Summer 2009

VO LU M E 6 N U M B E R 2 | S U M M E R 2 0 0 9

From Research,The Power to Cure

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Meeting The Stem Cell Challenge

B U r n h a m R eport

I n T h is I ssue

Founders

Trustees, continued

B urn h a m R ese a r c h

Willi am H . F is h ma n, Ph.D. Lilli an F is h man

Jeannie M. Fontana, M.D., Ph.D. Alan A. Gleicher W.D. Grant David F. Hale Jeanne Herberger, Ph.D. Brent Jacobs James E. Jardon II Daniel P. Kelly, M.D. Robert J. Lauer Sheila B. Lipinsky Gregory T. Lucier Papa Doug Manchester Robert A. Mandell Nicolas C. Nierenberg Douglas H. Obenshain Peter Preuss Stuart Tanz Jan Tuttleman, Ph.D., MBA Andrew J. Viterbi, Ph.D. Kristiina Vuori, M.D., Ph.D. Bobbi Warren Allen R. Weiss Judy White Gayle E. Wilson Diane Winokur Kenneth J. Woolcott

Meeting the Stem Cell Challenge

1

What is a Stem Cell?

3

The Stem Cell Community

5

B urn h a m N e w s

Science News

6

Florida News

8

P h il a nt h rop y

Updates

10

Bring It!

11

A Tribute to Malin Burnham

12

Around B urn h a m

Fulfilling the Promise of Stem Cells: President’s Message 13 Partners in Science

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Honorary Trustees Joe Lew is Conr a d T. P rebys T. D enny Sa nford

Trustees and Officers Malin B urn ha m Chairman Jo h n C. R eed , M.D., Ph.D. President & Chief Executive Officer Professor and Donald Bren Presidential Chair G a ry F. Ra isl , E d.D. Chief Administrative Officer Treasurer Marg a ret M. D unbar Secretary

Trustees Linden S. Blue Mary F. Bradley Brigitte M. Bren Arthur Brody Howard I. Cohen Shehan Dissanayake M. Wainwright Fishburn, Jr.

Ex-Officio Raymond L. White, Ph.D.

O n T h e Cover Vincent Chen, M.D., Ph.D., and Mark Mercola, Ph.D., investigate stem cells for new ways to treat heart disease—but come at the problem from different angles. Dr. Chen works with embryonic stem cells to create pacemaker cells and hopes to make a biological pacemaker. Dr. Mercola wants his stem cells to become cardiomyocytes or beating heart cells. Their collaboration is bearing fruit, as both cell types come from the same progenitors and failure in one lab can lead to success in the other.

B l air B lum Senior Vice President External Relations Eliza bet h G ianini Vice President External Relations Edg a r G illenwaters Vice President External Relations C hris L ee Vice President External Relations Andre a M oser Vice President Communications

Jos h Bax t Editor, Burnham Report G avin & G avin Advertising Design Howard Cohen Mar k Da strup Melissa Jac obs Nadi a Borowski Sc ott Photography Please address inquiries to: jbaxt@burnham.org

www.burnham.org

Burnham Institute for Medical Research 10901 North Torrey Pines Road, La Jolla, CA 92037 • 858.646.3100 Burnham Institute for Medical Research at Lake Nona 6400 Sanger Road, Orlando, FL 32827 • 407.745.2000/407.745.2001

B u r n h a m stem c ell rese a r c h

Meeting the

Stem Cell Challenge Smooth muscles cells derived from embryonic stem cells

Burnham scientists A few months ago my uncle was diagnosed with ALS (amyotrophic lateral sclerosis). It started with some speech problems but since then his condition is constantly worsening. It is very painful for me to know that he is in such a difficult position and that there is no cure for it. However, with the latest stem cell research, there might be some hope. He is very willing to participate in any kind of experiments. So my question is - is there any way that you can take him into your research program and see if there is any potential to cure ALS or at least to improve his condition? If not - can you recommend any programs?

Any help or suggestion would be very much appreciated. — Bellevue, Washington

other conditions. But where

frequently receive letters like

does the promise of stem cell

this. They remind everyone at

therapies meet the reality? And

the Institute how important

what will those therapies ulti-

the research is, as well as how

mately look like?

much work needs to be done.

