Actions Speak Louder Than Words

Late August saw another round of grants from the California Institute for Regenerative Medicine (CIRM).

CIRM, you may recall, was established by a voter-approved referendum in 2004, with a $3 billion budget (plus another $3 billion in interest) over 10 years.  Its mission was to fund stem cell research, with funding preference to go to human embryonic stem cell research (hESCR) and to human cloning for research. 

But as the late August grants (again) show, things have not turned out as anticipated. 

This round of grants is intended to encourage researchers to form teams in an effort to quicken the time frame for translating research into actual clinical trials.  As CIRM put it, the grants would encourage “the most promising approaches towards and into early phase clinical trials.”

So what are these “most promising approaches” to actually producing early phase clinical trials, especially in terms of CIRM’s mandate to give preferential treatment to hESCR and human cloning for research?

Well, projects involving adult stem cells were preferred over those utilizing embryonic stem cells – and by a whopping 3 to 1 margin. 

In total, CIRM handed out 19 grants amounting to $1.8 million in preliminary funding (a second round of grants will be worth up to $20 million each).  Of those 19, 16 involved the potential therapeutic uses of stem cells (other proposals addressed other research areas, such as proposals to study cancer stem cells).  Of those 16, 12 involved proposals to use adult stem and other non-embryonic stem cells to treat heart disease, Huntington’s and Alzheimer’s, among others. Eleven will use actual adult stem cells, while 1 will use non-embryonic induced pluripotent stem cells (iPSCs).

Only 4 of the approved grants were for projects using hESCs.  No grants were awarded to research using cloned human embryos.

This latest round of grants actually continues a pattern that has been developing for some time at CIRM. 

In October, 2009, a major round of CIRM grants totaling some $230 million went to 14 research projects – but only 4 of them involved the use of hESCs.  The rest, again, went to research using adult stem cells or more conventional approaches, such as drugs to treat cancer. 

The irony of an institute founded to give preferential support to hESCR and human cloning for research instead giving such extensive support to adult stem cell research was not lost to observers at the time.  

“In something of an irony, little of it is going to the reason the institute exists - to work with human embryonic stem cells,” the Knight Science Journalism Tracker commented.

The San Diego Union-Tribune noted: “One irony of the latest grants is that much of the work they support does not involve human embryonic stem cells, a contentious area because it requires the destruction of embryos. Bush administration funding restrictions on that work were a big reason the California institute was launched to begin with, but many of the current projects use less-controversial adult stem cells”.

And the New York Times said that the large number of grants to adult stem cell research compared to embryonic is a “tacit acknowledgment that the promise of human embryonic stem cells is still far in the future.”

While CIRM’s favoring of adult stem cell research may be ironic, it is nonetheless understandable.  CIRM knows it needs to show some tangible results to California taxpayers for what will eventually be their $6 billion investment in stem cell research.

Hype -- especially the hype over ESCR that played such a large role in CIRM’s creation – will only get you so far.  And as it noted in handing out the current round of grants, CIRM gives priority to those project which seem the “most promising” to actually result in clinical trials. 

Once again, adult stem research is proving the most promising approach toward achieving both these goals.

And the promise of hESCR still remains “far in the future.”

Scientific Sense and the Sense of Propriety

A student who was doing a project on stem cell research emailed DNH a series of questions, one of which was “Is there any scientific reason to not continue with stem cell research?”

It seems like a reasonable question, given that stem cell research – or, more correctly, human embryonic stem cell research (hESCR) --  is and remains very controversial.  The controversy arises over the ethics of destroying human embryos for research, which is the necessary basis of hESCR.  But, the questioner wanted to know, what about the science? Are there any scientific reasons for ending hESCR?

After some thought though, it becomes clear that the student’s question is based on a misguided assumption, but one that nonetheless has underlined much of the debate over the propriety of pursuing hESCR.  This assumption is that “science” is the ultimate arbiter of what “science” should or should not do.  Throughout the national debate on hESCR we frequently heard the argument that we should be “guided by the science” in determining whether the research should receive federal funding, and that those outside the scientific community had no business telling scientists what they could or could not do.  The ultimate logic of this assumption is that scientists should have the final say on what research projects to pursue, whatever – or in spite of— the ethical objections, however sound, other voices may raise.

Which brings us to a fascinating article in the August issue of Wired: “Seven Creepy Experiments That Could Teach Us So Much (If They Weren’t So Wrong).    

The title pretty much tells the story.  The article highlights seven proposed experiments that --  from a purely scientific perspective --  would benefit us and add to our store of knowledge, but would not (at least at present) be undertaken because of the ethical objections they raise. 

For example, one experiment calls for testing potentially toxic substances in human subjects, rather than in animals.  The benefits from such an experiment should be obvious – as should the ethical objections to it.   Another experiment calls for inserting a “reporter” gene into an embryo in order to directly observe the process of how genes turn on and off and guide the development of the embryo from just a few cells into a fully differentiated human.  “If ethics weren’t an issue” the author notes, the knowledge gained from such an experiment could provide a real boost to the field of regenerative medicine.  Yet another experiment proposes to breed a human-chimpanzee hybrid.  The experiment could help answer many questions surrounding evolution and the origins of humans.  The late biologist Steven Jay Gould called such a proposal “the most potentially interesting and ethically unacceptable experiment I can imagine.”

