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Scientific Achievements

Scripps Research Institute scientists have led numerous seminal studies. To highlight only a few of these as an example of their extraordinary work, over the last decades the institute’s investigators have made breakthroughs in studies of:

  • Addiction, providing evidence that the drug gabapentin is safe and effective in treating alcohol dependence. The medication, which is already approved by the U.S. Food and Drug Administration for treating seizures and pain, is the only medication shown to support abstinence and improve sleep and mood in people who are eliminating or reducing their alcohol intake. (Roberto, Koob, Siggins labs, 2008; clinical trial results, Mason lab, 2013)
  • HIV/AIDS, elucidating the structure of a number of human antibodies that neutralize many different strains of the virus—work that may one day contribute to an HIV vaccine.  (Wilson, Burton labs (with Ollmann Saphire), 2001 – 2014).
  • Drug discovery, creating a powerful new chemical toolkit that radically simplifies the creation of potential new drug candidates. The toolkit has already been adopted by drug companies and academic laboratories to speed the development of new therapies. (Baran lab, 2012)
  • Multiple sclerosis, developing the first of a new class of highly selective comopunds that effectively suppresses the severity of multiple sclerosis in animal models.  (Burris lab, 2011).
  • “Swine flu,” solving the structure of a key protein from the virus that caused the recent H1N1 influenza epidemic. The structure reveals that the virus shares many features with influenza viruses common in the early 20th century, helping to explain why, in general, older individuals have been less severely affected by the recent outbreak than younger ones. (Wilson lab, 2010)
  • Obesity, showing for the first time that addiction-like molecular changes are behind the compulsion to overeat. (Zorrilla lab, 2009; Kenny lab, 2010)
  • Regenerative medicine, reporting a breakthrough in which scientists successfully created live mice from mouse skin cells, without using embryonic stem cells or cloning techniques that require eggs. This milestone opens the door to the development of exciting therapies, such as using a patient's own cells to grow replacement organs. (Baldwin lab, 2009)
  • Deafness, elucidating the action of a protein, harmonin, which is involved in the mechanics of hearing. Defects in such genes can cause devastating diseases, such as Usher's syndrome, which is characterized by deafness, gradual vision loss, and kidney disease. (Mueller lab, 2009)
  • Huntington’s disease, developing an agent that reversed Huntington’s disease symptoms in mice, with minimal toxicity. (Thomas, Gottesfeld labs, 2008)
  • Blindness, achieving complete inhibition of new blood vessel growth in animal models of neovascular eye diseases and a vascular brain tumor with little or no effect on normal tissue. (Friedlander lab, 2007)
  • A large class of medically relevant compounds known as G protein-coupled receptors (GPCR),determining the first human structure of this type of receptor, called β2-adrenergic GPCR. Science magazine named the work as one of the top ten breakthroughs of the year. (Stevens lab, 2007)
  • Amyloid disease, developing the first disease-modifying agent targeting the underlying cause of this type of disorder, a class that includes Alzheimer’s disease. A drug based on this finding (tafamidis by FoldRX/Pfizer, Inc.) has been approved for use in Europe to treat a type of inherited disease known as Transthyretin amyloidosis. (Kelly lab, 2003)
  • Atherosclerosis, reporting evidence for the production of ozone in fatty atherosclerotic plaques taken from diseased arteries and describing how inflammation can lead to the production of reactive oxygen species such as ozone, triggering such pathological changes in the body. (Lerner, Wentworth labs, 2003)
  • Revolutionary chemical methodology, inventing “click chemistry,” a powerful and original new approach to drug design in which the chemical components used "click" together to bind as easily and reliably as the two pieces of a seatbelt buckle.  The buckle works no matter what is attached to it as long as the two pieces can reach one another. (Sharpless lab, 2002)
  • Unnatural amino acids, creating forms of bacteria and yeast with a genetic code that uses unusual amino acid building blocks to synthesize proteins—in addition to the 20 found in nature. Beyond its theoretical importance, the work provides scientists with a powerful new tool for research as well as for creating new protein therapeutics, forming the basis of the biotechnology company Ambrx. (Schultz lab, 2001)
