Harald Hess and Eric Betzig are both brilliant physicists. Both hate running in a bureaucratic herd. And both have a deep aversion to the administrative paper-shuffling of conventional modern science—especially the timid, risk-averse public mechanisms for doling out funding.
“I got to the point where I said ‘I’m really sick of the whole structure of academic science,’” states Betzig. And so he left. He became a househusband for a while, then went to work at his dad’s machine-tool company in Michigan, manufacturing and selling parts for the auto industry. Hess relates that “around that same time I also quit my job,” for many of the same reasons, “to move to a small startup business.”
Eventually, Hess’s enterprise was bought out, and Betzig “realized that I’m a really bad salesman.” So both men took another jump, into pure intellectual freedom—and unemployment. “We visited parks, talked and talked and explored, and asked ourselves where the untrodden paths in science are,” says Hess. “We finally came up with a new concept for a super-high-resolution microscope that could look deep into cells at the molecular level.”
The stumbling block was funding. Who would pay for this microscope? “Do we go for government grant money?” they wondered. The thought “created nausea for both of us,” says Hess. Too much paperwork to write proposals. Too much explaining and self-justifying in defense of a dramatically new approach. Too much arguing with reviewers, and waiting for slow responses.
A super-high-resolution microscope that led to a Nobel Prize was built by Eric Betzig and Harald Hess in the living room of Hess’s condo, using $50,000 of parts they purchased with their own money to avoid the “nauseating” process of winning public funding.
“So we decided to each put up about $25,000 of our own money and build it without a grant,” Hess recalls. “We set up a lab in my little condo and were able to work at lightning speed. We bought the necessary parts ourselves, and within a couple months we had the thing together.” (See this nearby photo of their contraption, the Photoactivated Localization Microscope, sitting somewhat comically amid the antique furniture, fireplace, and beige carpeting of Hess’s San Diego living room.)
This device established Eric Betzig and Harald Hess as leaders at a scientific frontier. It won them each directorship of a lab at Janelia Research Campus, the innovative facility created by the Howard Hughes Medical Institute, one of today’s most effective medical philanthropies. And in 2014 it transported Eric Betzig all the way to the Nobel Prize in chemistry. Not bad for a product of checkbook science.
The timidity of government science funding
The National Institutes of Health may do more to improve human life in the long run than any other corner of government. NIH is the world’s largest source of funding for medical research. Hundreds of thousands of investigators, and winners of 87 Nobel Prizes, have received its grants. “The NIH’s $30 billion annual investment is an indispensable driver of medical progress,” is how the Broad Institute’s Eric Lander and Louis Gerstner put it in 2014.
But there are downsides to being a huge public institution. “When today’s researchers are asked what they do for a living, some joke that their full-time job is grantwriting and their part-time job is research,” reports Anthony Atala, a world leader in the exciting field of regenerative medicine. “Even scientists with good ideas and a history of progress must now spend many, many hours applying for grants. Researchers have to apply for an average of six NIH grants to be awarded a single one.”
What’s worse than the red tape is the crippling timidity of the granting agencies. “When you apply for federal grants at a place like the National Institutes of Health the game is that you propose to do what you’ve just done. Everybody knows that, though they won’t say it,” states Rick Horwitz, one of the nation’s leading biological researchers, and the director of an important new lab just set up by philanthropist Paul Allen. (More on that later.)
Another eminent biologist, Leroy Hood, echoes Horwitz. “At the National Institutes of Health, if you haven’t completed two thirds of your research, you’re probably not going to get a grant, because everything is so competitive and so cautious.” Top New York University researcher Charles Marmar says the same thing: “Government research is powerfully conservative. I’ve been an NIH researcher for decades, and to get an NIH grant today you essentially have to already have solved the problem in question.”
When Internet entrepreneur Sean Parker announced in April that he was putting $250 million into an unconventional effort to apply the insights of immunotherapy to battling cancer, he decried the slow “incrementalism” that has “taken hold of” academic science in many places. This, he noted, is a symptom of the tendency of government agencies to fund only sure things. Most government research grants “aren’t really that interesting” because they are channeled to “the things that are already so obvious, experiments where the outcome is already so predictable.”
