Team:Cornell/project/background/lead

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<h1 style="margin-top: 0px;">Health Risks</h1>
<h1 style="margin-top: 0px;">Health Risks</h1>
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Lead has no known function, and therefore no place, in the human body<sup>[4]</sup>. The lack of any robust, evolved system to deal with lead means that when it enters the organism, it will not be filtered naturally, and instead act as a disruptive, persistent, and often unnoticed antagonist to normal function. What makes lead so insidious? As it accumulates, lead will begin to take the place of other metals in biochemical reactions, replacing zinc or calcium when it is available for chemical reactions. In fact, “Lead binds to calcium-activated proteins with much higher (105 times) affinity than calcium.<sup>[10]</sup>” As a result, 75-90% of lead body load is in mineralizing tissues such as teeth and bones.
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Mercury is usually released into the environment by manufactories as emissions or waste. Eventually this mercury is discharged into the water bodies and then is converted by bacteria living in the sediment into methyl mercury. Methyl mercury can be ingested by smaller aquatic plants and animals. The danger here is that, through biomagnification, animals higher in the food chain will have larger concentrations of methyl mercury in their systems. This is dangerous especially for large fish, birds, and humans. Additionally, through bioaccumulation, small amounts of consumed toxins can build up within one’s system over time, leading to mercury poisoning. The most common form of mercury poisoning comes from methyl mercury. According to the Environmental Protection Agency, almost everyone in the world has trace amounts of methyl mercury in their bodies because of its abundance in our environment, but in larger concentrations, it can be dangerous.
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Because of these issues, the United States’ Environmental Protection Agency, which was tasked to set safe levels of chemicals in drinking water by the 1974 Safe Drinking Water Act, has set 0 as the Maximum Contaminant Level Goal for lead. The U.S. Environmental Protection Agency sets the maximum allowable lead concentration at .015 mg/L (74.8 nM)<sup>[6]</sup>.  Any concentration above the set maximum requires additional treatment for removal of lead.  On January 4th, 2014 a new provision of the Safe Drinking Water Act requires that any pipe used for the transport of potable water must contain less than 0.25% lead--a reduction from 8% under the previous law.  Lowering levels of lead in piping will help to reduce lead in drinking water - especially since lead piping is the greatest cause of consumed lead in the US - but environmental routes of pollution still exist.
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Lead is especially dangerous for children, as their porous GI tracts, and the increased vulnerability and volatility of their developing body systems make them highly susceptible to the disruptive effects of even small amounts of lead. It also takes them much more time to clear it: the half-life of lead in the adult human body is 1 month, but 10 months in a child’s <sup>[5]</sup>. Low-level exposure can be quite harmful: an increase in blood lead level from 10μg/dL to 20μg/dL is associated with an almost 3-point drop in IQ all on its own<sup>[8]</sup>. Lead has also been shown to inhibit hippocampal long-term potentiation, a neural mechanism required for learning<sup>[8]</sup>.
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<b><font size=3>Side Effects of Mercury Poisoning:</font></b><br><br>
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Common effects in children: gastrointestinal distress, anemia, kidney failure, irritability, lethargy, learning disabilities, erratic behavior.<br>
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<b>For infants and children:</b>
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Common effects in adults: gastrointestinal distress, weakness, pins and needle, kidney failure <br>
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Extreme cases: neurological damage, death
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<li>Impaired neurological development</li>
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<li>Impaired cognitive thinking, memory, attention, and language skills</li>
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<li>Impaired fine motor and spatial visual skills</li>
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<b>For adults:</b>
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<li>"pins and needles” in the hands, feet, and around the mouth</li>
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<li>impairment of the peripheral vision</li>
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<li>lack of coordination of movements</li>
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<li>impairment of speech and hearing</li>
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<li>muscle weakness</li>
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<b>Extreme cases of high mercury poisoning:</b><sup>[3]</sup>
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<li>Kidney and respiratory failure</li>
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<li>Death</li>
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Onondaga Lake Park: Syracuse, NY
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<h1>Case Studies</h1>
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According to the Blacksmith Institute’s 2010 report on the world’s worst pollution problems, lead is the world’s number one toxic threat with an estimated global impact of 18 to 22 million people, more than the population of Syria<sup>[11]</sup>. Lead has long been in use in numerous industries that manufacture products intended for consumption by average families. Famously, tetraethyl lead was added to gasoline (hence leaded gasoline) to improve its octane rating and to increase longevity of motor vehicle components, a practice that began in the United States in 1923, continued through until regulations saw implementation in the 1970s, finally ending with a zero-tolerance ban through the Clear Air Act in 1996. A 1988 report to Congress by the Agency for Toxic Substances and Disease Registry estimated that 68 million children had toxic exposure to lead from lead gasoline between 1927-1987. <sup>[7]</sup>
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<b>Onondaga Lake:</b>
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Commonly known as the “Most Polluted Lake in America”, Onondaga Lake suffers from industrial waste and sewage pollution (i.e. ammonia and phosphorus which cause high algal blooms and suffocation of other organisms in the Lake).
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Other sources of lead include leaded paint, dust that gathers on lead products, contaminated soil, and others. Since lead cannot be absorbed through contact with skin, the metal must be consumed in some form for it to be toxic. Unfortunately, lead tastes sweet. This means that flaking lead paint or the dust that forms on vinyl blinds imported before 1997 might be consumed repeatedly. In fact, the United States Consumer Product Safety Condition found that if a child ingested dust from less than one square inch of blind a day for about 15 to 30 days they could have blood lead levels at or above 10μg/dL <sup>[9]</sup>.  
