Metro Nashville Public Schools: A System under Construction

About a month ago we were invited to the graduation ceremony of our neighbor's daughter at Hillsboro High School in Nashville, Tennessee. It was the first time I attended a U.S. high school graduation. I received my secondary school education abroad.

The ceremony was festive with hundreds of graduates and a huge crowd of family members filling a college basketball stadium. I was struck by the diversity of the students and their achievements. Scores were honored for their successful participation in advanced placement courses. Others had fulfilled the requirements for the international baccalaureate, permitting them to study overseas.

A number of students were recognized for their accomplishments in the sciences and the languages. Among the high achievers was a young man with Asperger's syndrome who addressed the audience in a passionate speech. The student who received the loudest cheers had Down syndrome. It was an evening of elation. Everyone was very proud. The students seemed equipped and ready for great careers to come.

These impressions are in stark contrast to the district-wide performance of Metropolitan Nashville Schools. The school system is in a deep crisis. A number of schools have missed government-set benchmarks for student performance (TCAP) for four years in a row. The passed director of schools was the second choice at the time of his appointment. He worked hard on improving instruction for the children of recent immigrants with poor knowledge of English. His rule was draconian. His personnel decisions were not well received. The teachers chafed under his reforms. The introduction of school uniforms complicated lives and did not make a difference. His days were eventually counted, when his unpopular measures did not deliver the successes that the school district direly needed.

Stipulated by the disastrous test results, the Tennessee Department of Education sent emissaries to institute reforms. A private company is being hired short-term to pay special attention to the students at schools with poor showing. Nashville is looking for a new superintendent. The search will not be easy. Apt candidates with career ambitions may hardly be interested in a position that may reduce them to expediters of state policy with little prospect of earning own acclaim. The public debate about Metro Schools' future is heated. Nashvillians want to improve their school system, but are wary of increased taxes. The local newspaper The Tennessean provides comprehensive coverage.

To date, most change precipitated from the top down. Yet, the student performance problems are specific to neighborhoods. The socioeconomic and geographical nature of the problems suggests that solutions must be sought at the individual schools in discussion between the educators teaching the affected children and the communities where the children live. Traditionally, these communities have had little confidence in the system. Great expectations have been raised in the past and proved too hard to fulfill in actuality. They have been disappointed many times. Any proposal for change may be perceived as yet another short change.

In this situation, newly created facts on the ground must disprove any false perceptions. Short-term fixes are not going to win the confidence of the affected communities. Solid investments have got to be made that produce lasting, palpable and visible results locally. The children and parents will embrace reforms only, when they are convinced that the offered help is more than just a promise.

Addenda

• Jesse Register, the newly appointed Director of Metro Nashville Public Schools, took office Jan. 15, 2009. Today The Tennessean's Jaime Sarrio in her article entitled "New schools chief calls for unity" on his first public statements about his vision of leadership for the school district delivered to the Metro council's education committee (02/03/09).
• Updated facilities constitute the smallest part of the effort. The greater part will consist of keeping the students to attend school. During the last summer, the implementation of truancy programs was widely discussed in the community as a measure too improve the abysmal attendance in the schools that did not meet the criteria of the No Child Left Behind Act, known as Title I schools. Here, attractive and affordable after-school care may motivate students to come to school on a regular basis.
  
  My children have been enrolled in a superbly-led after-school care program while at Eakin Elementary School in Nashville. The program has had a deep, positive influence on the development of their social skills and homework ethics. The prospect of meeting friends after school has been a cheerful motivator on dreary mornings. Exactly such programs are needed in the under-attended schools. The children would benefit highly from the exposure to a socially structured environment in the afternoons where conflicts can be resolved under adult supervision, where they can study, do homework, can explore computers, learn crafts and handiwork to develop their fine motor skills as well as have pure fun playing games and enjoy each others company. The children would wish to be at school.
  
