Could the next blockbuster drug be lab-rat free?

By EMILY ANTHES

In 1937, a U.S. drug company introduced a new elixir to treat strep throat — and unwittingly set off a public health disaster. The product, which had not been tested in humans or animals, contained a solvent that turned out to be toxic. More than 100 people died.

The following year, Congress passed the Federal Food, Drug and Cosmetic Safety Act, requiring pharmaceutical companies to submit safety data to the U.S. Food and Drug Administration before selling new medications, helping to usher in an era of animal toxicity testing.

Now, a new chapter in drug development may be beginning. The FDA Modernization Act 2.0, signed into law late last year, allows drugmakers to collect initial safety and efficacy data using high-tech new tools, such as bioengineered organs, organs on chips and even computer models, instead of live animals. Congress also allocated $5 million to the FDA to accelerate the development of alternatives to animal testing.

Other agencies and countries are making similar shifts. In 2019, the U.S. Environmental Protection Agency announced that it would reduce, and eventually aim to eliminate, testing on mammals. In 2021, the European Parliament called for a plan to phase out animal testing.

These moves have been driven by a confluence of factors, including evolving views of animals and a desire to make drug development cheaper and faster, experts said. But what is finally making them feasible is the development of sophisticated alternatives to animal testing.

It is still early for these technologies, many of which need to be refined, standardized and validated before they can be used routinely in drug development. And even advocates for these alternatives acknowledge that animal testing is not likely to disappear anytime soon.

But momentum is building for non-animal approaches, which could ultimately help speed drug development, improve patient outcomes and reduce the burdens borne by lab animals, experts said.

“Animals are simply a surrogate for predicting what’s going to happen in a human,” said Nicole Kleinstreuer, director of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods.

“If we can get to a place where we actually have a fully human-relevant model,” she added, “then we don’t need the black box of animals anymore.”

Animal attitudes

Animal rights groups have been lobbying for a reduction in animal testing for decades, and they have found an increasingly receptive public. In a 2022 Gallup poll, 43% of Americans said that medical testing on animals was “morally wrong,” up from 26% in 2001.

Reducing animal testing “matters to so many people for so many different reasons,” said Elizabeth Baker, the director of research policy at the Physicians Committee for Responsible Medicine, a nonprofit group that advocates for alternatives to animal testing. “Animal ethics is actually quite a big driver.”

But it is not the only one. Animal testing is also time-consuming, expensive and vulnerable to shortages. Drug development, in particular, is rife with failures, and many medications that appear promising in animals do not pan out in humans. “We’re not 70-kilogram rats,” said Dr. Thomas Hartung, who directs the Johns Hopkins Center for Alternatives to Animal Testing.

Moreover, some cutting-edge new treatments are based on biological products, such as antibodies or fragments of DNA, which may have targets that are specific to humans.

“There’s a lot of pressure, not just for ethical reasons, but also for these economical reasons and for really closing safety gaps, to adapt to things which are more modern and human relevant,” Hartung said.

(Hartung is the named inventor on a Johns Hopkins University patent on the production of brain organoids. He receives royalty shares from, and consults for, the company that has licensed the technology.)

Brave new biology

In recent years, scientists have developed more sophisticated ways to replicate human physiology in the laboratory.

They have learned how to coax human stem cells to assemble themselves into a small, three-dimensional clump, known as an organoid, that displays some of the same basic traits as a specific human organ, such as a brain, a lung or a kidney.

Scientists can use these mini-organs to study the underpinnings of disease or to test treatments, even on individual patients. In a 2016 study, researchers made mini-guts from cell samples from patients with cystic fibrosis and then used the organoids to predict which patients would respond to new drugs.

Scientists are also using 3D printers to produce organoids at scale and to print strips of other kinds of human tissue, such as skin.

Another approach relies on “organs on a chip.” These devices, which are roughly the size of AA batteries, contain tiny channels that can be lined with different kinds of human cells.

Researchers can pump drugs through the channels to simulate how they might travel through a particular part of the body. Compound computations

Not all the new tools require real cells. There are also computational models that can predict whether a compound with certain chemical characteristics is likely to be toxic, how much of it will reach different organs and how quickly it will be metabolized.