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Since the 1800s Allied Chemical, recently succeed by Honeywell International, is credited for dumping a total of 165,000 lbs of mercury into the lake, resulting in the contamination of about 7 million cubic yards of lake-bottom sediments.<sup>[4]</sup> Their continuous polluting only ceased in the last few decades and has fomented tragic damage to the environment.<sup>[4]</sup>
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Lead can usually only enter the body through ingestion, which is why pollution of drinking water supplies is of primary concern. When ingested at high enough concentrations, lead can be acutely toxic causing neurological damage and death. In 2008, 18 children in Dakar, Senegal died of acute lead poisoning associated with the recycling of lead car batteries.<sup>[2]</sup> Others associated with the recycling facility displayed symptoms ranging from an upset stomach to involuntary convulsions.<sup>[2]</sup>
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Mercury contamination usually is caused by industrial emissions. The mercury enters the environment as an industrial emission and then moves through the water system before entering the lake. Once in the lake, the mercury is transformed by sediment-dwelling bacteria into methyl mercury, which has a high tendency to bioacculumate in aquatic life.<sup>[5]</sup> Even now, the State Health Department advises staying clear of eating any fish that come out of the Lake. In addition, through biomagnification, the methyl mercury has made it’s way up the food chain and has been found in bats and birds surrounding Onondaga Lake area. Researchers found that the Spotted-Sand piper was the most affected bird.<sup>[6]</sup> The levels of mercury found in the animals is so high that only about 20% of all birds’ chicks survive. Furthermore, scientists have reasons to believe that the mercury poisoning will continue to work its way up the food chain unless direct action is taken.
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<b>Remediation Efforts:</b>
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The Upstate Freshwater Institute has been working to prevent the mobilization of methyl mercury from the deep sediments of the Lake. To do so, they have been adding a common agricultural fertilizer, calcium nitrate, solution to the bottom on the lake, which has been successful in lowering the concentration of mercury in fish dramatically.<sup>[7]</sup>  In addition, Honeywell International has been working since 2012, 24 hours a day, 6 days a week, between April and November on dredging the contaminated mud on the bottom of the lake.  Earlier this summer, Honeywell attorneys said that there were 800,000 cubic yards of dredging to complete and they estimated being able to complete this amount by the end of the season in 2014. The cost of such efforts is estimated at $451 million.<sup>[8]</sup> The Metropolitan Syracuse Wastewater Treatment Plant, which dumps about 20% of the water that goes into Onondaga Lake, has spent millions of dollars on making sure that there is no further lake pollution. Although major progress has occurred on the mercury levels on Onondaga Lake. It takes millions of dollars of remediation efforts to fix the polluted ecosystem and years for the biomagnification effects to resolve themselves.<sup>[9]</sup> has been successful in lowering the concentration of mercury in fish dramatically.<sup>[10]</sup>
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<b>Ithaca Gun Factory:</b> Originally founded in 1880, a towering brick smokestack stands as the only remnant of the once-bustling production facility, famous across the world for its shotguns and storied history. The area underwent a lead cleanup project in 2004, but two years later surface levels of lead were tested and contamination was as high as 184,000 ppm--460 times the goal set by the EPA for the 2004 cleanup.
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<h1>Current Remediation Techniques</h1>
<h1>Current Remediation Techniques</h1>
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Although the EPA is working with the National Institute of Standards and Technology to reduce mercury use and pollution, there are still a number of already contaminated areas that are being remediated now.<sup>[11]</sup>
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<b>Nitrate Immobilization:</b>
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The use of calcium nitrate to prevent methyl mercury from moving throughout bodies of water.<sup>[12]</sup>
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<b>Dredging:</b>
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Mercury containing sediments are removed or dug up from the lake bottom.<sup>[12]</sup>
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<b>ISMS (In Situ Mercury Stabilization):</b>
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Developed by Brookhaven researchers, the ISMS treats and removes mercury content from the soil, sludge, and other industrial waste; therefore stopping mercury from entering the water source.<sup>[13]</sup>
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<b>Thermal desorption:</b>
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This involves heating the contaminated soil to high temperatures so that the mercury will vaporize away and can be separated from the soil.<sup>[13]</sup>
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<h1>CBP4</h1>
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<h1><i>merT/merP</i></h1>
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The transport protein being utilized for our project is the calmodulin-binding protein <i>CBP4</i> from <i>Nicotiana tabacum</i>.  This protein is structurally similar to non-selective membrane channel proteins from other eukaryotes and has been shown to confer nickel tolerance and lead hypersensitivity.<sup>[1]</sup> Transgenic plants overexpressing <i>NtCBP4</i> were found to have increased uptake of Pb<sup>2+</sup> ions into cells, likely leading to the increased toxicity.<sup>[1]</sup>  While it has been suggested that <i>NtCBP4</i> could possibly be used for bioremediation purposes and other attempts have been made at lead removal from water using genetically engineered organisms, to the best of our knowledge no attempt has been made at utilizing <i>NtCBP4</i> for precisely this purpose.<sup>[1],[2],[3]</sup>. We believe that the specificity of this transport protein for lead and its readily available sequence make it an ideal candidate for bioremediation.
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The transport system being utilized for this project is a combination of the <i>merT</i> and <i>merP</i> genes from the transposon TN501 of <i>Pseudomonas aeruginosa</i>.  The genes  <i>merT</i> and <i>merP</i> are part of the <i>mer</i> operon which helps <i>P. aeruginosa</i> resist mercury toxicity.<sup>[14]</sup>  These two membrane proteins work together to transport Hg<sup>2+</sup> ions into the cell.<sup>[1]</sup>  Systems for sequestration of mercury have been successfully developed utilizing <i>merT</i> and <i>merP</i>.<sup>[15,16,17]</sup>  We hope to improve upon these systems by combining the <i>merT</i> and <i>merP</i> genes with a different regulatory system and by making all these genetic parts modular.
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Revision as of 04:11, 16 October 2014

