Some people give thanks for turkey or pumpkin pie. Some people give thanks for football. Others are truly thankful that they have been blessed with good fortune.
The Faculty of Arts & Science at the University of Toronto offers a program called "Human Biology." Students who complete the program will graduate with an Honours B.Sc. degree. One of the courses is HMB434H1: Complementary and Alternative Medicine. Complementary/ alternative medicine (“CAM”) is used in health care systems not only in North America, but also in countries such as China, India, and Vietnam (WHO, 2002). It involves the use of non-biomedical, “holistic” and/or culturally-specific health services and practices in the treatment of illness and disease (such as Chinese acupuncture), and an expanded concept of health, illness, and wellness. This course provides an introduction to the concepts, theoretical basis, evidence-based analysis, and pressing challenges and issues in CAM today. Specific topics include introductions to: complementary/ alternative medicine in industrialized countries and commonly used modalities such as homeopathy and naturopathic medicine; traditional medicine (TM) and primary health care (PHC); traditional Chinese Medicine (TCM) and China; Ayurvedic medicine in India; Canada’s First Nations; and integrative health systems and models. Course format includes lectures, guest-presentations, films/documentaries, and inter-active class discussions/exercises. Students will also have the opportunity to analyze CAM systems and modalities.I've been pretty nervous about this course ever since one of our students blogged about it last year [U of T has a course in complementary and alternative medicine]. I was hoping that the course would present both sides of the story.
"for their discoveries of important principles for drug treatment"
Gertrude B. Elion (1918 - 1995) and George H. Hitchings (1905 - 1998) won the Noble Prize for their work on the treatment of disease and organ transplantation. They developed a number of drugs that interfered with nucleic acid synthesis leading to effective treatment of malaria as well as bacterial and viral infections. They are especially noted for the development of drugs that inhibit the body's ability to reject the transplant. One of the most famous of these immunosuppression drugs is azathioprine, a drug that is still used in some cases to suppress the immune response.Studies of Nucleic Acid Synthesis Result in the Discovery of New DrugsGertrude Elion and George Hitchings have collaborated since 1945. Their original research idea was to look for differences in nucleic acid metabolism between normal human cells, cancer cells, protozoa, bacteria and virus, which could be utilized to develop drugs that selectively block the growth of cancer cells and of noxious organisms. Over the years this research philosophy has formed the basis for the development of drugs against a variety of disorders including leukemia, malaria, virus infections and gout.
When Elion and Hitchings presented their ideas at the end of the 1940s the knowledge about nucleic acid metabolism was very limited. It was known, however, that purines and pyrimidines are incorporated into nucleic acids. Elion and Hitchings studied the growth of the Lactobacillus casei, a bacterium dependent on folic acid or a combination of purines (hypoxanthine, guanine) and pyrimidines (thymine). The purpose was twofold, to characterize the metabolic pathways involved in the biosynthesis of nucleic acids and to identify antimetabolites in the nucleic acid metabolism (Figure 3).
Figure 3.Figure 3. Purine bases (adenine, guanine and hypoxanthine) are synthesized from simple precursors. Nucleosides are then formed by the addition of sugar moieties (deoxyribose or ribose) and subsequently converted into nucleotides by the addition of phosphate (mono-, di- and triphosphate). Nucleotides take part in cellular metabolism and are the building blocks in the synthesis of RNA and DNA. Structural analogues of the natural substances can specifically block the different metabolic steps. Some examples are given in the figure.Already in 1948 Elion and Hitchings discovered a substance, diaminopurine, an adenine antagonist, which inhibited the growth of L. casei (Figure 3). It was also found to have an effect on experimentally induced leukemia. Clinical trials in patients were initially promising but had to be interrupted due to toxic side effects. Stimulated by this finding Elion and Hitchings continued their research which soon resulted in two new chemotherapeutic drugs, thioguanine (1950) and 6-mercaptopurine (1951). In collaboration with the Sloan-Kettering Institute 6-mercaptopurine was tried in leukemic patients who were resistant to methotrexate. About one third of the patients responded with complete remission (1953). The finding was soon confirmed, and 6-mercaptopurine (as well as thioguanine) are still used in the treatment of leukemia (Table II).