The models can be adjusted to represent different types of patients. For instance, a drug developer could test whether a medication that works in young adults would be safe and effective in older adults, who often have reduced kidney function.

“If you can identify the problems as early as possible using a computational model that saves you going down the wrong route with these chemicals,” said Judith Madden, an expert on “in silico,” or computer-based, chemical testing at Liverpool John Moores University. (Madden is also the editor-in-chief of the journal Alternatives to Laboratory Animals.)

Some of the approaches have been around for years, but advances in computing technology and artificial intelligence are making them increasingly powerful and sophisticated, Madden said.

Virtual cells have also shown promise. For instance, researchers can model individual human heart cells using “a set of equations that describe everything that’s going on in the cell,” said Elisa Passini, the program manager for drug development at the National Center for the Replacement, Refinement and Reduction of Animals in Research, or NC3Rs, in Britain.

Reduce or replace

Many potential animal alternatives will require more investment and development before they can be used widely, experts said. They also have limitations of their own. Computer models, for instance, are only as good as the data they are built on, and more data is available on certain types of compounds, cells and outcomes than others.

For now, these alternative methods are better at predicting relatively simple, short-term outcomes, such as acute toxicity, than complicated, long-term ones, such as whether a chemical might increase the risk of cancer when used over months or years, scientists said.

And experts disagreed on the extent to which these alternative approaches might replace animal models. “We’re absolutely working toward a future where we want to be able to fully replace them,” Kleinstreuer said, although she acknowledged that it might take decades, “if not centuries.”

But others said that these technologies should be viewed as a supplement to, rather than a replacement for, animal testing. Drugs that prove promising in organoids or computer models should still be tested in animals, said Matthew Bailey, president of the National Association for Biomedical Research, a nonprofit group that advocates for the responsible use of animals in research.

“Researchers still need to be able to see everything that happens in a complex mammalian organism before being allowed to move to the human clinical trials,” he said.

Legal Notice

IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF PUERTO RICO MTGLQ INVESTORS LP

Plaintiff V. EDRIC ENRIQUE VIVONI RIVERA; ET AL Defendants

Civil Action Num.: 19-CV01599. (JAG). Matter: COLLECTION OF MONIES AND FORECLOSURE. NOTICE OF SALE.

To: EDRIC ENRIQUE VIVONI RIVERA and the GENERAL PUBLIC:

WHEREAS: On March 2, 2022

Default Judgment was entered and grated on same day in favor of Plaintiff to recover from defendants the principal amount of $77,007.64 plus interest at a rate of 3.375% per annum since January 1st, 2018, which continue to accrue until the debt is paid in full; a deferred principal balance of $55,200.67, which does not accrue interest; late charges on the amount of 5.00% of each and any monthly installment not received by the note holder within 15 days after the installment was due, all advances made under the mortgage note including but not limited to insurance premiums, taxes and inspections as well as 10% of the original principal amount $26,200.00 to cover, costs, expenses, and attorney’s fees guaranteed under the mortgage obligations. The records of the case and of these proceedings may be examined by interested parties at the Office of the Clerk of the United States District Court, Room 150 Federal Office Building, 150 Chardon Avenue, Hato Rey, Puerto Rico.