  In my experience, such programs do work for all children. One summer, my son attended a Boy Scout Summer Camp in Nashville's Shelby Park. Most children were from so-called distressed neighborhoods. My son was hesitant about meeting them at first, but got quickly acquainted with his new pals. The kids got along fine. The group experienced one troublesome incidence during the week. Nobody was hurt. The councilors immediately sat the boys down to discuss how to resolve the conflict. They told us parents about the event in the evening. I walked away convinced that social engineering can work. In addition to good teachers, effective after school care may be essential to progress at under-performing schools (02/24/09).
• I have written more about the value and the needs of education in this state in my posts dated Jan. 24 and Jun. 27, 2008 (03/12/09).
• Today The Tennessean's Jaime Sarrio reports in her article entitled "Nashville schools to tackle key needs all at once" on the reform plans of the new director of schools announced yesterday. The plan focuses on improvements for children with special needs and children who speak English as a second language. In addition, attention will be paid to improvements of school safety and climate (04/01/09),
• Nashville Mayor Karl Dean bought into the idea of boosting after-school care, according to Heidi Hall's post in the Tennessean entitled "Dean plans to expand after-school programs" yesterday (05/08/09).
• With incredulity, I found out today that our new Director of Schools decided to move one of the most competent principals I ever met, Roxie Ross, from our daughter's school, Eakin Elementary. Roxie oversaw the relocation of the school into newly built and restored facilities a few years ago and led the school with greatest professionalism and enthusiasm as a place of learning for all children. Eakin has performed above expectations under her guidance, fulfilling the requirements of the No Child Left Behind Act year after year. No reasons were given for the decision. No parents were consulted. It seems highly demoralizing for the teachers, the children and the parents to remove a principal from a post in which she excelled. Parents trust in the continuity of the system, when they commit their children to its schools. Functional schools are precious and should not be tampered with. Without them, a city loses its attraction as a place for families to raise their children (07/07/09).
• Last year the school board decided to rezone the district. The idea was that the rezoning would improve the underperforming schools by steering students to schools in their neighborhoods with the hope that this might facilitate parent school involvement. Most parents of the affected students were highly skeptical that rezoning was a step in the right direction. Many perceived the plan as an erosion of school integration. A federal law suit was filed. Regardless, the school board went ahead with a shaky implementation of its controversial plan this school year. Today The Tennessean's Chris Echegaray reports in his article entitled "North Nashville students get books day after judge's order" that as a result students of one rezoned middle school received their text books only now, that is three weeks after the school year began (09/03/09).

Professor Max Wertheimer's Synergy

Seventy-five years ago, the New School for Social Research began its graduate program in psychology. One pillar of this program was Prof. Max Wertheimer, co-founder of Gestalt Psychology. The Wertheimers had just moved from Frankfurt am Main to New York at the time. Wertheimer was one of the many Jewish scholars who lost their academic appointments to the race regulation the Nazi's introduced in German public service in 1933. It took Germany up to the present to recover from the gigantic brain drain that ensued.

Professor Wertheimer spent many productive years as a faculty member of the Johann Wolfgang Goethe University, Frankfurt am Main. The city had been a free city ever since Charlemagne's rule and has always been a free-spirited place that had comparably friendly relations with its Jewish community before the Nazis came to power. A bit more than one hundred years earlier the most prominent Jewish banking family of Frankfurt, the Rothschilds, had used their influence in France to save the City from plunder by the Napoleonic armies that were self-providing. Self-provision commonly meant that, at the least, there was no food left after the citizen soldiers were through. However, the French government had borrowed heavily from the Rothschilds for the war effort and the head of the household requested in a letter to the French commanding generals that the troupes please kindly pass Frankfurt by. The French granted the request and the City was spared one more time.

The Mertons were another Jewish family of importance, particularly to Professor Wertheimer. This family made a fortune with a now metal trading business that recently fell victim to fraudulent derivatives trading (die Metallgesellschaft) and raised funds for a Business School around the beginning of the last century. A few years later, state government took over and The Johann Wolfgang Goethe University where Wertheimer would teach grew from this seed.

I am certain that many Frankfurters were saddened by the forced departure of so many good citizens, colleagues, friends and neighbors. The City had been governed by Social Democrates during the Republic of Weimar. Support for the Nazis was not running very deep. Three years after the Wertheimers had left, der Fuehrer paid the City an official visit. A rally was to be held in the largest in-door venue (die Festhalle) on the City's fairgrounds. The multi-purpose sports complex could hold more than 30,000 people. Der Fuehrer arrived by train at the Main Train Station downtown and proceeded in an open convertible along the avenue that led from the station to the hall. It is a short distance. You can walk it in 15 minutes. But it was more impressive for der Fuehrer to ride in a procession. Masses of supporters and spectators lined the street. As usual, the affair was highly choreographed. Heavy security ensured that any opposition did not stand a chance of disrupting the event. Plenty prearranged public jubilation was put on display. On arrival at the hall, der Fuehrer walked up the podium set up high and began to speak. At a certain point, disturbance erupted in the crowd. Hecklers started shouting. Cat calls rang out. Der Fuehrer broke off his speech. The calls rang louder. He folded his script, turned round and left the podium without a word or looking back. He never returned to the City of Frankfurt. The incidence was hushed up. The hall, which is architectonically impressive, survived the war.