Elion and Hitchings tried to improve the therapeutic properties of 6-mercaptopurine by using sulphur-substituted compounds. The result was azathioprine (1957) which replaced mercaptopurine as an inhibitor of the immune response. For a long time azathioprine was the only drug available to prevent rejection of transplanted organs. It is still used for that purpose but also for the treatment of autoimmune diseases.
Attempts were also made to prolong the effect of 6-mercaptopurine by blocking its metabolism by xanthine oxidase which is involved in the endogenous production of uric acid (Figure 3). In 1963 this research resulted in another new drug, allopurinol, which blocks the formation of uric acid and therefore is used in the treatment of primary and secondary gout.
Hitchings and collaborators also developed pyrimethamine (1950) and trimethoprim (1956) which were found to be effective in the treatment of malara and bacterial infections, respectively. Both drugs have a strong affinity to the enzyme dihydrofolate reductase, but pyrimethamine is 2000 times more toxic to the enzyme system in the malaria parasite than in the host. Trimethoprim has 100 000 times higher affinity to the bacterial compared to the human enzyme. An important discovery was that the chemotherapeutic effects of these two compounds were markedly enhanced by sulphonamides, drugs which inhibit the synthesis of folic acid. This pharmacotherapeutic principle is used in the combination drugs trimethoprim-sulfa and pyrimethamine-sulfa which are used in the treatment of bacterial infections and malaria, respectively.
A more recent application of Elion's and Hitchings' research philosophy is acyclovir, a drug used in the treatment of infections with herpes virus. Already in the 1950s they had shown that antipurines had to be transformed into nucleotides in order to become active in the cell. The herpes virus carries information which leads to the production of a new enzyme which transforms nucleosides to nucleotides (thymidine kinase) in the infected cell. This enzyme has considerably less substrate specificity than the cell's normal enzyme. Therefore, acyclovir is transformed into its corresponding nucleotide which is the active antimetabolite and the growth of the virus is inhibited (Figure 3).
Acyclovir was described by Elion and coworkers in 1977 and is a modern example of the realization of the basic ideas from 1950. An even more recent application of these ideas is the development of azidothymidine (AZT) which was described in 1985 by other scientists from the same institute, and which is the hitherto best documented drug in the treatment of AIDS. It can be added that trimethoprim-sulfa is used in the treatment of Pneumocystis carinii, a relatively common complication to AIDS.
The clinical use of the drugs discovered by Elion and Hitchings is summarized in Table II.
Table 2.
References
G. Gahrton, B. Lundh: Blodsjukdomar. Lärobok i hematologi. Natur och Kultur, Stockholm, 1983.
Läkemedelsboken 1987/88, Apoteksbolaget, Stockholm, sid, 87-88, 150-151, 249, 625.
J.H. Shelley: Creativity in Drug Research. Trends in Pharmacological Sciences. 1983, vol. 4.
L. Stryer: Biochemistry, 3rd edition. W.H. Freeman and Company, San Francisco, 1988, chapter 25, 601-625.
[Photo Credit: George Hitchings and Gertrude Elion (top) from Welcome Images]
The venerable peppered moth (Biston betularia) has popped up a couple of times in recent posts. It seems that some of our Darwinian commenters (see, e.g., qwerty017 in comment [2] here) have not gotten the memo – the peppered moth myth has been completely exploded. Don’t take our word for it. Uber-Darwinist Jerry Coyne says in the November 1998 edition of Nature: “For the time being we must discard Biston as a well-understood example of natural selection in action.” Why else would the popular school text Biology pull its discussion of Biston as an example of “evolution in action”?Here are some examples of scientists who have not heard message from the IDiot's.
Until the 1930s, most evolutionary biologists followed Darwin in assuming that the intensity of natural selection is usually very slight. By the 1930s, however, examples of very strong selection came to light. One of the first examples was INDUSTRIAL MELANISM in the peppered moth (Biston betularia). ...There are many scientific papers on the "myth" as well. Here's the abstract from Saccheri et al. (2008).
