Patents – artdiamondblog.com

L.E.D. Pioneer Akasaki’s “Perseverance — Sheer Doggedness — Paid Off”

(p. B10) Isamu Akasaki, a Japanese physicist who helped develop blue light-emitting diodes, a breakthrough in the development of LEDs that earned him a Nobel Prize and transformed the way the world is illuminated, died on Thursday [April 1, 2021] in a hospital in Nagoya, Japan. He was 92.

. . .

Bob Johnstone, a technology journalist and the author of “L.E.D.: A History of the Future of Lighting” (2017), said in an email, “The prevailing opinion in the late 1980s was that, because of the number of flaws in the crystal structure of gallium nitride, it would never be possible to make light-emitting diodes from it, so why would you even try?”

Dr. Akasaki, he continued, “was willing to stick at what was almost universally recognized to be a lost cause, working away long after researchers at RCA and other U.S. pioneers of gallium nitride LED technology had given up.”

“Eventually,” Mr. Johnstone said, “his perseverance — sheer doggedness — paid off.”

. . .

Dr. Akasaki was awarded hundreds of patents for his research over the years, and the royalties from his groundbreaking work with Dr. Amano eventually funded the building of a new research institute, the Nagoya University Akasaki Institute, completed in 2006.

. . .

When asked in a 2016 interview with the Electrochemical Society to summarize the philosophy guiding his many years of single-minded research, Dr. Akasaki replied, “No pain, no gain.”

“I say this to younger people: Experience is the best teacher,” he continued. “That is, sometimes there is no royal road to learning.”

For the full obituary see:

Scott Veale. “Isamu Akasaki, 92, Nobel Laureate Whose LED Breakthrough Rippled Around the World.” The New York Times (Wednesday, April 7, 2021 [sic]): B10.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the obituary has the date April 6, 2021 [sic], and has the title “Isamu Akasaki, 92, Dies; Nobel Winner Lit Up the World With LEDs.”)

The book by Bob Johnstone mentioned above is:

Johnstone, Bob. L.E.D.: A History of the Future of Lighting. Scotts Valley, CA: CreateSpace Independent Publishing Platform, 2017.

Innovative Medical Project Entrepreneur Karikó Long Persevered to Develop mRNA Technology Behind Covid-19 Vaccines

The basic science and technology behind mRNA did not come easy and did not come quick. If the skeptics of Covid-19 vaccines knew this they might be less skeptical because one of the reasons they sometimes give for their skepticism is the speed with which the vaccines were developed. (Other reasons for skepticism I think are more defensible, such as the worry that the authorities downplayed the real side-effects that some vaccine recipients suffered from the vaccines. But on balance I still think the vaccines were a great achievement.) One of the heroes of the long slog is Katalin Karikó. Part of her story is sketched in the passages quoted below. She is a good example of an innovative medical project entrepreneur. When she was named a winner of the Nobel Prize she identified part of what it takes to succeed: “we persevere, we are resilient” (Karikó as quoted in Mosbergen, Loftus, and Zuckerman 2023, p. A2).

(p. A2) The University of Pennsylvania is basking in the glow of two researchers who this week were awarded the Nobel Prize in medicine for their pioneering work on messenger RNA.

Until recently, the school and its faculty largely disdained one of those scientists.

Penn demoted Katalin Karikó, shunting her to a lab on the outskirts of campus while cutting her pay. Karikó’s colleagues denigrated her mRNA research and some wouldn’t work with her, according to her and people at the school. Eventually, Karikó persuaded another Penn researcher, Drew Weissman, to work with her on modifying mRNA for vaccines and drugs, though most others at the school remained skeptical, pushing other approaches.

. . .

. . . on Monday [Oct. 2, 2023], when Karikó and Weissman were awarded the Nobel, on top of prestigious science prizes in recent years, the school expressed a different perspective on their work.

The reversal offers a glimpse of the clubby, hothouse world of academia and science, where winning financial funding is a constant burden, securing publication is a frustrating challenge and those with unconventional or ambitious approaches can struggle to gain support and acceptance.

“It’s a flawed system,” said David Langer, who is chair of neurosurgery at Lenox Hill Hospital, spent 18 years studying and working at Penn and was Karikó’s student and collaborator.

. . .

Penn wasn’t the only institution to doubt Karikó’s belief in mRNA when many other scientists pursued a different gene-based technology. In a reflection of how radical her ideas were at the time, she had difficulty publishing her research and obtaining big grants—prerequisites for those hoping to get ahead in science and gain academic promotions.

Another reason her relationship with the school frayed: Karikó could antagonize colleagues. In presentations, she often was the first to point out mistakes in their work. Karikó didn’t intend to offend, she just felt the need to call out mistakes, she later said.

For the full story see:

Gregory Zuckerman. “Penn Toasts Winning Scientist After Shunning Her for Years.” The Wall Street Journal (Thursday, Oct. 5, 2023 [sic]): A2.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the story has the date October 4, 2023 [sic], and has the title “After Shunning Scientist, University of Pennsylvania Celebrates Her Nobel Prize.”)

The source of the Karikó quote in my opening comments is:

Dominique Mosbergen, Peter Loftus and Gregory Zuckerman. “Pair Met With Doubts, Now Win Nobel Prize.” The Wall Street Journal (Tuesday, Oct. 3, 2023 [sic]): A1-A2.

(Note: the online version of the story was updated October 2, 2023 [sic], and has the title “Pioneers of mRNA Find Redemption in Nobel Prize.”)

