Talk:Alan B. Scott

Expanding

In the process of expanding this article. Hoping to find additional biographical sources, and to add a list of awards and honors, as well as publications. I know I need to work on the "botox" section to provide a better chronology. Just wanted to get the info in there Tribe of Tiger ^{Let's Purrfect!} 05:34, 30 August 2019 (UTC)

Apologies for the series of increment edits. I edit on an Ipad, and it is easier to do a bit at a time. In future, I will endeavor to avoid the practise, and consolidate my edits. Tribe of Tiger ^{Let's Purrfect!} 23:45, 31 August 2019 (UTC)

@Tribe of Tiger: Below we have worked on compiling a complete description of Dr. Scott's contributions to science, education, honors, and more. We have included items currently on the page and expanded on some of them, as well as added a lot of new ideas not currently on the page. Please let us know your thoughts! Also, if you are having trouble accessing things in the reference list, please let me know. Thank you so much for your help! ****(unsigned note from Carlatocchini)****

@Carlatocchini:, Oh my, this is wonderful! Thanks, so much. It will take some time to digest. Please see your talk page for further comments, for now. I will get to work... Tribe of Tiger ^{Let's Purrfect!} 23:29, 5 September 2019 (UTC)

@Tribe of Tiger:, I saw your post on my talk page-- please stay safe! You, your mother, and all the people being affected by the hurricane are in my thoughts. I cannot thank you enough for your help. I've edited the references, so I think they should all be updated with the correct links. Please let me know if there is anything else I can do to help!Carlatocchini (talk) 17:42, 6 September 2019 (UTC)

Ref 14 & 15

Carla, ref #14, does not have a url. However, I note that the url for ref #15 connects to the paper by JK Tsui on torticollis, NOT the one by LA Koman on cerebral palsy. So I moved the url on torticollis to the correct place at #14. Can you locate the correct url for ref#15, cerebral palsy? Thanks!

As an update, I have formatted all the refs and added them to the text as inline citations, which is the most time-consuming and techinically challenging part of "my" job. Next, I will start moving text from my sandbox into the article itself. I chose to do all the work in my sandbox, so I could correct my formatting errors there, rather than in the article. Although I was quite careful, I would appreciate it if you would double-check my work, once it is in the article, to be sure I do indeed have the correct ref for each text section.

As you will see, I have added a section for education & updated with your info. Same for professional experience and honors. Added his date of birth, too.

Once I have added your excellent text, I can begin to copyedit and tinker if needed. Thus far, the only change I have made was to expand "chicks" to "baby chickens"! That's all, for now. Tribe of Tiger ^{Let's Purrfect!} 05:31, 6 September 2019 (UTC)

Additional information

Alan B Scott

Alan Brown Scott, MD (born 1932-07-13, Berkeley CA) is an ophthalmologist specializing in eye muscles and their disorders (strabismus), with a long career distinguished by bold and practical creativity in service to his patients and science.

Alan Scott is best-known as the groundbreaking inventor of Botox® [1]. He developed and manufactured botulinum type A neurotoxin initially to treat strabismus, naming it Oculinum™ (“eye aligner”). Botox, dubbed “medicine’s answer to duct tape”, has been found to be effective for muscle spasms and contractures, severe sweating and drooling, migraines, urinary incontinence, and many other disorders [2, 3]. In pursuit of new ways to help his patients, Scott made many basic scientific advances concerning eye muscles, their coordination, and their modifiability [egs: 4, 5-7].

Strabismus is misalignment of the eyes caused by imbalances in the muscles that rotate them. Balance can be restored by weakening a muscle that pulls too strongly, and Scott wanted to do this with a simple, low cost injection, rather than with conventional surgery under general anesthesia. To reach muscles behind the eye for injection, Scott and colleagues developed EMG-guided injection, which monitors muscle activity to guide needle placement [8].

Scott was fascinated by the prospect of turning "a deadly poison into a miracle drug for obscure but devastating eye diseases” [9]. Botox acts locally to block activity at neuromuscular junctions, paralyzing the injected muscles for several months, allowing it to be stretched by its opposing muscle (if there is one) and grow longer, while the opposing muscle muscle grows shorter, resulting in long-lasting re-alignment.

