A YEAR IN THE LIFE OF CALIFORNIA'S STEM CELL RESEARCH PROGRAM
 
                                                By Don C. Reed
 
Imagine that you and I are involved in a terrible war, against a relentless enemy which fully intends to kill us and all our families. But we are fighting back hard, and despite tremendous odds against us, we are beginning to win.
 
Suddenly good news arrives: reinforcements are on the way!  
 
Should we respond by laying down our arms, to surrender?  
 
President Obama's reversal of the Bush stem cell restrictions is wonderful: a decision that will echo down the halls of history. But it is not victory.  
 
The Obama edict brings no guarantees of new stem cell funding. Those "extra" NIH funds you heard about? At best, they help make up for 5 years of flat-lined funding, when National Institutes of Health budgets remained stagnant, not even matching increases of inflation.
 
Now is the time to redouble our efforts, not relax them.

  
Let me show you why.
 
In the midst of all the economic gloom and doom, something shining has emerged in California: the beginning of a vastly better world.
 
Take a look at some highlights of what the California Institute for Regenerative Medicine (CIRM) did—with just twelve months of reliable funding, in 2008.
 
(You can verify the following amazements by going to http://www.cirm.ca.gov/  Scroll down the left side of the page, until you find a bright red picture of stem cells, click under that: 2008 report, download it for free.)
 
LABORATORIES: have you tried to find parking for your car at an overcrowded college campus lately? Imagine what a nightmare it is to find space for new stem cell laboratories, let alone equip them. Dedicated buildings are urgently needed.
 
But bricks and mortar costs a lot, and the last thing California wants is to spend precious research dollars on a bunch of unnecessary buildings. So, a limit was set: no more than 10% of the entire program's cost, $300 million, could be used for facilities. But, that's not much money. In today's market, it would pay for only about three or four hundred homes: nowhere near enough for serious labs.

How did the CIRM meet this challenge?
 
They authorized $271 million on facilities (buildings and equipment)—and, to make sure we got the most possible bang for its buck, a special requirement…. Any organization wanting a grant had to bring their own money as well.
 
This strategy brought in an additional $880 million dollars. Our $271 million in taxpayer money was leveraged (great word) into $1.15 billion dollars.
 
Twelve major facilities will be built—and soon. All these buildings are contractually obligated to be up and running by the end of 2010.

 

And of course, we must not forget the stem cells…
 
CIRM NEW CELL LINES AWARDS

After 8 years of being stuck with a tiny number of ancient stem cell lines, America desperately needs new ones--$25 million went to derive new cell lines.  Some were disease-specific: allowing us, for the first time in history, to watch the development of Alzheimer's disease in a Petri dish, instead of only seeing—too late—its devastating results on a person.
 
Other stem cell lines are needed to compare embryonic stem cells with the new kind of cells, induced Pluripotentiary Stem cells (iPS). As we struggle to find out if the new (iPS) method can be made safe for human use, or even as a research tool, we also need to know if it can really do the job.
 
And who will be allowed access to these new stem cell lines funded by CIRM?

 

These valuable biomaterials will be available to any responsible researcher working toward cures…

 

New buildings, new stem cell lines-- how about some new scientists?
 
TRAINING NEW SCIENTISTS: CIRM RESEARCH TRAINING PROGRAM II

 

For too long, only scientists in their mid to late forties, folks who had their PhD's for almost a decade, have been able to receive funding from the NIH.

 

But if we only fund scientists that far along in their career, how will the field grow? If young scientists cannot get grants, their options are limited. At best, they will  work for other scientists, doing research directed by them instead of blazing their own trail; or, financial need may drive them out of the field altogether.

The very first project CIRM funded was training grants, to help new scientists into our field, an oasis of funding in what had been barren desert. Training Program II continues providing funds for these young men and women and their labs: allocating $40 million for this vital effort.  

 

But even the greatest scientist cannot do his or her work alone.

TEAM ASSISTANCE:  Generals are nothing without soldiers; even so, scientists rely on the assistance of trained professionals; where will they come from?  

 

"An educated and properly trained workforce is essential if our state is to retain its premier position and fully realize the medical and economic benefits from this emerging industry."—joint statement, Senator Gloria Romero and Senate President Pro Tem Darrel Steinberg.
 
The "CIRM Bridges to Stem Cell Research Awards" program is designed to insure training exists for these incredibly valuable technicians: the workforce to make the miracles possible, perhaps becoming future superstars themselves– you never know where success in such a new enterprise may lead.

 

$17 million in these Bridges awards has been approved.

 

But what about the business side? The greatest stem cell idea in the world means nothing, if it is not translated into something real and usable: and that means biotech.
 
LOANS 

 

"Our new loan program for biotech companies is meant to provide… support for institutions testing the safety and efficacy of possible therapies."—Robert N. Klein, Chair, ICOC.
 