This fundamental timidity of government science funding, Horwitz points out, “creates terrible dilemmas for people experimenting at unproven boundaries, or young scientists. In theory a university will be willing to carry for a couple years a promising researcher who is trying something never done before. But universities are increasingly becoming as risk-averse as government funding agencies. So you end up with cases like Betzig and Hess, who had to put up their own money and deal with joblessness to make a breakthrough.”
“As a mentor for young, promising scientists with brilliant ideas, it is discouraging to see them struggling,” says Atala, who oversees hundreds of talented researchers at the Wake Forest Institute for Regenerative Medicine. “Of course there must be a vetting process for federal funds, but I think the current climate may discourage bright minds from entering—or staying in—research careers. It is increasingly common for doctoral and postdoctoral students, those with some of the most innovative and promising ideas, to leave research because they can’t get funded. Philanthropy dollars are therefore more important than ever. They allow us to overcome some of these challenges.”
Betzig warns young scientists of the terrible conformity and sluggishness at the heart of the government agencies that dominate science funding. “It’s a mistake too many people make to take the safe route from a funding perspective. That’s why they go into fields that are already fairly mature. The thing to do is to strike your own path. But you have to have the courage of your convictions and not be upset when you don’t get a grant.”
That is often easier said than done. Many of our most inventive scientists have run head-on into this serious obstacle. Often they find that the most practical way to jump the hurdle is to use philanthropy.
Making the genetics revolution possible
Leroy Hood was a professor at Caltech, and foresaw a genetics revolution that could completely transform medicine. He recognized, though, that automation of the decoding of genomes would be a necessary prerequisite. At the time, genes were “sequenced” by hand, by graduate students working with dangerous chemicals. It was painfully slow and expensive. Hood had an idea for a machine that would take over this labor-intensive process, and applied for NIH grants.
His bold new idea “got some of the worst scores the NIH had ever given,” Hood reports. “People said it was impossible. Or they said, ‘Why do this? Grad students can do it more easily.’”
So Hood tried something dramatically unconventional for an academic scientist. He approached the entrepreneurial wiz who had originated the warehouse superstore concept behind Costco and Sam’s Club. Sol Price was a tough, hustling son of immigrants who made a fortune peddling tires, books, peanuts, and TVs from cavernous buildings in unfashionable neighborhoods. He later became known as a very savvy philanthropist.
“When the NIH funding didn’t work out for the automated sequencer, I went to Sol,” says Hood, who describes Price as “really smart and flexible, and excited by innovation and new ideas…. He was a hard-nosed, critical guy who asked tough questions. But when he was done, he was satisfied, and he more or less gave me a blank check to spend as I felt was needed. And that was enormously valuable.”
Hood received $200,000 a year from Price for a few years, and by 1986 the Caltech professor had his machine up and running. It was soon capable of sequencing 150 million DNA base pairs without the touch of a human hand. Without this breakthrough, the historic mapping of the human genome would not have been feasible.
Several years ago the Battelle Foundation estimated that automated DNA sequencing and the decoding of the human genome had created in excess of $800 billion of economic value. It was philanthropy that opened the door to this, when neither government grants nor private investment funds were forthcoming. Those gifts will produce outsized human and financial benefits for generations to come.
Incubating systems biology
That was only the first time in Hood’s illustrious career that he relied on voluntary donors when public funders lacked the vision to keep up with his pathbreaking ideas. A few years after his DNA-sequencing triumph, Hood was perched at the University of Washington medical school and was yet again hatching some nontraditional plans, this time for a new department focused on molecular biotechnology. Once more he found it impossible to garner funding for his unproven concepts. So he approached another nearby business scion: Bill Gates.
This was in 1992. At that point Gates was, in his own words, “in my acquisition phase…not in my philanthropic phase.” But his eye for talent and powerful ideas kicked in, and after hearing Hood’s pitch, Gates decided (somewhat to his own surprise) to put up $12 million out of his own pocket to make the new venture possible.
”Hood’s donor-funded group soon became ground zero for blooming innovations in molecular biotechnology. Among other work, the team at Washington invented an inkjet device for creating DNA arrays that allowed tens of thousands of genes to be read at once. This instrument was soon commercialized and made available to other scientists, transforming genomics.