For more detailed accounts of Karikó’s life, struggles, and research see:

Karikó, Katalin. Breaking Through: My Life in Science. New York: Crown, 2023.

Zuckerman, Gregory. A Shot to Save the World: The inside Story of the Life-or-Death Race for a Covid-19 Vaccine. New York: Portfolio/Penguin, 2021.

Innovative Medical Project Entrepreneur Alan Scott “Coaxed” the F.D.A. to Approve Botox

Even though Alan Scott may have been a “lousy businessman,” he appears nonetheless to still have been an important innovative medical project entrepreneur. (I have not yet read the book discussed in the passages quoted below, but I hope to read it soon. Besides my admiration for innovative project entrepreneurs, an added reason that I am interested in the book is that I have always suffered from esophoria, which is one form of the strabismus that Alan Scott was trying to treat.)

(p. C9) Today botulinum toxin—purified, diluted and known as Botox—nets annual sales in the billions. It is used to treat everything from wrinkles to migraines, yet the pioneer largely responsible for fulfilling Kerner’s prophecy and bringing botulinum into medicine is virtually unknown. He was, it turns out, a laconic Bay Area ophthalmologist named Alan Scott, a self-described “lousy businessman” who barely recouped his own expenses as he coaxed the product to FDA approval.

Eugene Helveston seeks to rescue Scott from oblivion in “Death to Beauty,” a pandemic passion project and labor of love. As an ophthalmologist “of the same era,” Dr. Helveston knew Scott professionally and participated as a researcher in the original clinical trial of botulinum in the mid-1980s. Recognizing that only a few people were still around who could “tell the story firsthand,” Dr. Helveston resolved to document this medical history and corresponded with Scott from June 2021 until Scott’s death six months later, at age 89. The result is an absorbing insider’s account of an exceptional journey.

. . .

Scott was especially interested in strabismus, a disorder characterized by misaligned eyes. The condition was usually treated with surgery, with often disappointing results. Scott began to wonder if strabismus could be treated without surgery by injecting a substance that would weaken a specific eye muscle and thus help restore alignment. It was this line of research that led him to contemplate botulinum, which he requested and received from Schantz in 1972, delivered by the Postal Service in a sealed metal container. Fatefully, he reported promising results in animal models the next year without first filing a patent, which meant that his valuable intellectual property went unprotected.

To enable human testing, Scott submitted an application to the FDA in 1974; the document “lay on some FDA desk for almost four years,” he told Dr. Halversten, before a nudge from a colleague re-engaged the agency. Scott received testing authorization in 1978 and injected the first human subject with a low test dose to evaluate safety. There were no complications, and the trial proceeded.

. . .

Though Botox never gained much traction for the treatment of strabismus, the drug’s other uses lifted it to blockbuster status. Scott received only modest compensation for his foundational work, yet by all accounts he had no regrets. Allergan may have “got all the money,” he said, but “we had all the fun.”

For the full review see:

David A. Shaywitz. “Toning Up With a Toxin.” The Wall Street Journal (Saturday, Dec. 17, 2024): C9.

(Note: ellipses added.)

(Note: the online version of the review has the date February 9, 2024, and has the title “‘Death to Beauty’ Review: The Birth of Botox.”)

The book under review is:

Helveston, Eugene M. Death to Beauty: The Transformative History of Botox. Bloomington, IN: Indiana University Press, 2024.

A Cheap Nonrefrigerated Drug that Could Have Saved Tens of Thousands of Women’s Lives Languished for Half a Century Waiting for a Clinical Trial

They already knew tranexamic saved lives of bleeding soldiers and bleeding car crash victims. Why did regulators make the world wait 50 years, and finally do an expensive randomized double-blind clinical trial, to know that it also would save the lives of bleeding new mothers? You can’t blame drug companies. The drug’s patent had expired long ago, so no drug company would make profits from the sale of the drug sufficient to pay the expense of the clinical trial.

(p. D3) An inexpensive generic drug that saves the lives of wounded soldiers and civilian car crash victims has now been shown to rescue women suffering hemorrhages in childbirth.

. . .

In a major six-year trial involving over 20,000 women in 21 countries, researchers showed that tranexamic acid, a little-known blood-clotter invented in the 1950s, reduced maternal bleeding deaths by a third if it was given within three hours. It costs less than $2 a dose and does not require refrigeration.

The trial — known as Woman, short for World Maternal Antifibrinolytic — was led by doctors at the London School of Hygiene and Tropical Medicine and paid for by the Wellcome Trust, Pfizer, Britain’s health department and the Bill and Melinda Gates Foundation. Results were published in The Lancet on Wednesday [April 26, 2017].

. . .

The World Health Organization currently recommends treating birth hemorrhages by massaging the uterus and injecting uterus-shrinking drugs like oxytocin.

Tranexamic acid acts in a different way — it allows blood to clot more quickly — and so it should be given in addition to the usual measures and at the same time, said Dr. Ian Roberts, one of the study’s lead authors.

. . .

The drug was invented in Japan by a husband-wife research team, Shosuke and Utako Okamoto. They hoped it would be used to prevent birth hemorrhages, but local obstetricians declined to organize a clinical trial.

Ultimately, they turned the patent over to a Japanese pharmaceutical company, which sold it as treatment for heavy menstrual periods and as an ingredient in skin-whitening creams. Some oral surgeons used it when doing dental work on hemophiliacs, Dr. Roberts said.