Historical datasets documenting changes to gene frequency clines are extremely rare but provide a powerful means of assessing the strength and relative roles of natural selection and gene flow. In 19th century Britain, blackening of the environment by the coal-fired manufacturing industry gave rise to a steep cline in the frequency of the black (carbonaria) morph of the peppered moth (Biston betularia) across northwest England and north Wales. The carbonaria morph has declined across the region following 1960s legislation to improve air quality, but the cline had not been comprehensively described since the early 1970s. We have quantified changes to the cline as of 2002, equivalent to an interval of 30 generations, and find that a cline still exists but that it is much shallower and shifted eastward. Joint estimation of the dominant fitness cost of carbonaria and dispersal parameters consistent with the observed cline change indicate that selection against carbonaria is very strong across the landscape (s approximately 0.2), and that dispersal is much greater than previously assumed. The high dispersal estimate is further supported by the weak pattern of genetic isolation by distance at microsatellite loci, and it implies that in addition to adult dispersal, wind-dispersed first instar larvae also contribute to lifetime dispersal. The historical perspective afforded by this study of cline reversal provides new insight into the factors contributing to gene frequency change in this species, and it serves to illustrate that, even under conditions of high dispersal and strong reverse selection acting against it, complete erosion of an established cline requires many generations.Wow, this is a tough call. Who are you going to believe, evolutionary biologists like Futuyma and Sacheri et al., or an IDiot like Barry Arrington?
Saccheri, I.J., Rousset, F., Watts, P.C., Brakefield, P.M. and Cook, L.M. (2008) Selection and gene flow on a diminishing cline of melanic peppered moths. Proc. Natl. Acad. Sci. USA 105:16212-16217. [doi:10.1073/pnas.0803785105]
Yesterday (Nov. 24, 2008) marked the 149th anniversary of the publication of On the Origin of Species by Charles Darwin. Ms. Sandwalk just bought me an illustrated edition by David Quammen and I highly recommend it. The text is from the first edition of Darwin's work and the illustrations cover a wide range of topics including copies of Darwin's letters and letters from his friends. This is an excellent way to get people interested in one of the most important books ever published.In the four succeeding chapters, the most important and gravest difficulties on the theory will be given: namely, first, the difficulties of transitions, or in understanding how a simple being or a simple organ can be changed and perfected into a highly developed being or elaborately constructed organ; secondly, the subject of Instinct, or the mental powers of animals; thirdly, Hybridism, or the infertility of species and the fertility of varieties when intercrossed; and fourthly, the imperfection of the Geological Record.The second thing I re-discovered is the clarity and forcefulness of Darwin's writing, given the style of the Victorian era. Also his foresight and originality.
Although much remains obscure, and will long remain obscure, I can entertain no doubt, after the most deliberate study and dispassionate judgment of which I am capable, that the view which most naturalists entertain, and which I formerly entertained—namely, that each species has been independently created—is erroneous. I am fully convinced that species are not immutable, but that those belonging to what are called the same genera are lineal descendants of some other and generally extinct species, in the same manner as the acknowledged varieties of any one species are the descendants of that species. Furthermore, I am convinced that Natural Selection has been the main but not the exclusive means of modification.Thomas H. Huxley read an advance copy of On the Origin of Species and sent a letter to Darwin, which he received on the day before the book went public. Huxley knew what was coming ...
I trust you will not allow yourself to be in any way disgusted or annoyed by the considerable abuse and misrepresentation which, unless I greatly mistake, is in store for you. Depend upon it you have earned the lasting gratitude of all thoughtful men. And as to the curs which will bark and yelp, you must recollect that some of your friends, at any rate, are endowed with an amount of combativeness which (though you have often justly rebuked it) may stand you in good stead.The letter is published in the illustrated edition by David Quammen.
I am sharpening my claws and beak in readiness.
After being sent four of the letters of complaint, Professor Axelrod added on the 6 November: "Our paper (Chen et al, June 2008) underwent a strict process of peer review prior to publication. Concerns about the review process should be directed to Cell. We stand by our conclusions as stated in the paper, as well as by our use of citations."The incident raises a serious question. Is the pressure to publish so great that authors are tempted to deceive editors and reviewers by making their work seem more original and novel than it really is?
