new england primate research center southborough ma

Harvard primate lab’s end puzzles researchers

Center leaves legacy of discovery, dispute.

At a secluded research center 25 miles west of Boston, Harvard Medical School scientists have used primates to make key discoveries over the last half-century, earning the center a unique spot in the region’s landscape of prestigious biomedical research institutions.

They unambiguously showed that nicotine is addictive and did experiments that laid the basis for the ongoing quest to develop an HIV vaccine.

At the end of May, the long history of the New England Primate Research Center will come to an abrupt end as Harvard takes the unusual step — one that is baffling to many researchers — to close the Southborough facility.

It is one of eight national primate research centers, and in the past half-century, the only one to shut down. Closure is necessary, Harvard says, for “strategic” reasons — not because of a series of high-profile revelations of monkey deaths at the center.

Advertisement

But closure, at a cost to Harvard of $10.8 million so far, has meant the relocation of some 2,000 monkeys, mainly to other centers, layoffs of staff members, loss of faculty, and the end of roughly $25 million a year in research funding. It leaves Harvard in the unusual position of taking a major step back from primate research at a time when the science remains a powerful tool to examine both new and old biomedical threats.

“Primate research is stronger, if you will, more needed, than ever,’’ said John Harding, health scientist administrator for the Division of Comparative Medicine at the National Institutes of Health. “So certainly closing down the Harvard center — which I emphasize was Harvard’s decision not ours — doesn’t in any way speak to the lack of importance of research using non-human primates. Ebola is a very good example of that.”

By all rights, the center’s epitaph should be its long list of scientific contributions. But mounting evidence threatens to overshadow that legacy, evidence of problems that were deeper and more troubling than Harvard has admitted, with broken lines of communication between the remote center and the leading medical school that owns and operates it.

Those issues were revealed dramatically by the deaths, between 2010 and 2012, of four monkeys, animal care failures that resulted in a $24,000 fine by federal regulators. Then the Globe reported last month that a dozen monkeys were found dehydrated and dead in their cages or were euthanized for poor health between 1999 and 2011.

The deaths reignited complaints from animal rights activists about the center’s treatment of monkeys.

Documents obtained by the Globe show a startling level of disregard for protocols that govern animal research. An internal Harvard investigation of a monkey’s death in 2010, which first attracted public scrutiny to the center, reveals that the incident was only reported after a federal inspector showed up unannounced, 20 days after the death. A scientific journal is looking into a study done at the center because a former director has questioned its integrity, saying that he believes that many of the monkeys included in the research were treated in an inhumane way.

Harvard Medical School dean Dr. Jeffrey Flier said the decision to close the center was unrelated to these problems and the loss will not diminish the university’s research capabilities.

A report prepared by a Harvard committee investigating the initial monkey death in 2010 shows just how high the stakes were in running such a facility. These weren’t minor issues at an out-of-sight suburban campus; the committee saw the problems they uncovered as a direct threat to Harvard’s standing.

“The public at large rightfully expects research with animals to be carried out in the most ethical manner and with the utmost scrutiny as to the animal’s welfare,” the report said.

“Without such scrutiny,’’ the report continued, “we put the institution at risk’’ both reputationally and financially.

In the 1960s, the US government established the regional primate centers, where scientists could study and conduct experiments on animals that are closely related to human beings.

A 1962 Globe article touting the region’s industries and universities included the primate center among its assets: “Harvard Medical School has been given $2.5 million . . . to build a New England primate center to help throw light on man’s diseases.”

The eight centers scattered across the country are an enormous national investment. Harvard has received $268 million in taxpayer-funded base grants since 1980 to maintain its primates, $8 million since 1989 has been given for construction, and many millions more have supported individual research projects.

Compared with laboratory mice or cells in a dish, primates can provide deep insight into complex behaviors, infectious diseases, or neuropsychological ailments that afflict people. But it is precisely because the animals so closely resemble humans that the research comes with huge responsibilities.