For the full commentary see:

Donald G. McNeil Jr. “Global Health; A Cheap Drug Can Save Hemorrhaging Mothers.” The New York Times (Tuesday, May 2, 2017 [sic]): D3.

(Note: ellipses, and bracketed date, added. The Wednesday, April 26, 2017 date is the date The Lancet posted a co-author discussion of the results of the study.)

(Note: the online version of the commentary has the date April 26, 2017 [sic], and has the title “Global Health; Inexpensive Drug Prevents Deaths in New Mothers, Study Finds.” Where the more detailed online version differs from the print version, the passages quoted above follow the print [sic] version.)

The academic article in The Lancet and mentioned above is:

Shakur, Haleema, Ian Roberts, Bukola Fawole, Rizwana Chaudhri, Mohamed El-Sheikh, Adesina Akintan, Zahida Qureshi, Hussein Kidanto, Bellington Vwalika, Abdulfetah Abdulkadir, Saturday Etuk, Shehla Noor, Etienne Asonganyi, Zarko Alfirevic, Danielle Beaumont, Carine Ronsmans, Sabaratnam Arulkumaran, Adrian Grant, Kaosar Afsana, Metin Gülmezoglu, Beverley Hunt, Oladapo Olayemi, Ian Roberts, Iain Chalmers, Pisake Lumbiganon, Gilda Piaggio, Tony Brady, Haleema Shakur, Ian Roberts, Zarko Alfirevic, Diana Elbourne, Metin Gülmezoglu, Carine Ronsmans, Eni Balogun, Tracey Pepple, Danielle Prowse, Nigel Quashi, Lin Barneston, Collette Barrow, Danielle Beaumont, Lisa Cook, Lauren Frimley, Daniel Gilbert, Catherine Gilliam, Rob Jackson, Taemi Kawahara, Hakim Miah, Sergey Kostrov, Maria Ramos, Ian Roberts, Haleema Shakur, Phil Edwards, Tom Godec, Sumaya Huque, Bukola Fawole, Olujide Okunade, Olusade Adetayo, Rizwana Chaudhri, Aasia Kayani, Kiran Javaid, Bukola Fawole, Rizwana Chaudhri, Chrstine Biryabarema, Zahida Qureshi, Robert Tchounzou, Mohamed El-Sheikh, Hussein Kidanto, Mohan Regmi, Bellington Vwalika, Kastriot Dallaku, Mateus Sahani, Sayeba Akhter, Abdulfetah Abdulkadir, Nicolas Meda, Anthony Kwame Dah, Adesina Akintan, Olufemi Odekunle, Oluwabusola Monehin, Austin Ojo, Grace Akinbinu, Ifeoma Offiah, Saturday Etuk, Ubong Akpan, Uduak Udofia, Useneno Okon, Ezukwa Omoronyia, Okpe James, Oladapo Olayemi, Nike Bello, Blessed Adeyemi, Chris Aimakhu, Olufemi Akinsanya, Bamidele Adeleye, Oluwaseun Adeyemi, Kayode Oluwatosin, Abiodun Aboyeji, Abiodun Adeniran, Adebayo Adewale, Noah Olaomo, Lawrence Omo-Aghoja, Emmanuel Okpako, Lucky Oyeye, Francis Alu, John Ogudu, Ezekiel Ladan, Ibrahim Habib, Babasola Okusanya, Olatunde Onafowokan, David Isah, Abalaka Aye, Felix Okogbo, Egbaname Aigere, Mark Ogbiti, Temitope Onile, Olaide Salau, Yinka Amode, Kamil Shoretire, Adebola Owodunni, Kehinde Ologunde, Akintunde Ayinde, Moses Alao, Olalekan Awonuga, Babatunde Awolaja, Omololu Adegbola, Fatimah Habeebu-Adeyemi, Adeyemi Okunowo, Hadiza Idris, Ola Okike, Nneka Madueke, Josiah Mutihir, Nankat Joseph, Babatunde Adebudo, Adeniyi Fasanu, Olugbenga Akintunde, Olufemi Abidoye, Owigho Opreh, Sophia Udonwa, Gladys Dibia, Simeon Bazuaye, Arafat Ifemeje, Aniefiok Umoiyoho, Emmanuel Inyang-Etoh, Sununu Yusuf, Kayode Olayinka, Babalola Adeyemi, Olusegun Ajenifuja, Umar Ibrahim, Yusuf Baffah Adamu, Oluwarotimi Akinola, Grace Adekola-Oni, Paul Kua, Roseline Iheagwam, Audu Idrisa, Ado Geidam, Andrea Jogo, Joseph Agulebe, Joseph Ikechebelu, Onyebuchi Udegbunam, Jacob Awoleke, Oluseyi Adelekan, Hajaratu Sulayman, Nkeiruka Ameh, Nurudeen Onaolapo, Affiss Adelodun, William Golit, Dachollom Audu, Adetunji Adeniji, Folasade Oyelade, Lamaran Dattijo, Palmer Henry, Babalola Adeyemi, Olabisi Loto, Odidika Umeora, Abraham Onwe, Emily Nzeribe, Bartthy Okorochukwu, Augustine Adeniyi, Emmanuel Gbejegbe, Akpojaro Ikpen, Ikemefuna Nwosu, Abdulrasaq Sambo, Olubunmi Ladipo, Sola Abubakar, Ola Nene Okike, Enyinnaya Chikwendu Nduka, Eziamaka Pauline Ezenkwele, Daniel Onwusulu, Theresa Azonima Irinyenikan, Swati Singh, Amaitari Bariweni, Hadiza Galadanci, Peter Achara, Osagie Osayande, Mohammed Gana, Rizwana Chaudhri, Kiran Jabeen, Ayesha Mobeen, Sadaf Mufti, Maliha Zafar, Shehla Noor, Basharat Ahmad, Maimoona Munawar, Jeharat Gul, Naseema Usman, Fehmida Shaheen, Mariam Tariq, Nadia Sadiq, Rabia Batool, Habiba Sharaf Ali, Manahil Jaffer, Asma Baloch, Noonari Mukhtiar, Tasneem Ashraf, Raheela Asmat, Salma Khudaidad, Ghazala Taj, Roshan Qazi, Saira Dars, Faryal Sardar, Sanobar Ashfaq, Saeeda Majeed, Sadaqat Jabeen, Rukhsana Karim, Farzana Burki, Syeda Rabia Bukhari, Fouzia Gul, Musarrat Jabeen, Akhtar Sherin, Qurratul Ain, Shahid