Team:Cornell/project/background/lead

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Revision as of 01:32, 18 October 2014

Cornell iGEM

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Project Background

Health Risks

Lead has no known biological function, and therefore no place in the human body[4]. 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.[10]” As a result, 75-90% of lead body load is in mineralizing tissues such as teeth and bones.

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)[6]. 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.

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 purge it from the body: the half-life of lead in the adult human body is 1 month, but 10 months in a child’s [5]. 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[8]. Lead has also been shown to inhibit hippocampal long-term potentiation, a neural mechanism required for learning[8].
Side Effects of Lead Poisoning:

For infants and children:
  • Impaired neurological development
  • Gastrointestinal distress
  • Anemia
  • Kidney failure
  • Irritability
  • Lethargy
  • Learning disabilities
  • Erratic behavior.
For adults:
  • Gastrointestinal distress
  • Weakness
  • Pins and needles
  • Kidney failure
Extreme cases of high lead poisoning
  • Neurological damage
  • Death

Case Studies

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[11]. 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[7]. 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.[7]

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 [9].

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.[2] Others associated with the recycling facility displayed symptoms ranging from an upset stomach to involuntary convulsions.[2]

Ithaca Gun Factory:


Originally founded in 1883 by Henry Baker, a towering brick smokestack stands as the only remnant of a once-bustling production facility. The Ithaca Gun Company was famous across the world for its shotguns used by Annie Oakley and John Philip Sousa. Throughout its history of production, the factory emitted immense amounts of lead into the surrounding ground. In fact, a 2003 EPA assessment found the need for the removal of 2370 tons of the heavy metal. This mass is roughly equivalent to that of a space shuttle before launch [11]. As a result, the Ithaca Gun Company area underwent a lead cleanup project in 2004. However, 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. The lead pollution seeped into the Cayuga Watershed and has been a common issue ever since [4]. Even more disturbing, this lead contamination is currently located directly next to Ithaca Falls, a popular swimming and fishing site for locals and Cornell students alike. Cornell University, which use to own this property, sold it to the town from $1, so that the EPA could declare it a national Superfunds site, and pay for the cleanup necessary in the years to come.

Current Remediation Techniques

cbp4

The transport protein being utilized for our project is the calmodulin-binding protein CBP4 from Nicotiana tabacum. 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.[1] Transgenic plants overexpressing NtCBP4 were found to have increased uptake of Pb2+ ions into cells, likely leading to the increased toxicity.[1] While it has been suggested that NtCBP4 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 NtCBP4 for precisely this purpose.[1],[2],[3]. We believe that the specificity of this transport protein for lead and its readily available sequence make it an ideal candidate for bioremediation.

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