  • Cancer drug synthesis, completing the total synthesis of the anti-cancer drug Taxol®, approved by the Food and Drug Administration for the treatment of ovarian cancer. Before the synthesis, Taxol®, whose active compound was first isolated from the bark of the rare Pacific yew, demonstrated great promise as a cancer treatment, but its full impact was prevented by the problem that treating one patient required the destruction of more than three of these precious trees. Another example of a remarkable feat of synthesis includes developing an inexpensive and in many ways astonishing new method for economically synthesizing cortistatin A. This steroid, which was isolated in 2006 from a marine sponge discovered over 100 years ago, has shown huge promise for treating conditions ranging from macular degeneration to cancer. (Taxol®, Nicolaou lab, 1994; cortistatin A, Baran lab, 2008)
  • Leukemia and multiple sclerosis, first developing and successfully tested the anti-leukemia drug 2-CdA (marketed under the name cladribine (Leustatin®) by Ortho Biotech, Inc., an affiliate of Johnson & Johnson). An intravenous medication with remarkably few side effects, 2-CdA now cures or produces many years of freedom from hairy cell leukemia in almost all those receiving treatment. The compound was reformulated for use in multiple sclerosis, and is now under consideration by the F.D.A. as potentially the first oral therapy for this condition (hairy cell leukemia, U.S. Food and Drug Administration (F.D.A.) approval, 1993, resulting from Carson lab work, late 1970s; multiple sclerosis, Ernest Beutler lab, 1990s).
  • Respiratory distress syndrome, synthesizing surfactant, a lung material that keeps air sacs open and prevents respiratory distress syndrome, a major killer of premature babies and adults. A therapy based on this technology (lucinactant/Surfaxin, Discovery Laboratories) was approved by the U.S. Food and Drug Administration in March 2012. The compound also has potential to help people with cystic fibrosis, adults with acute lung injury, and patients with acute asthma. (Cochrane lab, 1990s)
  • Gaucher’s disease, cloning the gene for the enzyme that is deficient in people with the potentially fatal inherited disorder, and developed a method to predict the severity of the disease. (Ernest Beutler lab, 1991)
  • Catalytic antibodies, pioneering the development of catalytic antibodies—antibodies designed to function as enzymes in catalyzing specified chemical reactions, a method thought impossible using classical techniques. This work led to a new approach to drug design for cancer and other diseases, now being developed by the company COVX, now part of Pfizer, Inc. Here, catalytic antibodies, large, soluble molecules that remain in the body for long periods of time, are physically combined with small molecule drugs and peptides, which can kill disease-causing cells but may be expelled from the body too quickly to be effective as a therapy. These hybrid molecules have the desirable properties of each—killing disease-causing cells and staying in circulation long enough to dramatically enhance the drug's effectiveness. (catalytic antibodies, Lerner, Schultz labs, 1988; hybrid molecules, Barbas, Lerner labs, 1995)
  • A powerful drug-discovery technique, called combinatorial antibody library technology, providing a way to identify human antibodies—secreted proteins that help the body clear infections—that might be used therapeutically. By searching among billions of antibody variants taken from human blood samples, the method enables scientists to identify human antibodies that bind to a particular target involved in a particular disease. This research resulted in the company Cambridge Antibody Technology (now MedImmune, part of AstraZeneca), which developed the drug adalimumab (Humira®) for the treatment of intractable autoimmune diseases including rheumatoid arthritis. Belimumab (Benlysta®) was also approved by the US FDA in 2011 to treat lupus, becoming the first new drug to treat the chronic, life-threatening inflammatory disease in more than 50 years. Multiple other potential therapies for conditions from hepatitis C to cancer are under development thanks to this technology. (Lerner lab, 1980s)
  • Polio, determining the complete, three-dimensional, atomic structure of the poliovirus. (1985, Hogle lab)
  • Hemophilia, developing a method to purify Factor VIII, a coagulation protein lacking in people with hemophilia A. Use of the purified concentrate greatly reduces the risk to hemophiliacs of infection from blood-borne AIDS, hepatitis, and other viral infections. (Zimmerman lab, 1982)