Rao, Uzma Shaheen, Samina Manzoor, Shabween Masood, Shabana Rizvi, Anita Ali, Abida Sajid, Aisha Iftikhar, Shazia Batool, Lubna Dar, Shahenzad Sohail, Shazia Rasul, Shamsa Humayun, Rashida Sultana, Sofia Manzoor, Syeda Mazhar, Afshan Batool, Asia Nazir, Nasira Tasnim, Hajira Masood, Razia Khero, Neelam Surhio, Samana Aleem, Naila Israr, Saba Javed, Lubna Bashir, Samina Iqbal, Faiza Aleem, Rubina Sohail, Saima Iqbal, Samina Dojki, Alia Bano, Naseem Saba, Maimoona Hafeez, Nishat Akram, Naila Israr, Riffat Shaheen, Haleema Hashmi, Sharmeen Arshad, Rubina Hussain, Sadia Khan, Nighat Shaheen, Safia Khalil, Pushpa Sachdev, Gulfareen Arain, Amtullah Zarreen, Sara Saeed, Shamayela Hanif, Nabia Tariq, Mahwish Jamil, Shama Chaudhry, Hina Rajani, Tayyiba Wasim, Summera Aslam, Nilofar Mustafa, Huma Quddusi, Sajila Karim, Shazia Sultana, Misbah Harim, Mohd Chohan, Nabila Salman, Fareesa Waqar, Shamsunnisa Sadia, Lubna Kahloon, Shehla Manzoor, Samar Amin, Umbreen Akram, Ambreen Ikram, Samina Kausar, Tahira Batool, Brigadier Naila, Tahir Kyani, Christine Biryabarema, Ruth Bulime, Regina Akello, Bernadette Nakawooya Lwasa, Joselyn Ayikoru, Christine Namulwasira, Patrick Komagum, Isabirye Rebecca, Nayiga Annet, Nakirigya Nuulu, Elizabeth Nionzima, Rose Bwotya, Margret Nankya, Sarah Babirye, Joseph Ngonzi, Cesar Sanchez, Nkonwa Innocent, Kusasira Anitah, Ayiko Jackson, Elizabeth Ndagire, Christine Nanyongo, Dominic Drametu, Grace Meregurwa, Francis Banya, Rita Atim, Emmanuel Byaruhanga, Lema Felix, Hussein Iman, Vincent Oyiengo, Peninah Waigi, Rose Wangui, Faiza Nassir, Musimbi Soita, Rophina Msengeti, Zeinab Zubier, Hillary Mabeya, Antony Wanjala, Henry Mwangi, Brian Liyayi, Evelyn Muthoka, Alfred Osoti, Amos Otara, Veronicah Ongwae, Zahida Qureshi, Victor Wanjohi, Bonface Musila, Kubasu Wekesa, Alex Nyakundi Bosire, Etienne Asonganyi, Alice Ntem, Angeline Njoache, Alice Ashu, André Simo, Robert Tchounzou, Dorothy Keka, Kenfack Bruno, Amadou Ndouoya, Martin Saadio, Mesack Tchana, Odel Gwan, Pauline Assomo, Venantius Mutsu, Nji Eric, Pascal Foumane, Philemon Nsem, Jeanne Fouedjio, Ymele Fouelifack, Pierre Marie Tebeu, Georges Nko’ayissi, Eta Ngole Mbong, Wisal Nabag, Riham Desougi, Hadia Mustafa, Huida Eltaib, Taha Umbeli, Khalid Elfadl, Murwan Ibrahim, Abdalla Mohammed, Awadia Ali, Somia Abdelrahiem, Mohammed Musa, Khidir Awadalla, Samirra Ahmed, Mahdi Bushra, Omer Babiker, Hala Abdullahi, Mohamed Ahmed, Elhassan Safa, Huida Almardi, Duria Rayis, Saeed Abdelrahman Abdelgabar, Zarko Alfirevic, Gillian Houghton, Andrew Sharpe, Jim Thornton, Nick Grace, Carys Smith, Kim Hinshaw, Dawn Edmundson, Paul Ayuk, Alison Bates, George Bugg, Joanne Wilkins, Clare Tower, Alysha Allibone, Eugene Oteng-Ntim, Hussein Kidanto, Ahmad Kazumari, Anna Danford, Matilda Ngarina, Muzdalifat Abeid, Khadija Mayumba, Magreth Zacharia, George Mtove, Leonard Madame, Anthony Massinde, Berno Mwambe, Rwakyendela Onesmo, Sebastian Kitengile Ganyaka, Mohan Regmi, Shyam Gupta, Rabindra Bhatt, Ajay Agrawal, Pramila Pradhan, Nikita Dhakal, Punita Yadav, Gyanendra Karki, Bhola Ram Shrestha, Bellington Vwalika, Mwansa Lubeya, Jane Mumba, Willies Silwimba, Isaiah Hansingo, Noojiri Bopili, Ziche Makukula, Alexander Kawimbe, Mwansa Ketty Lubeya, Willard Mtambo, Mathew Ng’ambi, Kastriot Dallaku, Saimir Cenameri, Ilir Tasha, Aferdita Kruja, Besnik Brahimaj, Armida Tola, Leon Kaza, Mateus Sahani, Desire Tshombe, Elizabeth Buligho, Roger Paluku-Hamuli, Charles Kacha, Kato Faida, Badibanga Musau, Herman Kalyana, Phanny Simisi, Serge Mulyumba, Nzanzu Kikuhe Jason, Jean Robert Lubamba, Willis Missumba, Ferdousi Islam, Nazneen Begum, Sayeba Akhter, Ferdousi Chowdhury, Rokeya Begum, Farjana Basher, Nazlima Nargis, Abu Kholdun, Shahela Jesmin, Shrodha Paul, Hailemariam Segni, Getachew Ayana, William Haleke, Abdulfetah Abdulkadir, Hassen Hussien, Fikre Geremew, Moussa Bambara, Adolphe Somé, Amadou Ly, Roamba Pabakba, Horace Fletcher, Leslie Samuels, Henry Opare-Addo, Roderick Larsen-Reindorf, Kwadwo Nyarko-Jectey, Glen Mola, Malts Wai, Magdy El Rahman, Wafaa Basta, Hussein Khamis, Maria Fernanda Escobar, Liliana Vallecilla, and Gabriel Essetchi Faye. “Effect of Early Tranexamic Acid Administration on Mortality, Hysterectomy, and Other Morbidities in Women with Post-Partum Haemorrhage (Woman): An International, Randomised, Double-Blind, Placebo-Controlled Trial.” The Lancet 389, no. 10084 (May 27, 2017): 2105-16.