Hood then recognized that this huge flood of new data was going to require an entirely new kind of biology research, one that would cross disciplinary boundaries and look at health, disease, growth, and other processes in fresh ways. To encourage this, he proposed a new Institute for Systems Biology. It would rely on mathematical models, and focus on changes over time, not just frozen snapshots.
Once again, rustling up government grants (or commercial support) proved impossible in this new field. So the institute was established in 2000 as a nonprofit research organization supported by philanthropic funds. Individual donors like Bay Area financier Bill Bowes (whose foundation contributed $6 million) collectively put up $30 million to get the ISB launched. Philanthropic support has since exceeded $83 million.
By 2015, the Institute for Systems Biology had produced more than 1,300 research publications, and scored very high in international rankings of scientific impact. It had spun off 19 separate for-profit companies. Having proven the economic value of its insights, it was able to attract rich venture-capital investments. Systems-biology centers have now sprouted in places like Princeton, Rockefeller University, Cold Spring Harbor Laboratory, and many other locations. (Most of these were also incubated with philanthropic donations.) “That’s the kind of thing that brave front-end investment by donors can lead to,” comments Hood.
Challenging conventional thought
Stanley Prusiner is another Nobel winner who learned that private giving can be the difference between productive scientific breakthroughs and harsh rejection. In the mid-1970s he was at the University of California, San Francisco studying scrapie, a degenerative brain disorder related to “mad-cow” disease. He was coming up with puzzling findings, and having a hard time getting the National Institutes of Health to support his research. He and other experts assumed that the cause of scrapie must be a small virus, so when his data suggested it was some kind of infectious protein, a hitherto unknown threat, everything about his investigation seemed to be going wrong. He was informed by UCSF that he would not be given tenure, and his research funding was not renewed.
At that point, writes Prusiner in his Nobel biography, “I was extremely fortunate to receive much larger funding from the R. J. Reynolds Company” through a philanthropic program administered by former Rockefeller University president Fred Seitz, a legendary philanthropic entrepreneur, followed by money from the Sherman Fairchild Foundation. “These private sources were crucial in providing funds for the infrastructure” of his next stage of research—which required thousands of mice and hamsters. With private money supplying the animal models he needed, Prusiner dove back into his work.
“I grew more confident that my findings were not artifacts and decided to summarize that work in an article”—in which he minted the new term “prion” to describe the previously unknown protein that wreaked havoc in brains. The scientific establishment unloaded on Prusiner. His highly contrary study “set off a firestorm. Virologists were generally incredulous and some investigators…were irate.”
Prusiner had constructed a new paradigm that lay outside accepted scientific explanations, and “the media provided the naysayers with a means to vent their frustration” at him. “The personal attacks,” he says, “became very vicious.” Ultimately, though, his identification of “prions” as the source of this scary disease held up. Stanley Prusiner was awarded the Nobel Prize in medicine in 1997—having been bridged from ignominy to triumph by risk-taking philanthropy.
The medical establishment was similarly dismissive when immigrant physician George Papanicolaou suggested in 1928 that microscopic examinations of vaginal smears could detect the presence of cancer. “I found myself totally deprived of funds for continuation of my research,” he later wrote. “When every hope had almost vanished, the Commonwealth Fund…stepped in.” The Harkness family’s foundation offered what it knew was a “highly speculative” grant that allowed Papanicolaou to prove his theory. The Commonwealth Fund itself then published his findings in a groundbreaking study. The “Pap” smear, named for its originator, continues to be the most effective and affordable way to detect cervical cancer, heading off thousands of deaths every year.
Papanicolaou’s discovery was just one in a long chain of cancer treatments and preventions made possible by philanthropy. Take creation of the Sloan Kettering Institute in 1945. Charles Kettering was a famous inventor, best known for his automotive patents, but also maker of an incubator for premature infants, of magnetic devices for diagnosing bodily ills, and of treatments for venereal disease. He was a visionary philanthropist as well, and along with fellow General Motors executive Alfred Sloan put up the money and ideas for the first private biomedical research center focused on cancer. Today, Memorial Sloan Kettering Cancer Center treats more than 400 different subtypes of cancer with leading therapies, advances the state of the art in 120 research labs, and graduates its own Ph.D.s in cancer biology. It was bolstered in 2014 by a $100 million donation from Henry and Marie-Josée Kravis to create a new center for molecular oncology.