To appreciate the genius of Scott's work, consider that even a mind capable of identifying such a non-obvious treatment, and working out the medical, pharmacological, and practical aspects its safe application, would likely recoil from a procedure that involved pushing a hypodermic needle, without visual guidance, deep alongside the healthy eye of an awake patient for the purpose of injecting the most acutely toxic substance known.

Dr Scott and his colleagues are currently developing the anesthetic bupivacaine as an injectable treatment to strengthen, stiffen, and shorten weak eye muscles – effects roughly the opposite of Botox.

Biography

Education

University of California, Berkeley – AB, 1953

University of California, San Francisco – MD, 1956

University of Minnesota, Surgery – 1956-1957

University of Minnesota, Neurosurgery – 1957-1958

Stanford University, Ophthalmology – 1958-1961

Professional Experience

Smith-Kettlewell Eye Research Institute, Senior Scientist, 1961- 2013

Smith-Kettlewell Eye Research Institute, Director, 1982- 2004

California Pacific Medical Center, Vice-Chair Ophthalmology, 1997 - 2006

Strabismus Research Foundation, Director and Senior Scientist 2013 - present

Eidactics, Senior Scientist 2013 - present

Honors

Phi Beta Kappa (UC Berkeley)

Linksz Medal (International Strabismus Association)

Proctor Medal (Association for Research in Vision and Ophthalmology)

Costenbader Lecture (American Association of Pediatric Ophthalmology and Strabismus)

Parks Silver Medal (American Association of Pediatric Ophthalmology and Strabismus)

Lifetime Achievement Award (International Toxin Association)

Senior Honor Award (American Academy of Ophthalmology)

Major Contributions

Botulinum Toxin Treatment of Eye Muscles

Strabismus is a disorder of eye movement and alignment caused by imbalances in the actions of muscles that rotate the eyes. In many cases these imbalances can be corrected by weakening a muscle that pulls too strongly, or that has normal activity but overpowers an opposing muscle that has been weakened by disease or trauma. Conventional treatments are surgical, which restore balance by compensatory impairment: tissue is removed to tighten a muscle, and muscles are moved to relax them or to sacrifice one direction of action for another.

Muscles adapt to the lengths at which they are chronically held, so if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect. With good binocular vision, the brain mechanism of motor fusion (which aligns the eyes on a target visible to both) helps stabilize the corrected alignment [10].

Strabismus surgery has the undesirable side effect of scarring, which makes frequently needed followup surgeries more difficult, and may generally compromise the eye’s mechanics. Non-surgical injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and snake neurotoxins were therefore tried. Finally, inspired by Daniel Drachman’s [11] work with chicks at Johns Hopkins, Dr Scott and colleagues injected botulinum toxin into monkey extraocular muscles [12]. The result was remarkable: a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side-effects.

Botox is formed by spores of the bacteria Clostridium botulinum, which is found naturally in sediments as well as the intestinal tracts of some animals and fish. The drug binds to receptors in skeletal muscle, nerve endings, the brain, and some smooth muscle, preventing the release of the neurotransmitter acetylcholine. By blocking nerves from sending signals to the muscle to contract, Botox essentially paralyzes the muscles temporarily. After working-out techniques for preparing the toxin and assuring its sterility, potency, and safety, Scott was granted FDA approval for investigational use, and began manufacturing it in his San Francisco lab. He injected the first strabismus patients in 1977, reported its clinical utility [13], and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named OculinumTM (“eye aligner”).

Based on data from thousands of patients collected by 240 investigators, under the 1983 US Orphan Drug Act, Scott obtained FDA approval in 1989 to market Oculinum for clinical use in the United States to treat adult strabismus and blepharospasm. With the wide acceptance of OculinumTM, Dr. Scott had to “decide if he wanted to be in the pharmaceutical business business or be a research scientist”[9]. In 1991 he therefore sold rights to the drug to the pharmaceutical company Allergan, which rebranded it as Botox®, and promoted it initially as a cosmetic to smooth facial wrinkles.

Botulinum Toxin Treatment of Other Muscle Disorders

By 1982, eye muscles had been injected for strabismus and nystagmus (jerky, involuntary eye movements), eyelid muscles for retraction and blepharospasm (sustained, involuntary contractions of muscles around the eye), facial muscles for hemifacial spasm, and limb muscles for dystonia (sustained muscle spasm), all as predicted in Scott’s 1973 study.