In recent years, there has been

Bac k to Basi cs While stem cells (See box

intense focus on embryonic stem cells because they can

on page 3) offer great potential

form more than 200 different

as future therapies, they are not

tissue types. This flexibility,

always obedient. Sometimes

or plasticity, could make them

they differentiate into other cell

ideal to treat diabetes, neuro-

types when researchers want

degenerative diseases, heart

them to remain stem cells—or

problems, cancer and many

vice versa. They can become

w w w. b u rn h a m . o rg | T h e Bu r n h a m R e p o r t

B u r n h a m stem c ell rese a r c h

“Now we know quite a

other’s work, as both cardiomyo-

bit about the early steps of

cytes and pacemaker cells come

stem cell differentiation from

from the same precursor cells

embryology,” says Dr. Mercola.

but require different signals to

“But the major prize is to find

become the two types of heart

small molecules that influence

tissue. A practicing electro-

the latter steps. With those,

physiologist, Dr. Chen routinely

we could potentially create

implants electronic pacemakers

drugs that help damaged hearts

and recognizes how that tech-

rebuild themselves.”

nology has evolved over the past

To discover these molecules, his laboratory uses high-

glial cells (non-neuronal brain

cardiomyocytes, or other cell

cells) when the goal is to create

types, any more efficiently than

neurons. They can form tumors,

they would without human

called teratomas. To solve these

intervention.

problems, researchers must deci-

“We just didn’t know enough

very sophisticated algorithms

Conrad Prebys Center for

to make them pace the heart

Chemical Genomics.

appropriately and make them need to respond to exercise,

as well as a couple of existing

and they need to recognize

drugs, that are candidates to

when you are trying to sleep. If

stimulate a patient’s own heart

we want to create a biological

to regenerate cardiomyocytes,”

pacemaker, we need to match

says Dr. Mercola.

or exceed the standard of electronic pacemakers.”

Building a B iologi cal Pacem aker

about embryology,” says Dr.

that direct stem cells towards a

Mercola. “We needed to under-

wants to do, I want to do in

specific fate. By understanding

stand where the heart actually

mirror image,” says Vincent

the developmental biology, scien-

comes from and what natural

Chen, M.D., Ph.D., who works

tists can potentially replicate it

signals in the early embryo

and assert control over stem cells.

stimulate undifferentiated cells to form a heart.” Studying how

failsafe,” says Dr. Chen. “They

promising new compounds,

pher the signaling mechanisms

Mark Mercola, Ph.D.,

“Current pacemakers have

throughput screening in the

“We already have several

Brandon Nelson, manager of Burnham’s Stem Cell Core, removes cells from cryogenic storage.

The core provides expertise to grow, differentiate and analyze embryonic stem cells.

35 years.

“Everything Mark Mercola

The cellular pacemakers Dr. Chen envisions would fully integrate into the heart.

In other words, they would respond to the nervous system like the original cells they

The research being done by each laboratory informs the other’s work, as both cardiomyocytes and pacemaker cells come from the

same precursor cells

associate director of the Del

embryos make hearts was a

E. Webb Neuroscience, Aging

good strategy. Dr. Mercola and

and Stem Cell Research

others succeeded in unraveling

Center, has discovered signals

many of the signals that tell

that make embryonic stem

cells to form heart tissue.

cells differentiate into cardio-

Dr. Mercola then returned to

closely with Dr. Mercola.

must replace. Using human

myocytes (beating heart cells),

embryonic stem cells to find

Dr. Chen’s goal is to create

embryonic stem cells, he has

which could be used to repair

the right chemical compounds,

cardiac pacemaker cells to

developed a system to monitor

damaged heart muscle.

proteins or microRNAs (ribonu-

treat arrhythmias and other

the formation of pacemaker

Early on, Dr. Mercola and

cleic acids) to take pluripotent

dangerous heart rhythm disor-

cells — a critical step towards

other stem cell researchers were

stem cells through the multiple

ders. The research being done

discovering molecules to build a

frustrated by their inability to

stages they must travel to

by each laboratory informs the

biological pacemaker.

direct stem cells to become

become cardiomyocytes.

T h e B urnham Repor t | www.burnham.org

B u r n h a m stem c ell rese a r c h

Motivating Endogenous Cells A major goal of Burnham

Dr. Ruiz-Lozano. “In nature, if it happens at all, then it should be possible to stimulate those

researchers is to develop drugs

natural abilities to do more.

that can coax endogenous

We need to understand how

somatic stem cells (progenitor

various cells contribute to repair

cells within our bodies) to

processes to develop therapies.”

rebuild damaged tissue. In

The Ruiz-Lozano lab has

collaboration with other labs,

discovered important cells in the

Pilar Ruiz-Lozano, Ph.D.,

epicardium, the protective layer

is working to pinpoint the

surrounding the heart. These

heart cells that cause normal

epicardial cells provide signals

regeneration.

that minimize the impact of

“It appears that endogenous

heart disease on muscle cells.

stem or progenitor cells can

With Dr. Mercola, Dr. Ruiz-

heal very small traumas,” says

Lozano is working to discover

What is a Stem Cell?

Stem cells are cells that

but still have the flexibility

can both replicate themselves

to become different types of

and differentiate into other

tissue. In other words, the cell

types of cells. In a developing

knows its address and will

embryo, pluripotent stem

migrate to the heart, liver,

cells, which can differentiate

brain or other part of the body

into all cell types, are told

and differentiate into more

through complex signaling to

specific cells types. Certain

differentiate into other cells.

tissues in adults have their

Embryonic stem cells go

own multipotent stem cells,

through several stages before

often called somatic stem cells

becoming functional neurons,

or “adult stem cells.” However,

cardiomyocytes (beating heart

the latter term is somewhat

cells), pancreatic beta cells or

misleading as these cells are

other types of tissue.

also found in embryos and

Once an embryonic stem cell starts to differentiate,

children.

