8 Years After Prop 71: Industry Perspectives On CIRM

Earlier this week I had the opportunity to testify before a Review of the California Institute for Regenerative Medicine (CIRM) at the Institute of Medicine, to provide some perspective on the team at CIRM, their diligent efforts to advance the caus

e of stem cell research, and some of the 'blind spots,' from an industry standpoint, of CIRM's strategic plan. Below is the text of my statement to the committee:

April 10, 2012

Testimony of Michael D. West, Ph.D.
President & CEO BioTime, Inc.
Before the Institute of Medicine, Committee on a Review of the California Institute for Regenerative Medicine (CIRM)

Mr. Chairman and members of the Committee, my name is Michael D. West and I am the President and Chief Executive Officer of BioTime, Inc., a biotechnology company based in Alameda, California. A copy of my curriculum vitae is presented in attached Appendix A. I have been asked to comment on the effectiveness of CIRM, in particular to offer constructive criticisms from the perspective of industry. Let me begin by thanking you for the opportunity to speak on the subject of regenerative medicine. There are few areas of human endeavor with the potential to improve human health than this emerging field of medicine. And California’s leadership role as a means of accelerating the development of new cures is a model for the world. Therefore, given the importance of the effort in California, I will not hesitate to offer criticism in the confidence that it will be viewed in a constructive manner.

First, I must state unequivocally that I and many other scientists in the field of stem cell research are great admirers of the team at CIRM and its diligent efforts to advance the cause. Managing the shear volume of their workload is nothing less than heroic. Nevertheless, there is always room for improvement, and I would like to point out what in my opinion are blind spots in CIRMs strategic plan, that could use improvement.

The first blind spot relates to the manner in which new human therapeutic products are developed in the United States. To put it simply, stem cell research by itself will not lead to cures. Research and DEVELOPMENT leads to cures. In my opinion, if CIRM fails to deliver on its goal to deliver cures, it will not be a result of internal governance issues. Instead, it will be a result of inefficient capital allocation. A graphic way of visualizing my point is to say that CIRM has historically funded primarily research, and little product development, i.e. large “R” little “d”. Approximately 5% of CIRM’s expenditures have been allocated to biotechnology and health science entities whose expertise is product development, and 95% has been allocated to nonprofit institutions in the state for basic research. Human therapeutic product development in the United States requires a very intense and expensive process for approval that is primarily focused on development side of the equation. In this respect, therapeutic approvals differ significantly from the discovery and development of silicon-based technologies that have been so successfully commercialized in California.

Sometimes analogies help clarify an otherwise abstract considerations. So let me offer one. Imagine that instead of being a proposition to promote stem cell product development, Proposition 71 was instituted to promote computer technology, e.g. new laptops and smartphones where none previously existed. In the event that 95% of the funds were allocated to prestigious microelectronics research facilities such as the Paul Allen Center at Stanford University, and only 5% of the funds allocated to commercial entities such as Apple Computer and Microsoft, we might easily imagine that Steve Jobs would shut down his computer business shifting to his Pixar investment, and Bill Gates would move to Seattle. This helps us understand the reasons for Geron, the pioneer in commercializing embryonic stem cell-based therapies, shutting down its stem cell business, and Advanced Cell Technology shutting down its California operations moving all operations to Massachusetts. Let me add that these latter real-world events not only represented lost opportunity, but a loss of jobs in California (a net decrease in commercial employees) and a tragic loss of science from discarded programs, reagents, and knowhow.

Another potential blind spot relates to the research side of the equation. Human embryonic stem cells and related induced pluripotent stem cells are promising because to their ability to differentiate into all of the complex cell types in the human body. However, this is also their greatest challenge. They make ALL of the cell types in the human body. This logically leads to the manufacturing conundrum of how do we manufacture purified and identified cell types when thousands of diverse cell types emerge from these cultures. BioTime has benefitted from a $4.7 million grant from CIRM to further the development of ACTCellerate(TM), a novel manufacturing technology allowing the scalable manufacture of over 200 diverse highly purified cell types. This advance has highlighted the urgent need for a “Rand McNally road atlas” for this complex branching tree from pluripotent stem cells. Currently, for all the thousands of cell types that emerge from pluripotent stem cells, little to no information is available in an organized form for the scientific community to help identify the cells (i.e. where the scientist is on the road from pluripotent stem cells to the final desired cell type). As a result, to meet the rigorous standards of the FDA in regard to purity and identity, companies have found themselves paddling upstream against the very difficult challenge of identifying the cells contaminating their potential products. CIRM could provide a critically valuable research function by building an online database that for the first time laid out a roadmap of the cells of human development, their molecular markers, CD antigens, and other markers. Similar to the foundational impact that the mapping of the genome had on science and medicine, the mapping of the “embryome” would lay a broad and effective foundation for subsequent product development worldwide for decades to come (Regen. Med. 2007, 2(4):329-333).

Lastly, a third potential blind spot relates to a possible scenario where CIRM eventually ceases to fund programs in the State. In anticipation of the possibility of this event, there should be plan of transition to avert the possibility of a massive loss of effort, reagents, and trained personnel. Again, a logical solution would be expanded funding in the latter years of CIRM to support the California regenerative medicine industry with the goal of building an “economic engine” to continue the translation of CIRM-funded research into the clinic. In summary, I believe the citizens of the State of California as well as local biotechnology companies appreciate the dedication of the CIRM team, and look forward to finding a path to accelerate these new life-saving therapies to the people in need and thereby fulfill the historic mission of the California Institute for Regenerative Medicine.