The public trust in the taxpayer-funded enterprise, which is largely closed off to the public due in part to concerns about violence from animal activists, depends on institutions following the Animal Welfare Act and other policies. There are unannounced inspections, but oversight depends largely on the requirement that adverse events be promptly reported so that underlying problems can be quickly corrected.

At the Southborough primate center, that oversight appears to have been largely delegated to the leadership team in place at the remote, wooded campus. The center is so distant that Flier, the medical school dean, whose name is listed on $90 million worth of taxpayer-funded grants for the center since 2007, said he has been there only three or four times and never visited until after problems began to emerge.

“For many years, the New England Primate Research Center’s leadership team had a track record of advancing science, while Harvard Medical School administrators worked with the center’s on-site management team,” Flier said in a statement.

Ronald Desrosiers, the longtime former director of the center who now works at the University of Miami, did not respond to repeated requests for an interview. But the National Institutes of Health guidelines say the principal investigator on a grant — in this case, Flier — “agrees to accept responsibility for the scientific conduct of the project.”

Flier said that when problems were identified, medical school leadership decisively intervened to make large-scale changes to leadership and procedures.

However, evidence gathered by the Globe suggests that the problems did not happen overnight. Oversight appears to have broken down in fundamental ways and seeped into the culture of the center well before the medical school leadership discovered them.

The event that sparked attention to the center occurred on a Wednesday morning in June 2010. According to a report of the Harvard internal investigation obtained by the Globe, two animal technicians waited for a high-temperature wash of a primate cage to finish. When it was done, they made a horrifying discovery: the body of a 7-year-old female monkey on the cage floor. Overcome with emotion, one technician fled the room.

The disturbing event earned Harvard Medical School a slap on the wrist — a warning letter from federal regulators.

But the previously undisclosed internal report found the school’s own investigators were alarmed that nearly three weeks had passed without the animal death being reported to a Harvard committee. The report recommended that new guidelines be drafted, ensuring that this type of death would be reported “within 24 hours or sooner.”

The Harvard report called the delay “a poor decision.”

Official reports of the animal’s death have stated the monkey died prior to going through the wash, but the investigation also found that specialists involved in the necropsy “admit . . . it is nearly impossible to conclude definitively” whether the monkey was dead before the 170 degree wash.

“We implore our senior leaders to support” efforts to fix the relationship with the primate center, the report stated. It noted a problematic disconnect between the animal care technicians and senior management at the center. The report found that staff had “sincere and practical suggestions for improvements.”

The Globe recently also found that Harvard has no evidence that the dozen dehydrated monkey deaths beginning in 1999 were reported to its internal committee that oversees animal care.

Other documents sent by Harvard to federal regulators, obtained through the Freedom of Information Act, suggest that the problems Harvard began identifying in 2011 were wide-ranging.

There was a fundamental breakdown of basic procedures, including “unacceptable and inadequate record-keeping,” an instance in which animals were not euthanized on time, and questions about how federal grants were billed for blood draws. Tuberculosis tests were not administered properly and over a five-year period, six federal certificates required when monkeys are shipped to other facilities were signed by someone without the authority to do so. Harvard’s own letter to regulators mentions the “long-term nature” of the problems.

Harvard has repeatedly said that a committee of external experts was convened to evaluate the center and maintains that problems were self-identified and fixed.

The university has denied requests to see a full copy of the report by the consultants and instead provided a brief summary. A reporter’s request to visit the center as it was closing was also denied.

What may be most telling is that after a change in leadership in 2011, a slew of animal care problems was disclosed, when Harvard self-reported three primate deaths in the span of five months. In letters to regulators, Harvard officials praised Dr. Frederick Wang, the interim leader during this period, for the “transformative culture of transparency” he had brought to the center.

In late June 2012, a detailed, 21-page letter to regulators outlined many changes and ended on a strong note.