Perhaps the most

it becomes multipotent and

intriguing types of stem

can become many cell types.

cells are induced pluripo-

These cells are moving

tent stem (iPS) cells. These

towards a cellular identity

cells are created from fully

Pilar Ruiz-Lozano, Ph.D.

differentiated cells, often

models for Parkinson’s and

skin cells, which have been

figure out what is going wrong

reprogrammed to become

with those cells.”

pluripotent stem cells. Like

Currently, iPS cells have

their embryonic cousins,

their drawbacks. Some of the

iPS cells can form all cell

methods used to create them

types. This approach offers a

make them unsuitable for

number of benefits. For one,

clinical use. They replicate

iPS cells may be ideal for

slowly, making them difficult

transplantation, as they could

to study. Also, scientists don’t

be taken from a patient and

know if iPS cells are identical

would not face rejection from

to embryonic stem cells. More

the patient’s immune system.

study is needed, but break-

Also, iPS cells could be used

throughs are being announced

to study diseases on a cellular

with great frequency.

level.

“These iPS cells will give

“The technology for iPS cells is changing every day,”

us the ability to study the

says Dr. Lipton. “They have

molecular underpinnings of

great potential, but we need to

disease,” says Stuart Lipton,

learn whether they are iden-

M.D., Ph.D., director, Del E.

tical to embryonic stem cells,

Webb Neuroscience, Aging

and we just don’t know yet.”

and Stem Cell Research Center. “We can set up

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B u r n h a m stem c ell rese a r c h

synthetic compounds that can

(MD) causes debilitating

enhance or mimic the epicardi-

muscle weakness and eventu-

um’s regenerative effects.

ally death. Compounds that

Epicardial cells can also

encourage muscle progenitors

be isolated from patients

to form new muscle could be

and expanded in culture or

the next generation of treat-

chemically modified and used

ments for muscular dystrophy

for transplantation. “These

and other muscle disorders.

cells would be ideal, as they

But it’s important to know

would come from the patient

when intervention can be most

and would not cause an

effective.

immune response,” says Dr. Ruiz-Lozano.

Lorenzo Puri, M.D., Ph.D.,

“We need to understand whether there is a clock,” says Dr. Puri. “For a boy with MD,

is doing similar work with

18 might be too late. But at 3,

skeletal muscle progenitor cells.

we might be able to reset the

“Muscle cells continually turn

cells.” His research has led to

over,” says Dr. Puri. “When you

encouraging pre-clinical drugs

go to the gym for strenuous

that enhance regeneration by

exercise, the body perceives this

modulating native stem cells in

as damage and the muscle stem

muscle.

cells work to repair that damage.”

Controlling muscle stem cells could have important clinical implications. For example, muscular dystrophy

Th e Mystery of Canc er Stem Cells Stem cells, by definition, are cells that can either self-

Ph.D. student Karen Wei at work in the stem cell core.

renew to ensure a source of

mammary epithelial stem

continued growth or differen-

cells. MELK is often over-

tiate to become different cell

expressed in breast tumors.

types. Studying stem cells has

The Oshima lab has found

led to an interesting hypothesis

that MELK is also highly

about cancer: Perhaps some

expressed in mammary

cancers have their roots in

epithelial progenitor cells.

“cancer stem cells” that can continuously feed malignant

the role of MELK in these

cells to a tumor. This scenario

tumors,” says Dr. Oshima. “If

could be likened to an ant

you have a cancer stem cell,

colony: you can kill workers,

you can screen for chemicals

but to wipe it out you must

that will push it to differen-

get the queen. This could

tiate to a benign state and

explain why certain tumors

those could be less toxic.”

initially respond to treatment

Dr. Oshima is cautiously

but return with a vengeance.

optimistic. “The cancer stem

If this hypothesis is accurate,

cell idea could be valuable

clinicians must do more than

early on in a cancer’s progres-

shrink the tumor; they must

sion,” says Dr. Oshima.

also treat the source.

“However, tumors evolve and

Robert Oshima, Ph.D., co-director of the Tumor Development Program in Burnham’s Cancer Center, is investigating the role of Robert Oshima, Ph.D.

T he B urnham Repor t | www.burnham.org

“We’re trying to understand

the MELK gene in normal

find ways to grow.”

Stem Cells for Clini ca l Use The ultimate goal for stem cell research is clinical application. To get there, scientists

bu r n h a m stem c ell rese a r c h

must discover methods, or protocols, to consistently create the desired cells every single time.

