Joining Fields to Fight a Crisis

This summer, Harvard made national headlines when three of its medical researchers discovered that a small, easily synthesized molecule binds to the human immunodeficiency virus (HIV)--the virus that causes AIDS--and prevents it from infecting healthy cells.

But while that discovery garnered more than its fair share of media attention, scholars say it highlights but one of many areas of research now underway at Harvard's AIDS Institute.

Founded in 1988, the Institute represents Harvard's attempts to tackle the AIDS crisis from an inter-disciplinary approach--while some researchers are working to find a vaccine, others are studying ways of keeping the virus contained in underdeveloped countries.

At times, Harvard and the Institute have been scrutinized for not paying enough attention to the needs of current AIDS victims. But for the most part, the Institute receives strong praise from both outsiders and Harvard researchers alike.

For while many universities have made breakthrough scientific discoveries, scientists say Harvard's Institute is truly unique because it can tap into the University's greatest strength--its breadth of faculty.

"I don't think there's any institution anywhere that can rival Harvard's ability to respond," says Harvey V. Fineberg '67, dean of Harvard's School of Public Health.

The AIDS Institute was Fineberg's brainchild, and he says he founded it in the hopes that it "inspires communication and innovation in looking at research as an interdisciplinary and cooperative venture."

A quick look at the Institute's participating faculty shows that Fineberg's call has not gone unheeded--faculty at the Medical School and its affiliated hospitals, the School of Public Health, the Law School, the Kennedy School of Government and the Faculty of Arts and Sciences all work on projects at the Institute.

The Institute itself does not actually oversee research projects; rather, it encourages faculty interested in conducting AIDS research to apply for federal funding. In addition, it sponsors various lectures and seminars on AIDS.

Research Directions

Just what direction the research will take is determined by the directors of the Institute's five centers--biologic research, clinical research and care, policy and education, epidemiology and biometry and international cooperation.

Together, those five centers account for about 250 researchers who receive some $45 million each year--mostly from the federal government--says Alan G. Fein, executive director of the Institute.

AIDS research didn't really get off the grounduntil the mid-80s, when sufficient federal fundingfinally became available. And even today, manycriticize the government for holding on to thepurse strings a little too tightly.

"There is no concerted national AIDSleadership," says Michael L. Immel, a member ofthe Boston AIDS action group, AIDS Coalition toUnleash Power (ACTUP). "That results inlow-priority budgets for [AIDS research]."

But funding has soared in the last few years,and at the larger research centers--Harvard amongthem--money just isn't the problem, Fein says. It"isn't a lack of research funding, it's that [AIDSis] an incredibly hard problem to dissect," hesays.

Because the issue is so complex, publicattention often turns to the one place wheretangible results are expected--clinical testing.It's through clinical testing that victims of AIDScan directly--and quickly--benefit from whatscientists are digging up in the labs, and it'sthrough clinical testing that the scientificcommunity learns whether new discoveries reallywork.

Just ask Jerome E. Groopman, who co-directs theInstitute's Center for Clinical Research. He'llexplain how his center is doing some of the mostexciting work around on fighting the AIDS virus.

Right now, the Center's researchers areinvolved in several projects. Many of them arestill conducting extensive tests on AZT, thehighly touted drug that has been shown tochemically block the AIDS virus from replicating.Other researchers at the Center are working on anew generation of drugs, which work directly onthe virus' gene structure, Groopman says.

But the Center garners almost as much attentionfor its other role--providing experimentaltreatment to current AIDS victims. That fallsunder the domain of Professor of Medicine MartinS. Hirsch, the Center's other co-director, whooversees the AIDS Clinical Testing Unit (ACTU),which is one of only 47 such government-fundedunits across the country.

The ACTU conducts clinical trials on HIV, aswell as some of the diseases that result from abroken-down immune system, to determine howpatients with AIDS can best be treated. Hirschsays although researchers are much closer tofinding a vaccine than they thought they would bea year ago, there is still a long way to go.

"I don't think we're there yet, and it willprobably be about five to 10 years before we havea safe and available vaccine," he says.

Frustration With Research

In recent years, however, frustration with theslow pace of research has translated intofrustration with the ACTU, and the way itdispenses treatment. At times, activists havecriticized Harvard for not devoting sufficientresources to the care and treatment of peoplecurrently infected with HIV.

On several occasions, ACTUP stageddemonstrations to pressure the ACTU into makingAIDS treatments more available to those who mostdesperately need it. Of particular concern are theACTU's requirements for clinicaltesting--activists claim that in an attempt toobtain a "proper" scientific sample, the ACTUexcludes many AIDS victims from eligibility.

In response, Hirsch says he convened acommunity advisory board for the ACTU last spring,in an effort to bring clinical researcherstogether with representatives from the community,minority groups and AIDS activists.

Last August, that advisory board recommendedseveral changes in the clinical testingprocess--among them, making treatment moreaccessible to women, children and minorities--saysRochelle L. Rollins, spokesperson for the Blackcommunity on the ACTU advisory board. Rollins, whois director of research at the Multicultural AIDSCoalition, says the board has also suggested theACTU make more appointments during non-work hours,recruit a more multilingual staff and providechild care for women taking part in the trials.