Scott also injected the first cases of the painful, spastic twisting of the neck known as torticollis [14], but it was difficult to accept that the specificity and molecular tenacity that made ingested toxin so deadly also made it safe when injected into a target muscle, and no Bay Area physician would try Botox for the muscle contractures of stroke, dystonia, torticollis, or cerebral palsy, until L Andrew Koman of Wake Forest University in North Carolina pioneered its use to treat pediatric leg spasm in cerebral palsy [15].

Patient groups quickly spread the word that there were now effective treatments for previously untreatable motility disorders such as blepharospasm, which can result in functional blindness despite an otherwise normal visual system. Torticollis patients discovered that their pain could be markedly reduced, motility increased, and head position improved by toxin injection. But, in 1986, Oculinum Inc, Scott's micromanufacturer and distributor of botulinum toxin, was unable to obtain product liability insurance, and could no longer supply the drug. As stocks became exhausted, patients who had come to rely on periodic injections became desperate. For 4 months, pending resolution of liability issues, American blepharospasm patients traveled to Canadian eye centers for their injections [16].

Electrically Guided Injection

Precisely targeted eye muscle injections are useful for both diagnosis [8] and treatment [12], but the bodies of the 6 muscles that rotate the eye lie close together, adjacent to the eyeball, and are not normally visible. Scott and colleagues therefore developed EMG-guided injection, a system that uses a hypodermic needle that records the electrical activity of the muscle (the electromyogram or EMG) at its tip. The needle is introduced under local anesthesia, and as the awake patient looks in different directions, the pattern of muscle activity, played through a speaker, indicates when the belly of the target muscle has been entered, and the drug is then injected.

If the patient is not awake, movement-related EMG cannot be recorded. Scott and colleagues therefore developed another system in which the injection needle stimulates, rather than records, producing characteristic eye movements that identify the muscle in which the needle is placed.

Strengthening Eye Muscles

Botox injection can weaken and lengthen muscles, but weak, stretched muscles are often the primary problem in strabismus. Scott is therefore now developing the anesthetic drug bupivacaine as an injection to strengthen and shorten weak muscles. Bupivacaine injection stresses a muscle and triggers a growth process, analogous to how load-bearing exercise builds skeletal muscles.

Clinical studies over the past decade have demonstrated that bupivacaine injection in a weak muscle has a synergistic effect with Botox injected in its opposing muscle, resulting in permanent strabismus cures in many more cases [17-19]. Laboratory studies are underway to better understand the cellular effects of bupivacaine injection, and optimize its therapeutic benefits.

Blepherospasm

Blepharospasm is the uncontrollable closure of the eyes, which can leave sufferers functionally blind, despite the visual system itself being normal. The cause is unknown, and it may be present from birth or develop later in life. Botox injection can relieve the spasms, but leave patients unable to open their eyes or keep them open. Surgical lid elevation is the current treatment, but static repositioning impairs normal eye blinking and lid closure. Electrically stimulating the muscle that raises the eyelid could provide these patients with useful vision, and would be far superior to surgery, both functionally and cosmetically.

Dr Scott and his colleagues have therefore developed electrodes that are both safe and effective in animals tested with realistic, long-term stimulation regimens. Implantable pulse generators, approved for other applications, would be suitable to power and control these electrodes.

Pragmatic Research

Scott intends his research to be “directly helpful to people”. “There are interesting and difficult problems still to be solved”, he explains, “and I’m a practicing physician and I see them every day” [3].

The uniform patient populations and standardized treatments of controlled, so-called “explanatory” research are indeed essential for testing scientific hypotheses and finding small differences. But explanatory research treats patients as means more than ends. “Pragmatic research”, such as Scott’s, studies typical, rather than selected patients, and gives treatments customized to patients needs, rather than standardized test treatments [20]. Such research is sometimes considered only preliminary, but the results of pragmatic research are generalizable to broader patient populations, greater treatment variations, and are more likely to have real-world significance in decisions about how best to help people.