Alexey Terskikh, Ph.D., and colleagues have developed a protocol to rapidly differentiate human embryonic stem cells into neural progenitor cells that may be ideal for transplantation. Their research could be adapted to produce committed neural precursor cells, one of the key requirements for

The Stem Cell Community Like many in the research community, Stuart A. Lipton, M.D., Ph.D., was very pleased when President Barack Obama announced new federal rules governing embryonic stem cell research.

clinical applications. When the neural precursors created using this protocol were transplanted into mice, they became active neurons and integrated into the cortex and olfactory bulb. No signs of cellular overgrowth or tumors were found.

“The uniform conversion of embryonic stem cells into neural progenitors is the first step in the development of cell-based therapies for neurodegenerative disorders

He is particularly excited that the renewed federal support for basic stem cell research will mean more funding from the California Institute for Regenerative Medicine (CIRM) for disease-focused investigations.

“The landscape is changing,” says Dr. Lipton.

“The California money is going to become more about translational research

and finding treatments for disease.”

CIRM was established by Proposition 71, the California Stem Cell Research and Cures Initiative, which provided $3 billion to fund stem cell research. This stable source of funding has made California a leader in stem cell research, helping investigators find the preliminary data that is so important to getting NIH grants. CIRM plays a unique role by funding the stages between basic research and clinical trials, a critical gap that must be bridged to get treatments to patients.

or traumatic injuries,” said Dr. Terskikh. “Many of the methods used to generate neural precursor cells for research in the lab would never work in therapeutic applications. This protocol is very well suited for clinical application because it is controllable, robust and reproducible.”

Evan Snyder, M.D., Ph.D.

A Uni q ue Coll aboration In 2006, Burnham, The Scripps Research Institute, The Salk Institute and the University of California, San Diego united to create the San Diego Consortium for Regenerative Medicine. This collaboration is now known as the Sanford Consortium after receiving a $30 million gift from T. Denny Sanford in 2008. The consortium was created to unite the expertise of these four world-renowned research institutions to move stem cell research forward more quickly.

“The Sanford Consortium fills gaps,” says Evan Snyder, M.D., Ph.D., Program Director, Stem Cell and Regenerative Biology. “None of us researchers individually are as smart as all of us together.

So we fill each other’s gaps.

You don’t need to duplicate efforts, or replicate expertise that another member of the consortium has.”

To maximize this efficiency, the Sanford Consortium is building a research facility within walking distance of all four institutions. By putting the collective expertise under one roof, the Consortium hopes to reduce the distance to new treatments.

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B u r n h a m S c ien c e ne w s

Treating Baby Amy Infantile hypophosphatasia (HPP) is a horrible disease and often fatal. A rare form of rickets, HPP makes bones dangerously fragile.

When Baby Amy was flown from her home in Ireland to Winnipeg, Canada, to be treated for HPP, she was transported in an insulated box to prevent her bones from breaking. However, after receiving an enzyme replacement therapy developed by José Luis Millán, Ph.D., and

collaborators, Baby Amy was healthy enough to be held by her mother and make the trip home to Ireland.

“While physicians may be familiar with the feeling of helping other human beings and alleviating their suffering on a day-to-day basis, it is very rare for a basic scientist to experience that,” says Dr. Millán. “Baby Amy has allowed me to experience that satisfaction. It has been very rewarding to see this therapy improve the quality

of life of the first patient ever to receive it.”

The drug, called ENB-0040, progressed from design to orphan drug status in just three years and was the result of a strong collaboration between Dr. Millán’s lab, ENOBIA Pharma (a small Canadian biotech) and Michael P. Whyte, M.D., of Shriner’s Hospital for Children in St. Louis.

Dr. Millán is now working to prove that the treatment can also help patients with

José Luis Millán, Ph.D.

more advanced disease. His lab is developing models of adult hypophosphatasia and assessing if this treatment can improve quality of life for patients with milder, but still debilitating, disease.

Alzheimer’s Disease Linked to

Mitochondrial Damage The Lipton lab has demonstrated that attacks on the mitochondrial protein Drp1 by the free Stuart A. Lipton, M.D., Ph.D. radical nitric oxide, a process called S-nitrosylation, controls the synaptic degradation associated with Alzheimer’s disease. Mitochondria are the energy storehouses of the cell, and their compromise causes synaptic injury and eventually nerve cell death.

Prior to this study, the molecular mechanism by which betaamyloid proteins damaged neurons was unknown. These findings

T h e B urnham Repor t | www.burnham.org

suggest that preventing S-nitrosylation of Drp1 may reduce or even prevent neurodegeneration in Alzheimer’s patients. The paper was published in the April 3 issue of the journal Science.

The team, led by neuroscientist and clinical neurologist Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neuroscience, Aging and Stem Cell Research, showed that Snitrosylated Drp1 facilitates mitochondrial fragmentation, thus damaging synapses, which are critical for learning and memory.