Cell declined to respond to questions put by Times Higher Education. However, in a response to the complaint from Professor Lawrence, Cell's senior scientific editor Connie Lee said: "I can only assure you that the reviewers were experts in planar cell polarity and the consensus decision was that the model presented by Chen et al was thought-provoking, well supported and provided a sufficient conceptual advance beyond the existing literature."
Editors of leading journals reject the suggestion that standards are slipping in the face of heightened competition. "Nature has nothing to gain by the pursuit of glamour at the expense of scientific quality, considering, not least, the criticisms, corrections and retractions we would then habitually be forced to publish," argued this journal in an editorial comment earlier this month5. And many researchers who were interviewed for this article agree that the system is still working tolerably. If it ain't broke, they say, don't try to fix it.Speaking of the pursuit of glamour, Nature continues its policy of hiring science writers to promote and hype papers that have recently been published in its journal [Human genes are multitaskers].
Adam, D. and Knight, J. (2002) Journals under pressure: Publish, and be damned... Nature 419: 772-774. [doi:10.1038/419772a]
Another of Mendel's seven genes has been identified. This one is described in his 1865 paper Experiments in Plant Hybridization [MendelWeb] as character number 2.2. To the difference in the color of the seed albumen (endosperm). The albumen of the ripe seeds is either pale yellow, bright yellow and orange colored, or it possesses a more or less intense green tint. This difference of color is easily seen in the seeds as their coats are transparent.Mendel's reference to the color of albumin, or endosperm, is inaccurate. He was actually observing the color of the cotyledons—the "seed leaves" that surround the embryo in the pea seed. These tiny leaves are covered by a seed coat that is partially transparent.
A paper published in Science identifies the "stay-green" gene that Mendel worked with (Armstead et al. 2007). This work is based on several decades of study of the "stay-green" phenotype by Howard Thomas and his colleagues at the Institute of Grassland and Environmental Research, Aberystwyth, UK (Armstead et al. 2006; Thomas, 1987; Thomas et al. 1996; Thomas and Stoddart, 1975). [Photo Credit: The photograph of mutant and wild-type pea seeds is taken from Figure 1 of Sato et al. (2007)]
Armstead, I., Donnison, I., Aubry, S., Harper, J., Hörtensteiner, S., James, C., Mani, J., Moffet, M., Ougham, H., Roberts, L., Thomas, A., Weeden, N., Thomas, H., and King, I. (2007) Cross-species identification of Mendel's I locus. Science 315: 73. [DOI: 10.1126/science.1132912]
Armstead, I., Donnison, I., Aubry, S., Harper, J., Hörtensteiner, S., James, C., Mani, J., Moffet, M., Ougham, H., Roberts, L., Thomas, A., Weeden, N., Thomas, H., and King, I. (2006) From crop to model to crop: identifying the genetic basis of the staygreen mutation in the Lolium/Festuca forage and amenity grasses. New Phytologist 172: 592-597.
Bhattacharyya, M. K., Smith, A. M., Ellis, T. H., Hedley, C., and Martin, C. (1990) The wrinkled-seed character of a pea described by Mendel is caused by a transposon-like insertion in a gene encoding starch-branching enzyme. Cell 60:115-122.
Martin D.N., Proebsting W.M., Hedden P. (1997) Mendel's dwarfing gene: cDNAs from the Le alleles and function of the expressed proteins. Proc. Natl. Acad. Sci. (USA) 94:8907–8911.
Sato Y., Morita R., Nishimura M., Yamaguchi H., and Kusaba M. (2007) Mendel’s green cotyledon gene encodes a positive regulator of the chlorophyll-degrading pathway. Proc. Natl. Acad. Sci. (USA) 104: 14169-14174. [doi: 10.1073/pnas.0705521104].
Thomas, H. (1987) Sid: a Mendelian locus controlling thylakoid membrane disassembly in senescing leaves of Festuca pratensis. Theoretical and Applied Genetics 73: 551 555.
Thomas, H., Schellenberg, M., Vicentini, F., Matile, P. (1996) Gregor Mendel's green and yellow pea seeds. Botanica Acta 109: 3-4.
