together they are, the more likely they are to remain on the same chromosome.
When scientists begin searching for a gene that may be related to a complex human characteristic, they usually know nothing about the likely location of the gene, the protein that it specifies, or the function of that protein. Instead of directly examining whether a particular gene causes a particular characteristic, they use easily traceable pieces of DNA, called genetic markers, to narrow down the possible location of such a gene. If a marker is consistently found in individuals who have a particular characteristic, and not found in other individuals, then it is inferred that there is a gene near the marker which is "linked" to the characteristic. The gene need not include the marker; if they are sufficiently close together, they will tend to remain together despite crossing over. Thus, linkage between a marker and a trait does not indicate that a relevant gene has been identified, but may indicate that a relevant locale has been found. In some cases, investigators begin with an educated guess: rather than using random genetic markers, they look for linkage to particular genes that have already been identified, called candidate genes, which they believe might function in the behavior under study. Experiments on non-human animals sometimes suggest candidate genes, but this by no means guarantees that a similar gene in human beings will be linked to the behavior of interest.
This type of research has been very successful in locating genes that cause a disease in an all-or-none manner. Huntington's disease, for example, is a complex behavioral disorder which is known to be caused by a single gene. Proponents of genetic determination can point to this example and suggest that many other complex behavioral disorders are probably determined by single genes. But the inheritance pattern for Huntington's disease is very different from inheritance patterns for conditions like manic- depression, schizophrenia, and alcoholism.
For more than a century, Huntington's disease was known to be caused by a single gene on the basis of its strikingly reliable pattern of inheritance: half the offspring (on average) of each victim of Huntington's disease develop the disease. This means that the disease is caused by a single gene that only needs to be present in one copy; it was just a matter of finding the gene.
In contrast, patterns of occurrence within families are very irregular and unpredictable for manic- depression, schizophrenia, and alcoholism. These patterns of occurrence are not consistent with there being a single gene that determines whether or not one develops the condition (Risch 1994). Instead, if indeed there are genes that can have important effects on these conditions, there are likely to be several genes, each of which has only a small effect on its own, that may interact in a non-additive manner with one another and with environmental factors to generate each condition. An assumption of single-gene causation can lead to an unwarranted conclusion that linkage has been demonstrated, in addition to overinterpretation of genuine linkage.
A closer examination of one example will illustrate some of the difficulties of genetic linkage studies of complex human characteristics. In 1987, Janice A. Egeland and colleagues reported in the journal Nature that they had localized "a dominant gene conferring a strong predisposition to manic depressive disease" on human chromosome 11, and demonstrated "by a linkage strategy that a simple genetic mechanism can account for the transmission" of manic-depression in the family they studied. Nature highlighted this report, saying, "[t]he use of DNA markers has shown that manic- depressive illness can be caused by a single gene" (Robertson 1987). In the same journal issue, Nature published two related studies (Detera-Wadleigh et al. 1987, Hodgkinson et al. 1987); each reported that they had found no linkage between the same genetic markers used by Egeland and manic-depression, in other families. These negative findings received relatively little attention.
There were at least three possible reasons for the discrepancies in linkage results. First, either Egeland's study or both of the other studies could have been in error; in the former case, the apparent linkage might have occurred purely by chance. Second, manic-depression might have been caused largely by a single gene in the family Egeland studied, but caused by non-genetic factors and/or the interaction of several genes, each having a small effect, in the other families. Third, manic-depression might have been caused largely by a single gene in each of the families studied, but by a different gene, in a different location, in the families with no linkage to the chromosome 11 markers, a situation known as heterogeneity. Surprisingly, only the third possibility was considered. Hodgkinson and colleagues concluded "that there is genetic heterogeneity of linkage in manic depression," despite the fact that Hodgkinson's study had found no evidence at all for a gene linked to manic depression. Nature said, "[t]his means there are at least two different genes predisposing to affective disorder."
There was apparently great eagerness to support a hypothesis of simple genetic causation for manic-depression. Meanwhile, another group of researchers published a report of linkage between manic- depression and a different region of DNA, on a different chromosome, also in Nature (Baron et al. 1987). They concluded that their results "provide confirmation that a major psychiatric disorder can be caused by a single genetic defect."
In 1989, Egeland's group published a "re-evaluation" of their own findings (Kelsoe et al. 1989), also in Nature, based on a change in diagnosis for two family members, as well as new data from additional family members. The updated analysis demolished the statistical argument; they now "excluded" their proposed linkage. In discussing this reversal, they introduced the possibilities that the original linkage was "due merely to chance," that a single gene might not have a major effect on manic depression, and "that non- genetic factors may contribute." They suggested that the reevaluation had highlighted "problems that can be anticipated in genetic linkage studies of common and complex neuropsychiatric disorders."
In 1993, Baron et al. also published what amounts to a retraction of their linkage claims, based on a similar reevaluation. Despite these retractions, a recent human genetics textbook (Lewis 1994) informs students that manic-depression "can be inherited as a sex-linked recessive trait or as an autosomal recessive trait," without citing evidence. In 1994, there were two more reports of genetic links to manic-depression, each pointing to yet another chromosome (Berrettini et al. 1994, Straub et al. 1994). Similar events have already undermined the reported genetic linkages to schizophrenia (Kennedy et al. 1988) and alcoholism (Gelernter et al. 1991, 1993).
Why did the genetic linkage studies of manic-depression go astray? Joseph S. Alper and Marvin R. Natowicz (Alper and Natowicz 1993) have argued that a "preconceived belief that the primary cause of these illnesses is in fact genetic" can lead to "erroneous conclusions". Ambiguity and bias can potentially creep into at least two important phases of genetic linkage studies of complex human characteristics: the diagnosis or categorization of the characteristic and the statistical evaluation of linkage.
Given the variety and complexity of human behavior, it may be difficult, or even impossible, to assign each person unambiguously to a category such as "normal" or "manic- depressive". Is there exactly one condition that goes by the name "manic-depression"? Can the diagnosis be shaped partly by the currently available methods and categories for diagnosis or by the objectives of the study?
Analogous questions need to be asked regarding diagnoses or assignments for many other complex human characteristics, including schizophrenia, alcoholism, homosexuality, and intelligence. For example, following the 1990 report of a gene linked to alcoholism, authored by Kenneth Blum, Ernest P. Noble, and colleagues, several other scientists expressed skepticism (Peele 1990) and later reported that they were unable to replicate this finding (Gelernter et al. 1991, 1993). Noble initially countered that the gene they studied was not linked to alcoholism per se, but to "pleasure-seeking behaviors" (Peele 1990). Later, Blum and Noble amended this to "addictive-compulsive behaviors" (Blum and Noble 1994). Their claim thus became a moving target.
The appropriate statistical methods for concluding that there is genuine linkage to a complex human characteristic are a matter of considerable debate within the field. In order to calculate the probability of linkage to a complex human trait, researchers have usually proposed a "model" for genetic transmission of the trait which includes values of several parameters that cannot be measured independently. These parameters include the frequency of occurrence of each form of the gene of interest and the probability that a person carrying the gene will in fact exhibit the trait (this probability is often less than 100%, even when a single gene is linked to the trait). Researchers estimated or assumed values for these parameters in the families they studied. The calculated probability of linkage, as well as its interpretation, depend importantly on the validity of these assumptions.
Many human behavioral geneticists now believe that each of these more complex behavioral disorders is caused by a combination of several disrupted or altered genes (see Gershon and Cloninger 1994). Each of these genes may have only a small effect, they may interact in non-additive ways, and different abnormal forms may occur in different families. So each of these disorders might be due to genes alone, but the complexity of the genetic mechanisms might preclude a definitive finding with current techniques.