Synaptic impairment leads to the dementia seen in Alzheimer’s.

“We now have a better understanding of the mechanism by which beta-amyloid protein causes neurodegeneration in Alzheimer’s disease,” says Dr. Lipton. “By identifying Drp1 as the protein responsible for synaptic injury, we now have a new target for developing drugs that may slow or stop the progression of Alzheimer’s.”

B u r n h a m S c ien c e ne w s

Pancreatic Beta Cells and the Immune System Pam Itkin-Ansari, Ph.D., Seung-Hee Lee, Ph.D., and colleagues have demonstrated in mice that transplanted pancreatic beta cells are protected from the immune system when encapsulated in a polytetrafluorethylene (PTFE) device.

The study, which suggests a new approach to treating type 1 diabetes, was published online on April 8 in the journal Transplantation.

The team showed that, after transplantation, the precursor cells mature into functional beta cells that are glucose-responsive and control blood sugar levels. Also, the study demonstrated that using precursor cells, instead of more committed beta cells, enhanced the cell transplant’s chances of success.

“The results exceeded our expectations,” said Dr. Itkin-Ansari, assistant adjunct professor at Burnham and the UC San Diego School of Medicine. “We thought that T-cells, although unable to penetrate the device, would cluster around it. But we found no evidence of an active immune

Pam Itkin-Ansari, Ph.D.

response, suggesting that the cells in the device were invisible to the immune system.”

The investigators used two different mouse models in the study. The team transplanted mouse islet cells into other mice to show that the cells were protected from the immune system when encapsulated in PTFE. Human cells encased in PTFE were then transplanted into immunodefi-

Wolf Lab Deciphers

Yeast Investigators in the Wolf lab have deciphered a Dieter Wolf, Ph.D. large percentage of the total protein complement (proteome) in Schizosaccharomyces pombe (S. pombe) fission yeast.

Laurence Brill, Khatereh Motamedchaboki, Ph.D., and lead investigator Dieter Wolf, Ph.D., developed a novel method to identify 4,600 proteins in the organism using an array of sophisticated techniques. The research was published online on March 9 in the journal Methods.

cient mice to study the viability and function of both mature beta cells and precursor cells inside the device. Itkin-Ansari’s team found that by using precursor cells that had not completely differentiated, the transplanted cells could regenerate into fully functional beta cells. This has important implications for how stem cell-derived tissue should be transplanted in the future.

Proteome

“Analysis of the proteome of an organism tells us so much more than simple DNA sequence analysis,” says Dr. Wolf. “Proteome analysis gives us a snapshot of what proteins are being expressed in the cell at any given point in time. This can tell us how protein expression changes in response to certain stimuli and in disease states, which may help identify new biomarkers for diseases. We are now applying the methodology to protein profiling of human stem cells in collaboration with Burnham’s stem cell program director, Dr. Evan Snyder.”

DNA analysis of the yeast’s genome predicts 5,027 proteins.

The team identified 4,600 proteins, which is not quite the entire proteome. The remaining 400 are only expressed during S. pombe’s mating state.

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B u r n h a m F l o r i d a ne w s

Anatomy

of a Move

In late April, Burnham began the three-week process of packing and transporting files, beakers and high-tech equipment to its new campus at Lake Nona in Orlando, Florida.

More than a dozen moving companies and equipment specialists participated in the multi-phase move.

Layton Smith, Ph.D.

This was not a simple feat. Moving sensitive microscopes, robots and finely calibrated equipment requires specially-designed crates to protect the cargo, liquid nitrogen to freeze delicate cells to minus 346 degrees Fahrenheit (10 times colder than ice), labtrained movers and 3,000 feet of bubble wrap.

Björn Tyrberg, Ph.D., a diabetes researcher, moved a sophisticated microscope while taking special precautions to protect tiny insulin-producing cells during transport. Layton Smith, Ph.D., who studies obesity-related heart disease, froze 10 million cells in advance, so he could quickly restart his research.

“This is a complicated process,” said Cyril Doucet, vice president of operations for Burnham Lake Nona. “But we started planning for the move more than eight months ago. We had to plan thoroughly to minimize the impact on our research and to keep our science moving forward.”

Layton Smith, Ph.D., who studies obesity-related heart disease, froze 10 million cells in advance, so he could quickly restart his research.

In all, scientists moved more than 350 pieces of equipment, from a vortexer (the size of a tea kettle), to a four by eight-foot bio-safety cabinet. Each piece of equipment was disassembled, reassembled and recalibrated. Because the equipment is so sensitive, if a piece breaks, it can take months to repair or replace.

Burnham is the first facility to be completed at the new medical city at Lake Nona, which will include the University of Central Florida College of Medicine, Nemours Children’s Hospital, VA Medical Center, M.D. Anderson Cancer Center Orlando and a proposed University of Florida research facility.