Developed by our new Vice-Chairman Duane Roth and Finance subcommittee Chairman Michael Goldberg, (and of course Chairman Klein, who is pretty much everywhere) the new loan program is for $500 million—and hopefully an additional $500 million in federal loan guarantees as part of the stimulus package.
 
Numbers that big numb my brain like novocaine at the dentist's.   

 

But wait, there's more! 
 
"That amount would be scaled up by recycling an additional $1 billion in repayment proceeds over the first decade of the program. In short, with $500 million in federal long-term guarantees and recycled principal repayments, interest and stock warrant revenue from borrowers, over $1.5 billion in additional resources could be added to the Proposition 71 portfolio."—BK.
 
As I understand it (always an element of doubt about that) this would be astonishing.

 

Leveraging five hundred million in state dollars to two billion, perhaps even two and half billion, so that California got five times the value of its initial investment?
 

And, these loans are targeted: designed to answer an unmet and colossal need.
 
CLINICAL TRIALS

Taking just one new product from idea to pharmacy costs hundreds of millions of dollars, due to safety testing.

 

The time between basic research and clinical trials completion is called the "Valley of death" because so many products and companies die during that period. What an agony it would be to have a great cure for paralysis, for example, and then watch it fail-- for lack of money to pay for those tests.
 
The new loan program is designed to help turn the ideas of cure into products everyone can use: promising new medicines or therapies through the grueling cycle of tests, so they can be submitted to the FDA for approval.

 

MODEL FOR THE COUNTRY

 

Look at the path that CIRM has laid down for cure: educating and supporting scientists, helping train their support staff, setting up loans for the companies that will risk so much to develop products for patients… this is something which should be shared, and imitated.
 
COMMUNICATION:
 
Next ICOC meeting you go to, look for a crew-cut, glasses-wearing individual with tremendous energy, listening to everything, hardly ever sitting still—this is Don Gibbons. Very often, he has the honor of being the voice of the CIRM. 

 

A tough job indeed. For starters, he has to understand enough of the science to be able to translate it into people talk, enough legalese to do the same for those complicated aspects.
 
In addition to sharing information through public outreach, some of Gibbons' projects include: updating the CIRM website, (major improvements just days away, btw) Town Hall Meetings (You MUST come to one of these—the first one was last week, and it was terrific—three outstanding scientists use people talk to share where their corner of the science is at—more info at bottom of page.

 

And what a message he has to share, as the CIRM's influence grows, even leaping beyond the artificial boundaries of lines drawn on a map.
 
COOPERATING WITH OTHER STATES AND NATIONS:

 

"…no one state or nation (can) do this alone," stated Governor Arnold Schwarzenegger,"…collaborations…which bring together leading medical researchers from around the globe have a great potential in improving the lives of not only Californians, but all the people around the world."

 

The CIRM has already made agreements for combined research with countries including Australia, Spain, Japan, the United Kingdom and Canada, bringing in additional funds to the effort. Those countries have already committed over $200 million dollars to collaborative efforts with CIRM.

 

For example, Canada will be teaming with California to fight cancer.

There is more to come. California money must always be spent inside the borders of our state (as required by Prop 71 statute), but knowledge can and should be shared.

 

State to state cooperation will, increase our strength. Consider the example set by Dr. Dennis Clegg of UC Santa Barbara. Working with colleagues in Massachusetts, he found a molecule that helps embryonic stem cells multiply faster, while still maintaining their stability, vital characteristics for the large quantities of pure cells we will need for cure.

 

CALIFORNIA GOLD

 

It is not enough just to labor endlessly—everybody wants results.  As President Alan Trounson puts it: "I tell my colleagues here at CIRM probably at least once a week: "We are in a hurry; we have a short time frame, and we need to get genuine cures to Californians."

 

The opening page of the 2008 report shows the official motto of the CIRM:

 

"turning stem cells into cures".—Roman Reed.

 

That is my son who wrote those words, in case you did not know—and that is our goal.

 

Success will come in careful reliable steps, and we are taking them right now.

 

We benefit from the leadership of chief science officer Marie Csete (pronounced chet-uh) an energetic little exclamation point of a person, and the indefatigable Director of Scientific Activities, Patricia Olson.

 

Do you know them? If you live in California, you should. Walk up and say hello to them at the next CIRM meeting.

 

Are they approachable? You bet. Here is an example.

 

There will soon be an autism workshop: for scientists only. This is fairly common, giving the scientists a chance to speak their own language, and interchange ideas—very important.  BUT— such knowledge should be shared. So, seeing Dr. Csete at another public meeting (there have been about 150 public meetings so far) I asked her if there was a way to make the autism meeting more open, because there were literally millions of people interested in this all-too-common condition. She thought about it for a minute, and then said, there should be a transcript, print and video, and that could be made available on the web. (Something I forgot to ask was: could parents of autistic children send in questions to be asked of the scientists?)