“Our goal is to ensure that the important science of the [New England Primate Research Center] will continue to further medical breakthroughs, guided by our unwavering commitment to animal welfare,” the unidentified medical school official wrote in the letter.

Ten months later, Flier stunned the research community with the announcement the center would close due to financial reasons.

“Is this really where we want to put the school’s resources at a time when we have to make tradeoffs?’’ Flier said in a recent interview. “It just reached a point after 50 years where we said, ‘You know, maybe for the next 50 years, we won’t have a primate center.’ ”

The closure cost includes the expense of shipping the animals to new homes, mostly at other research centers.

Welkin Johnson, a former Harvard faculty member who moved to Boston College from the primate center, said that one of his biggest concerns is for the animals. Extensive precautions and health checks are taken to ensure their welfare before and during transport, but shipping hundreds of monkeys to new homes could cause stress, he said.

Harvard is currently under an open investigation by federal regulators after six monkeys that arrived healthy at the Oregon Zoo last May died two days later.

Pamela Caudill, chief research operations officer for the medical school, said Harvard is still in discussions with the National Institutes of Health about whether it will have to return any money from the federal construction grants given to the center.

Harvard is also still reviewing its options on what to do with the land. The campus is home to a storage facility for a depository that houses books and other media.

Closing costs are “money that would have been better used to support research that ultimately could have continued to combat diseases like AIDS and Parkinson’s, rather than shutting down a productive research enterprise, mothballing a valuable research campus, and walking away from” millions in federal funding, said R. Paul Johnson, a former director of the primate center who now leads the Yerkes National Primate Research Center at Emory University.

The fact that Harvard, with its considerable resources and its commitment to cutting-edge research, is shutting its center might be seen as a signal that such studies are no longer important or possible, but scientists — including Flier — said the opposite was true.

“Non-human primate research is alive and well and is definitely financially viable,” said Johnson, of the Yerkes center.

At that center, Johnson said grant awards in the last fiscal year 2014 were up 13 percent over the previous year, to a record $73 million.

Flier said the closure does not create a scientific gap at Harvard and will not erode its leadership in any area. Other scientists disagreed.

“I think that Harvard will grow to regret their loss of preeminence in the primate infectious disease research field, once the dust settles,” wrote Nancy Haigwood, director of the Oregon National Primate Research Center.

Carolyn Y. Johnson can be reached at [email protected] . Follow her on Twitter @carolynyjohnson .

An official website of the United States government

Here's how you know

Official websites use .gov A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS A lock ( Lock Locked padlock ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

• U.S. Department of Health & Human Services
• National Institutes of Health
• Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI)

Closure of the New England National Primate Research Center

On May 31, 2015 Harvard Medical School (HMS) officially closed the New England National Primate Research Center, which had been funded by the NIH for five decades. The HMS statement, entitled “Legacy Continues as Center Closes” is at  http://hms.harvard.edu/news/legacy-continues-center-closes .

• Election 2024
• Entertainment
• Newsletters
• Photography
• AP Investigations
• AP Buyline Personal Finance
• AP Buyline Shopping
• Press Releases
• Israel-Hamas War
• Russia-Ukraine War
• Global elections
• Asia Pacific
• Latin America
• Middle East
• Election results
• Google trends
• AP & Elections
• AP Top 25 College Football Poll
• Auto Racing
• Movie reviews
• Book reviews
• Financial Markets
• Business Highlights
• Financial wellness
• Artificial Intelligence
• Social Media

Monkey deaths prompt investigation of Harvard primate center

• Copy Link copied

SOUTHBOROUGH, Mass. (AP) — The U.S. Department of Agriculture is investigating the New England Primate Research Center run by Harvard Medical School in Massachusetts in response to the deaths of six monkeys at the Oregon Zoo last year, shortly after they arrived from the center.

The Boston Globe reported Friday ( http://bit.ly/1I0mF3K ) that the department confirmed the investigation, but didn’t release details.