T h e B urnham Repor t | www.burnham.org

B u r n h a m F l o r i d a ne w s

Intellectually Sound,

Energy Efficient Burnham’s new facility in Lake Nona, Florida was designed with open labs and extensive telecommunications technology, so scientists can easily collaborate with colleagues in the next lab or around the world.

The new facility will house a variety of specialists, from biochemists to cell biologists, pharmacologists and medicinal chemists, and is intended to encourage collaboration among these specialties to advance science.

“When you put different disciplines together in a building like this, exciting things happen,” says architect Gary C. Shaw.

In addition, the 175,000 square foot facility is poised to become the largest private research institute in Florida with a Gold Level Leadership in Energy and Environmental Design (LEED) certification, which will be awarded after two to three months.

“Burnham is on its way to a Gold Level certificate, which indicates that it is one of the greenest of the green, and has been built to the highest environmental standards,” says Shaw.

The building’s design and construction must meet a variety of criteria to gain LEED certification. For example, a project must use at least 10 percent of its materials from regional sources to reduce emissions from long distance transportation. More than 20 percent of Burnham’s materials were made within 500 miles of the site.

Building an energyefficient scientific building offered unique challenges because of the labs’ extensive exhaust and air filtration needs. “We incorporated a tremendous amount of reflective, glazed window glass into the construction to allow low levels of solar heat while welcoming ample natural light,” says Shaw.

Burnham Lake Nona

Measuring the Savings While building a green facility is very demanding, the rewards are substantial, both environmentally and monetarily. For example, 95 percent of construction waste was diverted from landfills.

Metal was recycled, concrete waste was crushed and used for road base and wood was chopped into mulch. Even leftover drywall scraps were ground into fertilizer for local sod farmers.

Energy costs at Burnham Lake Nona are expected to be 25 percent below those of a comparable building.

The roof is made of a special membrane that reflects heat, and labs and offices have motion sensors to control lighting. The building is oriented east/west with over-

hangs and shading devices on exterior walls to minimize heat and sun reflection.

More than 90 percent of the interior spaces have an outside view, decreasing the energy needed to light them.

Burnham’s annual energy savings will be equivalent to the average yearly consumption of 6,600 homes.

“Burnham is proud to have participated in the design and construction of a state-ofthe-art research facility that was built using environmentally-friendly methods and will require less energy and water than a similar scientific structure,” says Daniel Kelly, M.D., Burnham’s Scientific Director at Lake Nona.

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P h i l a n t h r o p y upd a te

Save the Date:

The 2009 Burnham Gala

The Power to Cure will be held at the Hyatt Regency La Jolla Aventine on November 14.

Caroline Nierenberg and Kathryn Stephens will chair this year’s gala. No strangers to high-profile charitable events, both have independently chaired the Las Patronas Jewel Ball.

Why focus on the power to cure? Burnham discoveries benefit people of all ages, and Burnham researchers have discovered valuable new treatments. The Institute has generated more than 250 patents, and applications are pending on 300 more.

“The benefit that Burnham research brings to the world is beyond calculation,” says Nierenberg. “We want to celebrate that contribution and highlight the beauty of the work they do.”

This year’s presenting sponsor is Life Technologies. Greg Lucier, CEO of Life Technologies, is vice chair of Burnham’s Board

Honoring an

Caption: Gala co-chairs Caroline Nierenberg and Kathryn Stephens stand next to Burnham’s Shimadzu Xcise robot, which Las Patronas helped purchase.

of Trustees. Additional lead sponsors include Jeanne and Gary Herberger, Peggy and Peter Preuss and Roberta and Malin Burnham.

For more information, please contact Chelsea Jones at 858-795-5239 or cjones@burnham.org.

Angel

By Patt y Fuller

For 32 years, Melvin Clause worked for Convair as a test pilot, flight engineer and field service engineer.

He was onboard a 42-hour, non-stop, non-refueling flight, tested the XC99 transport (one of the largest planes ever flown) and flew everything from 2-cylinder prop planes to 168-cylinder jets. But the biggest challenge he ever faced was watching his wife Phyllis McArdle die of Alzheimer’s disease.

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“Phyllis lived in fear that she would inherit the disease, which did indeed happen,” says Clause.

“She was diagnosed in 2001 and passed away in 2008.”

Phyllis had a long career as a school counselor and teacher in Salt Lake City. She played violin in the symphony and liked to camp, fish and four-wheel drive through the back country.

“She tolerated my accordion, and even put up with a month in a tepee,” says Clause.

Melvin Clause pays tribute to Phyllis through the Melvin

The B urnham Repor t | www.burnham.org

Phyllis McArdle and Melvin Clause

and Phyllis McArdle Clause Scholarship Fund at Burnham.

Created through a bequest, the scholarships are both a gift and a challenge to the next generation of scientists: find a cure for Alzheimer’s disease.