This suggestion is theoretically possible and may in itself lead to useful experiments in which additional relevant genes are identified. However, it also may be an "unfalsifiable hypothesis". That is, there may be no way of disproving it even if it is false; a proponent of genetic causation could always argue that there has been no reliable demonstration of the effect of a particular disease gene because there are additional unknown disease genes or gene interactions that cloud the picture.
In essence, this view retains the mind-set that applies for a single-gene disorder, while recognizing that several genes may be involved. As will be argued below, if interactions between a gene and other genes or environmental factors are acknowledged to influence a condition, it becomes difficult to describe or quantify the effect of one gene, or all genes, on the condition.
In the absence of definitive evidence, the language of human behavioral genetics may create a bias in favor of simple genetic explanations. For example, by defining any mental condition or characteristic as a "trait," one suggests that the characteristic is somehow like Mendel's traits of wrinkled or smooth peas and thus may show a regular pattern of inheritance. Similarly, "disease" suggests a biological process that is relatively independent of psychological influences. Attaching a name like "schizophrenia" or "intelligence" to a set of behaviors or functions suggests that the named category corresponds to a physiologically well-defined entity or state, which it may not. Even if a gene has a real effect on a cognitive or behavioral characteristic, such categorization may create a distorted view of what the gene's effect really is (Cloninger 1994).
Sometimes, researchers find that a characteristic (or "phenotype") can be caused entirely by non-genetic factors; these non-genetic cases are termed "phenocopies" (i.e., copies of the phenotype), as if they are facsimiles of the condition rather than the real thing. For example, fruit flies develop with four wings instead of two if they have a mutation in the bithorax gene or if they are exposed to heat or chemical stress at a critical phase of embryonic development (Capdevila and Garcia-Bellido 1978). The environmentally induced effects are termed phenocopies of bithorax, but one might just as well term the bithorax mutation a "genocopy," following Steven Rose (1995).
The less we know about the chain of events linking a gene to a behavior, the greater the likelihood that a correlation is established that does not indicate causation. Even if a correlation between a stretch of DNA and a well-defined, complex human characteristic can be firmly established, what does this tell us? We would like to know what causative role a gene plays in the chain of events leading to a behavioral outcome. This chain of events should include which gene is involved, which protein it codes for, what the function(s) of this protein is, and how this protein could produce changes in the nervous system that could underlie the mental characteristic. This is obviously a daunting task, but it is a necessary one. Research addressing such questions, mainly using non-human animals, in fact constitutes a major part of current biological research. But such causal schemes can be elucidated only gradually, while new linkages between genes and human behaviors can appear at any time.
To see how misleading linkage studies might be in the absence of a plausible causal scheme, consider genes that we already know something about. If I have one of the genes that contributes to pale skin, and I sit in the sun for several hours without sunscreen, I will probably get a bad sunburn. If I do it enough, I may stand a higher risk of getting skin cancer. If we knew only that there was linkage between that segment of DNA and occurrences of sunburn or skin cancer, we might conclude that it was a gene for sunburn or even a gene for skin cancer. Consider a gene that contributes to extraordinary growth. Suppose that researchers found linkage between this segment of DNA and the tendency to play NBA basketball; would we say that this is a gene for basketball-playing?
Twin Studies
When human genetic linkage studies are unable to provide definitive evidence for a gene's role in causing a complex condition, proponents of genetic causation often fall back on twin studies to demonstrate that genes are crucially involved in the condition. For example, following retraction of Egeland's reported genetic linkage to manic-depression in 1989, Nature stated, "this leaves us with no persuasive evidence linking any psychiatric disease to a single [genetic] locus." Nonetheless, Nature argued on the basis of twin studies that readers "should have no reason to doubt the existence of genetic predisposition to psychiatric disease, nor the ability of molecular geneticists eventually to identify the genes responsible" (Robertson 1989). In 1993, following the retraction of the Baron et al. reported genetic linkage to manic-depression, with no substantiated evidence remaining for genetic linkage to either manic- depression or schizophrenia, David L. Pauls, one of Egeland's co- authors, nonetheless asserted that "there is overwhelming evidence that genetic factors play an important role in the manifestation of all major neuropsychiatric conditions" (Pauls 1993).
Twin studies are also used as evidence that genes play a large role in determining normal mental characteristics, such as those labeled "personality type" or "general intelligence". Such categories of normal cognitive function are not generally expected to derive from a single gene, even if some complex disorders are due to alteration of a single gene. As an analogy, one can break a transistor radio by removing one component, but no one would seriously argue that the missing component alone normally causes the radio to play a particular radio station. (In support of this argument, no one has yet claimed to have located a gene for intelligence.) But twin studies are used to estimate the net effect of all genes on a characteristic.
Twin studies are often based on the premise that one can estimate the percentage "heritability" for complex human traits. Heritability here is a technical term, indicating the proportion of variation (or variance) in a measurable trait (or phenotype) that is statistically associated with genetic variation.
There are several major problems with the use of this measure in human studies (Hartl and Clark 1989, Kempthorne 1978, Lewontin 1974). The first is that heritability can only be estimated accurately if one can compare the effects of different sets of genes (or genotypes) in organisms that face controlled environments throughout development. This requires that individuals mate randomly with respect to their environments, to eliminate gene-environment covariance, a situation that cannot be achieved in studies of human beings. Then one can estimate how much variance is associated with the genotype, provided that one can first estimate the variance associated with the environment and the variance associated with gene-environment interactions, because the effects of genes and environments are not generally additive. This is also not possible in human studies. In the absence of such controlled experiments, researchers have attempted to estimate the variation associated with different genotypes by comparing individuals that are categorized by the researchers as having faced similar environments.
Even in breeding studies of plants or non-human animals, where heritability can often be estimated accurately, heritability only indicates the proportion of variance associated with genotypic variation for the particular population of genotypes and the particular range of environments tested. Even if a trait has a high heritability within each of two groups of genotypes (for example, African- Americans and Caucasian Americans), this says nothing about the source of any differences between these groups. Even if a trait has a high heritability in the environments tested, a major change in the environment (which might include improving education or health care in human cases) may dramatically alter not only the phenotypes but the heritability as well. In short, heritability cannot be measured accurately in human studies and would not indicate the relative importance of genes and environments anyway. Proponents of genetic causation have probably gotten a lot of mileage out of human heritability estimates (especially of I.Q.) by confusion of the statistical term "heritability" with the ordinary use of the word "heritable".
In human twin studies, heritability is estimated by comparing phenotypic variance in identical twins, who share 100% of their genes, and fraternal twins or other siblings, who share 50% of their genes (on average). This estimate also assumes that the similarity in environment for identical twins is no greater than for fraternal twins. However, there are many reasons for thinking that identical twins share an unusually similar environment. For example, parents often dress them identically and involve them in the same activities; in addition, identical twins often have an extraordinarily close relationship with one another.
The heritability estimates produced by these studies have generally ranged between 40% and 70% for general intelligence or personality type (Bouchard et al. 1990, Plomin et al. 1994). Billings and colleagues (1992) have pointed out that for complex characteristics influenced by combinations of genes, these numbers are likely to be overestimates for the general population, because identical twins share all their genes, whereas even a small change in the combination of genes, such as is likely to occur for fraternal twins, can have a large effect on the characteristic.