Twentieth-century magnate Daniel Ludwig, having built a shipping fleet from nothing, bequeathed almost his entire fortune to fighting cancer—$2.5 billion in gifts distributed to research organizations.
Johns Hopkins investigators Bert Vogelstein and Kenneth Kinzler, who have more citations in scientific papers over a decade than any other researchers in the world, are among the beneficiaries of Ludwig’s unusually open-ended grants.
“Our focus is not decided by committee,” states Kinzler when asked why his lab outperforms much larger counterparts in uncovering scientific breakthroughs. “We try to develop research projects that are not in the mainstream…. Our Ludwig funding allows us to do what’s important. We do the most groundbreaking research without having to worry about where the next level of funding would come from.”
Kinzler notes that “compared with treatment research, early detection and prevention research is underfunded, but it can potentially make more of an impact on reducing cancer deaths. It takes a long time and a sustained effort to see the results of cancer prevention and early detection studies. Ludwig funding will enable us to carry this and many other research projects forward.”
“The Ludwig bequests have revolutionized what we’ve been able to do,” agrees Vogelstein. “We’ve pursued some of the most important questions in cancer. Not necessarily the most fundable ones.”
Private risks bring public rewards
New scientific information is perhaps the surest and deepest root of economic growth and prosperity in modern society. But true breakthroughs in science are inherently chancy, and require funding systems that are risk-tolerant.
The federal science bureaucracies are hugely biased toward scientists who have already made their mark—the average age at which researchers receive their first federal grant is 43, and only 1 percent of NIH grants go to researchers 35 or younger! Yet most science breakthroughs originate from precisely those young inquirers, who haven’t yet fallen into conventional ways of approaching topics.
Private funders are vastly more likely to support young investigators. An excellent illustration is the trust set up by Lucille Markey to support biomedical careers. It operated only from the mid-1980s to 1997, when it shut its doors for good after distributing more than $500 million.
The Markey funding was tremendously flexible. Preliminary investigations and risky science of the sort that give NIH or NSF funders lockjaw? No problem. Spend money recruiting new scientists or graduate students whose exact roles will be determined in the future? Can do. Build or equip a lab before the exact experiments that will unfold there have been plotted? Sure. Shift money from one year to another, or one project to another, to fuel the most promising avenues as they open up? Yup. Dramatically change research directions in response to unexpected experimental results? You’d be stupid not to! Yet almost none of those things can be done with government funding.
The rules that allowed the Markey grants to fuel so much innovation by recipients were explicit: Favor young investigators with promise and nurture them through the “valley of death” that extends from the end of their training until their reputations are established. Trust outstanding researchers with wide discretionary powers in using their funds. Support fields with the biggest upside. Fund areas that are important but not popular. Allow not just basic science but also “translational” research that turns new discoveries into usable treatments and technologies. Pay for the infrastructure necessary for great research, not just the research itself. Be patient.
”The Markey Scholar Awards offered funding for five to seven years to each recipient, plus money to establish his or her own lab. The 113 Markey awardees turned out to be extraordinarily successful and productive. Eric Lander is an example. During his fellowship he refined new concepts of gene mapping in the lab Markey supported, and today he heads one of the world’s leading genome and medical-research centers, the Broad Institute of MIT and Harvard (created with a $700 million gift from Edythe and Eli Broad).
Another supporter of risky projects and investigators is the Howard Hughes Medical Institute, endowed by the eccentric billionaire. It was founded primarily to conduct its own research, instead of handing money to facilities with their own agendas. It focuses on scientific fundamentals: cell biology, genetics, immunology, neuroscience, and structural biology. A 1985 sale of gifted stock made it the wealthiest medical philanthropy in the world.
About 325 Hughes Investigators operate at more than 60 universities, hospitals, or labs across the country in an unusual organizational structure. Their dispersal allows them to benefit from cross-fertilization of ideas, yet they are employed by the institute rather than their host, and benefit from its independence and patience. HHMI also runs a large program to fund promising scientists at early stages of their career, as well as a program to support outstanding scientists working outside the U.S. (who do not qualify for federal support).