Cornell iGEM

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Project Background

Health Risks

Mercury is usually released into the environment by manufactories as emissions or waste. Eventually this mercury is discharged into the water bodies and then is converted by bacteria living in the sediment into methyl mercury. Methyl mercury can be ingested by smaller aquatic plants and animals. The danger here is that, through biomagnification, animals higher in the food chain will have larger concentrations of methyl mercury in their systems. This is dangerous especially for large fish, birds, and humans. Additionally, through bioaccumulation, small amounts of consumed toxins can build up within one’s system over time, leading to mercury poisoning. The most common form of mercury poisoning comes from methyl mercury. According to the Environmental Protection Agency, almost everyone in the world has trace amounts of methyl mercury in their bodies because of its abundance in our environment, but in larger concentrations, it can be dangerous.
Side Effects of Mercury Poisoning:

For infants and children:
  • Impaired neurological development
  • Impaired cognitive thinking, memory, attention, and language skills
  • Impaired fine motor and spatial visual skills

For adults:
  • "pins and needles” in the hands, feet, and around the mouth
  • impairment of the peripheral vision
  • lack of coordination of movements
  • impairment of speech and hearing
  • muscle weakness

Extreme cases of high mercury poisoning:[3]
  • Kidney and respiratory failure
  • Death

Case Study

Onondaga Lake: Commonly known as the “Most Polluted Lake in America”, Onondaga Lake suffers from industrial waste and sewage pollution (i.e. ammonia and phosphorus which cause high algal blooms and suffocation of other organisms in the Lake).

Since the 1800s Allied Chemical, recently succeed by Honeywell International, is credited for dumping a total of 165,000 lbs of mercury into the lake, resulting in the contamination of about 7 million cubic yards of lake-bottom sediments.[4] Their continuous polluting only ceased in the last few decades and has fomented tragic damage to the environment.[4]

Mercury contamination usually is caused by industrial emissions. The mercury enters the environment as an industrial emission and then moves through the water system before entering the lake. Once in the lake, the mercury is transformed by sediment-dwelling bacteria into methyl mercury, which has a high tendency to bioacculumate in aquatic life.[5] Even now, the State Health Department advises staying clear of eating any fish that come out of the Lake. In addition, through biomagnification, the methyl mercury has made it’s way up the food chain and has been found in bats and birds surrounding Onondaga Lake area. Researchers found that the Spotted-Sand piper was the most affected bird.[6] The levels of mercury found in the animals is so high that only about 20% of all birds’ chicks survive. Furthermore, scientists have reasons to believe that the mercury poisoning will continue to work its way up the food chain unless direct action is taken.