“She was an angel, or as close to one as you could find,” says Clause. “The hardest part is that the woman I loved grad-

ually faded away. I want to keep her memory alive through this scholarship fund and support scientists in search of a cure.”

If you would like to establish a named scholarship fund to support graduate and postgraduate education at Burnham through an estate gift, please contact Patty Fuller at 858-7955231 or pfuller@burnham.org.

P h i l a n t h r o p y upd a te

Bring It! Forget the fine food and wine, the cheering crowd, the red carpet, the noisemakers. Forget all that.

At 7:30, the games began and people got down to some serious fun. On April 30, more than 300 guests packed a transformed Mission Tower Ballroom at the Del Mar Fairgrounds to Bring It! Presented by Burnham and the HeadNorth Foundation, the event was a crazy combination of trivia questions, game show enthusiasm and spirited competition to support stem cell research at Burnham to treat chronic spinal cord injuries.

Imagine 30 teams of 10 facing off in a series of trivia contests with wacky challenges thrown in, leading to the final face-off for the championship. Between games, Eric Northbrook introduced the fund-a-need; Stand Up for Eric. And people did stand up. Bring It! raised nearly $170,000 to support the HeadNorth Chronic Spinal Cord Injury Project.

Congratulations to 2009 Bring It! champions, Team HeadNorth. Also, many thanks to emcee Bill Menish, lead sponsors Life Technologies and Biomed

Realty and co-chairs Stath and Terry Karras.

Did you miss it? Sorry to hear that, but it’s okay.

Burnham and HeadNorth are doing it again next year—bigger, better, faster, funner—on April 24, 2010, at the Del Mar Fairgrounds. Is someone going to take the title away from Team HeadNorth?

They dare you.

For more information, contact Chelsea Jones at 858-795-5239 or cjones@burnham.org.

5Above, Ryan Baker belts out the song he’s listening to during the iPod challenge.

4Right , Team HeadNorth: Matt Carlson, Eric Northbrook, Chris High—Bring It! 2009 Champions 6Below, the frost-a-cake challenge nearly escalated into an on-stage food fight. Andrew Morse, James Pires, John Garrigan, David Thomas, Ron Lack, Dawn Saunders, Chris High and Mary Macie.

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B u r n h a m L e a ders h ip

A Tribute to Malin Burnham As Malin Burnham steps down as Board of Trustees chair, many people are noting what a profound impact he and his family have had on the Institute. For nearly three decades, the Burnham family has donated their time, talent and treasure to grow the organization and advance basic biomedical science.

Here are some reflections on Malin Burnham’s 14 years as chair and his ongoing passion for Burnham Institute for Medical Research.

“At the first National Cancer Institute (NCI) site visit, in response to our application for a cancer center grant, we needed to demonstrate wide community support. Malin appeared in person to testify on our behalf. To this day, we are still supported by an NCI cancer center grant.

“But Malin’s efforts did not end there. He contributed significantly by joining the board of trustees. His leadership as chairman set the stage for our future growth, and he also helped build the board by recruiting strong leaders who were enthusiastic about our mission.”

— Lillian Fishman, co-founder

“Malin is one of those larger than life people who has an impact on everything he gets involved with. He is broadly focused on San Diego and is the guardian of our region’s wellbeing. Adding his name to the Institute and serving as chairman of the board put the Institute on the local map. The scientific team followed through by putting Burnham on the world map of best research institutes.”

— Duane Roth, CEO, Connect

“There are no shortage of positive adjectives to describe Malin Burnham. He is dedicated to the mission, decisive, experienced, persuasive, engaged and proactive. He is completely vested in the success of Burnham Institute for Medical Research.”

— Gayle Wilson, Burnham Trustee Editor’s note: The Institute recently commissioned a formal portrait of Roberta and Malin Burnham that will hang in the executive suite.

It will serve as a reminder to Burnham leadership, staff and all who visit our campus of the impact the Burnham family has had on the Institute.

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The B urnham Repor t | www.burnham.org

In His

Own Words Malin and Roberta Burnham

When I first visited the La Jolla Cancer Research Foundation (LJCRF) in 1982, I was extremely impressed.

I especially liked what I heard and saw about cofounders Dr. William and Lillian Fishman. I recognized their scientific talent and the quality of the culture they had established, which was very open and transparent.

Everyone was in it together, and there were no silos, artificial walls or rules to inhibit collaboration. I came to the conclusion that LJCRF was a hidden gem, and that I should do what I could to help.

One of the more personal aspects of my relationship with the Institute was my

own experience, about seven years ago, with cancer. I had a PSA test come back high, and the biopsy showed that I did indeed have prostate cancer.

I was lucky we found it early.

But it’s important to note that the PSA was perfected as a result of work done by Dr. Eva Engval, a Burnham researcher.

Roberta and I, along with the Burnham family, have had the wonderful opportunity of supporting the Burnham Institute for Medical Research.