After the war, the Jewish community began to return to the City. It would take many years of reconstruction and healing before any Jewish academic would consider living and working there. Yet, ever so slowly times changed. Thirty-six years after the incidence with Hitler's speech, The Rolling Stones gave a series of great concerts in the very same hall. Mick Jagger sang "Sympathy for the Devil" and the Frankfurter audience chimed enthusiastically. Professor Wertheimer might have had a ball, had he been able to witness this.

Professor Wertheimer was born and raised in Prague He began studies at Charles University, but moved on to continue at German universities. He completed his doctorate at Julius Maximilians University in Würzburg. History has it that his most famous idea struck him while he was traveling by train across Germany in 1910. From the rolling train, he watched the sequential blinking of twin red lights at railroad crossings and discovered that when the speed was right, the separate red dots fused into one dot racing back and forth. He deduced that the perceived whole, that is the dot in motion, was more than the sum of the pieces and conceived a series of psycho-physical experiments on the perception of motion to test his fresh hypothesis.

He mused about simple motion pictures like the crude flip book shown in the clip below.

Viewing a single picture frame does not reveal the action. The frames have to be viewed in a particular sequence. The presentation speed needs to be constant and in the appropriate range to project meaningful action.

By the time the train reached Frankfurt, he was supposedly so excited that he abandoned his trip, hastened to the University's Department of Psychology, where he parlayed his ideas into a job. Gestalt Psychology was born.

Although it is unlikely that the events unfolded precisely like that, they make a great story of discovery. Years ago, I had the opportunity to retrace Wertheimer's steps described in E. G. Boring's History of Experimental Psychology.
The path is still there. But the ambiance changed.

Figure 1: My Vaterstadt!

The photographs in Fig. 1 show from top left counterclockwise, a view of the modern City from the opposite bank of the Main River, the interior of the Main Train Station, the composer quarters, and Wertheimer's destination. The Professor would have been astounded to see the skyline of the modern city. Much of what he must have been familiar with perished on a weekend in late 1943. The Rothschilds' old family seat and 19^th century mansion went with it. The Professor would have recognized the shed of the train station, though. It is still the same as in his day. However, the trains have changed. He would have been enthralled by the white high-speed ICE trains of today. At 200 miles/h, the red dot he saw would have raced at hyper speed.

Embarking from the Main Train Station's North side, it is an easy walk of about 25 minutes to Wertheimer's destination, half ways following the route der Fuehrer took 30 years later. But before we reach the multi-purpose hall, we veer right into the composer's quarter of Frankfurt's posh Westend. On the third picture, we find ourselves in Schumannstrasse, the street he most likely walked westward toward the University until he reached Kettenhofweg across from the old university campus. At the intersection of Schumannstrasse and Kettenhofweg we find the address where Wertheimer must have knocked on the door. The last picture shows the villa. The building has survived and still houses a part of the Department of Psychology. I saw no plaque of commemoration. But, this must have been the cradle of Gestalt Psychology.

Professor Wertheimer's idea on the train applies far beyond Gestalt Psychology. In organic chemistry, molecules are known to possess the same sum formula, that is they are composed of the same atoms. Yet, they exhibit distinctly different chemical and physical properties depending on the differences in structural formula, that is the arrangement of the atoms. For example, propionaldehyde and acetone are composed of three carbons, six hydrogens and one oxygen atom.

Figure 2: Proprionaldehyde

Figure 2 shows a molecular model of propionaldehyde. The carbons are gray, the hydrogens white, and the oxygen is red. The oxygen is bound to a carbon at the end of the molecule.

Figure 3: Acetone

Figure 3 shows a molecular model of acetone. The oxygen is bound to the carbon in the middle of the molecule. The molecular models were rendered with BallView (Moll and others, 2006).

The difference in arrangement of the pieces, that is the atoms, leads to distinct differences in properties of the whole, that is the molecule. To highlight one difference, propionaldehyde melts at -81° C, whereas acetone melts at -94.9° C. In other words, the qualities of the whole result from the relationships among its pieces.