Thomas, H., and Stoddart, J.L. (1975) Separation of chlorophyll degradation from other senescence processes in leaves of a mutant genotype of meadow fescue (Festuca pratensis). Plant Physiology 56: 438-441.
Name this molecule. This time we need the common name and the systematic (IUPAC) name. A Nobel Prize was awarded for discovering this molecule and showing how it is involved in cell metabolism. 
By now everyone has heard the story. There are almost as many species of beetle as all the rest of the insects put together. This is what prompted J.B.S. Haldane to say that God has "an inordinate fondness for beetles." Another year, another incarnation of the Canadian Blog Awards, and another request to please delete CC HQ from any and all categories in which we've been nominated for a fairly simple reason -- we're not interested in any popularity contest in which voters seriously have to choose between CC HQ and batshit crazy, racist, white supremacist, Nazi sympathizer loons like Kate McMillan and Kathy Shaidle for "best blog."I wish I could take the same stance but nobody nominated me for anything. Damn, I don't even get to withdraw my nomination.
It's true. Checkout the Stephen Harper website, which incidentally, is supposed to be the Prime Minister's website.The Honourable Gary GoodyearIt's bad enough that we have a chiropractor advising the government about science but this particular one seem especially unqualified. He also practiced acupuncture when he was actively seeing patients. Dr. (sic) Goodyear is strongly supported by evangelical christians (e.g. Christian Conservatives). That may not have anything to do with his ability to understand modern science. Gary Goodyear was endorsed by Vote Marriage Canada, a group that opposes gay marriage.
Minister of State (Science and Technology)
Cambridge (Ontario)
Gary Goodyear was first elected to the House of Commons in 2004 and re-elected in 2006 and 2008.
Prior to entering federal politics, Dr. Goodyear practised chiropractic medicine and worked as an advisor to investment firms in the biomedical industry.
Dr. Goodyear was a co-designer of a three-year post-graduate sports fellowship program. He also co-authored “Practice Guidelines” and was Public Relations Director and Past President for the College of Chiropractic Sports Sciences in Toronto. Dr. Goodyear has taught at the Canadian Memorial Chiropractic College and the University of Waterloo. He has worked with many athletes, both amateur and professional, including serving as medical services chair for the Ontario Special Olympics.
Dr. Goodyear is a graduate of the University of Waterloo and the Canadian Memorial Chiropractic College.
“The single biggest criticism of politicians,” explains Dr. Colin Carrie, Class of ’89 and Member of Parliament for the electoral district of Oshawa, Ontario, “is that they don’t listen.” Chiropractors, he says, are educated to be exceptional listeners. “Regardless of our political stripes, we want to do what’s right for our patients and our constituents.”I'm beginning to see the parallels between being a politician and a chiropractor. This is not complimentary to politicians.
It’s people skills, agrees his colleague and fellow Conservative Dr. Gary Goodyear (MP for Cambridge, Ontario). “Every chiropractor has to be a people person, that’s what we were taught at CMCC.”
Goodyear, Class of ’83, and Chair of the Committee of Procedure and House Affairs, adds with a laugh that his advisors have had occasion to remind him not to be quite so hands-on when dealing with his constituents. “My election team has actually told me to stop touching people so much, but I can’t help it. It’s just natural to me. As a chiropractor, you automatically love people. Chiropractic is a touchy-feely profession—that transfers.”
Interestingly, all four chiropractic MPs tell similar stories about how—for each in his or her own way—they have come to view their constituents in much the same light as chiropractors perceive their patients: “You can’t be a successful chiropractor without good interpersonal skills,” explains Dr. James Lunney, (Class of ’83, Nanaimo-Alberni, BC). “Our job as chiropractors is taking complicated issues, and finding ways of explaining them—interpreting X-rays, for example—you have to be able to communicate to your patient what needs to be communicated.” The job requirements are strikingly similar, he says, on Parliament Hill. “Any chiropractor who deals with patient issues successfully has the skills to make the transition into politics. If you can manage a practice, you have an aptitude for politics.”