A Harvard Medical School spokeswoman said the deaths of the six tamarin monkeys in Oregon last May triggered the USDA investigation. The medical school said in a statement that the monkeys arrived at the zoo in good condition.

The Primate Research Center in Southborough is scheduled to close in May.

Oregon Zoo officials could not determine how the six monkeys died, but said they all showed signs of systemic shock.

Information from: The Boston Globe, http://www.bostonglobe.com

• The Nutshell

Harvard to Close Primate Center

The nih-funded new england primate research center is to be shuttered after 50 years of operation because of the grim outlook for federal funding..

Animal death at Harvard Primate Center investigated

From today’s Metrowest Daily News :

The federal government is weighing whether it will launch a formal probe into the practices of the New England Primate Research Center following the death of an animal there in June. “The preliminary step is simply making the routine inspection,” said David Sacks, spokesman for the U.S. Department of Agriculture. “Research facilities are responsible for following protocol to the letter.” During a June 29 inspection, the USDA’s Animal and Plant Health Inspection Services said it found the body of a primate on the floor of a cage that had been sent through a cage-washing system on June 9.

The primate center operated by Harvard Medical School is located off Parmenter Road in Southborough. It houses about 1,800 primates.

I am familiar with the group “Stop Animal Exploitation Now”–they are the group by which this entire situation came to light by. If not for these groups institutions such as Harvard would keep moving forward without a sideways glance. And no, it is not always in the spirit of medical science– if you think that is always is then you have been brainwashed. Not only am a bit skeptical that the primate was dead before it went through the cage washers but if you have such a horrendous occupation would you not at least check to see if there was a breathing creature in it? I mean really, what? were you texting and just pushed the button a bit too quickly?

and if the poor animal who had been tested upon was already dead would you not have some compassion and remove it from the cage?

shame on HARVARD!

“i don’t eat anything that has caused me harm”

realized that i forgot the “not” in my quote althought i would not eat anything that has caused me harm either!

I agree with Carrie. This place makes me sick to my stomach. Never enough regulations to protect these animals. Let’s hope some of the animal advocate groups get involved! The thought of Havard enlarging their facility is equally disturbing…maybe this will hinder that process.

• Utility Menu

Harvard Property Information Resource Center

• PIRC Catalog
• Buildings / Sites
• Collections
• Firms & People
• Shared Favorites
• Advanced Search

Research Building 6 [Demolished]

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• My Bibliography
• Collections
• Citation manager

Save citation to file

Email citation, add to collections.

• Create a new collection
• Add to an existing collection

Add to My Bibliography

Your saved search, create a file for external citation management software, your rss feed.

• Search in PubMed
• Search in NLM Catalog
• Add to Search

Transcriptomic profiling of the ventral tegmental area and nucleus accumbens in rhesus macaques following long-term cocaine self-administration

Affiliations.

• 1 Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, United States; University of Mississippi Medical Center, Jackson, MS 39216, United States; Tulane National Primate Research Center, Covington, LA 70433, United States. Electronic address: [email protected].
• 2 Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, United States; Boston University, Boston, MA 02118, United States.
• 3 Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, United States; University of Massachusetts-Amherst, Amherst, MA 01003, United States.
• 4 Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, United States.
• 5 Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, United States; SUNY Upstate Medical University, Syracuse, NY 13210, United States.
• 6 Harvard Medical School, New England Primate Research Center, Southborough, MA 01772, United States; University of Mississippi Medical Center, Jackson, MS 39216, United States; Tulane National Primate Research Center, Covington, LA 70433, United States; University of Massachusetts-Amherst, Amherst, MA 01003, United States.
• PMID: 28376414
• PMCID: PMC5693237
• DOI: 10.1016/j.drugalcdep.2017.01.030

Background: The behavioral consequences associated with addiction are thought to arise from drug-induced neuroadaptation. The mesolimbic system plays an important initial role in this process, and while the dopaminergic system specifically has been strongly interrogated, a complete understanding of the broad transcriptomic effects associated with cocaine use remains elusive.

