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Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

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The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

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A cone snail hunting and ingesting a fish. The Biodiversity pages of the BioInteractive website have videos of several different species hunting.
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Figure 1: A cone snail hunting and ingesting a fish. The Biodiversity pages of the BioInteractive website have videos of several different species hunting.

Mentions: Analgesics like aspirin are an important group of painkillers primarily for treating relatively minor aches and pains. There is also a great need for treating pain-associated chronic debilitating illness as well as the intense pain that can follow certain traumatic injury or some surgical procedures. The best-known drugs for chronic pain management are the opioids and other narcotics, which also have the well-known downside of being addictive. Have a look at the University of Utah Learn Genetics website for an excellent feature on addiction (http://learn.genetics.utah.edu/content/addiction). There is a long-standing need for drugs that manage chronic pain more effectively, with fewer side effects, and without being addictive. The opening scene of my first story features a consummate predator stalking her prey (Figure 1). But this predator is a snail, of the genus Conus. The cone snails are a large and diverse group of marine mollusks. They prey on worms, other snails, and even fish, but like all snails, their locomotion is slow. Unlike more familiar predators, they don't have strong jaws and sharp teeth. The cone snails have evolved several fascinating hunting strategies that include netting and harpooning prey. They depend on delivering a complex mixture of toxins that disrupt the nervous and neuromuscular systems of their prey. The venom must work quickly to overcome prey that are fast and strong. To avoid delay or failure, the toxins overpower the prey's neuromuscular system with dozens of different peptide toxins. It's memorable to watch these hunters in action, and you can find several videos on the Howard Hughes Medical Institute (HHMI) BioInteractive webpages at www.hhmi.org/biointeractive/biodiversity/video.html (Figure 1). Jason Biggs of the University of Guam has a very nice 14-min video presentation on the diversity of hunting styles of different cone snail species (www.hhmi.org/biointeractive/biodiversity/2009_versatile_hunters.html).


Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

A cone snail hunting and ingesting a fish. The Biodiversity pages of the BioInteractive website have videos of several different species hunting.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105917&req=5

Figure 1: A cone snail hunting and ingesting a fish. The Biodiversity pages of the BioInteractive website have videos of several different species hunting.
Mentions: Analgesics like aspirin are an important group of painkillers primarily for treating relatively minor aches and pains. There is also a great need for treating pain-associated chronic debilitating illness as well as the intense pain that can follow certain traumatic injury or some surgical procedures. The best-known drugs for chronic pain management are the opioids and other narcotics, which also have the well-known downside of being addictive. Have a look at the University of Utah Learn Genetics website for an excellent feature on addiction (http://learn.genetics.utah.edu/content/addiction). There is a long-standing need for drugs that manage chronic pain more effectively, with fewer side effects, and without being addictive. The opening scene of my first story features a consummate predator stalking her prey (Figure 1). But this predator is a snail, of the genus Conus. The cone snails are a large and diverse group of marine mollusks. They prey on worms, other snails, and even fish, but like all snails, their locomotion is slow. Unlike more familiar predators, they don't have strong jaws and sharp teeth. The cone snails have evolved several fascinating hunting strategies that include netting and harpooning prey. They depend on delivering a complex mixture of toxins that disrupt the nervous and neuromuscular systems of their prey. The venom must work quickly to overcome prey that are fast and strong. To avoid delay or failure, the toxins overpower the prey's neuromuscular system with dozens of different peptide toxins. It's memorable to watch these hunters in action, and you can find several videos on the Howard Hughes Medical Institute (HHMI) BioInteractive webpages at www.hhmi.org/biointeractive/biodiversity/video.html (Figure 1). Jason Biggs of the University of Guam has a very nice 14-min video presentation on the diversity of hunting styles of different cone snail species (www.hhmi.org/biointeractive/biodiversity/2009_versatile_hunters.html).

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

Show MeSH