As a companion to these investigators spread far afield, Hughes created a major research campus of its own in northern Virginia, where it has concentrated more than 400 biologists to do high-risk, long-term research in large interdisciplinary teams. This campus is now a happy home for both Eric Betzig and Harald Hess, whose novel approaches and disgust with traditional science funding led them to pay out of pocket for the high-resolution microscope described earlier.
A 2009 study by the National Bureau of Economic Research found that the Howard Hughes philanthropic model is remarkably effective. “Investigators of the Howard Hughes Medical Institute, which tolerates early failure, rewards long-term success, and gives its appointees great freedom to experiment…produce high-impact papers at a much higher rate than a control group of similarly accomplished NIH-funded scientists,” the study concluded.
Harald Hess agrees. “Eric Betzig and I certainly benefit by having HHMI open its doors to us and provide the research environment that matches our nonconformist style. And science benefits by having such alternative research ecosystems financed by philanthropy.”
The fact that private giving usually comes without onerous strings attached is one of the things that lab directors of all sorts most prize about philanthropy. “Unrestricted funds are gold; they’re magic,” says the Broad Institute’s Eric Lander. Thanks to private giving, “when we have a good idea we’re able to say ‘Let’s start investing in it now rather than write a grant and start working on it two years from now after it wends its way through the NIH system.’
Setting the stage for scientific breakthroughs
Private donors are also vastly more willing to buy machines, erect buildings, and hire technology aides—creating the structures within which discoveries can take place. Government grants are notoriously unwilling to pay for this sort of foundation-laying. Federal grants generally must be tailored for one discrete experiment and its immediate costs only. That makes it hard for directors to keep their labs operating and continuously improving.
For instance, in the late 1970s, researchers at the California Institute of Technology were ramping up all-new technology-intensive approaches to human biology research. But they needed a vessel in which researchers from the Caltech biology and chemistry and math faculties could be mixed, along with some very advanced equipment and labs. Fortunately, five foundations, four major individual donors, and two companies offered gifts that allowed Caltech to build and open its new Braun Laboratories in 1982. The building almost immediately became an important center for new kinds of scientific collaboration, jump-starting work in recombinant DNA, monoclonal antibodies, and other early innovations in biotechnology. “We’re talking about investigations of the fundamental structure and mechanisms of life itself,” stated Caltech president Marvin Goldberger at the building’s dedication. One researcher called the Braun gifts “a beautiful example of philanthropy encouraging innovation and creating new opportunities that didn’t exist before.”
Asked why the laboratory was so important, Leroy Hood explains that “federal funding has almost always focused on specific kinds of projects. It isn’t focused on creating the infrastructure of a house that really good people can work in. With the Braun building suddenly we had 200,000 square feet into which we could bring all sorts of new people and things. And without that enabler we couldn’t have made that jump. You don’t get federal grants to build new buildings and create new visions. It’s philanthropy that opens up opportunities in such ways.”
Prioritizing public health
Another valuable contribution of philanthropy is the way it takes interest in neglected disciplines. One non-glamorous corner of medical science that has never attracted much government funding is public health. The biggest feet in this area for more than a decade have belonged to Bill and Melinda Gates. They have engineered many massive upgrades in public health in foreign lands—from hygiene, water, and vaccination improvements to systematic suppression of diseases like polio, Guinea worm, enteric disorders, snail fever, river blindness, trachoma, HIV, malaria, tuberculosis, and others.
What is less well known is that donors are making big pushes to upgrade research and training in public health within the U.S. as well. When he announced his unprecedented $350 million gift to the public-health school at Harvard in 2014, investor Gerald Chan made the case: “While medical doctors give health benefits to individual patients, public health is a field that helps to give benefit to the whole population.” Other recent gifts to university public-health departments include $40 million from Michael Milken, $50 million donations from the Rollins family and from the Gillings family, Joseph Mailman’s $33 million investment, and the hundreds of millions of dollars Michael Bloomberg has channeled into this cause at Johns Hopkins University.
”Donors often bring entrepreneurial energies into medical research. The AIDS epidemic was just a blurry terror when the Aaron Diamond Foundation ripped into it with a nimbleness, speed, and tolerance for risk that allowed it to pioneer some key research and treatment findings needed to battle the disease. By the time the foundation closed down at the end of 1996, it had invested $220 million and become the largest private supporter of AIDS research in the U.S., from basic research to drug development. Thanks in part to its breakthroughs, the death rate from HIV in America is now one fifth of what it was 20 years ago.