 

That is how this program works. The decisions are made in public, and anyone who wants to get involved is welcome.

 

Come to the meetings; California wants you! (to find out when and where the meetings are, go to http://www.cirm.ca.gov/  and click on Meetings; it is up near the top of the page.

 

Already, CIRM scientists have authored more than 70 scientific publications, adding to the world's understanding.

 

If you go to the meetings, you will get to hear Dr. Trounson talking about the latest breakthroughs in stem cell science. Such as:

 

Remember one huge difficulty with the new stem cell method,  iPS, induced Pluripotent Stem cells, mainly that the use of viruses might cause cancer? At Scripps Institute, a scientist named Sheng Ding may have found a way around that obstacle, using "small molecules rather than viruses to carry reprogramming genes into cells, moving the iPS cells closer to being safe for clinical use."

 

And speaking of genes, this miniscule marvels which turn body processes on and off, it is vital we know exactly which genes do what-- and  Dr. Jean Loring and her team "published a database of gene expression profiles", vital information for the sorting of cells.

 

(Both those scientists, by the way, received CIRM grants.)

 

Sometimes, a step in one area helps in another; look at the next two paragraphs.

 

First, If we can learn how healthy cells are turned into cancer cells, (as Dr. Wei Guo of UCLA did with blood cells), maybe we can learn how to do the reverse-- and turn cancerous cells back into healthiness.

 

Second, at Stanford, Dr. Emmanuelle Passegue showed that a "family of cancer-fighting proteins also helps blood-forming stem cells divide normally."

 

As CIRM President Dr. Alan Trounson observed, "These two push-and-pull findings hold great promise for uncovering novel ways of treating cancer and preventing its spread."

 

CIRM helped Dr. Catriona Jamieson of UCSD as she brought a new approach to fighting leukemia to human trials.

 

So much more: at Stanford, human embryonic stem cells were grown into "primitive cardiac tissue (which) repaired heart damage in mice".

 

At UCLA, scientists matured human embryonic stem cells into T cells and inserted a gene—why does that matter? "Their eventual goal is to insert a gene that makes the cells immune to HIV/AIDS, then replace a person's infected cells with the resistant ones…"
 
Yet there are still dark days ahead, much work to do, battles yet to fight—including financial ones.

 

WILL THERE BE MONEY TO PAY FOR EVERYTHING?

 

If the financial equivalent of Hurricane Katrina crashes down upon us, (and it did) we have only two choices: adjust, or let the program die. 

 

First, every new grant comes with a proviso that the money will be provided if and when it is available. Some extremely worthwhile projects may have to be delayed a year. This is just a fact of economic life.

 

Our program depended on selling bonds. 

 

If California cannot sell bonds, will we be able to keep the stem cell program alive?

 

Here is the official CIRM answer.

 

"CIRM's Financial Commitments Are Secure… CIRM currently has significant cash reserves of $160 million, which can fund all existing commitments through at least September. The agency's plans have always called for raising new capital on a cash-flow, as-needed basis. We expect the traditional bond market will open soon with resolution of California's budget situation. To supplement this public bond market, CIRM is working with the State Treasurer's office on a CIRM private placement of $200 million in general obligation bonds this year and $200 million again next year… The Agency intends to continue the planning and review needed to maintain its mission on schedule…"

 

The men and women of California's stem cell program have taken up the gauntlet, accepting this new challenge.

 

They deserve the support and thanks of a nation.

 

SO WHAT DO WE DO NOW?

 

In California we have funded a solid beginning. We must build on that, in "synergistic cooperation" (Gibbons' phrase) with the federal government, each side strengthening the other, and the same with other states across the land.

 

Ten thousand stem cell advocates developed Proposition 71; seven million Californians voted it into law; what we need now is more of the same.

 

Not every state wants or needs to be a California or New York, with major biomedical infrastructure employing hundreds of thousands of workers in excellent and good-paying jobs. But every state should at least have funding for regenerative research, and the freedom to do it. 
 
As patient advocates, you and I are involved in a war against chronic disease and disability. And it is a war, make no mistake about that. Millions of lives are at stake, as well as the economies of every nation.

 

Our motivation is continual; for those who themselves are suffering, the pain and distress is a constant reminder. For we who have the luck of health, our loved ones must be fought for.
 
But ours is a war like none that ever was before. It is a very civilized combat.

 

We have two sides essentially throwing words at each other. We pound the keyboards for a while—argue, argue, argue—then rest, do some other chores for a while, and then come back to the computer, fight some more.

 

These are epic confrontations, on which the future of the world depends; yet, nobody is killed. There are no ruined families, no widows made, nor orphans, no silent graveyards, no white crosses on a hill.

 

In this war, we are fighting to save lives, not take them. 

 

And when we win, there will be no reason for tears: save only those of joy.