In analogy, the dynamic reorganization of connections among nerve cells in the brain produces changes in behavior, although the nerve cells remain the same.

Addenda

• Amos Elon wrote a concise and compelling early history of the Rothschilds in Frankfurt entitled "Founder: A Man and His Time" (03/03/10).
• Cinematography captures motion. As Max Wertheimer recognized, the temporal sequence of still pictures bestows a new quality on the ensemble, weaving a tapestry of visual language depicting action. No one is better positioned to describe the fundamental impact of movies on our mind's eye, their harnessing of time and their power of witnessing history to unfold than the distinguished film director Martin Scorsese in his National Endowment for the Humanities Jefferson Lecture in the Humanities at the JFK Center of Performing Arts in Washington, DC, with the title "Persistence of Vision: Reading the Language of Cinema" delivered Apr. 1, 2013. Watch the snippet of a British movie describing the discovery of motion pictures at the beginning of Scorsese's presentation. While the clip is concerned with the method of recording motion on film, Wertheimer on his train ride was pre-occupied with our mind's perception of motion. Presentation and perception constitute crucial components of cinematography. Martin Scorsese devotes his lecture to the importance of preserving old films. He emphasizes that motion pictures so powerfully resonate our zeitgeist that they must be preserved as part of our cultural heritage for generations to come (09/02/2013).

References

• Boring EG (1970) History of Experimental Psychology. Appleton, New York.
  
• Moll A, Hildebrandt A, Lenhof HP, Kohlbacher O (2006) BALLView: A tool for research and education in molecular modeling. Bioinformatics 22:365-366.

Glioblastoma multiforme: The Octopus in the Brain

Cancer is a life-changing experience. Senator Edward Kennedy has been diagnosed with brain cancer. The ensuing media attention to this horrible disease has touched on a number of fundamental issues. However, the reporting has remained often vague. The vagueness is the inevitable result of the uncertainties involved.

To begin with, uncertainty is an integral part of any cancer. Prognoses of outcome for cancer therapies are probabilistic, diametrically opposed to our craving for definitive answers. We are challenged to beat odds. Yet, we only feel safe, when we know for sure what is going to happen to us. With cancer therapy there can be no assurance of success, only indications from prior experience that the therapy may prolong our lives and hope.

Senator Kennedy's tumor was located in the parietal lobe of the cerebral cortex. This area is large. Nerve cells on its borders process sensory information of mainly one modality. Nerve cells in its interior process multi-modal input, integrating information across multiple senses. The cortical regions that truly fit the idea of the center for a particular function are few. Primary sensory areas may fulfill this requirement best. They receive the most direct input from a particular sense organ and process predominantly information of this sense's modality. For example, a stroke in the primary somatic sensory area at the forward border of the parietal lobe predictably impairs the sense of touch. Therefore, this area may be designated a cortical center for touch. By contrast, injuries in the large swath of parietal cortex stretching backward from the primary somatic sensory area may only lead to subtle loss of sensory function. Attention, speech comprehension and short-term memory may be affected, dependent on the location of the damage. Hence, the uncertainty in the prognosis of the tumor's impact on brain function is rooted in our incomplete understanding of parietal lobe function. More research is needed in this area.

Even less is known about the nature of Senator Kennedy's tumor. Nerve cells and glia represent the most prevalent cell types in brain tissue. Nerve cells multiply at high rate only in the developing brain. In the mature brain, nerve cell proliferation is much reduced and restricted to a small number of regions. In contrast, glia retain the ability to multiply throughout life. The glia in the brain's gray matter essentially consist of astrocytes and microglia.

Astrocytes play vital roles in support of nerve cell function. For example, astrocytes remove the excitatory neurotransmitter glutamate from the space between cells. Neurotransmitters are substances that mediate the transfer of information between nerve cells. Too much glutamate in the extracellular space triggers a program in nerve cells leading to their death (apoptosis). Microglia support the brain's immune response.

After an insult to the brain, astrocytes and microglia increase in number at the site of the injury, owing to cell division and migration. Astrocytes form a glial scar encapsulating the damaged tissue. Microglia are known to incorporate debris of severed nerve cell connections (axons). The glial reaction extends from the site of the injury, following the tracts of severed connections. If the glial reaction progresses normal, the debris is digested and the tissue heals. The glia cease dividing and decrease in number.