All of these proposed experiments are as scientifically sound as they are ethically unsound.  All of them, from a purely scientific perspective, make sense, are designed to be carried out as efficiently and effectively as possible, and would add to our store of knowledge and even result in tangible benefits such as preventing and treating disease. 

So, if we were guided first and foremost by science, we would be doing these experiments.  But because of the ethics, we do not.  In other words, while science may be competent to tell us what we are able to do, and the most efficient way to do it, it is not within the competence of science to tell us what we should or should not do.  That judgment must come from outside of science. 

The same is true for human embryonic stem cell research.  Which is why the argument that we should let the “science” determine whether or not to pursue hESCR is so misleading and disingenuous.  As the examples from Wired show, science can make no such determination; it can only come from disciplines outside of science.

During one of the many Congressional hearings on stem cell research, Dr. Stuart Newman, a professor at New York Medical College, laid out the following scenario: in addition to human embryonic stem cells there is another class of pluripotent stem cells called human embryonic germ cells (n.b., Dr. Newman’s testimony [3/5/02] was given before the discovery of induced pluripotent stem cells [iPSCs]).  “On purely scientific grounds,” Newman noted, “embryo germ cells show even greater promise than embryo stem cells.”  However, while embryonic stem cells are typically harvested no later than seven days after conception, embryonic germ cells are derived from eight to nine week embryos.  

Deriving cells from such later term embryos would now be a “hot potato” Newman noted, but not for any scientific reason: “I emphasize that all of this makes perfectly good scientific and medical sense. The only thing that stands in the way is the sense of propriety concerning the uses to which developing human embryos and fetuses may be put. Some of you may draw the line at the tiny clump of cells, others at the two-month embryo, still others somewhat short of full term. Wherever each of you decides to leave this particular train, there will be others who will insert their right to take it to the next station” (please note, Dr. Newman favors abortion rights and noted at the outset of his testimony that his views “do not derive from any notion of the sanctity of the embryo”).

“All of this makes perfectly good scientific and medical sense.” In the context of hESCR, letting science lead the way leads to the commodification of human life.  It turns human life – and the human embryo is human life – into a commodity to be exploited as a means to what someone else deems a worthy end.  And worthy has now come to include something as mundane as desiring smoother skin, as some cosmetic companies now boast the use of fetal cells in their preparations).     

If we used the same standard proponents used to justify hESCR – let “science” have the final say – there would be no reason to judge as “creepy” the experiments described in Wired.   But they are, as is destroying and exploiting human life as a means to someone else’s potential benefit.      

Add hESCR as the eighth experiment on Wired’s list.

New Hope for Treating Kidney Disease

Two recent studies have been published which once again highlight the vast potential of induced pluripotent stems cells (iPSCs) to benefit patients, this time patients with kidney disease.  Both studies were published in the Journal of the American Society of Nephrology

In the first, scientists at Australia’s Monash University, led by Dr. Sharon Ricardo, extracted human kidney cells and reprogrammed them into iPS cells, which could then be transformed into other kidney cells that could potentially be transplanted to repair the damaged organ. 

In the second report, researchers at the Chinese Academy of Sciences in Guangzhou, led by Dr. Miguel Esteban, found they could gather kidney cells from a patient’s urine and reprogram them into iPS cells.  The reprogrammed cells, also, could be transformed into other kidney cells for potential transplant.  An additional benefit is that scientists could freeze the urine cells for future use when needed.

Other researchers into kidney diseases hailed the reports.  Dr. Ivonne Schulman, an assistant professor of clinical medicine and nephrologist at the University of Miami's Interdisciplinary Stem Cell Institute in Florida, said that "Two papers back-to-back show that two different kidney cell types are able to be reprogrammed…This is very significant."  She added: "It could theoretically help all types of kidney disease…it just depends on the ability of these cells to differentiate back into the cell types needed for that disease."

Dr. Jeffrey I. Silberzweig, co-medical director of the Rogosin Institute Manhattan Dialysis Center in New York City, also welcomed the reports: "The idea that you can have the ability to do stem cell transplants during the early stage of kidney disease and regenerate the damaged part of the kidney would be a tremendous benefit for patients and the country as a whole."

In addition to their potential use in transplants, the reprogrammed kidney cells could also be beneficial for disease modeling, to study the origins and development of kidney disease and for drug screening of new medications to treat kidney disease.

Both these studies come soon after a report that scientists working with insulin producing beta cells successfully reprogrammed such cells to become iPSCs, and that these reprogrammed cells were very efficient in producing more beta cells for potential transplant.  The researchers believe the reason for such efficiency is because the reprogrammed cells retain a “memory” of their origin as beta cells so they already have an “understanding,” as it were, of their purpose to generate additional beta cells.  It may well be that scientists working with the reprogrammed kidney cells will find the same phenomenon at work here as well (see previous blog “Advances in Diabetes Research –Without hESCs”).

Meanwhile, research using human embryonic stem cells (hESCs) to treat kidney disease shows that it has the potential to generate, well, a lot of talk about the potential of hESCs to treat kidney disease…