Diamond also did important work on prevention. One project, for instance, demonstrated that the rate of transmission of HIV from mothers to infants could be reduced from over 30 percent to less than 1 percent. The organization’s researchers also pursued various HIV vaccination strategies right through the stage of clinical trials, including some work using very innovative techniques that was co-funded by the Gates Foundation. Though never numbering more than about 75 researchers, the Diamond Center’s no-strings philanthropic money gave it a fast-moving vigor that allowed it to repeatedly precede and outperform government labs. Its research saved hundreds of thousands of lives.
The list of “orphan” maladies that neither government nor corporate funders were much interested in before donors became involved is long. A great many tropical diseases, retinitis pigmentosa, Huntington’s disease, malaria, geriatric medicine, and other illnesses that once lay neglected are now being aggressively untangled. “Diseases like schizophrenia, bipolar disorder, and autism have been moved” out of obscurity by philanthropists, reports eminent neuroscientist Steven Hyman, former director of the National Institute of Mental Health. “Without private philanthropy, we wouldn’t be able to take risks or get our research up to scale.”
For instance, Hyman, who is investigating the genetic bases of mental illness, wanted to do work in Africa because of its unusually diverse genetic pool. “But it would take a huge administrative or bureaucratic effort to run federal grants there. We couldn’t think of doing that without private money.”
Trailblazers
There is a rich history behind these current efforts. John Rockefeller and the organizations he set up almost single-handedly created the discipline of “public health,” first by eradicating the hookworm plague that sapped the energy and productivity of millions of American Southerners, and then by creating the International Health Commission in 1913 to carry out similar work abroad. Rockefeller established the first school of public health at Johns Hopkins University in 1916, which he then duplicated at Harvard in 1921. In all, he spent $25 million establishing public-health programs at scores of universities across the globe.
Rockefeller was the trailblazer in all kinds of medical research as we know it today. He first poured money into disease study and treatment in 1901, after the death of one of his grandsons from scarlet fever. At the time, there was scant effort to fight back against common threats to human health like tuberculosis, diphtheria, typhoid, and bacterial infection. Rockefeller created the Rockefeller Institute for Medical Research, which eventually grew into Rockefeller University. It produced landmarks like blood typing, blood banking, vital knowledge of the structure of antibodies, of electrical signaling in the nervous system, on the operation of optic nerves, and fundamental new understandings of DNA and genetics.
Many lifesaving drugs and therapies emerged from Rockefeller’s walls: penicillin, Simon Flexner’s anti-meningitis serum, Hideyo Noguchi’s treatments for syphilis and yellow fever, Louise Pearce’s drugs to treat African sleeping sickness, methadone to manage heroin addiction, anti-AIDS “cocktail” drugs, and much more. Two dozen individuals associated with the institution have received the Nobel Prize, and 20 have been awarded the National Medal of Science. When scientists working elsewhere with Rockefeller Foundation funding are included, the tally of Nobel winners who were influenced by Rockefeller support exceeds 60.
The modern template for supporting biomedical research was established by Rockefeller and succeeding donors like the Harkness family (and their Commonwealth Fund), Albert Lasker, John Hartford, and Lucille Markey. It was difficult even to accurately discuss medical maladies until the Commonwealth Fund financed and published the Standard Classified Nomenclature of Disease in 1933, creating medicine’s first universal definitions and standards. This both aided clinical practice and made accurate health statistics possible for the first time. Creation of the Albert Lasker Awards for medical research likewise helped set priorities and recognize successes within the field. Since first being presented in 1945, the Lasker prizes have anointed 87 American scientists who subsequently went on to win a Nobel.
New ways of attacking complex problems
Major breakthroughs funded by philanthropy are not a musty thing of the past. Donors today are continuing to create new fields and approaches to research. “What we are doing would be absolutely impossible to fund except via philanthropy,” Rick Horwitz tells me in describing the new Allen Institute for Cell Science that he runs. “It’s too large, too novel, too complex, too collaborative, too speculative. It’s not conventional prove-the-hypothesis science. It’s not traditional heroic-lone-researcher work. What we’re pursuing requires the long-term, cooperative work of a large team. The conventional funding mechanisms just don’t match up to what we’re doing.”