I particularly enjoy providing a combination of our financial resources with shoe leather and brain power. Of all the things I have done, business and community-wise, helping the Burnham Institute has given me the most satisfaction.

p r e s i d e n t ’ s M ess a ge

Fulfilling the Promise of Stem Cells In 1974, Burnham co-founder Dr. William Fishman discovered placental alkaline phosphatase, a pregnancy protein, in an adult human lung tumor. Soon thereafter, Dr. Fishman found several examples of tumors producing fetal proteins, prompting him to hypothesize that cancer might be caused by adult cells reverting back to the primitive fetal state during which cells divide rapidly and migrate through the developing body. This breakthrough helped create the field of oncodevelopmental biology and informed much of the early research at Burnham. We now recognize that the primitive cells Dr. Fishman observed were actually adult stem cells that had become cancerous.

Our bodies have small numbers of stem cells that constantly renew tissues and organs with fresh cells. Today, scientists believe that these adult stem cells are the source of many cancers. By delving into the relationships between fetal development and cancer, Dr. Fishman’s work set the stage for Burnham’s current work in stem cell biology.

John C. Reed, M.D., Ph.D. President and CEO Professor and Donald Bren Presidential Chair

Stem cell research provides a powerful approach to unlocking the mysteries of human disease.

Burnham scientists, for example, make disease models by synthetically creating the equivalent of embryonic stem cells from patients with genetic predispositions to diseases, then converting those synthetically-derived stem cells into specific types of cells in which the disease manifests (brain cells, heart cells, insulin-producing cells). With these disease-specific cell lines, we can expand our understanding of the complex biological mechanisms that lead to cancer, Parkinson’s disease, diabetes and other conditions. We can test new medicines, rapidly gaining insights into the best

15. John Reed essay

candidates to take, eventually, to clinical trials.

In addition, regenerative therapies have the potential to treat many conditions by replacing cells lost to disease, trauma or aging. Once clinical protocols are perfected, stem cells will be grown and differentiated into heart cells, nerve cells, insulin-producing cells and other therapeutically useful cell types and transplanted into patients. But transplantation is only one way stem cells can benefit human health. As forecasted by Dr. Fishman’s seminal work, our bodies also contain endogenous adult stem cells that heal tissue damage, though inefficiently. Burnham researchers are working to harness these cells and boost their efficiency. This research may lead to medicines that mobilize endogenous adult stem cells to regenerate the heart, brain, spinal cord, liver or other tissues.

While we are excited about the enormous potential of stem cell research, we must recognize that this line of investigation is at an early stage. Because stem cell-based therapies are largely

With these diseasespecific cell lines, we can expand our understanding of the complex biological mechanisms that lead to cancer, Parkinson’s and other diseases and test

new generations of medicines to treat them.

unproven, pharmaceutical companies are reluctant to invest resources to study how they work, and thus that responsibility falls to non-profit organizations like Burnham. We encourage you to join in supporting our mission to make stem cell-based therapeutics not just the passion of dedicated scientists and the dream of those suffering from debilitating disease, but a reality that saves lives.

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Nonprofit Organization U.S. Postage 10901 North Torrey Pines Road La Jolla, CA 92037

PAID The Burnham Institute

Philanthropy

Partners

in Science:

Northbrook and Dr. Evan Snyder Eric

“Living with a chronic spinal cord injury is a serious challenge,” says Northbrook. “The HeadNorth Chronic

Spinal Cord Research Project could be the solution

for thousands who live with this condition.”

After a motorcycle accident severed his spinal cord, Eric Northbrook founded the HeadNorth Foundation to support those with similar injuries and champion spinal cord research. His efforts led him to Evan Snyder, M.D., Ph.D., director of Burnham’s Program in Stem Cell and Regenerative Biology, whose groundbreaking stem cell research could lead to new treatments for paralysis. Dr. Snyder and Dr. Mark Tuszynski at UC San Diego have received a grant from HeadNorth to develop stem cell therapies for chronic spinal cord damage.

Printed on recycled paper

Nonprofit Organization U.S. Postage

PAID 6400 Sanger Road Orlando, FL 32827

The Burnham Institute

Philanthropy

Partners

in Science:

Northbrook and Dr. Evan Snyder

Eric

“Living with a chronic spinal cord injury is a serious challenge,” says Northbrook. “The HeadNorth Chronic

Spinal Cord Research Project could be the solution

for thousands who live with this condition.”

After a motorcycle accident severed his spinal cord, Eric Northbrook founded the HeadNorth Foundation to support those with similar injuries and champion spinal cord research. His efforts led him to Evan Snyder, M.D., Ph.D., director of Burnham’s Program in Stem Cell and Regenerative Biology, whose groundbreaking stem cell research could lead to new treatments for paralysis. Dr. Snyder and Dr. Mark Tuszynski at UC San Diego have received a grant from HeadNorth to develop stem cell therapies for chronic spinal cord damage.

Printed on recycled paper