WHEREAS: Pursuant to the terms of the aforementioned Judgment, Order of Execution, and the Writ of Execution thereof, the undersigned Special Master was ordered to sell at public auction for U.S. currency in cash or certified check without appraisement or right of redemption to the highest bidder and at the office of the Clerk of the Court, Room 150 – Federal Office Building, 150 Carlos Chardón Avenue, Hato Rey, Puerto Rico, to cover the sums adjudged to be paid to the plaintiff, the following property described in Spanish: RUSTICA: Parcela de terreno en el Barrio Caimito Alto del término municipal de San Juan, Puerto Rico, con un área superficial de cinco mil ciento cuarenta y dos metros cuadrados con tres mil trescientos setenta y una diez milésimas de otro (5,142.3371 m.c.), equivalentes a una cuerda con tres mil ochenta y cuatro diez milésimas de cuerda (1.2084 cdas) (así surge) identificada en el Plano de Inscripción con el número dos (2). En lindes por el NORTE, en tres alineaciones que suman ochenta y cuatro metros lineales con mil quinientos siete diez milésimas de otro (84.1507 ml) con la faja de uso público del Plano de Inscripción; por el SUR, en seis (6) alineaciones que suman treinta y cinco metros lineales con cuatro mil cuatro setecientos treinta y cuatro diez milésimas de otro (34.4734 ml) con el solar número uno (1) del Plano de Inscripción; por el ESTE, en cuatro (4) alineaciones que suman ochenta y siete metros lineales con cuatrocientos treinta y una diez milésimas de otro (87.0431 ml) con la faja de uso público del Plano de Inscripción; por el OESTE, en cuatro (4) alineaciones que suman ochenta y siete metros lineales con tres mil setecientos quince (87.3715 ml) con terrenos de Tomas Guzmán. Contiene una estructura para fines residenciales. The property is recorded at Page 189 of Volume 807 of Rio Piedras Sur, Property Registry of Puerto Rico, and lot number 22,359, Section IV of San Juan. Property address: PR 1 KM 27.4, Caimito Alto Ward, San Juan, P.R. 00926. The deed of mortgage is recorded at Page number 190 of Volume number 807 of Rio Piedras Sur, lot number 22,359, 4th inscription in the Property Registry of San Juan, Fourth Section. The deed of modification # 27 is recorded at Page 490 of volume 807 of Rio Piedras Sur, 6th inscription. WHEREAS: This property is subject to the following liens: Senior Liens: NONE. Junior Liens: NONE. Other Liens: NONE. Potential bidders are advised to verify the extent of preferential liens with the holders thereof. It shall be understood that each bidder accepts as sufficient the title and that prior and preferential liens to the one being foreclosed upon, including but not limited to any property tax, liens, (express, tacit, implied or legal) shall continue in effect it being understood further that the successful bidder accepts them and is subrogated in the responsibility for the same and that the bid price shall not be applied toward their cancellation. THEREFORE, the FIRST PUBLIC SALE shall be held on the 4TH DAY OF APRIL OF 2023, AT: 9:00 AM. The minimum bid that will be accepted is the sum of $262,000.00. In the event said first auction does not produce a bidder and the property is not adju- dicated, a SECOND PUBLIC AUCTION shall be held on the 11TH DAY OF APRIL OF 2023, AT: 9:00 AM, and the minimum bid that will be accepted is the sum $174,666.67, which is two-thirds of the amount of the minimum bid for the first public sale. If a second auction does not result in the adjudication and sale of the property, a THIRD PUBLIC AUCTION will be held on the 18TH DAY OF APRIL OF 2023, AT: 9:00 AM, and the minimum bid that will be accepted is the sum of $131,000.00, which is one-half of the minimum bid in the first public sale. Should there be no award or adjudication at the third public sale, the property may be awarded to the creditor for the entire amount of its debt if it is equal to or less than the amount of the minimum bid of the third public sale, crediting this amount to the amount owed if it is greater. The undersigned Special Master shall not accept in payment of the property to be sold anything but United States currency (cash), or certified checks, except in case the property is sold and adjudicated to the plaintiff, in which case the amount of the bid made by said plaintiff shall be credited and deducted from its credit; said plaintiff being bound to pay in cash or certified check only any excess of its bid over the secured indebtedness that remains unsatisfied. WHEREAS: Said sale to be made by the undersigned Special Master subject to confirmation by the United States District Court for the District of Puerto Rico and the deed of conveyance and possession to the property will be executed and delivered only after such confirmation. Upon confirmation of the sale, an order shall be issued cancelling all junior liens. For further particulars, reference is made to the judgment entered by the Court in this case, which can be examined in the Office of Clerk of the United States District Court, District of Puerto Rico. In San Juan, Puerto Rico, this 10th day of February of 2023. PEDRO A. VÉLEZ BAERGA, SPECIAL MASTER, 787-672-8269.

Legal Notice

ESTADO LIBRE ASOCIADO DE PUERTO RICO TRIBUNAL DE PRIMERA INSTANCIA

SALA SUPERIOR DE BAYA-

MÓN REVERSE MORTGAGE FUNDING LLC.