Because studies of twins raised together are ambiguous, much of the weight of genetic causation of complex human mental characteristics sits on the shoulders of the relatively few studies of identical twins raised apart; about 300 pairs of such twins have now been studied (Powledge 1993). These cases appear to provide well- controlled accidental experiments that demonstrate the role of genes alone. However, there are subtle reasons why this may not be so. Twins in such studies often were raised by relatives or close family friends; in some cases, the twins came into contact with each other and became close friends, as has been documented by psychologist Leon J. Kamin (Kamin 1974, Lewontin et al. 1984). These kinds of events confound the effect of identical genes with the effects of similar environments; moreover, information on potentially correlated environments is often not available for reexamination.
Another factor now recognized to be important is the different responses (and hence different environments) elicited by children who have different characteristics early on (including race, sex, size, attractiveness, and activity level). That is, children partly create their own environments, and children who are initially similar (due mainly to their genes) will tend to create similar environments, which in turn lead to additional similarities.
Thomas J. Bouchard, Jr. and colleagues, the authors of some of the most influencial twin studies, have argued that identical twins "tend to elicit, select, seek out, or create very similar effective environments and, to that extent, the impact of these experiences is counted as a genetic influence" (Bouchard et al. 1990). Richard Dawkins, an ethologist and popular author of The Selfish Gene, claims that "[i]f a genetic sex difference makes itself felt through the medium of a sex-biased education system, it is still a genetic difference" (Dawkins 1982). These comments underscore the fact that even the simple term, "genetic," can be used in a manner that misleads the unwary reader into believing in a simple scheme of genetic causation.
A common- sense view of this situation is that interactions between genes and environment in human child-rearing may be too complex to disentangle by examining such cases. In fact, one might argue that any comparisons of identical twins are rigorously useful only for measuring non-genetic factors; any differences in individuals who have identical genes must be due to non-genetic factors.
In addition to the methodological drawbacks of twin studies, there is a fundamental difficulty with heritability estimates: they supply a number in place of an explanation. A satisfying explanation of the cause of a human mental characteristic would describe a chain of causal events (including activation of genes), rather than just arithmetic. If we knew everything we would want to know about a single gene whose protein interacts with the environment to produce additional effects, we might end up with a progression like, "A caused B, which combined with C to produce D, which was modified by E," and so on. How does one then quantify the role of A or C? It is a bit like asking what percentage contribution George Washington made to the establishment of the United States. Any sensible answer would not be a percentage; it would be a story.
Gene Regulation
An indication of the kind of story that is likely to emerge for complex human mental characteristics can be gained by examining recent findings in the areas of gene regulation and the neurobiological mechanisms of behavior. It has become clear in recent years that the story of how a particular gene leads to production of a particular protein at the right time and place, and in the right amount, is often much richer than was previously believed.
Our current understanding is based on a large number of careful studies by molecular biologists working with non-human animals or with generations of cells grown outside the body. For many genes, there is a sophisticated network of regulatory mechanisms that fine- tunes the production of the protein. This regulatory network includes pieces of DNA adjacent to the gene and other pieces of DNA quite distant from the gene, both of which strongly influence the amount of protein produced. These regions of DNA can have their effects modified by interactions with multiple proteins produced by other genes and with substances acquired from the diet. Interactions with intermediary RNA molecules are also common. Each interaction can either increase or decrease the amount of protein produced; these interactions are not necessarily additive. The net effect of all these interactions is that the amount of protein produced from a particular gene in a particular cell can depend on its history of cell division, its location in the body, its hormonal environment, and the amount and existence of substances from the diet found in the bloodstream. The picture is one of an immensely complex regulatory system, something like the federal bureaucracy, but one that runs smoothly and efficiently in most circumstances.
Many gene regulatory systems probably include important environmental contributions at the molecular level. Such influences are still difficult to study in human beings, but some have been studied in detail in microorganisms. For example, when the bacteria E. coli. is grown in the presence of two sugars, glucose and lactose, it uses all of the glucose first, then switches to lactose. To do so, it activates several genes for lactose metabolism only when lactose is present and glucose is absent, via interactions among several types of sugar and protein molecules.
If such complex interactions with food molecules occur in single-celled organisms, which are often thought of as being entirely programmed by their genes, interactions with the environment are likely to be very extensive in human beings, leading to a variety of changes in metabolism and physiological functions. Most genetic and environmental effects on behavior are mediated by the nervous system. Environmental conditions have been shown to affect the growth of individual nerve cells (neurons) and the number and strength of connections amongst neurons, both during development and in adults (Greenough and Bailey 1988).
For example, adult rats develop more structural elaborations in neurons if they live in a complex environment, full of toys, than if they live in a blank cage. More dramatic changes can occur in early development. For example, if a cat or monkey is reared with one eye closed during the first several weeks of life, the organization of inputs to a visual portion of the cerebral cortex is permanently altered, and neurons that would normally respond to an object seen by either eye now respond only via the eye that has remained open throughout (Purves and Lichtman 1985).
In embryonic stages, when the numbers, types, and locations of all cells are determined, genes specify players and rules for an extraordinarily complex game, which must be played out to create the body design. The conditions of the playing field can play a critical role. Imagine that the Los Angeles Raiders are playing football against the Chicago Bears; it could make a great difference whether the game is played on a warm, sunny day in Los Angeles or in Chicago in a snowstorm.
For example, a human fetus is normally exposed to sex hormones that have diverse effects on gene regulation, leading to changes in the brain and laying the groundwork for all external sex differences (Breedlove 1994). Most, but not all of the hormones are produced by the fetus itself. However, if for some reason the fetus or the mother produces too little or too much of a specific hormone (for example, testosterone or another androgen), or if the fetus lacks appropriate receptor molecules for the hormone, the results can be dramatically different. In cases of androgen-insensitivity syndrome, for example, a genetically male human being can become a completely normal female, except that her internal reproductive organs are inadequately formed; in these cases, the fetus has a defective gene for the androgen receptor protein. In other cases, the amount of circulating androgen can be too great and cause prenatal masculinization of genetic females, transforming the clitoris partly or completely into a penis; this condition can be caused either by a genetic defect (producing adrenal hyperplasia) or by treatment of pregnant women with the hormone progestin (a practice that occurred in the 1950s, before the effects were realized; Money and Erhardt 1972).
For most genes, it is difficult to predict what will happen if you delete or alter one gene. The effects are not likely to be limited to the amount of the protein coded for by that gene. Instead, there may be positive or negative effects on several other proteins, because each gene may interact with other DNA, RNA, proteins, hormones, and substances from the diet to mediate gene regulation. An analogy can be drawn between these interactions and the interactions amongst neurons that mediate behavior. The concept that each neuron can affect many other neurons in a complex interactive network has received considerable attention in neurobiological research. Findings from neurobiological research may thus be useful for understanding gene regulation.
What Can We Learn From Neurobiology?
Since the 19th century, neurobiologists have debated whether particular functions can be identified with particular regions of the brain. It is now recognized that particular sets of neurons and connections amongst neurons do serve particular functions. However, the functions they serve do not necessarily correspond to categories of behavioral function that we have names for. Also, within a given small region of the nervous system, one may find neurons that are involved in quite different functions. If one region of the brain is damaged, particularly in children, functions formerly subserved by that region may not be disrupted seriously or permanently; remaining neurons may continue to mediate the function reasonably well and other regions may gradually take over the functions of the damaged region. These insights have led to the concept of a "distributed network" to describe the nervous system. I suggest that the regulation of protein production from genes, and thus genetic effects on behavior, may also be mediated by a distributed network.
