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Editorial

There should be an international code of ethics between scientists in industrialized and developing countries, that is, a balance of power in research collaboration according to French research agency.

It seems as through everyone is talking about stem cells. Why all the fuss? Because stem cells types that make up complex organisms and they promise to perform this remake able feat on demand. These have already become and important clinical tool---read on in "Stem Cells ------Hype and Hope". 

The fact that cancer is a multistep process and that all tumors contain chromosomal alterations and exhibit variable degrees of chromosomal instability has been known for some time. Recent scientific advance have provided new assays and novel test systems that are beginning to supplement and in the future may even replace, the well established tests that have been widely used for the last few decades. With the advent of chromosomal banding techniques, FISH, and wide range of molecular techniques in a row, for identifying genomic rearrangements, more detail about the specific genetics alteration involved in or associated with the formation of a tumor had been obtained. Read details of FISH assay inside.

ODDS AND ENDS

Partial Redemption of Neem

After six years of legal battles, the European Patent Office in May revoked a patent for a fungicide derived from Neem tree roots. The European panel judged that there was no invention step involved in the patent, because Neem has traditionally been used as a fungicide.

The patent is held by multiple nations, and in the United States, it is unlikely to be overturned. Together with the research Foundation of India, Linda Bullard, President of the International Federation of Organic Agriculture Movements, challenged the Neem patent on the grounds that the patent holders capitalized unfairly on Indian indigenous knowledge, an activity that is commonly referred to as biopiracy.
(Enviro. Sci. Technol., Aug 2000)

World Environment Day

In 1972, the UN General Assembly designated 5 June as World Environment Day to bring attention to environmental problems and the need for action by governments, individuals, businesses, NGOs and community groups. With the theme "2000-The Environment Millenium - Time to Act", this year's World Environment Day was marked by calls for genuine and effective efforts to reverse environmental damage and to work towards sustainable development. World Environment Day was celebrated in ITRC with local schools participating in several competitions.

Message from the UN Secretary General on the Occasion of World Environment Day

Our quest for a healthy environment is a never ending process. It should be an integral part of our way of life. The theme for this year's World Environment Day, "2000-The Environment Millennium-Time to Act", is a timely reminder of our role in the ecosystem.

In the last millennium, and particularly in the last century, realizing this role has proved to be a great challenge. Never in the history of mankind have we done so much, in so little time, to destroy the wonderful ecosystem that sustains us. The repercussions of our destructive action will be felt for generations to come. Indeed, it may take another millennium to put things right.

We celebrate World Environment Day in the knowledge that environmental issues are inextricably linked to those of peaceful coexistence, international cooperation and economic development.

Despite the great strides made in recognizing that development must coexist with the environment, we continue to search for economic progress in ways that erode the ecological foundations of our existence. Our very survival as a species may depend on our ability to reconcile technological progress with moral progress.

On this World Environment Day, and in this United Nations International Year for the Culture of Peace, let us resolve to take positive steps to fight the degradation of our environment. Let us combine our technological and creative skills with true wisdom, and reverse the trend of violence against nature and our fellow beings.

Otherwise, we may not have another thousand years to correct our mistakes.
[Kofi A. Annan, Secretary General of the United Nations, 5 June, 2000]

New Drugs Engineered to Fight Asthma

Environmental allergens such as those associated with dust mites and cockroaches can trigger asthma attacks in predisposed individuals when they overwhelm the immunoglobulin E (IgE) cascade, a system believed to protect the body against parasitic invasion. About 5,000 people die each year from asthma attacks, and doctors believe that all those deaths could be prevented. At the American Academy of Allergy, Asthma and immunology annual meeting, held 3-8 March 2000 in San Diego, California, doctors detailed how investigational bioengineered drugs target and soak up IgE and interleukin-4 (IL-4) key modulators of the IgE cascade. The drugs may eventually replace corticosteroids, currently the drug of choice, as preventive medication.

Henry Milgrom, a senior staff physican at National Jewish Medical and Research Center in Denver, Colorado, described progress in clinical trials with anti-IgE, a compound developed jointly by the drug companies Genentech, Novartis Pharma AG, and Tanox. "This is a breakthrough- anti IgE was designed to perform a specific function in suppressing a disease process and it works", Milgrom said.