Methods: Using next generation sequencing approaches, we performed a comprehensive evaluation of gene expression differences in the ventral tegmental area and nucleus accumbens of rhesus macaques that had self-administered cocaine for roughly 100days and saline-yoked controls. During self-administration, the monkeys increased daily consumption of cocaine until almost the maximum number of injections were taken within the first 15min of the one hour session for a total intake of 3mg/kg/day.

Results: We confirm the centrality of dopaminergic differences in the ventral tegmental area, but in the nucleus accumbens we see the strongest evidence for an inflammatory response and large scale chromatin remodeling.

Conclusions: These findings suggest an expanded understanding of the pathology of cocaine addiction with the potential to lead to the development of alternative treatment strategies.

Keywords: Cocaine; Genetics; Mesolimbic pathway; Neuroinflammation; Rhesus monkey.

Copyright © 2017 Elsevier B.V. All rights reserved.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

No conflict declared.

Grouped data is shown for…

Grouped data is shown for 5 rhesus makes self-administering cocaine. Average number of…

Volcano plots comparing the normalized…

Volcano plots comparing the normalized expression of genes in long-term cocaine self-administering animals…

Canonical pathway enrichment analysis of…

Canonical pathway enrichment analysis of genes differentially expressed in the VTA (A) and…

Heatmap showing the effects of…

Heatmap showing the effects of long-term cocaine self-administration on gene expression in the…