Some of the most popular targets for research on genes affecting mental characteristics are genes that code for neurotransmitter receptors. Neurotransmitters are the substances that mediate communication between neurons; they produce an electrical signal in a recipient neuron by altering the structure of neurotransmitter receptors, which in turn prevent or allow positively or negatively charged molecules to enter or leave the neuron. Drugs that affect cognition or behavior, including drugs that are used to treat depression and schizophrenia, produce their effects by attaching to specific neurotransmitter receptors.
The reported genetic linkage to alcoholism, by Blum, Noble, and colleagues in 1990, claimed linkage to a candidate gene, which was a form of the gene for a particular receptor of the neurotransmitter dopamine. It would not be surprising if alterations in a neurotransmitter receptor had widespread effects on the nervous system, but how likely is it that a particular neurotransmitter or neurotransmitter receptor can be identified with one of our categories of human mental and behavioral characteristics?
Each neurotransmitter is used by a very large number of neurons that are distributed over much of the nervous system. Neurons that communicate using one neurotransmitter are often interspersed with neurons that use others instead. There are generally several types of neurotransmitter receptors for a given neurotransmitter; each type can confer distinct electrical properties on the neurons that house them.
Even just a single type of receptor for a single neurotransmitter is generally distributed over much of the nervous system, in a complex but reliable pattern. Such patterns do not appear to delimit the set of neurons that participate in any single function that we can name. Instead, it now appears likely that each neurotransmitter receptor is like a component of an electrical circuit. Different types of components are useful for different electrical purposes. For example, one neurotransmitter receptor, called the NMDA receptor, has special properties that produce an electrical signal only when multiple, associated events occur simultaneously; in this case, the electrical signal lasts for an especially long time. Each cognitive or behavioral process probably involves a variety of such specific components deployed as needed in different portions of its "circuit".
Neurobiologists have tried to understand the roles played by particular neurons or connections among neurons in distributed networks. They have found that even after a network of interactions has been almost completely described, it is difficult to define the role of any single element. Such detailed knowledge of a network is currently available only for very small neural systems, such as one responsible for swimming in a marine mollusk named Tritonia and another responsible for digestion in lobsters and crabs. Researchers have drawn "circuit diagrams" of these systems, but examination of these diagrams, in which each neuron is connected to several other neurons, has not revealed what each neuron does during operation of the circuit.
Even these relatively simple systems involve interactions that are too complex for human understanding to assimilate directly. Instead, researchers have found it useful to create computer-based models of these networks, in which they can easily alter just one neuron or one interaction and see what outcome the network then produces, which can be surprising.
For example, physiological experiments revealed a set of neurons that are active during swimming in Tritonia, but it was not clear how their interaction could produce swimming, nor whether these neurons alone are sufficient to generate swimming. Some of the connections among these neurons are very complex, involving both inhibition and excitation of each recipient neuron, each with a distinct time course. A computer simulation of this network showed that this set of neurons could produce an output very similar to swimming and that the network created swimming by effectively alternating between two patterns of neuronal connectivity on each cycle of swimming (Getting 1983). Computer experiments like these gradually increase our understanding of the role of each neuron and each interaction.
This line of research may provide a lesson for the study of gene regulation. Understanding the full behavioral effect of altering a particular gene may require knowledge of all the interactions that involve that gene and their functional consequences. Even then, the effects of a gene may not correspond to a particular category of function. '
We may find that a network of interactions, rather than a gene, can be more accurately identified with a particular function. In other words, there may be "emergent" properties of the network that are not evident in the effects of most single genes or single proteins on their own. In such cases, the same gene may have quite different effects on a behavior depending on the context, which may include important environmental influences.
In addition, the same gene may have effects on multiple types of behavior or cognitive function. Thus, even if a genuine genetic link to manic-depression, for example, is someday found, it might turn out that the gene can exacerbate certain symptoms of manic-depression, but only if combined with other factors, and that the gene also can have effects on individuals who are not categorized as manic-depressive. In such a situation, the notion that the gene's effect is to cause manic- depression could be quite misleading.
The Allure of Simple Genetic Explanations
Given the complex interactions that appear to mediate the development and operation of human cognitive and behavioral functions, why do some scientists and journalists apparently search for simple genetic explanations? The search for a gene for each category of experience and behavior may partly be a result of the culture of modern science. Scientists generally seek to reduce complex phenomena to simple descriptions. Such simplification has proven to be extremely useful in devising experiments that will give clear and informative results. Scientists often choose an object for study (such as a particular function in a particular organism) because it is simple and thus more tractable. Such choices have facilitated remarkable progress in understanding principles of function. However, in the desire to extrapolate findings from simple systems to the most sophisticated functions of human beings, it is sometimes forgotten that different or additional principles may apply to the most complex systems.Some simplification is also key to any understanding of a phenomenon. In providing any scientific explanation, scientists define the essential factors at work, extracting them from a morass of detail, much of which is unimportant for the questions at hand. But the type of explanation that provides us with the most understanding is not necessarily the simplest. The reductionism that most scientists espouse leads to descriptions in terms of progressively simpler and usually smaller elements. But many phenomena have emergent properties that cannot be observed or appreciated in descriptions of the smallest components.
Instead, explanations that describe processes at a level of organization not too distant from the phenomenon itself often provide the most understanding. For example, an explanation of a human behavior that includes a description of how certain networks of neurons are active during the behavior may provide greater understanding of how the behavior is produced than an explanation solely at the level of genes or smaller components. If we had a complete description of alcoholism in terms of subatomic particles alone, would you feel that you now understood alcoholism?
There is also a danger of oversimplification by omission or inaccurate portrayal of factors that are crucial to research objectives. Scientists are often schooled to provide the most parsimonious explanations of phenomena, on the grounds that a complicated explanation should not be put forward if the evidence supports a simple scheme just as well. The problem is that the desire for parsimony can sometimes lead researchers to choose a simple explanation even when the evidence actually points to a more complicated scheme. For example, it has been known for some time that concordances (the odds that two individuals will either both have or both not have a given trait) for schizophrenia are much higher for identical twins (39-46%) and for children of two schizophrenic parents (34-43%) than for first-degree relatives (4- 12%). This situation is incompatible with single-gene causation of schizophrenia independent of the environment, yet that is exactly what many investigators looked for (Cloninger 1994).
An additional misinterpretation of studies claiming linkage between a gene and a human behavior is the notion that the behavior is therefore destined. There is a widespread and yet completely false notion that if something has a genetic cause, it is unalterable, but if it has an environmental cause, it is alterable. Some people respond to new claims of linkage between a gene and a certain characteristic-- for example, alcoholism or homosexuality--by arguing that this proves that the characteristic was fixed from birth.
Such an explanation may seem attractive if one wishes to deny that either personal choice or societal conditions contribute to the characteristic. For example, in a recent report on the mouse obese gene (Monmaney 1995, p 21), the Los Angeles Times stated: "An important social implication of the obesity gene research, researchers say, is that it shows that obestity is not a weakness or a failure of willpower. In that sense, this high-tech lab work may help erase some of the stigma of being fat."
In fact, some conditions known to be caused by genes alone can be prevented or reversed by non-genetic means, such as providing a phenylalanine-free diet to children who have the genetic disorder, phenylketonuria (PKU). On the other hand, some environmental events, such as alcohol abuse by pregnant women, can often have permanent effects (Spohr et al. 1993).
The idea that our genes make us who we are has been so successful that even scientists occasionally mistake evidence of a biological correlate of a mental or emotional characteristic for evidence that the characteristic is determined genetically . For example, when a group of researchers reported in 1994 that they had isolated the mouse "obese" gene, they introduced their work by stating, "[a]lthough obesity is often considered to be a psychological problem, there is evidence that body weight is physiologically regulated" (Zhang et al. 1994). In fact, psychological influences are necessarily mediated by physiological mechanisms.