As part of our efforts to support academic freedom on evolution, we are teaming up with the IDEA Center (Intelligent Design and Evolution Awareness) to help students in starting an IDEA chapter on their campus. Such campus clubs are a fun and educational way for students to examine all sides of the debate over evolution.Here's a challenge for everybody no matter which side you are on. Finding anti-evolution articles on the IDEA Center website is trivial. All the standard lies are there, sometimes in multiple articles. But can anyone find a single bit of evidence that supports Intelligent Design Creationism?
IDEA Clubs are student-initiated clubs that foster academic freedom as students learn about scientific evidence that supports intelligent design and also learn about modern evolutionary theory. IDEA Clubs are a growing network of student-led clubs on university and high school campuses around the United States with thirty new chapters formed to date. (my emphasis)
Human aerial bombardments might have pushed Neanderthals to extinction, suggests new research. Changes in bone shape left by a life of overhand throwing hint that Stone Age humans regularly threw heavy objects, such as stones or spears, while Neanderthals did not.The paper by Jill Rhodes of the Department of Anthropology, Bryn Mawr College and Steven E. Churchill of the Department of Evolutionary Anthropology, Duke University appears in The Journal of Human Evolution under Article in Press.
"The anatomically modern humans would have this more effective and efficient form of hunting," says Jill Rhodes, a biological anthropologist at Bryn Mawr College in Pennsylvania, who led the new study. A warmer Europe would have opened up forests, enabling longer range hunting, she says.
Rhodes and a colleague studied changes to the arm bone that connects the shoulder to the elbow – the humerus – to determine when humans may have begun using projectile weapons.
"If we're trying to understand whether anatomically modern humans had projectiles, then why not read the signature that it can imprint in the skeleton," Rhodes says.
Rhodesa, J.A. and Churchill, S.A. (2008) Throwing in the Middle and Upper Paleolithic: inferences from an analysis of humeral retroversion. [doi:10.1016/j.jhevol.2008.08.022M]Here's the complete text of the conclusiosn from that paper.
Clinical evidence from professional and college-level throwing athletes reveal differences in the humeral retroversion angle both between athletes and comparative (non-throwing) samples and between the dominant (throwing) and non-dominant limbs in the athletes. Comparative analysis of humeral architecture, specifically the humeral retroversion angle, in Pleistocene fossil humans has the ability to contribute new insights into the origins of projectile weaponry by examining the individuals who would have wielded those weapons. While the data is equivocal (in part because of confounding variables that affect humeral retroversion and in part because of small fossil sample sizes), we can reach two conclusions. First, while Neandertals tend to have high amounts of humeral retroversion, the overall pattern between limbs and between sexes strongly suggests that it is not due to habitual throwing behavior. The humeral retroversion data is largely consistent with other lines of evidence pertaining to projectile weaponry; the preponderance of evidence, ranging from fossil spears and Mousterian lithics to the articular and diaphyseal morphology of upper limb bones, suggests that Neandertals did not habitually employ long-range projectile weapons ([Churchill et al., 1996], [Schmitt et al., 2003], [Shea, 2003a], Shea, 2006 J.J. Shea, The origins of lithic projectile point technology: evidence from Africa, the Levant, and Europe, J. Archaeol. Sci. 33 (2006), pp. 823–846. Article | PDF (774 K) | View Record in Scopus | Cited By in Scopus (15)[Shea, 2006] and [Churchill and Rhodes, in press]). It is worth noting that earlier hominins also lack humeral torsion, further demonstrating that the increased retroversion found in Neandertals is unlikely to be linked to throwing. Second, we cannot reject the suggestion of projectile weapon use in the European Upper Paleolithic. The patterns seen in bilateral asymmetry in humeral retroversion angle suggest a variable use of throwing in the middle Upper Paleolithic (and thus great inter-individual variation in asymmetry), perhaps related to regional differences in hunting practices or the importance of projectile-based hunting. The levels of asymmetry seen in late Upper Paleolithic males are consistent with the regular use of projectile technology by this time.Is it just me, or does there seem to be a disconnect between what's in the paper and what's in the press release? Why would the author allow the press release to say something that cannot be found anywhere in the paper?