Similar articles

• Cocaine-induced alterations in nucleus accumbens ionotropic glutamate receptor subunits in human and non-human primates. Hemby SE, Tang W, Muly EC, Kuhar MJ, Howell L, Mash DC. Hemby SE, et al. J Neurochem. 2005 Dec;95(6):1785-93. doi: 10.1111/j.1471-4159.2005.03517.x. J Neurochem. 2005. PMID: 16363995 Free PMC article.
• Neutralization of neutrophin-3 in the ventral tegmental area or nucleus accumbens differentially modulates cocaine-induced behavioral plasticity in rats. Freeman AY, Pierce RC. Freeman AY, et al. Synapse. 2002 Nov;46(2):57-65. doi: 10.1002/syn.10123. Synapse. 2002. PMID: 12211082
• Tropomyosin-related kinase B in the mesolimbic dopamine system: region-specific effects on cocaine reward. Graham DL, Krishnan V, Larson EB, Graham A, Edwards S, Bachtell RK, Simmons D, Gent LM, Berton O, Bolanos CA, DiLeone RJ, Parada LF, Nestler EJ, Self DW. Graham DL, et al. Biol Psychiatry. 2009 Apr 15;65(8):696-701. doi: 10.1016/j.biopsych.2008.09.032. Epub 2008 Nov 6. Biol Psychiatry. 2009. PMID: 18990365 Free PMC article.
• Extracellular dopamine in the rat ventral tegmental area and nucleus accumbens following ventral tegmental infusion of cocaine. Chen SY, Burger RI, Reith ME. Chen SY, et al. Brain Res. 1996 Aug 12;729(2):294-6. Brain Res. 1996. PMID: 8877004
• Tribute to: Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area [William Corrigall, Kathleen Coen and Laurel Adamson, Brain Res. 653 (1994) 278-284]. Leri F, Vaccarino FJ. Leri F, et al. Brain Res. 2016 Aug 15;1645:61-4. doi: 10.1016/j.brainres.2015.12.064. Epub 2016 Feb 8. Brain Res. 2016. PMID: 26867702 Review.
• Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings. Serra M, Simola N, Pollack AE, Costa G. Serra M, et al. Neural Regen Res. 2024 Sep 1;19(9):1908-1918. doi: 10.4103/1673-5374.390971. Epub 2023 Dec 15. Neural Regen Res. 2024. PMID: 38227515 Free PMC article.
• Low Dopamine D2 Receptor Expression Drives Gene Networks Related to GABA, cAMP, Growth and Neuroinflammation in Striatal Indirect Pathway Neurons. Guerri L, Dobbs LK, da Silva E Silva DA, Meyers A, Ge A, Lecaj L, Djakuduel C, Islek D, Hipolito D, Martinez AB, Shen PH, Marietta CA, Garamszegi SP, Capobianco E, Jiang Z, Schwandt M, Mash DC, Alvarez VA, Goldman D. Guerri L, et al. Biol Psychiatry Glob Open Sci. 2022 Sep 8;3(4):1104-1115. doi: 10.1016/j.bpsgos.2022.08.010. eCollection 2023 Oct. Biol Psychiatry Glob Open Sci. 2022. PMID: 37881572 Free PMC article.
• Cocaine Regulates NLRP3 Inflammasome Activity and CRF Signaling in a Region- and Sex-Dependent Manner in Rat Brain. Cheng Y, Dempsey RE, Roodsari SK, Shuboni-Mulligan DD, George O, Sanford LD, Guo ML. Cheng Y, et al. Biomedicines. 2023 Jun 23;11(7):1800. doi: 10.3390/biomedicines11071800. Biomedicines. 2023. PMID: 37509440 Free PMC article.
• Toll-like receptor 4 antagonists reduce cocaine-primed reinstatement of drug seeking. Brown KT, Levis SC, O'Neill CE, Levy C, Rice KC, Watkins LR, Bachtell RK. Brown KT, et al. Psychopharmacology (Berl). 2023 Jul;240(7):1587-1600. doi: 10.1007/s00213-023-06392-w. Epub 2023 Jun 7. Psychopharmacology (Berl). 2023. PMID: 37286899 Free PMC article.
• Circular RNA regulation and function in drug seeking phenotypes. Daws SE, Gillespie A. Daws SE, et al. Mol Cell Neurosci. 2023 Jun;125:103841. doi: 10.1016/j.mcn.2023.103841. Epub 2023 Mar 17. Mol Cell Neurosci. 2023. PMID: 36935046 Free PMC article. Review.
• Albertson DN, Pruetz B, Schmidt CJ, Kuhn DM, Kapatos G, Bannon MJ. Gene expression profile of the nucleus accumbens of human cocaine abusers: Evidence for dysregulation of myelin. J Neurochem. 2004;88:1211–1219. - PMC - PubMed
• Baliki MN, Mansour A, Baria AT, Huang L, Berger SE, Fields HL, Apkarian AV. Parceling human accumbens into putative core and shell dissociates encoding of values for reward and pain. J Neurosci. 2013;33:16383–16393. - PMC - PubMed
• Bannon M, Kapatos G, Albertson D. Gene expression profiling in the brains of human cocaine abusers. Addict Biol. 2005;10:119–126. - PMC - PubMed
• Bannon MJ, Johnson MM, Michelhaugh SK, Hartley ZJ, Halter SD, David JA, Kapatos G, Schmidt CJ. A molecular profile of cocaine abuse includes the differential expression of genes that regulate transcription, chromatin, and dopamine cell phenotype. Neuropsychopharmacol. 2014;39:2191–2199. - PMC - PubMed
• Bannon MJ, Savonen CL, Hartley ZJ, Johnson MM, Schmidt CJ. Investigating the potential influence of cause of death and cocaine levels on the differential expression of genes associated with cocaine abuse. PloS one. 2015;10:e0117580. - PMC - PubMed
• Search in MeSH

Related information

• PubChem Compound (MeSH Keyword)

Grants and funding

• P51 OD011103/OD/NIH HHS/United States
• R01 DA021420/DA/NIDA NIH HHS/United States
• T32 AT000051/AT/NCCIH NIH HHS/United States

LinkOut - more resources

Full text sources.

• ClinicalKey
• Elsevier Science
• Europe PubMed Central
• PubMed Central

Other Literature Sources

• scite Smart Citations
• Citation Manager

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.