A discovery of a biological correlate addresses neither the role of genes nor the role of non-genetic factors. The notion that "biological" implies "genetic" seems to assume that non-genetic events affect us without affecting our bodies, and in particular our brains. Within a scientific world-view, at least, such a view is untenable. One expects all effects on cognition or behavior to be mediated by changes in the body, usually in the nervous system. This says nothing about the original cause of the change, nor our responsibility for it.
Research into gene regulation and neurobiology has revealed intricate interactions among genes, proteins, hormones, food, and life experiences. These findings suggest that lasting explanations of most human mental and behavioral characteristics will not be simple and will arise only gradually. A real understanding of the causation of complex characteristics may require us to come to terms with the emergent properties of multiple interactions. In the meantime, pronouncements of simple genetic causation should be met with a critical eye and with questions about exactly what has and has not been demonstrated.
Monday, May 4, 2009
POISON
Make most of these points:
- Most drugs cause vomiting. To help stop this, take one or two anti- histamine tablets (travel sickness, allergy, hayfever tablets etc) about an hour before, on a fairly empty stomach.
- If the drugs are in tablet form, take the first 20% as they are, and the rest crushed and dissolved / mixed in with strong alcohol / food. This helps the drugs to hit at the same time.
- Alcohol helps dissolve the drugs. Don't drink any beforehand, but wash the tablets down with vodka or similar, and then drink afterwards while you're still conscious.
- Use a large airtight plastic bag over your head, + something around your neck to hold it on. This transforms a 90% certainty method into a 99%...
- Friday night is a good time if you life alone - nobody will miss you until Monday if you work. Bolt all the doors you can. Say you'll be out over the weekend visiting someone, so people don't expect a reply to telephone.
- Some painkillers etc have less effect if you use them normally (tolerance).
- In general, you need to stay away from medical help until you actually die, but there are exceptions to this (that have been pointed out in the text).
Common drugs:
Cyanide (HCN, KCN)
Dosage: 50 mg Hydrogen Cyanide gas, 200-300 mg Cyanide salts
Time: seconds for HC, minutes Cs (empty stomach) hours (full s)
Available: very difficult to get hold of
Certainty: very certain
Notes: It helps to have an empty stomach (since the salts react with the stomach acids to form H.C.). A full stomach can delay death for up to four hours with the salts. Antidotes to cyanide poisoning exist, but they have serious side effects. What you can do, is instead of taking the salts directly, drop 500mg or so into a strong acid, and inhale the fumes. This will be pure Hydrogen Cyanide, and you should die in 10 to 20 seconds.
[3]:
"Hydrocyanic acid is one of the most poisonous substances known; the inhalation of its fumes in high concentration will cause almost immediate death. Hydrogen cyanide acts by preventing the normal process of tissue oxidation and paralyzing the respiratory center in the brain. Most of the accidental cases are due to inhaling the fumes during a fumigating process. In the pure state it kills with great rapidity. Crystalline cyanides, such as potassium or sodium cyanide are equally poisonous, since they interact with the hydrochloric acid in the stomach to liberate hydrocyanic acid. This poison has been used for both homicide and suicide; in recent history, a number of European political figures carried vials of cyanide salt for emergency self-destruction and some used them. Death resulted from amounts of only a fraction of a gram. A concentration of 1 part in 500 of hydrogen cyanide gas is fatal. Allowable working concentration in most of the United States is 20 ppm. Two and one-half grains of liquid acid has killed. The acid acts fatally in about 15 minutes. The cyanide salts kill in several hours. The average dose of solution is 0.1 cc. [1, DGHS talking about KCN]: on an empty stomach, take a small glass of cold tap water. (Not mineral water nor any sort of juice or soda water because of it's acidity). Stir 1 -> 1.5 grammes of KCN into the water. More than that causes irritation to the throat. Wait 5 minutes to dissolve. It should be drunk within several hours. Consciousness will be lost in about a minute. Death will follow 15 -> 45 minutes later.
Aspirin (Acetylsalicylic Acid)
Dosage: 20-30+ grammes (too many cause vomitting)
Time: hours to days, variable
Available: easy to get hold of (get soluble ones, & dissolve them)
Certainty: unreliable
Notes: Not recommended, fatal dose varies wildly, could cause liver & kidney damage instead of death. OD causes strange noises in your ears (like a video arcade) & projectile vomiting after about 10 hours. Medical help generally effective, so stay out of hospital for a couple of days. May cause bleeding in your stomach/upper intestines. Take with sodium bicarbinate (eg, bicarb. of soda), which speeds up the absorption (sp?) significantly. Take 1 or 2 antihistamine tablets.
Paracetamol (Aka Acetaminopren / Tylenol)
Dosage: 15+ grammes, 20+ is better
Time: 10 hours fatal damage, but 2 weeks to actually die
Available: easy to get hold of
Certainty: fairly reliable
Notes: Once 10-12 hours is up, you've had it, but you still live for a week or two after that. Probably better to wait 15 hours just to make sure. Horrible side effects during this time (some of which are: acute toxic hepatitis, renal failure, cerebral oedema, intra-abdominal bleeding, aspiration pneumonia, haemophilia). Too small dose causes severe liver damage. Accidental deaths are very common. There are few if any side effects before the damage becomes fatal; occasionally vomitting and nausea.
Sleeping Tablets (See Specific Notes For Each Kind)
- amobarbital
- butabarbital
- diazepam
- flurazepam
- glutethimide
- chloral hydrate
- hydromorphone
- meprobamate
- methyprylon
- meperidine (pethidine)
- methadone
- morphine
- orphenadrine
- phenobarbital
Alcohol (Spirits Preferably, Your Choice)
Dosage: 1/2 litre vodka?, similar. Varies from person to person.
Time: about 8 hours
Available: good
Certainty: unreliable
Notes: will cause liver and kidney damage if 'rescued' before death. Drink it all at the same time, quickly as possible. Dosage is questionable, I don't have any figures. Taking the spirits as an enema is supposed to be a very quick way of absorbing alcohol, but a less unpleasant way is to inject it. The dosage it takes to kill you depends on whether you drink normally, the state of your liver, whether you pass out on your back or not. [3]: "The fatal dose of pure alcohol in an average adult is 300-400 mL (750-1000 mL of 40% alcohol) if consumed in less than one hour. Apart from the effects of overdosage, death after alcohol consumption can occur as a result of choking on vomit while unconscious. ..... Consequences such as liver damage occur after chronic consumption." Alcohol helps other drugs to dissolve. Don't drink it in advance, wash down tablets with it, & follow by drinking another few glasses of spirits.
Water
Dosage: 14 litres mentioned
Time: 12 hours or so?
Available: always available
Certainty: unknown
Notes: works by washing out the salts in your body, until the cells fail (osmotic balance buggered up). You need to keep drinking continually until you collapse. Unusual method. Someone suggested it would also cause cramps. The following is something from [2]: "About a year ago a local newspaper carried a story about a woman who had drunk herself to death. Apparently she had ingested something mildly poisonous, and when she called her doctor asking him what to do, he told her to drink lots of water and see him in the morning. She got to it and managed to drink no less than 14 litres of water before the osmotic balance in her body was so upset it could no longer function and she died (don't know how quickly)".
Bleach And Other Corrosives (Lye, Drain Cleaning Fluids)
Dosage: A bottle (litre or half litre)
Time: Hours/days
Available: Easily available
Certainty: Uncertain
Notes: Bloody painful - depends on your stomach getting corroded, the stomach acids escaping, and doing their dirty work in your vital organs. [1] says: "I have heard of people throwing themselves through plate glass windows in their death agonies after drinking lye."