At times, however, glia begin to proliferate abnormally without any known reason and the cells do not stop dividing. Aggressive, fast growth of a tumor ensues. Astrocytes develop the most malignant tumors known as glioblastoma multiforme, or GBM for short. Once the tumor reaches a certain size, the blood-brain-barrier is breached. Fluid invades the brain tissue, forming an edema. Nerve cell function is severely impaired, leading to seizures and often hemiparesis. Glia hitherto uninvolved in neoplastic growth react to the injury. The glial reaction possibly recruits abnormal glia and fans out along the disrupted nerve cell connections, infiltrating healthy brain tissue.

At this juncture, the steps to be taken for Senator Kennedy seem straight to the point. The tumor's bulk has been excised. The edema has been addressed. Now, the remaining abnormal astrocytes have to be stopped from dividing. Ionizing radiation will be used to damage the DNA of the cells dividing in the margins of the tumor, arresting the cycle of cell division. Cytostatic chemotherapeutics will be administered to stop astrocytic division in regions outside the focus of radiation. In addition, the growth of blood vessels into cancerous tissue may be slowed with drugs that inhibit angiogenesis (but see addendum, dated Apr. 10, 2009).

I lost my father and two good friends to glioblastoma multiforme and sincerely wish that this regimen will benefit Senator Kennedy in the best possible ways. However, as scientist I know that this vicious disease will only be defeated, once we identify the molecules that signal glial proliferation and devise a method that permits us to specifically inhibit the proliferation of astrocytes.

Addenda

• Most likely, the molecule signaling glial proliferation is epidermal growth factor (EGF) and the EGF tyrosine kinase receptor needs to be inhibited (8/30/08).
• Perhaps, the phosphorylated protein is Annexin/Lipocortin 1 (Melzer and others, 1998) (10/02/08).
• Glioblastoma multiforme is a rapidly growing tumor, showing regional differences from normal brain tissue in its metabolism of sugar as a source of energy. F.M. Santandreu and others (2008) provide a comprehensive description of such metabolic aspects in Cellular Physiology and Biochemistry 22:757-768. Since the tumor cells can store little sugar, the resource has to be delivered constantly with the bloodstream. The fast tumor growth induces growth of blood vessels. Therefore, anti-angiogenic drugs that inhibit vessel growth may help to shrink the tumor (02/18/09).
• Hai Yan and others (2009) report somatic mutations of the mitochondrial enzyme isocitric acid dehydrogenase crucial for sugar metabolism in 70% of astrocytomas and oligodendrogliomas as well as glioblastomas that developed from these tumors (New England Journal of Medicine 360:765-773). The mutations are discussed as potential predispositions for tumorigenesis (02/19/09).
• Microglia reactive to nerve cell injury are shown in my post dated Oct. 17, 2008 (03/04/09).
• To date, there is no compelling evidence that the use of contemporary cell phones causes glioblastoma multiforme. See my post dated Aug. 21, 2008 (03/05/09).
• You may be interested in reckoning with the odds in my post dated Mar. 5, 2009 (03/06/09).
• Erika Check Hayden summarizes the latest insights into the effectiveness and pitfalls of angiogenesis inhibitors in this weeks issue of the journal Nature, vol. 458: 686-687 (04/10/09).
• Using RNA interference (RNAi), Australian scientists developed a method with which the expression of tyrosine kinase receptors can be blocked, making tumor cells more vulnerable to chemotherapeutics and diminishing the tumor cells' ability of developing resistance against the drugs (MacDiarmid and others, 2009). Michael Perry reported on this progress in his post with the title "Scientists kill cancer cells with 'trojan horse'" published online on Reuters yesterday (06/30/09).
• Senator Kennedy passed away yesterday (08/26/09).
• Last Tuesday, Sep. 7, 2009, National Public Radio's Talk of the Nation aired an interview by Neil Conan with the British neurosurgeon Henry Marsh on his charity work in the Ukraine and general aspects of his profession. National Public Television's POV showed a movie on his work that evening. The movie, "The English Surgeon", will available on DVD Nov. 3. Particularly towards the interview's end, Dr. Marsh highlights in striking clarity the importance of finding an experienced neurosurgeon for the successful removal of a glioblastoma (09/10/09).
• A recent clinical study by Sampson and others (2010) reported promising results in the treatment of glioblastoma multiforme (GBM), using vaccines that target epidermal growth factor receptor variant III, or EGFRvIII for short. The receptor is extraordinarily prevalent on the surface of the most-aggressively growing GBM cells, owing to a genetic mutation. Thirty-five patients with GBM were enrolled in the phase II clinical trial; all underwent surgery, radiation therapy and chemotherapy with temozolomide. In addition, 18 were inoculated with vaccines.  Adding vaccines almost doubled median survival time from 15 to 26 months, extending the progression-free period from 6.3 months to 14.2 months. The vaccination eliminated all cancer cells carrying EGFRvIII, except in one patient. Half of the patients showed an immune response. Six developed antibodies specific for the receptor and three showed a T-cell response, supporting the contention that the increased survival may be associated with the immune response. Nine of eleven patients, whose recurring tumors were examined, tested negative for EGFRvIII, indicating that the cells with this mutation had been persistently eradicated. Taken together, the findings suggest that vaccines may prove a promising new avenue of treatment, though not a cure, for glioblastoma muliforme. Celldex Therapeutics and Pfizer developed the currently tested vaccine known as rindopepimut or CDX-110 and PF-04948568, respectively (10/05/10).
• Listen to this interview with Gordon Murray by Robert Siegel broadcast on National Public Radio's All Things Considered today and find words of strength and encouragement from a man with GBM who is making the best of his situation (12/17/10).
• Siddhartha Mukherjee, a hematologist/oncologist at Columbia University, wrote an informative book entitled "The Emperor of All Maladies: A Biography of Cancer" on recent advances in cancer medicine. The author was awarded a Pulitzer Prize for his exploration earlier this month. Note that he specializes in blood cell cancer and the particular experience influences his assessment of the role of stem cells in tumorigenesis and metastasis. Terry Gross interviewed him Nov. 11, 2010, on National Public Radio's Fresh Air in her show with the title "An Oncologist Writes 'A Biography Of Cancer'" (04/22/11).