Demandante Vs. RAMONITA SOLLA

SERRANO T/C/C

RAMONITA SOLLA

SERRAN T/C/C

RAMONITA SOLLASERRANO T/C/C

RAMONITA SOLLA; ESTADOS UNIDOS DE AMERICA

Demandados

Civil Núm.: BY2021CV01094.

Sobre: EJECUCIÓN DE HIPOTECA. EDICTO DE SUBASTA. ESTADOS UNIDOS DE AMÉRICA, EL PRESIDENTE DE LOS ESTADOS UNIDOS, EL ESTADO LIBRE ASOCIADO DE PUERTO RICO, SS.

A: LA PARTE DEMANDADA, AL (A LA) SECRETARIO(A) DE HACIENDA DE PUERTO RICO Y AL PÚBLICO

GENERAL:

Certifico y Hago Constar: Que en cumplimiento con el Mandamiento de Ejecución de Sentencia que me ha sido dirigido por el (la) Secretario(a) del Tribunal de Primera Instancia, Sala Superior de Bayamón, en el caso de epígrafe, venderé en pública subasta y al mejor postor, por separado, de contado y por moneda de curso legal de los Estados Unidos de América y/o Giro Postal y Cheque Certificado, en mi oficina ubicada en el Tribunal de Primera Instancia, Sala de Bayamón, Cuarto Piso, Oficina de Alguaciles de Subastas, el 18 DE ABRIL DE 2023, A LAS 10:45 DE LA MAÑANA, todo derecho título, participación o interés que le corresponda a la parte demandada o cualquiera de ellos en el inmueble hipotecado objeto de ejecución que se describe a continuación: URBANA: Solar radicado en la Urbanización Sierra Bayamón, situada en el Barrio Hato Tejas de Bayamón, Puerto Rico, que se describe como sigue: Solar numero veinticinco (25) de la Manzana sesenta y tres (63), con un área de ciento setenta y cinco punto cero cero (175.00 m/c) metros cuadrados. En lindes por el NORTE, con la calle cincuenta y cuatro (54), distancia de siete punto cero cero (7.00) metros; por el SUR, con el solar numero treinta y tres (33), distancia de siete punto cero cero (7.00) metros; por el ESTE, con el solar numero veintiséis (26) distancia de veinticinco punto cero cero (25.00) metros; y por el OESTE, con el solar numero veinticuatro (24), distancia de veinticinco punto cero cero (25.00) metros. Enclava una casa. Finca número 3,001 inscrita al folio 1 del tomo 65 de Bayamón Norte, Registro de la Propiedad de Bayamón, Sección III. La Hipoteca Revertida consta inscrita al Tomo Karibe de Bayamón Norte, Registro de la Propiedad de Bayamón, Sección III, inscripción 8ª. Propiedad localizada en: URB. SIERRA BAYAMON, 63-25 CALLE 54, BAYAMON, PR 00961. Según figuran en la certificación registral, la propiedad objeto de ejecución está gravada por las siguientes cargas anteriores o preferentes: Nombre del Titular: N/A. Suma de la Carga: N/A. Fecha de Vencimiento: N/A. Según figuran en la certificación registral, la propiedad objeto de ejecución está gravada por las siguientes cargas posteriores a la inscripción del crédito ejecutante: Nombre del Titular: Secretario de la Vivienda y Desarrollo Urbano. Suma de la Carga: $129,000.00.