Among the 268 adult patients suffering from moderate to severe asthma who received injections of anti IgE in the first phase of a 28 week study, only 14.6% had asthma attacks, compared with 23.3% of the 257 patients on placebo. There were also reduced exacerbations of asthma during the second phase of the study when steroid medication was withdrawn.

In a second study involving 334 asthmatic children, 55% of the children receiving anti IgE were able to discontinue all steroid medication without suffering asthma attacks, compared to about 39% of patients receiving placebo injections.

"This is an exciting approach to treatment of asthma", said Michael Wein, chief of allergy at Indian River Memorial Hospital in Vero Beach, Florida. "If you found something to remove IgE from the body, you wouldn't have allergies". Milgrom said anti-IgE also has potential for people who have food or latex allergies, atopic dermatitis, and other conditions. He said a new drug application for anti IgE will be filed with the Food and Drug Administration this summer.

Larry Borish, an associate professor of medicine at the University of Virginia Medical Center in Charlottesville, reported that another new drug, IL-4R (for IL-4 receptor), is effective for 5-7 days with just one inhaled dose IL-4 is responsible for the respiratory inflammation associated with asthma. Borish said the drug soaks up circulating IL-4 like a sponge.

Borish reported administering either placebo or three different dosages of IL-4R to 15-16 patients per group in 12 weekly inhalations. the patients were all suffering from moderate to severe asthma and had been taking inhaled corticosteroid medication, which was stopped on the first day of the study. The group taking the placebo showed a significant decline in lung function, whereas this decrease in function did not occur in the treatment group, borish said, demonstrating the efficacy of the experimental drug. Borish said a larger study of IL-$R will be reported this summer.

In almost all chronic diseases long term patient noncompliance is probably the major reason why treatment eventually fails. So says Charles Feldman, an associate professor of pediatrics at Columbia University in New York, the great promise of IL-4R is that if further studies prove its effectiveness, its ease of use should improve patient compliance - a key to keeping asthma in check - Ed Susman.
(EHP Vol.108#8 2000)

An Eruption of Silicosis

Scientists have long known that volcanic ash creates minor health problems such as eye irritation and exacerbates existing problems such as asthma. But the study, led by community medicine specialist Peter Baxter of the University of Cambridge, reveals that certain types of volcanic ash may create long term problems such as silicosis, an irreversible scarring disease of the lungs that occurs over long periods of exposure. The study is the first to link a technical mechanism of eruption to a specific health hazard, and is also one of the most detailed studies to date to quantify and define the ratio of silica minerals in volcanic ash versus glass and other particles.

In the ash generated at Soufriere Hills by pyroclastic flows- mixtures of volcanic ash and gases that hug the ground and flow down valleys - the team found high levels of a form of crystalline silica ash called cristobalite, which is known to cause silicosis. After assaying the ash around the island, the team found that the majority of particles under 10 micrometers in diameter contained 10-24% crystalline silica, mainly cristobalite, by weight. Moreover, large amounts of the particles were less than 3 micrometers in diameter- small enough to penetrate deep into the lungs.

The team also found that the hazard is increased during long lived eruptions, which spew ash over years or decades. Dome eruptions, in which a mass of magma builds up over the volcano's vent, generating myriad pyroclastic flows and ash plumes, also increase the hazard because they produce more fine ash and more fine crystalline silica. "The amount of fine respirable ash generated in such eruptions and the content of crystalline silica in the ash are significantly increased by crushing processes and transport processes in the pyroclastic flows formed by dome [eruptions]", explain Bristol University geologist and volcanologist Steve Sparks, a study coauthor. In contrast, the 1980 eruption of Mount St. Helens in Washington State produced short live ash falls with vastly fewer the particles containing only 4% cristoballite by weight.

The team measured suspended particle concentrations in areas where there was human activity and found that such activity is an important factor in resuspending ash and increasing exposure of populations, Sparks says, Reoccupation of some of the devastated and evacuated areas was delayed because of the poor air quality conditions caused by the ash, which had to be removed before people were allowed back.

Laboratory experiments indicate that cristobalite can be more toxic than quartz, a known cause of silicosis in workers with long term exposure to silica dusts, but the reason for cristobalite's increased toxicity is not known, says Sparks. Cristobalite toxicity varies greatly according to the age of the stone, heating, and other treatments, he adds.