• 

  Color-coded image of a transaxial FDG PET scan from a GBM patient with a recurrent tumor in the left cortical hemisphere.  High local cerebral metabolic rates for glucose starkly delineate the tumor (low rate - blue; high rate- white; courtesy L. Sokoloff). 

  The functional image above was acquired from a patient with a glioblastoma multiforme in the left cerebral hemisphere. The initial primary tumor and had been surgically removed. The removal was incomplete. When symptoms suggested a recurrence of the tumor, the surgery had altered the anatomy of the cortical hemisphere to such extent that an evaluation of structural brain scans was impossible. However, a new tumor could be localized with positron emission tomography and the [¹⁸F]fluorodeoxyglucose (FDG) method (Di Chiro and others, 1982). This method allows us to image and measure the local glucose consumption of brain tissue. The rate of glucose utilization was highly increased in the core of the new tumor. Under normal physiological conditions, brain cells metabolize glucose to produce adenosine-triphosphate (ATP) in an oxygen-consuming metabolic pathway called aerobic glycolysis. ATP represents a ubiquitous high-energy molecule that cells need to maintain vital functions. Because glia possess only a small capacity of storing glucose and oxygen cannot be stored at all in the brain, the blood supply must continuously deliver both to the brain tissue. An increase in demand stimulates angiogenesis, that is blood vessel growth. However, in fast growing tumors angiogenesis cannot keep pace with demand. Moreover, the activity of certain types of key enzymes for glucose metabolism, known as mitochondria-associated hexokinases I and II, can be increased as much as 200-fold in tumor cells, leading to extremely high rates of aerobic glycolysis (Warburg effect) which compound the local oxygen shortage. Moreover, using tumor genome sequencing Yan and others (2009) identified a mutation that changes arginine 132 in the product of gene IDH1 isocitrate dehydrogenase. Isocitrate dehydrogenase is a key enzyme in the Krebs cycle providing substrates for aerobic glycolysis. This change in amino acid modifies the function of the enzyme such that the enzyme's substrate isocitric acid is turned into a novel product which cannot be used in the Krebs cycle, hampering the efficiency of aerobic glycolysis. More than 70 percent of 445 tested central nervous system tumors were astrocytomas, oligodendrogliomas and glioblastomas that had developed from lower-grade tumors. These rapidly-growing, malignant cancers possessed the mutation. As a consequence, glucose may be metabolized in the malignant tumor's core without the use of oxygen, though this anaerobic glycolysis is much less efficient in generating ATP than aerobic glycolysis. The observations may be taken to suggest the possibility of starving neoplastic astrocytes to death with a diet extremely low in carbohydrates. Alas, cells in other tissues of our body, e.g. muscles, routinely use vast amounts of glucose in anaerobic glycolysis to meet rapidly increasing energy demands while oxygen is in short supply. A no-carb diet is not going to be selective for the tumor and may rather weaken the body's overall resilience. By contrast, avoiding high-fructose corn syrup and sucrose used to sweeten countless foods and beverages may be beneficial, because the fructose in these sugars may stimulate insulin-like growth factors that promote neoplastic growth (see Gary Taubes' article with the title "Is Sugar Toxic?" published online in The New York Times on Apr. 13, 2011) (01/13/2012).