In an interview shortly before her death, and before the clinical trial was completed, Utako Okamoto said that she already knew that the trial would show that tranexamic acid works to stop bleeding:

Tranexamic Acid (TXA) History

With Metformin Patent Expired, No Firm Has Incentive to Fund $50 Million Randomized Clinical Trial to Show It Aids Longevity

The article quoted below was published eight years ago. Dr. Barzilai and his team are still, even now, trying to raise the (probably higher) funds to conduct the metformin clinical trial. Firms have no incentive to conduct the clinical trial. Since the patent for metformin (originally issued for its efficacy against diabetes) expired in the year 2000, even if the clinical trial succeeded, no firm would be able to recover in revenue the $50 cost of conducting the clinical trial. Clinical trials are so hugely expensive largely due to the large and long Phase 3 component, intended to prove efficacy. That is why I salute Milton Friedman’s suggestion that a step in the right direction would be for the FDA to only mandate the smaller and quicker Phase 1 and Phase 2 components, mainly intended to prove safety. If the total cost of the clinical trial was much lower, it might be easier to find non-profit or academic funding. (It’s hard to raise $50 million on a GoFundMe page!)

The system is set up so that cheap (off-patent) drugs like metformin do not get tested, and so do not get FDA approval for off-label uses. So the system is set up to reduce the use of low cost, but possibly effective, medicines.

(p. D5) “Aging is by far the best predictor of whether people will develop a chronic disease like atherosclerotic heart disease, stroke, cancer, dementia or osteoarthritis,” Dr. James L. Kirkland, director of the Kogod Center on Aging at the Mayo Clinic, said in an interview. “Aging way outstrips all other risk factors.”

He and fellow researchers, who call themselves “geroscientists,” are hardly hucksters hawking magic elixirs to extend life. Rather, they are university scientists joined together by the American Federation for Aging Research to promote a new approach to healthier aging, which may — or may not — be accompanied by a longer life. They plan to test one or more substances that have already been studied in animals, and which show initial promise in people, in hopes of finding one that will keep more of us healthier longer.

As Dr. Kirkland wrote in . . ., “Aging: The Longevity Dividend”: “By targeting fundamental aging processes, it may be possible to delay, prevent, alleviate or treat the major age-related chronic disorders as a group instead of one at a time.”

. . .

The team, which includes Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in The Bronx, and Steven N. Austad, who heads the biology department at the University of Alabama at Birmingham, plans to study one promising compound, a generic drug called metformin already widely used in people with Type 2 diabetes. They will test the drug in a placebo-controlled trial involving 3,000 elderly people to see if it will delay the development or progression of a variety of age-related ailments, including heart disease, cancer and dementia. Their job now is to raise the $50 million or so needed to conduct the study for the five years they expect it will take to determine whether the concept has merit.

. . .

Several studies have . . . found that individuals with exceptional longevity experience a compression of morbidity and spend a smaller percentage of their life being ill, Dr. Barzilai and his colleague Dr. Sofiya Milman wrote in the “Aging” book.