Remediation Efforts: The Upstate Freshwater Institute has been working to prevent the mobilization of methyl mercury from the deep sediments of the Lake. To do so, they have been adding a common agricultural fertilizer, calcium nitrate, solution to the bottom on the lake, which has been successful in lowering the concentration of mercury in fish dramatically.[7] In addition, Honeywell International has been working since 2012, 24 hours a day, 6 days a week, between April and November on dredging the contaminated mud on the bottom of the lake. Earlier this summer, Honeywell attorneys said that there were 800,000 cubic yards of dredging to complete and they estimated being able to complete this amount by the end of the season in 2014. The cost of such efforts is estimated at $451 million.[8] The Metropolitan Syracuse Wastewater Treatment Plant, which dumps about 20% of the water that goes into Onondaga Lake, has spent millions of dollars on making sure that there is no further lake pollution. Although major progress has occurred on the mercury levels on Onondaga Lake. It takes millions of dollars of remediation efforts to fix the polluted ecosystem and years for the biomagnification effects to resolve themselves.[9] has been successful in lowering the concentration of mercury in fish dramatically.[10]

Current Remediation Techniques


Although the EPA is working with the National Institute of Standards and Technology to reduce mercury use and pollution, there are still a number of already contaminated areas that are being remediated now.[11]
Nitrate Immobilization: The use of calcium nitrate to prevent methyl mercury from moving throughout bodies of water.[12]
Dredging: Mercury containing sediments are removed or dug up from the lake bottom.[12]
ISMS (In Situ Mercury Stabilization): Developed by Brookhaven researchers, the ISMS treats and removes mercury content from the soil, sludge, and other industrial waste; therefore stopping mercury from entering the water source.[13]
Thermal desorption: This involves heating the contaminated soil to high temperatures so that the mercury will vaporize away and can be separated from the soil.[13]

merT/merP


The transport system being utilized for this project is a combination of the merT and merP genes from the transposon TN501 of Pseudomonas aeruginosa. The genes merT and merP are part of the mer operon which helps P. aeruginosa resist mercury toxicity.[14] These two membrane proteins work together to transport Hg2+ ions into the cell.[1] Systems for sequestration of mercury have been successfully developed utilizing merT and merP.[15,16,17] We hope to improve upon these systems by combining the merT and merP genes with a different regulatory system and by making all these genetic parts modular.

References


  1. Arazi, T., Sunkar, R., Kaplan, B., & Fromm, H. (1999). A tobacco plasma membrane calmodulin-binding transporter confers Ni2 tolerance and Pb2 hypersensitivity in transgenic plants. The Plant Journal, 171-182
  2. Song, W., Sohn, E., Martinoia, E., Lee, Y., Yang, Y., Jasinski, M., Forestier, C., Hwang, I., & Lee, Y. (2003). Engineering tolerance and accumulation of lead and cadmium in transgenic plants. Nature Biotechnology, 914-919.
  3. Eapen, S., & Dsouza, S. (2004). Prospects Of Genetic Engineering Of Plants For Phytoremediation Of Toxic Metals. Biotechnology Advances, 97-114.
  4. "Public Health - Seattle & King County." Lead and Its Human Effects. King County Government, n.d. Web. 15 Oct. 2014.
  5. "Pathophysiology and Etiology of Lead Toxicity ." Pathophysiology and Etiology of Lead Toxicity. Medscape, n.d. Web. 15 Oct. 2014.
  6. "Consumer Factsheet on Lead in Drinking Water." Home. Environmental Protection Agency, n.d. Web. 15 Oct. 2014.
  7. "Why Lead Used to Be Added To Gasoline." Today I Found Out RSS. N.p., n.d. Web. 15 Oct. 2014.
  8. Schwartz, Joel. "Low-level lead exposure and children′ s IQ: a metaanalysis and search for a threshold." Environmental research 65.1 (1994): 42-55.
  9. "CPSC Finds Lead Poisoning Hazard for Young Children in Imported Vinyl Miniblinds." U.S. Consumer Product Safety Commission. US Consumer Product Safety Commission, n.d. Web. 15 Oct. 2014.
  10. "Lead Induced Encephalopathy: An Overview." International Journal of Pharma and Bio Sciences 2.1 (2011): 70-86. Web. http://ijpbs.net/volume2/issue1/pharma/_6.pdf.
  11. McCartor, A., & Becker, D. (2010). Blacksmith Institute's World's Worst Pollution Problems 2010. Retrieved from: http://www.worstpolluted.org/files/FileUpload/files/2010/WWPP-2010-Report-Web.pdf