Fortunately Horwitz has a philanthropic sponsor who is not only willing but anxious to help; indeed, this institute was the donor’s idea. Microsoft co-founder and major philanthropist Paul Allen personally recruited Horwitz and created the new lab with an initial $100 million gift in 2014. The goal is to better understand how living cells change and interact with each other.
Relying on current genetic, molecular, and chemical information about cells to understand how they develop, and anticipate what they will do, is like trying to appreciate a car by looking at a list of parts, explains Horwitz, or trying to understand
San Francisco by reading the phone book. What the Allen Institute aims to do is to create a kind of “Google Maps” of cells.
“Nobody studies how these entities function as complex systems, and how they interact to determine cellular behaviors. Instead, people focus on just a small, manageable part,” he says. This is mostly because of the way academic labs are structured (to support deep dives on narrow slices of a problem) and the way government research money is distributed (to tightly defined projects, not for exhaustive, boundary-breaking macro-examinations).
“To get a clearer picture of the ways cells transform themselves, signal each other, migrate, and take various kinds of “action,” one must watch the whole sprawling “movie” of what the cell does over time. That essentially is what Paul Allen has asked Rick Horwitz to do.
The cell-science institute’s 70 researchers will work as one interdisciplinary team. They will use induced pluripotent stem cells—a new technology that allows a common skin cell, for instance, to be converted into a stem cell. This stem cell is capable of growing into other specialized cells, such as blood or bone. By taking long, complete sequences of images of those stem cells transforming themselves into something more complex, the Allen Institute scientists believe they will gather tremendous amounts of big-picture information about the workings of life. The institute will advance biology by releasing to all interested researchers both the original “movies” and any analysis the Allen investigators put together.
Another sector where new approaches and new funding are needed is regenerative medicine—where things like replacement organs and new skin are being grown in labs for transplanting into desperately ill patients. The problem for regenerative medicine is that it is breaking all new ground. Anthony Atala notes that “practically everything we do is beyond the commonly accepted limits of science. We are a whole new field. The long established regulatory guidelines do not fit.”
“We need funds that will allow us to explore new territory. We need funds that will allow us to take one disease issue all the way from bench to patient,” argues Atala. Fortunately, “some of our most promising translational research with the most potential to treat patients is beginning to be funded by private donors. It is thanks to them that we have treatments now showing promise in the clinical-trial phase.”
Sean Parker is one donor who understands that the most important thing a philanthropist brings to the table is often openness to new approaches and a willingness to fund pioneering efforts. When he donated $250 million from his Facebook proceeds to found his unusual cancer institute this April, he explained his reasons for backing cancer immunology (use of the body’s own immune system to fight tumors). Until very recently, states Parker, immunology was “the red-headed stepchild of the oncology world. There was a dedicated band of scientists who were convinced that the immune system played an important role in cancer, but they were essentially refugees from the cancer establishment.”
“So Parker took two new approaches. First, he put up a lot of money to allow more thorough experimentation with cancer immunotherapy. And, second, he launched this through an unconventional structure that will push six top cancer centers that don’t always share information smoothly to collaborate much more in order to speed progress. Memorial Sloan Kettering, Stanford, UCLA, UCSF, M. D. Anderson, and the University of Pennsylvania will be required to share resources and pool findings.
Philanthropy, Parker notes in explaining his effort to eliminate intellectual barriers, is not “giving away money so much as trying to solve a set of not-easily-addressable problems.” He told the Financial Times recently that if you “form a scientific advisory board composed of the luminaries in the field—who are all at that point the establishment—and then you let those people determine how your resources are going to be allocated, you’re going to end up doing essentially more of the same thing that everyone else is doing.” Smart philanthropy often looks instead for roads not taken and new tacks by fresh thinkers. There are topics and approaches, summarizes Parker, that are “either too far ahead, or they’re unpopular for some reason, or the establishment isn’t yet interested, where private philanthropists can step in and have a huge impact.”