For the full commentary see:

Jane E. Brody. “Pursuing the Dream of Healthy Aging.” The New York Times (Tuesday, February 2, 2016 [sic]): D5.

(Note: ellipses added.)

(Note: the online version of the commentary has the date February 1, 2016 [sic], and has the title “Finding a Drug for Healthy Aging.”)

Dr. Kirkland’s co-edited book mentioned above is:

Olshansky, S. Jay, George M. Martin, and James L. Kirkland, eds. Aging: The Longevity Dividend, A Subject Collection from Cold Spring Harbor Perspectives in Medicine. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2015.

One study that documents that those who live 107 or more years do not have more years of illness and morbidity (the “compression of morbidity hypothesis”) is:

Sebastiani, Paola, and Thomas T. Perls. “The Genetics of Extreme Longevity: Lessons from the New England Centenarian Study.” Frontiers in Genetics 3 (Nov. 30, 2012).

After Safe Drinking Water, Vaccines Were the Second “Most Successful Medical Interventions of the 20th Century”

(p. B11) Dr. Paul D. Parkman, whose research was instrumental in identifying the virus that causes rubella and developing a vaccine that has prevented an epidemic of the disease in the United States for more than 50 years, died on May 7 [2024] at his home in Auburn, N.Y., in the Finger Lakes region. He was 91.

. . .

In 1966, Dr. Parkman, Dr. Harry M. Meyer Jr. and their collaborators at the National Institutes of Health, including Maurice R. Hilleman, disclosed that they had perfected a vaccine to prevent rubella. Dr. Parkman and Dr. Meyer assigned their patents to the N.I.H. so that the vaccines could be manufactured, distributed and administered promptly.

“I never made a nickel from those patents because we wanted them to be freely available to everybody,” he said in an oral history interview for the N.I.H. in 2005.

President Lyndon B. Johnson thanked the researchers, noting that they were among the few who could “number themselves among those who directly and measurably advance human welfare, save precious lives, and bring new hope to the world.”

Still, after Dr. Parkman retired from the government in 1990, as director of the Food and Drug Administration’s Center for Biologics Evaluation and Research, he expressed concern about what he called the unfounded skepticism that persisted about the value of vaccines.

“With the exception of safe drinking water, vaccines have been the most successful medical interventions of the 20th century,” he wrote in 2002 in Food and Drug Administration Consumer, an agency journal.

For the full obituary see:

Sam Roberts. “Paul D. Parkman, 91, Researcher Whose Work Helped to Eliminate Rubella.” The New York Times (Friday, May 24, 2024): B11.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the obituary has the date May 21, 2024, and has the title “Dr. Paul Parkman, Who Helped to Eliminate Rubella, Dies at 91.”)

The 2002 article by Parkman mentioned above is:

Parkman, Paul D. “We Can’t Forget the Value of Vaccines.” Food and Drug Administration Consumer 36, no. 4 (July-Aug. 2002): 40.

A Miraculous Machine in the Middle-Ages That Did Nothing to Improve the Lives of the Masses

Before the industrial revolution clever inventors sometimes devised elaborate and amazing machines. The Antikythera mechanism is a famous example. Though these machines amaze us, they usually did little to improve the lives of those who lived at the time of invention. Why? Maybe the answer is that just before the industrial revolution, entrepreneurs were encouraged and enabled (through property rights and patents) to apply amazing inventions to the betterment of the people.

(p. C9) What kind of a book do we have in “Miracles and Machines: A Sixteenth-Century Automaton and Its Legend”?

. . .

The authors call the book a “clockwork”; its many disparate parts are joined in scrupulous devotion to a 16th-century automaton—an object, they write, which is at once “a sculpture, a machine, an icon, and a messenger.”

The figure is of a Franciscan friar, about 16 inches tall, carved out of wood, cloaked in a modern replica of the garb he once wore. His 5-pound weight is due to an intricate iron mechanism that fits inside his wooden body; it is wound with a key.

. . .

Imagine, Ms. King and Mr. Todd suggest, what it would have been like to see this automaton at the time of its creation. He is placed upon a candlelit table. His feet take steps under his tunic—but he actually glides on three wheels, making his movement seem ethereal. He is deliberately slow. This is not a mechanism meant to thrill us with speed and virtuosity. His movements are graceful, solemn.

As he moves, the friar raises and lowers a cross in his left hand and strikes his chest with his right, as if declaring “mea culpa.” He also lifts the cross to his lips and fixes his gaze steadily, perhaps at an observer at the opposite end of the table. He looks down at the cross, up at the observer, and begins to turn: “You let out half a breath,” the authors tell us, “but as his full body pivots on the table, feet in motion, head forward, his eyes slide left in their sockets to stay fixed on you!” Then he changes direction, staring at what might be another observer. There is no doubt about his seriousness; the impact on believers, in the half-light, would have been considerable.

. . .

In seeking to learn more about the friar’s provenance, Ms. King contacted Servus Gieben, a Dutch-born Franciscan who served as the director of the Franciscan Museum in Rome. In his correspondence with Ms. King, Gieben, who died in 2014, reaffirmed his theory that it may have been commissioned by Philip for his son Carlos. In 1562, at the age of 17, Carlos fell down a flight of stairs and so gravely injured his skull that he was not expected to survive (either the injury or the era’s “treatments”).