Harvard officials say they are working on suchrecommendations, but activists like Immel, whorepresents ACTUP on the community advisory board,say they feel Harvard is still out of touch withthe needs of those infected with HIV. He describesthe ACTU's criteria for drug trials as "reallyanal" and too restrictive.

"They're not in touch with the people who havethe disease. They treat them as subjects, not aspeople," Immel says.

Immel also says Harvard does not try enough newdrugs, instead relying on older ones that havealready proven unsuccessful but are nonethelesssupported by the pharmaceutical companies thatproduce them and fund research.

But Harvard clinical researchers say they arewill aware of the community's needs, and arereceptive to the advice of the advisory board.

"I think we handle it better now than we did inthe past," Hirsch says.

Groopman, who also sits on the board, says, "Ithink most thoughtful researchers who have directinvolvement with people with AIDS clearly feel thefrustration and pain that the patients have ifthey are prevented from getting access."

And while Immel may disagree about Harvard'sunderstanding of community needs, he concedes thatthe mere existence of a board is a step in theright direction.

"There's a sense that the doors are open and wecan talk," he says.

Social and Legal Issues

Far less controversial but nonetheless uniqueis Harvard's work on the social and legal issuesassociated with the AIDS crisis.

Out of the Center for Policy and Education havecome conferences on alternatives to hospital-basedcare and new reimbursement mechanisms to helppatients set off treatment costs.

Doctors are also studying patterns ofdiscrimination against AIDS victims, designingeducational programs for schools and the workplaceand assessing the effectiveness of current AIDSlegislation.

But the institute's hidden strength, many say,is its ability to communicate its researchglobally. Thanks to the International AIDS Center(IAC), which is also part of the Institute,Harvard doctors can work on controlling AIDS inforeign countries, both by travelling abroad forresearch and training foreign doctors. Today,Harvard's work can be found in such countries asSenegal, Zaire, Mexico and Puerto Rico.

Jonathan M. Mann '69, who last month left hisstewardship of the World Health Organization'sGlobal Program on AIDS to direct the IAC, says hefeels strongly the IAC should go beyond merelystudying the disease to understanding the issuesraised by the crisis.

"I see the IAC as doing research and providingservice, but also helping develop key issues ofglobal importance that apply not only to AIDS,"Mann says.

Of course, because scientists still have muchto learn about the AIDS virus, discoveries oftencome from where they are least expected. Thissummer's discovery, in fact, came not from theAIDS Institute but rather the Harvard-affiliatedDana Farber Cancer Institute.

Now, the three scientists who discovered thatthe molecules called CDFs keep the AIDS virus frombinding to human cells--Professor of PediatricsSteven J. Burakoff, Professor of Medicine RobertW. Finberg and Professor of Chemistry Stuart L.Schreiber--are working to take their discoverybeyond the test tube.

Current experiments include tagging CPFmolecules with radioactive chemicals to betterunderstand how the drug interacts with the virus,Burakoff says. In addition, he says, theresearchers will try to implant both human immunecells and the AIDS virus into mice with no immunesystem, to see whether the CDF molecule reallyblocks the disease from spreading.

"Just because you can block something in a testtube doesn't mean it works on a patient," Finbergsays.

Burakoff agrees, noting that test tubeexperiments don't reveal whether a drug will betoxic to humans, or for how long a drug might beeffective. All three researchers say much researchstill needs to be done.

But the team is already working to contractwith a pharmaceutical firm, enabling them tomanufacture and test 50 or 100 differentvariations of the CPF molecule, Burakoff says. Andwhile nobody will offer a timetable, the teamseems optimistic.

Assessing Harvard's Impact

Regardless of whether the CPF discovery pansout, Harvard researchers say the University hasalready proven a global leader in AIDS research.

For instance, a Harvard microbiology professor,Max E. Essex, was the first to suggest that aretrovirus causes AIDS and was also the first toidentify a second, less virulent form of thevirus, called HIV-2.

Essex, who now chairs the Institute, alsodiscovered the simian immunodeficiency virus,which is found in monkeys and causes an illnesssimilar to AIDS.

Groopman was one of the first to test AZT, oneof the most common drugs used today to treat AIDSpatients. Hirsch was among the first to showincreased effectiveness of a combination of AZTand another preventative drug, CD4.

And the list goes on.

Thus, it should come as little suprise thatoutside researchers also look to Harvard as avaluable contributor to research. Paula M.Pitha-Rowe, an AIDS specialist at Johns HopkinsMedical School, says that while Harvard may not bethe leading institution for AIDS research, it iscertainly among the top few institutions for suchresearch.

"There are several places which do very goodresearch, and Harvard is one of them," she says.

And Groopman, at least, goes even further. "Ithink honestly, if you look at the quality ofresearch and the level of productivity, I thinkthere's no institution in the country or the worldthat has done as much as Harvard," he says.CrimsonAndrew D. CohenJEROME E. GROOPMAN, co-director of theHarvard AIDS Institute's Center for ClinicalResearch, directs several projects on the cuttingedge of research in drug treatments for AIDS.