A current donor focus: brain research
Brain research is an area where philanthropists have powered many important gains in recent years. The latest boost came in May, when Sanford Weill announced a $185 million gift to create a new center for neuroscience at the University of California, San Francisco. “We’ve always liked to support the underdog,” he explained, and “research on the brain is far behind other areas of medicine.” The donation will pay for work extending from “research bench to bedside,” said Weill. UCSF chancellor Sam Hawgood underlined this, saying the gift “will remove the completely artificial boundaries that we in academia use.”
Other donors like Ted Stanley, Paul Allen, Peter O’Donnell, Patrick McGovern, Fred Kavli, Mortimer Zuckerman, and many small-to-moderate givers have poured billions of dollars into brain science of late. After concluding that government health agencies were massively underresearching maladies like schizophrenia and bipolar disorder, Stanley became a leader. He started putting what eventually totaled more than a billion dollars into the field, funding between a quarter and a half of all the research on those illnesses. His investment paid off in January of this year when scientists announced that the Stanley Institute may have narrowed the single greatest genetic risk factor for schizophrenia to a single aberrant gene variation—a finding they described as “amazingly consequential.” (See “Big Payoff on Brain Philanthropy” in the Briefly Noted section of Philanthropy’s Spring 2016 issue.)
Paul Allen’s Institute for Brain Science is another deeply influential donor creation. The Seattle nonprofit has been launched with $500 million of gifts from Allen, and a mandate to improve the tools of neurobiology. It created interactive online atlases of the mouse brain and the human brain, for instance, that have become staple instruments for experimenters worldwide. The productivity of the Allen Institute isn’t just a function of being freed from the need to repeatedly apply for government grants. Its 350 staff are organized in flexible teams—more like an Internet firm or a corporate lab—and this has yielded rapid progress.
“The philanthropic brain-science blitz now underway also involves thousands of everyday givers. One pioneering effort was the Brain & Behavior Research Foundation, launched in 1981 by a group of family and friends of persons afflicted by mental illness. In 1987 the group began to pool donations to provide grants and prizes to promising young researchers having a hard time qualifying for government support. It also sponsored more senior scientists pursuing novel approaches unlikely to receive conventional funding. The group gathers and distributes more than $30 million in a typical year, and has now awarded $346 million to 4,000 scientists to increase understanding of brain functioning and improve treatments.
Brain injuries suffered by veterans of the Iraq and Afghanistan wars are another aspect of neuroscience that has recently drawn strong philanthropic interest. Large portions of a $243 million donation to servicemembers by hedge-fund founder David Gelbaum were used to create centers for researching and treating brain injuries and traumatic stress. Home Depot co-creator Bernie Marcus has given more than $100 million to build up centers for treatment of brain injuries, for general studies in neuroscience, and for trailblazing explorations of autism. This April, financier Steven Cohen and his wife, Alexandra, pledged $275 million to mental-health clinics for vets. They had earlier donated $17 million to a five-year program at New York University to detect biomarkers (like distinctive brain images, blood chemistry, or hormone levels) linked to traumatic stress disorders. NYU psychiatrist Charles Marmar says his lab hopes to find concrete “physical standards” that can take some of the subjectivity out of mental-health treatment. Because of the speculative nature of his lab’s work, says Marmar, philanthropy was essential to getting it launched. “Donors,” he notes, “tend to have business acumen and know how to get things done.
The invaluable catalyst
Even with the billions of dollars gushing out of federal science funders, philanthropy remains crucial to scientific progress. MIT professor Fiona Murray recently studied the 50 universities that top the list for science-research spending in the U.S. and found that private donors now provide about 30 percent of the total research funding at these places. The sheer volume of private dollars is consequential. What’s even more important about science philanthropy, though, is the way it is structured: adaptable, tolerant of risk, patient, willing to fund the infrastructure that scientific discoveries require, open to unproven innovators.
“What I’ve always loved about philanthropy is it’s money that has a potential to be flexible. It’s money that can catalyze new ideas. It’s money that lets you push the frontiers, follow the leading edge,” states Leroy Hood. “So a philanthropist who is willing to say ‘Yes, I’ll step in and help you find something new’ is a jewel.”
Karl Zinsmeister created The Almanac of American Philanthropy, which offers many other rich examples of science philanthropy.
Illustrations: Vladimir Stankovic