Fecha de Vencimiento: 1 de mayo de 2092. Se entenderá que todo licitador acepta como bastante la titularidad de la propiedad y que todas las cargas y gravámenes anteriores y los preferentes al crédito ejecutante antes descritos, si los hubiere, continuarán subsistentes. El rematante acepta dichas cargas y gravámenes anteriores, y queda subrogado en la responsabilidad de los mismos, sin destinarse a su extinción el precio del remate. Se establece como tipo de mínima subasta la suma de $129,000.00, según acordado entre las partes en el precio pactado en la escritura de hipoteca. De ser necesaria una SEGUNDA SUBASTA por declararse desierta la primera, la misma se celebrará en mi oficina, ubicada en el Tribunal de Primera Instancia, Sala de Bayamón, Cuarto Piso, Oficina de Alguaciles de Subastas, el 25 DE ABRIL DE 2023, A LAS 10:45 DE LA MAÑANA, y se establece como mínima para dicha segunda subasta la suma de $86,000.00, 2/3 partes del tipo mínima establecido originalmente. Si tampoco se produce remate ni adjudicación en la segunda subasta, se establece como mínima para la TERCERA SUBASTA, la suma de $64,500.00, la mitad (1/2) del precio pactado y dicha subasta se celebrará en mi oficina, ubicada en el Tribunal de Primera Instancia, Sala de Bayamón, Cuarto Piso, Oficina de Alguaciles de Subastas, el 2 de mayo de 2023, a las 10:45 de la mañana. Dicha subasta se llevará a cabo para, con su producto satisfacer a la parte demandante, el importe de la Sentencia dictada a su favor ascendente a la suma de $48,602.21 por concepto de principal, más la suma de $10,520.62 en intereses acumulados al 30 de junio de 2021 y los cuales continúan acumulándose a razón de 4.475% anual hasta su total y completo pago; más la sumas de $5,036.87 en seguro hipotecario; $334.00 en seguro; $1,360.00 de tasaciones; $520.00 de inspecciones; $5,820.30 en honorarios de abogado; más la cantidad de 10% del pagare original en la suma de $12,900.00, para gastos, costas y honorarios de abogado, esta última habrá de devengar intereses al máximo del tipo legal fijado por la oficina del Comisionado de Instituciones Financieras aplicable a esta fecha, desde este mismo día hasta su total y completo saldo. La venta en pública subasta de la referida propiedad se verificará libre de toda carga o gravamen posterior que afecte la mencionada finca, a cuyo efecto se notifica y se hace saber la fecha, hora y sitio de la PRIMERA, SEGUNDA Y TERCERA SUBASTA, si esto fuera necesario, a los efectos de que cualquier persona o personas con algún interés puedan comparecer a la celebración de dicha subasta. Se notifica a todos los interesados que las actas y demás constancias del expediente de este caso están disponibles en la Secretaría del Tribunal durante horas laborables para ser examinadas por los (las) interesados (as). Y para su publicación en el periódico The San Juan Daily Star, que es un diario de circulación general en la isla de Puerto Rico, por espacio de dos semanas consecutivas con un intervalo de por lo menos siete (7) días entre ambas publicaciones, así como para su publicación en los sitios públicos de Puerto Rico. Expedido en Bayamón, Puerto Rico, hoy 17 de febrero de 2023. FRÁNCES TORRES CONTRERAS, ALGUACIL REGIONAL. MARIBEL LANZAR VELÁZQUEZ, ALGUACIL PLACA #735.

LEGAL NOTICE

ESTADO LIBRE ASOCIADO DE PUERTO RICO TRIBUNAL DE PRIMERA INSTANCIA SALA SUPERIOR DE SAN JUAN

REVERSE MORTGAGE

FUNDING LLC.

Demandante Vs.

SUCESION BALBINO

ANTONIO COLON

MARTINEZ T/C/C

BALBINO A. COLON

MARTINEZ T/C/C

BALBINO COLON

MARTINEZ COMPUESTA

POR NESTOR COLON

MORALES, IVAN COLON

MORALES, RUBEN

COLON MORALES; JOHN DOE Y JANE DOE COMO

The San Juan Daily Star

POSIBLES HEREDEROS DESCONOCIDOS; SUCESION FELIPA

NERI MORALES PAGAN

T/C/C NERY MORALES

PAGAN T/C/C NERY MORALES DE COLON

T/C/C NERY MORALES

COLON COMPUESTA

POR NESTOR COLON MORALES, IVAN COLON MORALES, RUBEN

COLON MORALES; JOHN ROE Y JANE ROE COMO

POSIBLES HEREDEROS DESCONOCIDOS; ESTADOS UNIDOS DE AMERICA; CENTRO DE RECAUDACION DE INGRESOS MUNICIPALES (CRIM)

Demandados

Civil Núm.: SJ2019CV08341.

Sobre: EJECUCIÓN DE HIPOTECA. EDICTO DE SUBASTA. ESTADOS UNIDOS DE AMÉRICA, EL PRESIDENTE DE LOS ESTADOS UNIDOS, EL ESTADO LIBRE ASOCIADO DE PUERTO RICO, SS.