Insulin (Injected)
Dosage: No idea
Time: death in hours to days
Available: Difficult to get hold of unless you're a diabetic or a vet
Certainty: reasonable
Notes: Supposed to be quite pleasant (eg insulin shock treatments used for some psychiatric condition).
Petrol (In Lungs/Injected)
Dosage: "A Thimble-full" -20 ml?
Time: Seconds/minutes
Available: Common
Certainty: I'm not sure of the dosage, but fairly certain if correct
Notes: Can also use LPG (propane/butane) on skin surface (since these are light enough to go through the skin). Stick your hand in a bucket of propane and see how many seconds you last...
Oil Of Wintergreen/Methyl Salicylate (In Lungs/Injected)
Dosage: Probably similar to petrol (20 ml)
Time: Don't know
Available: Not available in concentration
Certainty: Don't know
Notes: Don't have enough information on this one to be able to say anything about it. If it is just taken normally, it is the same as aspirin.
Malathion (Insecticide) (Entry Revised By Calle)
Dosage: A few bottles, at least
Time: 2 to 3 hours
Available: From a large garden centre or DIY shop
Certainty: not so good
Notes: A correspondent mentions that the LD50 of this stuff is 1 g/kg in rats, and adds that there is not nearly that much in a bottle. He also mentions that it is treatable. Instead of this, he recommends parathion, if you really want to use an insecticide.
Phosphine Gas From Aluminium Phosphide Pesticide (ALP)
Dosage: Single 3 gramme tablet (".. is enough to kill 10 people")
Time: About 2 hours
Available: Difficult. Used in India, sold on black market.
Certainty: Without medical help, and using fresh pill, very good
Notes: This is a common way of committing suicide in Indian villages. There is no specific antidote to this. The pills are 3 grammes of ALP, which produces lethal phosphine gas when it comes in contact with hydrochloric acid or water in the stomach. After severe vomiting, the victim loses consciousness, the blood vessels rupture, and body cavities fill with blood. While the pill is exceedingly lethal, some escape death because the rate of the gas' release declines with the pill's age and use, and exposure to moisture. Trouble with this one is the availability, and it also looks like a rather unpleasant.
Rat Poison (Warfarin)
Dosage: not known
Time: Hours to terminal damage, days to actual death
Available: Available
Certainty: Certain given suffient dosage. Most probably treatable.
Notes: This is one of the truly unpleasant poisons, along with Paracetamol/Acetylminopren. I think it causes cerebral haemorage (rat poison works by giving the unfortunate rat haemophillia). Doctors can't do anything about it, they just leave you to die in agony on an intensive care ward. Calle: Since human haemophiliacs usually live quite ordinary lives, the above sounds rather improbable.
Caffeine
Dosage: 20 grammes (someone said 8 -> 10 grammes)
Time: not known
Available: Caffeine tablets available in Chemist shops
Certainty: don't know
Notes: I don't know very much about this. There isn't all that much caffeine in coffee, maybe 200 mg.
Potassium Chloride (Injected In Solution)
Dosage: not known (try 20cc injection of strong solution)
Time: Seconds to minutes
Available: Widely available
Certainty: Certain given correct dosage
Notes: Causes heart attack (which is painful). May be difficult for coroner to realise it was suicide rather than a natural heart attack. An excess of K+ in the blood interferes with nerve signals, and stops muscles and nerves from working. So when it reaches your heart, the heart stops.
Nitrogen Gas (Or Other Inert Gas)
Dosage: Several litres uncompressed is minimum
Time: Minutes
Available: Try plumber, or welding supplies company
Certainty: Certain
Notes: This is really a form of asphyxiation, (see later), but is particularly good since you don't experience the lack of oxygen (what people really experience is the EXCESS of carbon dioxide).
Nitrous Oxide (N20? NO2?)(NO2 /Ingvar)
Dosage: Unknown
Time: Minutes
Available: Dentists supply would be good
Certainty: reasonable
Notes: Asphyxiate yourself with laughing gas. Nice.
Carbon Monoxide (CO)
Dosage: 5% concentration or so?
Time: Minutes to hours depending on concentration
Available: You get it out of a car exhaust, you used to be able to use "town gas" (eg, stick your head in the cooker) but this is no longer available
Certainty: Fairly certain, as long as you aren't "rescued"
Notes: Causes brain damage.
Chlorine Gas
Dosage: not known
Time: not known
Available: tricky
Certainty: Good
Notes: This was used in the first world war in the trenches. Probably very unpleasant, does something to the lungs.
Hydrazine
Dosage: As produced by reaction
Time: Not known, fortnight?
Available: Bottle of bleach & bottle of ammonia
Certainty: not known
Notes: [2]:
"This is no joke, D----. Several years ago at my high school, one of the janitors innocently mixed together half a bottle of bleach with half a bottle of of ammonia in a small closet where the cleaning fluids were kept. He passed out due to the hydrazine (not chlorine) gas released in the reaction between the two chemicals. This man was in agony for two weeks in an intensive care unit in a local hospital with the majority of the inside surface of his lungs damaged and untreatable before he got lucky and died."
Chloroform
Dosage: not known, just put a splash onto a rag
Time: several minutes probably
Available: not known
Certainty: good
Notes: If you tape the rag over your mouth so that you get knocked out, you should die as you continue getting the stuff into your lungs.
Digitalis (Foxglove, Digitalis Purpurea)
Dosage: not known
Time: not known
Available: extract from foxgloves
Certainty: bad due to vomiting
Notes: [4]:
Gives you a heart-attack. Symptoms: nausea, vomiting, abdominal pain, diarrhoea, headache, and slow irregular pulse. Also sometimes trembling, convulsions, delirium, and hallucinations. Its difficult to take a fatal amount because vomiting usually gets rid of it.
Yew (Taxus Baccata, The "English Yew")
Dosage: not known
Time: Can be very rapid (minutes), occasionally 3 or 4 days.
Available: Grows wild in the UK, don't know about elsewhere.
Certainty: not sure, but it sounds good if you eat enough
Notes: [4]:
All parts of the plant, _except_ for the fleshy red bit of the fruit, contain poisons. The seeds are poisonous, so if you eat the berries, chew them. Symptoms: nausea, abdominal pain, coma, death. The mode of death is a heart attack which occurs rapidly after eating sufficient. If no heart attack occurs, you'll probably survive. Sometimes the sudden collapse leading to death is preceded by lethargy, trembling, staggering, coldness, dilation of the pupils, rapid pulse that becomes weak, and convulsions. Other species in this genus are said to be equally poisonous. See "plants in general".
Mezerein, Daphnetoxin (Mezereon, AKA Daphne Mezereum, AKA D. Laureola)
Dosage: "a few". Probably 10 or more.
Time: not known
Available: Garden plant. Seeds are particularly poisonous.
Certainty: not known, dosage is questionable.
Notes: [4]:
The berries taste horrid, but you only need to eat a few to cause death. Symptoms: burning sensation in mouth, nausea, vomiting, stomach pains, diarrhoea, weakness, disorientation, convulsions, followed by death. The seeds can be dried and stored without affecting the poisons. Don't confuse this with laurels in the Prunus genus, Rosacea family. See "plants in general".
Atropine (Atropa Belladonna AKA Deadly Nightshade. Also Potato Fruits)
Dosage: 5 berries in young children.. maybe 30 in adults?
Time: 6 to 24 hours
Available: from fruits of some plants in the potato family.