. . . The corpse of a Franciscan friar, Diego de Alcalá (ca. 1400-63), had remained free of decay after his death that it was thought to have healing powers. And behold: Once it was laid upon the dying prince, Carlos soon began to recover. Philip II spent 26 years petitioning four consecutive popes to recognize the miracle and declare Diego a saint. (He ultimately was, as the city of San Diego now affirms.)

Gieben suggested that the facial resemblance between the automaton and Diego was evident. And what better way, he thought, for Philip to honor Diego than by providing his often wayward son with an admonitory reminder in the form of the penitential friar himself, created by the most brilliant clockmaker in the empire. As Don Carlos was brought back to life, so an inanimate automaton would turn animate.

Even today, the authors suggest, the friar remains “a small miracle. Or the image of a small miracle. Or the metaphor of a large miracle. Or an artificial miracle.”

For the full review see:

Edward Rothstein. “A Wonder of Another Age.” The Wall Street Journal (Saturday, December 23, 2023): C9.

(Note: ellipses added.)

(Note: the online version of the review has the date December 22, 2023, and has the title “‘Miracles and Machines’ Review: Mystery of the Clockwork Man.”)

The book under review is:

King, Elizabeth, and W. David Todd. Miracles and Machines: A Sixteenth-Century Automaton and Its Legend. Los Angeles: Getty Publications, 2023.

Zoliflodacin Is First New Antibiotic in Decades

(p. A12) A new antibiotic, the first to be developed in decades, can cure gonorrhea infections at least as effectively as the most powerful current treatment, a large clinical trial has found. The drug, zoliflodacin, is taken as a single dose, and it has not yet been approved for use in any country.

. . .

Pharmaceutical companies have largely abandoned antibiotic development as unprofitable. The development of zoliflodacin represents a new model: G.A.R.D.P., which is funded by many Group of 20 countries and the European Union, developed the drug in collaboration with an American pharmaceutical company called Innoviva Specialty Therapeutics.

The nonprofit sponsored the Phase 3 trial of the drug. In exchange, it holds the license to sell the antibiotic in about 160 countries while Innoviva retains marketing rights for high-income countries.

“I’ll go out on a limb and say that’s probably the only way in which we develop antibiotics going forward, because the old model is simply not going to work,” said Ramanan Laxminarayan, a senior research scholar at Princeton University who chairs the G.A.R.D.P. board.

. . .

“Nobody’s making a boatload of money off treatment of gonorrhea, especially when you’re using a single dose of an oral antibiotic,” said Dr. Jeanne Marrazzo, director of the National Institute of Allergy and Infectious Diseases.

“This is a path forward to solve the dilemma of getting pathways for products that don’t guarantee profits,” Dr. Marrazzo said.

For the full story, see:

Apoorva Mandavilli. “A New Drug Is Developed To Combat Gonorrhea.” The New York Times (Friday, November 11, 2023): A12.

(Note: ellipses added.)

(Note: the online version of the story has the date Nov. 10, 2023, and has the title “Gonorrhea Is Becoming Drug Resistant. Scientists Just Found a Solution.”)

“Serendipitous” Discoveries Related to Two “Odd-Looking” Animals Was Source of Weight-Loss Drugs

(p. A1) The blockbuster diabetes drugs that have revolutionized obesity treatment seem to have come out of nowhere, turning the diet industry upside down in just the past year. But they didn’t arrive suddenly. They are the unlikely result of two separate bodies of science that date back decades and began with the study of (p. A2) two unsightly creatures: a carnivorous fish and a poisonous lizard.

In 1980, researchers at Massachusetts General Hospital wanted to use new technology to find the gene that encodes a hormone called glucagon. The team decided to study Anglerfish, which have special organs that make the hormone, simplifying the task of gathering samples of pure tissue.

. . .

After plucking out organs the size of Lima beans with scalpels, they dropped them into liquid nitrogen and drove back to Boston. Then they determined the genetic sequence of glucagon, which is how they learned that the same gene encodes related hormones known as peptides. One of them was a key discovery that would soon be found in humans, too.

It was called glucagon-like peptide-1 and its nickname was GLP-1.

After they found GLP-1, others would determine its significance. Scientists in Massachusetts and Europe learned that it encourages insulin release and lowers blood sugar. That held out hope that it could help treat diabetes. Later they discovered that GLP-1 makes people feel fuller faster and slows down emptying of food from the stomach.

. . .

The key to the first drug would come from a serendipitous discovery inside another odd-looking animal.

Around the time Goodman was cutting open fish, Jean-Pierre Raufman was studying insect and animal venoms to see if they stimulated digestive enzymes in mammals.

“We got a tremendous response from Gila monster venom,” he recalled.

It was a small discovery that could have been forgotten, but for a lucky break nearly a decade later when Raufman gave a lecture on that work at the Bronx Veterans Administration. John Eng, an expert in identifying peptides, was intrigued. The pair had collaborated on unrelated work a few years before. Eng proposed they study Gila monsters.

. . .

Eng isolated a small peptide that he called Exendin-4, which they found was similar to human GLP-1.

Eng then tested his new peptide on diabetic mice and found something intriguing: It not only reduced blood glucose, it did so for hours. If the same effect were to be observed in humans, it could be the key to turning GLP-1 into a meaningful advance in diabetes treatment, not just a seasickness simulator in an IV bag.

Jens Juul Holst, a pioneering GLP-1 researcher, remembers standing in an exhibit hall at a European conference next to Eng. The two had put up posters that displayed their work, hoping top researchers would stop by to discuss it. But other scientists were skeptical that anything derived from a lizard would work in humans.