Michael West Full Testimony – CIRM – Apr 10 2012

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Cellular Purity: Key to the Stem Cell Race

“Rare is the union of beauty and purity”
Juvenal

The confluence of supply and demand is the engine of commerce. Today, the aging U.S. baby boom population is creating one of the fastest growing sectors for new product demand in our history. Th

is 76 million-person strong segment of our population is facing a surge of degenerative diseases, many having no known cure. Examples would be Parkinson’s disease, osteoarthritis, heart failure, macular degeneration, and so on. On the supply side of the equation is the emerging field called “regenerative medicine.” Regenerative medicine was a term coined to refer to medicine’s new-found ability to manufacture any cell type in the human body, based on embryonic stem (ES) cells. Normally, the confluence of such powerful economic forces would generate enormous new industries to connect the tides of supply and demand. And yet, in the United States today, the industry of regenerative medicine is still in its infancy, and we are hearing about the difficulties some companies face in commercializing the new products. This leads us to ask, “Where are the bottlenecks, and how will industry rise to the occasion to deliver on these desperately-needed new products?”

The problems facing our nation in regard to an aging population and the rising national health care bill have received high visibility in the media. Less well known, perhaps, is the daily struggle behind the scenes, as scientists seek to bring the promise of regenerative medicine to the marketplace. As we have said, ES cells, and their related cells called induced pluripotent stem (iPS) cells, have the impressive ability to become all the cell types in the human body. What is not as well appreciated is that this protean power resident in the cells is also an enormous hurdle for people working in biotechnology who wish to actually produce these products on an industrial scale. The challenge is one of purity. How do we consistently manufacture only the cell type of interest when there are hundreds of cell types in the body? If we do not solve these technical challenges, preclinical development costs can rise into the hundreds of millions of dollars, squelching product development.

These difficulties in the first decade of regenerative medicine will likely be addressed in the second decade by new methods to completely isolate and scale up defined lineages from ES or iPS cells. BioTime is using a proprietary approach we call ACTCellerate™ which has already resulted in the isolation of >200 different cell types of the human body. The use of these purified cell types is expected to simplify the manufacturing process and ease the concern of regulators over product safety. BioTime’s announcement of a partnership with GeneCards is the beginning of our effort to steer regenerative medicine into a new era wherein many new human cell types can be manufactured to scale at an unprecedented level of purity and identity. This new generation of manufacturing technologies, or as we say Manufacturing 2.0, is expected to simplify product development and speed the transfer of supply to demand.

But for the research scientist, accessing for the first time the purified cellular building blocks of the human body, and being able to map out their gene expression profiles, is as much an appreciation of the beauty of human development as it is a quest for cures and products. Seeing for the first time in the laboratory dish the cellular components of the human body, and being able to map out the genes that cause the cells to weave themselves into human tissues, gives the bench scientist a vision of what life could be, how medicine could fashion new life-saving therapies. Our nation cannot afford to lag behind in the commercialization of regenerative medicine in such a critical time in our nation’s history. Never before have we faced such opportunity in medical research, and never before has it mattered so much for so many people.

 

An Update on iPS Cell Technology

“Look here,” said the Medical Man, “are you perfectly serious? Or is this a trick – like that ghost you showed us last Christmas?”

H.G Wells
The Time Machine

Most people in touch with current events, in particular, developments relating to

science and medicine, have observed the growth of the industry called regenerative medicine. The field was born with the first isolation of human embryonic stem cells in 1998. These cells when propagated under laboratory conditions have the potential for the first time in history of being transformed into all the cell types of the human body. Therefore, the vision of this emerging industry is to invent a new field of medicine wherein the hundreds of cell types of the human body are manufactured to repair or regenerate tissues worn out from aging, trauma, or disease. Some salient examples would be cells that have the potential to regenerate heart muscle after a heart attack (something the heart cannot do on its own), or cells capable of rebuilding the brain destroyed in a stroke, or skin cells lost in a body burn, pancreatic cells missing in diabetes, retinal cells for macular degeneration, and so on. [Read more...]

Mr. Monk, Stem Cells, and Cancer

“It’s a jungle out there
Disorder and confusion everywhere…
You better pay attention
or the world we love so much
might just kill you.” (Monk theme song)

The lead character in the television program “Monk” is a detective named Adrian with o

bsessive-compulsive disorder who vainly attempts to organize the world around him, lining up bullet casings in a row as he explains the details of the murder plot.

The cells in our bodies, like Mr. Monk, hate disorder and confusion. And there is a very good reason for this. Packed away inside the trillions of cells in our body is a set of each and every human gene, highly organized in a row along the string of DNA. This genetic blueprint contains all the information to make us who we are. These genes even direct human development (the amazing process that allows us to live even while we are being formed from a single cell). If this precise organization of DNA becomes disordered, powerful and deadly changes can be unleashed. Some deleterious changes have an effect similar to a stuck accelerator in a car, causing the cells to divide rapidly. Other genes, if broken, function like a defective brake, eliminating the normal mechanisms that regulate tissue size. Lastly, the inappropriate expression of the immortalizing gene called telomerase can give cells an infinite fuel supply, i.e. an unnatural ability to replicate without limit. These disorderly events, if they occur together in one cell, can lead to the disastrous outcome similar to a car with a stuck accelerator, a broken brake, and an infinite fuel supply all at the same time. This would be a very dangerous result indeed – somebody is going to die as a result. And they do die, because this cellular calamity is known as cancer. [Read more...]

The Cyclic Nature of Biotech Revolutions

We all can probably remember a time when we met someone who indelibly impacted our lives. In the mid 1990s my life was influenced by a series of meetings I had with Bob Swanson, one of the founders of Genentech. Bob was a man with extraordinary vi

sion, a near clairvoyant ability to sense business trends. Upon being briefed on the then-confidential project to isolate human embryonic stem cells, he pulled me aside and whispered something like the following: [Read more...]