References

1. Alan B. Scott, MD. 2018 2019 [cited 2019 08 31 2019]; Available from: http://ascrs.org/node/23318.

2. Singer, N., So Botox Isn’t Just Skin Deep. 2009. https://www.nytimes.com/2009/04/12/business/12botox.html

3. McCutcheon, C., The Creator of Botox Never Cared about Wrinkles. Scientific American, 2016. https://blogs.scientificamerican.com/guest-blog/the-creator-of-botox-never-cared-about-wrinkles/

4. Robinson, D.A., et al., Mechanical components of human eye movements. J Appl Physiol, 1969. 26(5): p. 548-53. http://e.guigon.free.fr/rsc/article/RobinsonDAEtAl69.pdf

5. Scott, A.B., Force and velocity tests in strabismus. Trans Am Acad Ophthalmol Otolaryngol, 1975. 79(5): p. 727-32.https://www.ncbi.nlm.nih.gov/pubmed/1189170

6. Collins, C.C., et al., Extraocular muscle forces in normal human subjects. Investigative Ophthalmology & Visual Science, 1981. 20(5): p. 652-664.https://www.ncbi.nlm.nih.gov/pubmed/7216678

7. Scott, A.B., J.M. Miller, and C.C. Collins, Eye muscle prosthesis. J Pediatr Ophthalmol Strabismus, 1992. 29(4): p. 216-8.https://www.ncbi.nlm.nih.gov/pubmed/1512661

8. Magoon, E., et al., Diagnostic injection of Xylocaine into extraocular muscles. Ophthalmology, 1982. 89(5): p. 489-91.https://www.ncbi.nlm.nih.gov/pubmed/7099568

9. Weiss, M., For S.F. doctor, drug Botox became a real eye-opener - Toxin's cosmetic use a lucrative wrinkle, in www.sfgate.com. 2002.https://www.sfgate.com/health/article/For-S-F-doctor-drug-Botox-became-a-real-2852000.php

10. Scott, A.B., Change of eye muscle sarcomeres according to eye position. J Pediatr Ophthalmol Strabismus, 1994. 31(2): p. 85-8.https://www.ncbi.nlm.nih.gov/pubmed/8014792

11. Drachman, D.B., Atrophy of Skeletal Muscle in Chick Embryos Treated with Botulinum Toxin. Science, 1964. 145(3633): p. 719-21.https://www.ncbi.nlm.nih.gov/pubmed/14163805

12. Scott, A.B., A.L. Rosenbaum, and C.C. Collins, Pharmacologic weakening of extraocular muscles. Investigative Ophthalmology, 1973. 12(12): p. 924-7.https://iovs.arvojournals.org/article.aspx?articleid=2203304

13. Scott, A.B., Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology, 1980. 87(10): p. 1044-9.https://www.ncbi.nlm.nih.gov/pubmed/7243198

14. Tsui, J.K., et al., A pilot study on the use of botulinum toxin in spasmodic torticollis. Can J Neurol Sci, 1985. 12(4): p. 314-6.https://www.ncbi.nlm.nih.gov/pubmed/4084867

15. Koman, L.A., et al., Management of cerebral palsy with botulinum-A toxin: preliminary investigation. J Pediatr Orthop, 1993. 13(4): p. 489-95. https://www.ncbi.nlm.nih.gov/pubmed/8370782

16. Boffey, P., Loss of drug relegates many to blindness again, in The New York Times. 1986. https://www.nytimes.com/1986/10/14/science/loss-of-drug-relegates-many-to-blindness-again.html

17. Scott, A.B., D.E. Alexander, and J.M. Miller, Bupivacaine injection of eye muscles to treat strabismus. Br J Ophthalmol, 2007. 91(2): p. 146-8.https://www.ncbi.nlm.nih.gov/pubmed/17135337

18. Miller, J.M., et al., Bupivacaine injection remodels extraocular muscles and corrects comitant strabismus. Ophthalmology, 2013. 120(12): p. 2733-40. https://www.ncbi.nlm.nih.gov/pubmed/23916485

19. Debert, I., et al., Pharmacologic injection treatment of comitant strabismus. J AAPOS, 2016. 20(2): p. 106-111 e2.https://www.ncbi.nlm.nih.gov/pubmed/27079589

20. Schwartz, D. and J. Lellouch, Explanatory and pragmatic attitudes in therapeutical trials. J Chronic Dis, 1967. 20(8): p. 637-48. https://www.ncbi.nlm.nih.gov/pubmed/4860352

Carlatocchini (talk) 23:11, 5 September 2019 (UTC)