“He was extremely frustrated,” recalled Holst. “Nobody was interested in his work. None of the important people. It was too strange for people to accept.”

After three years, tens of thousands of dollars in patent-related fees and thousands of miles traveled, Eng found himself standing with his poster in San Francisco. This time, he caught the attention of Andrew Young, an executive from a small pharmaceutical company named Amylin.

“I saw the results in the mice and realized this could be druggable,” Young said.

When an Eli Lilly executive leaned over his shoulder to look at Eng’s work, Young worried he might miss his chance. Not long after, Amylin licensed the patent.

They worked to develop Exendin-4 into a drug by synthesizing the Gila monster peptide. They weren’t sure what would happen in humans. “We couldn’t predict weight loss or weight gain with these drugs,” recalled Young. “They enhance insulin secretion. Usually that increases body weight.” But the effect on slowing the stomach’s processing of food was more pronounced and Young’s team found as they tested their new drug that it caused weight loss.

To get a better understanding of Exendin-4, Young consulted with Mark Seward, a dentist raising more than 100 Gila monsters in his Colorado Springs, Colo., basement. The lizard enthusiast’s task was to feed them and draw blood. One took exception to the needle in its tail, slipped its restraint and snapped its teeth on Seward’s palm—the only time he’s been bitten in the decades he’s raised the animals. “It’s like a wasp sting,” he said, “but much worse.”

Nine years after the chance San Francisco meeting between Eng and Young, the Food and Drug Administration approved the first GLP-1-based treatment in 2005.

The twice-daily injection remained in the bloodstream for hours, helping patients manage Type 2 diabetes. Eng would be paid royalties as high as $6.7 million per year for the drug, . . .

For the full story, see:

Rolfe Winkler and Ben Cohen. “Two Monsters Spawned Huge Drugs.” The Wall Street Journal (Friday, June 24, 2023): A1-A2.

(Note: ellipsis added.)

(Note: the online version of the story has the date June 23, 2023, and has the title “Monster Diet Drugs Like Ozempic Started With Actual Monsters.” The sentence about “a serendipitous discovery” appears in the online, but not the print, version of the article. The passages quoted above also include several other sentences that appear in the more extensive online version, but not in the print version.)

Medical Research Focuses More on Antibiotics Than on Phages Partly Because Antibiotics Are Easier to Patent

(p. 13) While recent events have provided a painful reminder of the very bad viruses that prey on us, Tom Ireland’s “The Good Virus” is a colorful redemption story for the oft-neglected yet incredibly abundant phage, and its potential for quelling the existential threat of antibiotic resistance, which scientists estimate might cause up to 10 million deaths per year by 2050. Ireland, an award-winning science journalist, approaches the subject of his first book with curiosity and passion, delivering a deft narrative that is rich and approachable.

In the hands of d’Herelle and others, the phage became a potent tool in the fight against cholera. But, in the 1940s, when the discovery of the methods to produce penicillin at an industrial scale led to the “antibiotic era,” phage therapy came to be seen as quackery in Europe and America, in part, Ireland suggests, because antibiotics, unlike phages, fit the mold of capitalist society.

Capitalists love patents. A funny quirk of the patent system is that you cannot patent entire natural things, but you can sometimes patent the way you extract their byproducts. The first antibiotics, being the secretions of fungi, were easier to patent in the United States than phages, which were whole viruses.

For the full review, see:

Alex Johnson. “Going Viral.” The New York Times Book Review (Sunday, September 17, 2023): 13.

(Note: the online version of the review has the date Aug. 15, 2023, and has the title “A Reason to Cheer for Cells and the Viruses That Feed on Them.”)

The book under review is:

Ireland, Tom. The Good Virus: The Amazing Story and Forgotten Promise of the Phage. New York: W. W. Norton & Company, 2023.

In “Hashing Things Out” to Save Lives Bateman “Could Be a Pit Bull”

(p. 20) Don Bateman, an engineer who invented a cockpit device that warns airplane pilots with colorful screen displays and dire audible alerts like “Caution Terrain!” and “Pull Up!” when they are in danger of crashing into mountains, buildings or water — an innovation that has likely saved thousands of lives — died on May 21 [2023] at his home in Bellevue, Wash.

. . .

Bob Champion, a former scientist at Honeywell who worked with Mr. Bateman, said in a telephone interview: “Don had a true passion for saving lives. He was a peach, but behind closed doors, when we were hashing things out, he could be a pit bull.”

. . .

“He never lost his childlike wonder about flying,” Ms. McCaslin said by phone. “He did a lot of his great work from his 40s on.”

. . .

Mr. Bateman told the National Science and Technology Medals Foundation in 2011 that in the late 1960s there were fatal accidents nearly every month, during which a pilot would “fly into something, like a mountain, or go in short on the runway.”

. . .

Determined to do something, Mr. Bateman developed — and in 1974 patented — his first ground proximity warning system: a small box that integrated data from within the aircraft, including the radar altimeter and airspeed indicator, and gave the pilot a 15-second warning of an approaching hazardous condition.

. . .

In the 1990s, the system improved exponentially. Engineers working with Mr. Bateman added GPS and critical terrain data, including topographical maps of Eastern Europe and China that had been charted by the Soviet Union as far back as the 1920s; they had been acquired in Russia at Mr. Bateman’s request.

“We knew, as engineers, that if we could get the terrain data, we could do an awful lot,” he told The Seattle Times.