Although dome eruptions are fairly common worldwide, the study findings may not apply to domes of other volcanoes, especially those of different chemical compositions, which may produce different minerals in varying percentages. Plus, other hazards associated with the creation of volcanic clouds, including hydrochloric and hydrofluoric acid gases and sulfuric acid particles, are largely unstudied.

Indeed, much work remains to determine the specific long term health risks volcanoes pose to humans. Even though follow up studies such as a chest X ray survey of islanders most exposed to ash are being undertaken, getting hard data on human exposure and health effects may take years. "Conditions like silicosis take very long time to develop", says - Julie Wakefield.
(EHP July 2000)

Stem Cells - Hype and Hope 

Studies of stem cells will help in understanding the development and function of organs in mammals. They may also offer a way of treating diseases ranging from liver failure to Parkinson's disease.

All cells come from other cells, so what does it mean to be a stem cell? There are complex academic definitions, but the most important idea is that stem cells are undifferentiated - unspecialized cells that can renew themselves and also give rise to one or more specialised cell types with specific functions in the body.

Stem cells are defined by their developmental potential. The idea of a stem cell has a natural meaning in the context of the germ line; after all, the germ line of animals produces eggs or sperm, which together generate whole organisms. 

The embryonic stem also exist in humans, and it has become possible over the past few years to grow them in the lab.

The fact that adult stem cells exist is exciting enough, but even more intriguing is that the potential of stem cells does not seem to be restricted by their source. For example, a series of startling observations indicates that muscle and blood might be obtained from stem cells found in the tissues of either system. With all the genetic markers and protocols at our disposal for identifying (haematopoietic stem cells).HSCs, it will not take long to test this proposition that exactly the same stem cells can generate the entire blood system as well as the striated muscle that allows you to run for the bus.

Mammals appear to contain some 20 major types of somatic stem cell. For example, stem cells have been described that can generate liver, pancreas, bone and cartilage. So it may be possible to obtain a wide range of stem cells from sources other than ES cells. This solution would effectively sidestep the ethical problem of using ES cells. But we have much to learn about how stem cells replicate and differentiate, and ES cells may offer essential technical advantages over other sources of somatic precursors. 

One reason for studying stem cells is their usefulness in cell replacement therapy. The manipulation of HSCs is already an important clinical tool, and human HSCs have been essential in bone marrow grafts that are in wide clinical use, for example in treating leukaemia patients. skin cells can also be grown in large numbers, providing a life saving grafting treatment for burn victims. And diabetes might be treatable by generating from stem cells the insulin producing cells found in the normal pancreas and grafting them into the pancreas of diabetic patients (Nature July 2000).

Stem Cells and Cancer

Genetically engineered stem cells can hunt down and kill cancerous brain cells, say researchers in the US. Evan Snyder of Harward Medical School, Boston and his colleagues, after seeing that neural cells can also migrate throughout the brain wondered if they are drawn to injured areas, such as tumors. They injected neural stem cells into rats with brain cancer. Some of the animals got injections into the tumor, but other were injected on the opposite side of the brain, even the tail. Within a few days the transplanted stem cells had migrated through healthy tissue to get to cancer cells. In all cases, the neural stem cells were found to have migrated throughout the tumor, but stopped at its edge.

The researcher repeated the experiment with stem cells modified to make an enzyme that converts a non toxic substance into a cancer killing agent. Injecting both the producing and stem cells into rats reduced tumor mass by 80 percent, they found (Proc. Nat. Acad. Sci. 97, 2000).

Fluorescence In Situ Hybridization (FISH)
M. Lohani

A number of molecular and cytogenetic studies have emphasized the importance of genetic alterations such as deletions, translocations, recombination and aneuploidies in the development of neoplasia. These genetic alterations have also been widely recognized in several other cases as infertility, spontaneous abortion and mental retardation etc. Till recent times analysis of the metaphase spread of chromosome has been relied as to detect the structural and numerical chromosomal aberrations for cytogenetic analysis, but the limitations have been that such analyses are restricted primarily to actively dividing cells and tissues, secondly these studies are labor intensive, require highly skilled personnel and are prone to technical artifacts such as chromosomal loss during metaphase preparation.