A: LA PARTE

DEMANDADA, AL (A

LA) SECRETARIO(A) DE HACIENDA DE PUERTO RICO Y AL PÚBLICO

GENERAL:

Certifico y Hago Constar: Que en cumplimiento con el Mandamiento de Ejecución de Sentencia que me ha sido dirigido por el (la) Secretario(a) del Tribunal de Primera Instancia, Sala Superior de San Juan, en el caso de epígrafe, venderé en pública subasta y al mejor postor, por separado, de contado y por moneda de curso legal de los Estados Unidos de América y/o Giro Postal y Cheque Certificado, en mi oficina ubicada en el Tribunal de Primera Instancia, Sala de San Juan, el 4 DE ABRIL DE 2023, A LAS 9:00 DE LA MAÑANA, todo derecho título, participación o interés que le corresponda a la parte demandada o cualquiera de ellos en el inmueble hipotecado objeto de ejecución que se describe a continuación: URBANA: Solar marcado con el numero dieciséis (16) del Bloque “H” en el plano de inscripción de la Urbanización University Gardens, en el Barrio Hato Rey Sur, del término municipal de San Juan, Puerto Rico, con un área superficial de cuatrocientos sesenta y siete punto cincuenta y dos (467.52 m.c.) metros cuadrados. En lindes por el Norte, en veintidós punto quinientos (22.500 m.) metros, con el solar número diecisiete (17) del bloque “H”; por el Sur, en veintidós punto quinientos (22.500 m.) metros, con el solar número quince del bloque “H”; por el Este, en veinte punto cero cero (20.00 m.) metros, con la calle número ocho (8) hoy denominada Harvard; y por el Oeste, en veintiuno punto quinientos cincuenta y tres (21.553 m.) metros, con los solares numero dos (2) y tres (3) del bloque “H”. Enclava una casa. Inscrita al folio 154 del tomo 859 de Rio Piedras Norte, finca 19,100, Registro de la Propiedad de San Juan, Sección II. La Hipoteca Revertida consta inscrita al folio 127 del tomo 1571 de Rio Piedras Norte, finca 19,100, Registro de la Propiedad de San Juan, Sección II, inscripción 14ª. Propiedad localizada en: URB. UNIVERSITY GARDENS, 903 CALLE HARVARD, SAN JUAN, PR 00927. Según figuran en la certificación registral, la propiedad objeto de ejecución está gravada por las siguientes cargas anteriores o preferentes: Nombre del Titular: N/A. Suma de la Carga: N/A. Fecha de Vencimiento: N/A. Según figuran en la certificación registral, la propiedad objeto de ejecución está gravada por las siguientes cargas posteriores a la inscripción del crédito ejecutante: Nombre del Titular: Secretario de la Vivienda y Desarrollo Urbano. Suma de la Carga: $459,000.00. Fecha de Vencimiento: 26 de mayo de 2076. Se entenderá que todo licitador acepta como bastante la titularidad de la propiedad y que todas las cargas y gravámenes anteriores y los preferentes al crédito ejecutante antes descritos, si los hubiere, continuarán subsistentes. El rematante acepta dichas cargas y gravámenes anteriores, y queda subrogado en la responsabilidad de los mismos, sin destinarse a su extinción el precio del remate. Se establece como tipo de mínima subasta la suma de $306,000.00, según acordado entre las partes en el precio pactado en la escritura de hipoteca. De ser necesaria una SEGUNDA SUBASTA por declararse desierta la primera, la misma se celebrará en mi oficina, ubicada en el Tribunal de Primera Instancia, Sala de San Juan, el 12 DE ABRIL DE 2023, A LAS 9:00 DE LA MAÑANA, y se establece como mínima para dicha segunda subasta la suma de 204,000.00, 2/3 partes del tipo mínima establecido originalmente. Si tampoco se produce remate ni adjudicación en la segunda subasta, se establece como mínima para la TERCERA SUBASTA, la suma de $153,000.00, la mitad (1/2) del precio pactado y dicha subasta se celebrará en mi oficina, ubi-