Certainty: unknown, particularly dosage is questionable
Notes: [4]:
AB also contains hyoscyamine and hyoscine (scopolamine). Symptoms: dry mouth, flushed face, dilation of pupils, rapid pulse. Possibly also breathing difficulties, constipation, convulsions, hallucinations, and coma. AB is often confused with other Nightshade species, which aren't as poisonous. The berries are black in AB, and red in Woody Nightshade. In addition, the flowers are larger (1.2 in) in the true Deadly Nightshade. Present in unripe deadly nightshake fruits, fruits of potato, and fruits of other members of this family (not tomato though!), but stick with AB. See the "plants in general" entry.
Calle: A correspondent mentions that Jimsonweed will also do, and that a specific antidote exists.
Oleander (Nerium Oleander. Poison Similar To Digitalis)
Dosage: not known, but fairly small amounts.
Time: unknown.
Available: leaves, wood of the plant. From garden centres.
Certainty: unknown.
Notes: [4]:
Deaths have been caused by using wood from this plant in fires, and making tea from the leaves. In a few hours there is abdominal pain, nausea, vomiting, bloody diarrhoea, rapid pulse, and visual effects. Later, a slow, weak, irregular pulse and fall in blood pressure, followed by failure of heart. See the "plants in general" entry.
Death-Cap / Destroying-Angel Toadstool (Amanita Phalloides)
Dosage: Fraction of one can kill, but eat 1 or 2 just in case.
Time: Week or so
Available: Have to know what it looks like.. similar edible ones
Certainty: Definite without med. treatment; unknown with.
Notes: [5, Volume 7, pp591-592]:
"Poisoning by toxic Amanita species is characterised by a delay in onset of 4 to 12 hours. At this point, nausea vomiting, colic-like pain, and diarrhea occur. There then follows a period of respite, which can last for two to four days. This phase does NOT signify recovery: damage to the liver and kidneys continues to develop and the respite gives way to hepatic and renal failure. Death usually occurs a week or so after poisoning.". See "plants in general".
Ricin (Castor Oil Plant, Ricinus Communis)
Dosage: death has occured from eating 1 bean, but take more than 10
Time: within 3 to 5 days
Available: From eating the castor beans
Certainty: depends on ricin content of the beans. Pure ricin is deadly
Notes: [2] and [4]:
Symptoms begin within a few hours with abdominal pain, vomiting and bloody diarrhoea for several days. Decreased production of urine and a fall in blood pressure. Note that people have survived eating more than 10 beans, *with treatment*. Presumably the fatal dose without medical intervention is less. Surviving more than 3 to 5 days usually means recovery. Ricin is described as "..one of the most potent toxins known".
In 1978 a Bulgarian journalist (Georgi Markov) was assassinated in London by being prodded with an umbrella. The umbrella had a tiny ball coated with ricin on its tip, which lodged into the dissident. He died a few days later in hospital. See "plants in general".
Colchicine (Acetyltrimethylcolchicinic Acid, Autumn Crocus, Royal Lily)
Dosage: 7 mg to 60 mg (why so wide variation?)
Time: symptoms in about 4 hours, death in about 4 days
Available: Easily available (from large garden centre)
Certainty: certain
Notes: [New Scientist article:]
From the Autumn crocus (Colchicum Autumnale) / royal lily (Gloriosa Superba). One flower of CA is about 12 mg, so take at least five of them. 20g tuber of GS provides 60mg, single seed of CA provides 3.5mg (so take 18). Damages blood vessels and nerves, and stops cell division. Don't know whether its painful or not, but that bit about damaging nerves is worrying. I just _love_ the name of the acid! See See the "plants in general" entry.
Aconitine (AKA Wolfsbane, Monkshood, Aconitum Napellus, A. Anglicum)
Dosage: "a few grams"
Time: 10 mins to few hours
Available: Garden plant, so get from garden centre
Certainty: unknown (can be treated in hospital)
Notes: [2] and [4]:
The poison is concentrated in the unripe seed pods and roots. During winter, the roots are particularly poisonous. Symptoms develop in less than an hour. Burning sensation, feelings of coldness, sweating. Later, numbness, vomiting and diarrhoea with abdominal pain. Finally, slow pulse, convulsions and coma. Death may occur within 2 hours. The poison kills by causing a cardiac failure, and it is painful. See the "plants in general" comment.
Cicutoxin (Cowbane, Cicuta Virosa)
Dosage: ".. a few bites .. can cause serious poisoning or death".
Time: a few hours or more.
Available: rare in most parts of UK, don't know about elsewhere.
Certainty: good, but resembles wild carrot & wild parsnip.
Notes: [4]:
The poison is strongest in the yellow juice of the underground parts. Symptoms after half an hour: burning of mouth, excessive saliva, flushing, nausea, vomiting, dizziness, dilation of pupils, and later a bluish tinge to the skin. Muscular contractions and convulsions, with difficulties in breathing are followed by unconsciousness and death, often within a few hours of eating the plant. See "plants in general".
Coniine, Gamma-Coniceine, Others (Hemlock, Conium Maculatum)
Dosage: unknown
Time: unknown
Available: Grows throughout UK, except north. Don't know about elsewhere.
Certainty: unknown
Notes: [4]:
NOTE: There are many plants called "hemlock", some of which aren't poisonous at all. It can also be mistaken for wild parsley and carrot, and is in the same family as Cowbane. Symptoms appear in 15 mins to 2 hours. Initially burning and dryness of the mouth, muscular weakness leading to paralysis that affects the breathing. Sometimes also dilation of pupils, vomiting, diarrhoea, convulsions, and loss of consciousness. If this is survived, birth defects may be caused in pregnant women. This is said to be the plant that Socrates took in 399 BC.
Oenanthetoxin (Hemlock Water Dropwort, Oenanthe Eroeata)
Dosage: "..dangerously poisonous, even in small quantities".
Time: Two to twelve hours.
Available: Grows in chalky wet areas, particularly S and W Britain.
Certainty: Fairly good, if you get the right species.
Notes: [4]:
The tubers contain more poison than the rest of the plant, particularly in winter and early spring, and may be cooked or dried. Symptoms within an hour or two, nausea, salivation, vomiting, diarrhoea, sweating, weakness of legs, dilation of pupils. Later loss of consciousness with convulsions before death. See "plants in general" entry. Same family as Hemlock.
plants in general (hemlock, foxglove, oleander)
Dosage: N/A
Time: N/A
Available: garden centre
Certainty: questionable
Notes: [1] says:
"Everything I have ever read about death from plant poisoning indicates that it is risky and painful. Symptoms range from nausea and vomiting to cramping and bloody diarrhea. .... .. Altogether, I consider poisonous plants as a means of exit far too unreliable and painful. No matter how desperate you are, don't even think about it!"
Nicotine (Rewritten By Calle)
Dosage: extract from 100g tabacco? 40-60 mg pure.
Time: Several hours, coma may set in much earlier. Much quicker if taken in large doses.
Available: Easily available
Certainty: Fairly certain, given a large enough dose.
Notes:
This is what Mike wrote:
"Soak 100 grammes of tabacco for a few days. You get a brown mess. Strain off the tabacco, then simmer slowly until most of the liquid has gone, leaving about 2 teaspoons of brown treacle-like stuff. Add it to your night-time drink, and never wake up. Someone said the other day that 150mg of pure nicotine would be fatal in seconds. See the "plants in general" entry."
It is correct, as far as I have found out. It can be added that the effects include violent convulsions and that the direct cause of death is respiratory failure. Smokers should use larger doses than non-smokers.