FISH is a recently developed molecular cytogenetic method with chromosomes specific DNA probes which permits cytogenetic information to be obtained rapidly and more accurately from morphologically preserved chromosomes, cells or tissue sections. The technique was originally developed by Pradue and Gall (1969) and by John et al. (1969) (independently) using autoradiography to detect radio labeled hybridized sequences. Hybridization of the fluorescent labeled chromosome specific DNA probes with the target sequence brought revolution in this area. It results in compact staining of the particular region, permitting the recognition of the copy number, the location of the chromosome of interest and the detection of chromosomal breakage or other aberration to be detected rapidly in large number of cells.

There are two types of non-radioactive in situ hybridization methods, direct and indirect. In the former method, the detectable fluorochrome molecules (reporter) are bound directly to the nucleic acid probe; thus the probe-target hybrids can be visualized under a fluorescent microscope, immediately after hybridization reaction. For the direct hybridization method it is essential that reporter molecule does not interfere with the hybridization reaction and the probe-reporter bond survives the rather harsh hybridization, and post hybridization washing conditions. Bauman et al. (1980; 1984) and Kurz (1984) have developed the probes meeting these criteria. Boehringer Mannheim also have introduced several fluorochrome labeled nucleotides that can be used for labeling and direct detection of DNA or RNA probes. For direct methods, the target sequence should be highly repetitive and large enough to give a large visible signal.

On the other hand indirect hybridization method involves a DNA probe containing a reporter molecule, which can be detected by affinity cytochemistry. After hybridization of these probes with the target sequence, primary signal is amplified using "Sandwich" procedure where detector (antibodies) molecules with fluorochromes are applied to bind with the reporter molecules. 

Small and non repetitive, such as a few hundred base pair long DNA sequences can efficiently be detected using indirect method. The most popular systems, used in indirect method are:

Innovative technical advances in the field have lead the FISH to progress to the point where 27 different DNA painting probes can be hybridized simultaneously and detected with specialized filter sets and computer software.

Apart from experimental toxicology, FISH has its tremendous use in clinical diagnostics also, like in detection of microdeletion syndrome, cryptic translocations, marker chromosome detection and for transplant follow up as interphase FISH.

The technique is being increasingly used by more and more investigators for the analysis of different tumors types where the application conventional cytogenetic methods are cumbersome. Though there are some limitations with this technique the foremost being the synthesis of probes which requires high accuracy and skill, further the technique is little expensive as the chemicals used are costly. 

For the further details of the techniques one is referred to the recent literature.

CURRENT CONCERNS

This year the MoEF announced an Environment Protection Fund on June 5, to create mass awareness. On this day the ministry also announced a 15-25% increase in funds for soil and water conservation (Down to Earth, June 30, 2000).

REGULATORY TRENDS

The balance of power in research collaboration between scientists in industrialized and developing countries could be redressed by adopting an international code of ethics, according to French research agency.

Phillippe Lazar, president of the Institut de Recherche pour le Development (IRD), the French National Agency for Scientific Research for Development, has drawn up a draft text setting out a series of broad principles. Lazar has informally presented it to several other countries worldwide. Ultimately, an international declaration could be one possibility, though at present the proposals are essentially a list of good intentions and need more work on the details. The declaration would not be legally binding.

Main points of the draft declaration:

IN A LIGHTER VEIN

Sayings We'd like on inspirational posters

MINIPROFILE OF POTASSIUM CYANIDE

Pottassium cyanide (KCN) the most infamous toxin of all known poisons, has a molecular weight of 65.12 This chemical often used in Preparation of mirrors, chemicals, photography, fumigation, extraction of silver, gold electroplating, gilding of precious metals, soldering, hardening of metals, copper, zinc and bronze platings. It is a White hygroscopic crystals with faint odour of almonds. b.p. 1625 °C; m.p. 635 °C; r.d. (water=1) 1.5; sol. In water, g/100 ml at 20 °C: 75. Aqueous solution is strongly alkaline. Reaction with acids violent, toxic flammable HCN gas liberated. Corrosive to Al and Zn, incompatible with strong oxidants. When heated to decomposition emits very toxic fumes of CN- and Nox. Incompatible with I2, alkaloids, sodium nitrite, perchloryl fluoride, NCl3.

Uses:

Occupational Safety Parameters:

Personal Protective Equipments: Protective gloves, protective clothing, face shield, breathing apparatus.