• Dang and others (2009) report that when IDH1 mutations turn arginine 132 into histidine, the gene's changed product isocitric acid dehydrogenase may catalyze the formation of R(-)-2-hydroxyglutarate known to be conducive to tumor growth (02/06/2012).
• The leader of the four-decade effort to develop the deoxyglucose method for the use in tumor imaging (see image above) Dr. Louis Sokoloff presented a historical lecture for the public with the title "Development of the [18F]Fluorodeoxyglucose Method: A Serendipitous Journey From Bench to Bedside" on the endeavor at Brookhaven National Laboratory Oct. 19, 2012, to celebrate the designation of its Chemistry Department by the American Chemical Society as a historical site for its role in this accomplishment (10/29/2012).
• Personal accounts of GBM patients describing their experience with treatment are rare. Two days ago (Sep. 23, 2013), the Washington Post published Fritz Anderson's post with the title "Surgery, radiation and chemo didn’t stop the tumor, but an experimental treatment did" published online. Dr. Anderson, a retired cardiologist, writes about his situation eloquently with great sensitivity and encouragement. After surgery, radiation therapy and chemotherapy his tumor regrew and he decided to participate in an experimental phase I trial of a therapeutic that consists of an altered polio virus (PVS-RIPO) that glioblastoma cells preferentially bind, infecting and destroying the cells. The trial is led by Prof. Matthias Gromeier at Duke University's Preston Robert Tisch Brain Tumor Center. The procedure is invasive, requiring a craniotomy, because the drug must be administered directly to the tumor tissue in one six-hour session. The therapy shrunk the tumor decisively, and Dr. Anderson continues to enjoy life. Four of five treated patients were blessed with success to date (Sep. 25, 2013).

References

• Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden M G, Su SM (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739-744.
• Di Chiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston GS, Manning RG, Wolf AP (1982) Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography. Neurology 32:1323-1329.
• De Vleeschouwer S, Fieuws S, Rutkowski S, Van Calenbergh F, Van Loon J, Goffin J, Sciot R, Wilms G, Demaerel P, Warmuth-Metz M, Soerensen N, Wolff JE,Wagner S, Kaempgen E, Van Gool SW (2008) Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme. Clin Cancer Res 14:3098-3104.
• Check Hayden E (2009) Cutting off cancer's supply lines. Nature 458:686-687.
• MacDiarmid JA, Amaro-Mugridge NB, Madrid-Weiss J, Sedliarou I, Wetzel S, Kochar K, Brahmbhatt VN, Phillips L, Pattison ST, Petti C, Stillman B, Graham RM, Brahmbhatt H (2009) Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug. Nat Biotechnol 27:643-651.
• Melzer P, Savchenko V, McKanna JA (2001) Microglia, astrocytes, and macrophages react differentially to central and peripheral lesions in the developing and mature rat whisker-to-barrel pathway: a study using immunohistochemistry for lipocortin1, phosphotyrosine, s100 beta, and mannose receptors. Exp Neurol 68:63-77.
• Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, Friedman HS, Gilbert MR, Herndon II JE, McLendon RE, Mitchell DA, Reardon DA, Sawaya R, Schmittling RJ, Shi W, Vredenburgh JJ, Bigner DD (2010) Immunologic Escape After Prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol: doi: 10.1200/JCO.2010.28.6963.
• Santandreu FM, Brell M, Gene AH, Guevara R, Oliver1, Couce ME, Roca P (2008) Differences in mitochondrial function and anti- oxidant systems between regions of human glioma. Cell Physiol Biochem 22:757-768.
• Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765-773.

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