Iron (Diet Suppliments)
Dosage: unknown
Time: unknown
Available: diet, health food shops
Certainty: good
Notes: [2]:
"Well it seems that iron pills achieve death. They oxydize in the stomach and eat a hole in it. The only reason I know this is that someone at my school just recently OD'd and died from this. It was ruled suicide since no person could accidently take that many iron pills. They didn't say how many she took or how many it takes to kill yourself though." [sounds unpleasant]
Cocaine
Dosage: 1 ounce (don't know what that is in real weights..)
Time: 2 to 3 hours?
Available: Difficult
Certainty: not known
Notes: Read something in a newspaper... a coke dealer died after eating an ounce of it, when the police raided his house. Cause of death was a cardiac arrest 2 1/2 hours after the overdose. However, a cocaine OD is painful, and causes paranoia / breathing problems. One form of cocaine smuggling is to swallow condoms filled with the stuff. From time to time, a "mule" has a condom burst inside him, and dies in pain reasonably quickly.
LSD (Lysergic Acid Diethylamide) Nonfatal
Dosage: infinite!
Time: never
Available: who cares?
Certainty: will not kill you
Notes: LSD can't kill you by overdose.. you might go psychotic if you take tens/hundreds of thousands of times the normal dose, but thats hardly surprising, since you'd have to be insane to take that much in the first place. General warning - even for normal use, if you are depressed, it'll just amplify the depression, not lift it, and the chances of a bad trip are probably higher. Probably, the only way to kill yourself with this stuff is to drop two tonnes of it on yourself.
Heroin (Morphine)
Dosage: 120 to 500 mg in non-users.
Time: unknown
Available: From your friendly neighbourhood drug dealer.
Certainty: unknown
Notes: Combine it with alcohol, since a combination of alc & H is much more dangerous than alc or H alone.
Rotenone
Dosage: very low, similar to cyanide
Time: depends on dosage
Available: extremely difficult
Certainty: probable
Notes: Rotenone is used by microbiologists to kill potentially dangerous bacteria cultures. It is extremely poisonous.
Mercury (Salts, Soluble)
Dosage: 1 gramme of salts
Time: unknown
Available: unknown (what are the _soluble_ salts? how to make?)
Certainty: good
Notes: Note that contrary to popular opinion, pure mercury metal isn't all that poisonous. The soluble salts are, however. The "mad hatter" story refers to brain damage that hat makers used to get from using mercury salts.
Amobarbital (Amytal, Amal, Eunoctal, Etamyl, Stadadorm)
[this entry from [1]]
Dosage: 4.5 grammes, typically 90 50mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable
Notes: use an airtight plastic bag, and a rubber band to get a very effective method. Alcohol speeds it up and makes it more reliable. Take an antihistamine about 10 minutes earlier. Empty stomach. Dissolve most of them in drink / food, and eat the remaining ones first so that it all peaks at the same time.
Butabarbital (Secbutobarbitone, Butisol, Ethnor) [this entry from [1]]
Dosage: 3 grammes, typically 100 30mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach.
Codeine (Combo. With Aspirin: Empirin Compound No. I -> IV)
[this entry from [1]]
Dosage: 2.4 grammes, typically 80 30mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: reliable with plastic bag and rubber band
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. People can become tolerant to this drug, and it will no longer be effective.
Diazepam (Valium, Apozepam, Aliseum, Ducene)
[this entry from [1]]
Dosage: 500 milligrammes, typically 100 5mg tablets
Time: N/A
Available: needs to be prescribed
Certainty: unreliable, use in combination with something else (alcohol?)
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. Valium is not effective by itself, but by mixing it with other drugs or alcohol it makes it more certain.
Flurazepam (Dalmane, Dalmadorm, Niotal) [this entry from [1]]
Dosage: 3 grammes, typically 100 30mg tablets
Time: N/A
Available: needs to be prescribed
Certainty: unreliable, use in combination with something else
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. This is not effective by itself, but by mixing it with other drugs or alcohol it makes the other drug more certain.
Gluthethimide (Doriden, Doridene, Glimid)
[this entry from [1]]
Dosage: 24 grammes, typically 48 500mg tablets
Time: N/A
Available: needs to be prescribed
Certainty: unreliable, use in combination with something else
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. This is not effective by itself, but by mixing it with other drugs or alcohol it makes the other drug more certain.
Chloral Hydrate (Noctec, Chloratex, Somnox)
[this entry from [1]]
Dosage: >10+ grammes, typically 20+ 500mg tablets
Time: N/A
Available: needs to be prescribed
Certainty: unreliable, use in combination with something else
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. This is not effective by itself, but by mixing it with other drugs or alcohol it makes the other drug more certain.
Hydromorphone (Dilaudid, Pentagone)
[this entry from [1]]
Dosage: 100 -> 200 milligrammes, typically 50 -> 100 2mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable with plastic bag and rubber band
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. People can become tolerant to this drug, and it will no longer be effective.
Meprobamate (Miltown, Equanil)
[this entry from [1]]
Dosage: 45 grammes, typically 112 400mg tablets
Time: N/A
Available: needs to be prescribed
Certainty: unreliable, use in combination with something else
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. This is not effective by itself, but by mixing it with other drugs or alcohol it makes the other drug more certain.
Methyprylon (Noludar)
[this entry from [1]]
Dosage: 15 grammes, typically 50 300mg tablets
Time: N/A
Available: needs to be prescribed
Certainty: unreliable, use in combination with something else
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. This is not effective by itself, but by mixing it with other drugs or alcohol it makes the other drug more certain.
Meperidine (Pethidine, Demerol, Dolantin)
[this entry from [1]]
Dosage: 3.6 grammes, typically 72 50mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable with plastic bag and rubber band
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. People can become tolerant to this drug, and it will no longer be effective.
Methadone (Dolophine, Adanon)
[this entry from [1]]
Dosage: 300 milligrammes, typically 60 5mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable with plastic bag and rubber band
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. People can become tolerant to this drug, and it will no longer be effective.
Morphine (In Brompton'S Mixtures)
[this entry from [1]]
Dosage: 200 milligrammes, typically 14 15mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable with plastic bag and rubber band
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. People can become tolerant to this drug, and it will no longer be effective.
Phenobarbital (Luminal, Gardenal, Fenical)
[this entry from [1]]
Dosage: 4.5 grammes, typically 150 30mg tablets
Time: N/A
Available: needs to be prescribed
Certainty: unreliable, use in combination with something else
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. This is not effective by itself, but by mixing it with other drugs or alcohol it makes the other drug more certain.
Secobarbital (Quinalbarbitone, Seconal, Immenox, Dormona, Secogen, Seral, Vesperax (Combo With Brallobarbital))
[this entry from [1]]
Dosage: 4.5 grammes, typically 45 100mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable with plastic bag and rubber band
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. [Vesperax is Humphry's favorite]
Propoxyphene (Darvon, Dolotard, Abalgin, Antalvic, Depronal)
[this entry from [1]]
Dosage: 2 grammes, typically 30 65mg tablets
Time: death in an hour or so. Does not make you unconscious
Available: needs to be prescribed
Certainty: suggest combine with something to make you sleep, then use bag.
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach. Since this one doesn't make you unconscious for a long time, try combining with one that does, so you can use the good old bag method.
Pentobarbital (Nembutal, Carbrital Only If In Combo With Pentobarbital)
[this entry from [1]]
Dosage: 3 grammes, typically 30 100mg tablets
Time: unconscious in 5 -> 15 minutes, death in 20 -> 50 minutes
Available: needs to be prescribed
Certainty: very reliable with plastic bag and rubber band
Notes: use bag & band. Alcohol as well as antihistamine on an empty stomach.
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