STEL: 5 mg/m3.

Environmental Risk: 

Humans: Symptoms of illness : 560 ppm/70 kg/1.5 M.
Severe toxic symptoms : 560 [ppm/70 kg/8.5 M.

Bioaccumulation reported in smokers and industrial workers.

Environmental Quality Standards

W.E.C.: 4.7 ppm.
Aquatic Toxicity Rating : TLm 96: <10 ppm.
Occupational exposure recom. Std. : Air: CL5 mg/m3/10 M.
Persistence in the Environment:

Biotransformation to thiocyanate is reported.
Half life for the conversion of cyanide to thiocyanate from a non lethal dose in man is 20-60 M.

Toxicity Data:

orl-hmn LDLO: 2857 mg/kg
orl-rat LD50: 10 mg/kg
ipr-rat LD50: 4 mg/kg
orl-mus LD50: 8500 ug/kg
orl-rbt LD50 : 5 mg/kg
scu-rat LD50: 9 mg/kg

Disaster Management:

Collect spilled substance, sweep up the remainder

Packaging and Labelling

Unbreakable packaging.
UN: 1680
Label: Poison.

Storage:

Away from acids, dry, ventillation.

Transport:

Poison label required; TREMCARD for potassium cyanide to be carried by the driver of the vehicle.

DO YOU KNOW

For the soft drink industry, 55% of total material costs is spent on packaging materials
(Connor JM & Schiek WA (1997) Food Processing An Industrial Powerhouse in Transition. John Wiley and Sons N. York.)

BOOK STOP

Phytoremediation of Toxic Metals
I.Raskin and B.D. Ensley
John Wiley & Sons, Inc
2000, pages: 304
ISBN 0-471-19254-6

This collection of technical papers explores various aspects of phytoremediation: the use of plants to remove contaminants from the soil. It also includes information on the biological and molecular processes involved in phytoremediation.

The Chemistry of Pollution
G. Fellenberg
John Wiley & Sons, Inc
2000, pages: 192
ISBN 0-471-61391-6

The book surveys the chemical aspects of pollutants in air, water and soil. It covers common toxic such as carbon monoxide (CO), sulphur dioxide (SO2) and heavy metals. It also discusses chemical processes that affect the toxicity of compounds in food and consumer goods and includes a brief section on radioactivity.

Environmental Toxicants: Human Exposures and Their Health Effects.
M. Lippmann
John Wiley & Sone, Inc
2000, pages : 987 
ISBN 0-471-29298-2

This book summarizes the characteristics of chemical contaminants, including their physical properties, techniques for measuring environmental concentrations and the routes of human exposure through air, water, food or direct contact. It addresses the problems associated with estimating exposure rates and the relationship between exposure and adverse health effects.

State of the World 2000
Worldwatch Institute
1776, Massachusetts Ave.
NW, Washington, DC 20036-1904, USA
2000, pages: 262
ISBN 0-393-31998-9

This is the Worldwatch Institute's 17th annual report. The authors call for rapid transition to an environmentally sustainable economy, in order to avoid permanent damage to the natural systems that support global civilization. They recommend ways to use political systems to manage the complex relationship between the global economy and the Earth's ecosystems.

ON THE WEB

http://www.leeds.ac.uk/mbiology/fullproj/proj1.htm 

Developed as a Leeds University student project, this site contains a review of Medical Microbiology on the Web. For those interested, it also contains a nice 'history of the Internet' section.

http://www.medmicro.mds.qmw.ac.uk/underground/ 

The Microbial underground collection of Web pages covers microbiology, molecular biology and medicine on the Web. Although no longer supported, the site still has many useful URLs.

http://www.osf-facts.org/ 

This is the home page for the authors of the book "Our Stolen Future", published in 1996 that explores endocrine disruption. The hypothesis is that there are chemicals present in the environment of humans and wildlife that, by virtue of their ability to interact with the endocrine system, are causing a variety of adverse health effects. The site contains many links to existing and new research in this field.

www.indexedvisuals.com

This is a searchable online index of stock medical illustration and visuals. The site contains artists' drawings and photographs covering a vast array of subjects from DNA helices to "See Thru' Man". All images are owned by the artist who created them and cannot be used without permission.

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