President Obama's repeal this week of his predecessor's ban on using federal funds to support research on human embryonic stem cell lines will "benefit" drug discovery in two ways, according to some hESC experts.
Firstly, from the point of view of academics and academic institutions looking for better drug-development models, sometimes these models are only available from hESCs, said Joydeep Goswami, vice president of stem cells and regenerative medicine at Life Technologies, formerly Invitrogen.
As a result, "that [research] will definitely get a boost," because now researchers will have access to a number of other lines, including several preimplantation genetic diagnostic lines, which are often derived from embryos that are unhealthy, or have a specific disease that can be identified, he said.
Indeed, the Bush administration's restrictions, enacted in August 2001, prevented scientists funded by the National Institutes of Health from accessing these PGD lines, which Goswami said "are fairly important in getting research done."
He added that lifting the ban will yield "additional benefits to having more cell lines, or more differentiated cell types available, from hESCs, and of course in larger quantity and [more] variety."
Secondly, "I think part of what the whole Bush policy did in some ways was to almost illegitimize ESC research, and I think a lot of big pharma companies really took that to heart, in terms of treating hESC research like a pariah topic, even though they kind of had a feeling that it was useful," Goswami said.
Pharmaceutical companies were unable to leverage as much knowledge from academia and academic research as would normally have been the case. "I think this repeal allows pharma to once again enter this field with some confidence, and to benefit from the greater amount of research that will be going on in the public domain," said Goswami.
"I think from that point of view, you will see a lot more use of ESCs and ESC derivatives in the drug discovery arena, from both the academic and pharma sectors," he said.
Goswami added that, over the past six months or so, Life Technologies has seen pharma companies and others in this field "talk a lot more about this research than they have in the past six to eight years."
Another researcher, Joseph Hammang, senior director of science policy for Pfizer, said that the policy shift will free up additional federal money and potentially improve understanding of hESC technology.
It could also have a long-term, positive impact on the use of these cells as drug-discovery tools, and on the use of these cells in transplantation, Hammang said. In addition, increased federal funding should increase discoveries of new assay systems, cellular-differentiation pathways, and small molecules.
Hammang also said Pfizer is interested in both the use of these cells as drug-discovery tools and their use in regenerative medicine. As knowledge of hESCs continues to grow, more applications in drug discovery and regenerative medicine can be developed. What scientists learn while developing these cells as tools will directly affect their use in regenerative medicine, he said.
Chris Kendrick-Parker, vice president and chief commercial officer of Cellular Dynamics International, added: "Primarily, [the policy change] changes the environment and atmosphere around stem cell research, making the field in general more open to bright scientists and additional academic funding, as well as lifting the ethical cloud to promote commercial investment.
Human ESC research is still important, even in the context of Yamanaka and Thomson's seminal 2007 papers in Cell and Science, respectively, on induced pluripotent stem cells, said Goswami (see CBA News, 11/20/07).
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"If you go and listen to Yamanaka and Thomson, they are careful to say that iPS cells [are] a new technology, and that it does not undermine or obviate the need for hESCs," said Goswami. He added that he believes that iPS cells are an interesting technology, and that there is still a lot to learn and to study about them.
"Maybe in the long run, iPS cells may completely obviate the need for hESCs. No one knows," Goswami said. "But to get to that understanding, it is absolutely imperative that one is able to compare [iPS cells] to what is more 'normal' in the biologic state. The only such tools that we have today to do that are the hESCs."
Much of the work done using iPS cells is actually impossible without having a comparator, and whatever discoveries being made using hESCs, and that actually have been made using hESCs, benefit iPS research and vice versa.
"I do not think it's either/or," Goswami said, adding that he does not think that Life Technologies or the scientific community at large "see them as replacements for each other."
Since Thomson and Yamanaka published their papers, researchers have been working with iPS cells and have created disease-specific cell lines. And last week, Andras Nagy and his team in Canada reported in Nature that they had derived iPS cells and removed the viral transformation vectors later.
"Again, I think that this is all very interesting work. And I think that iPS cells provide certain advantages," Goswami said. "But remember, it is really taking the cell back into a state that it is not normally in.
So there are a lot of questions about how "normal" these iPS cells are, and how they are going to behave in the long run, and how one would gage the "normalcy" of the behavior of iPS cells, even if the viral components and the oncogenes are removed," Goswami said. "I think that all of the research that is going on in the field of iPS cells is very good, but do not forget that the gold standard to which it's being compared is hESC work that has been carried out by the very groups, by the way, that have been coming up with these iPS cells."
"Every one of the iPS 'stalwarts,' so to speak, including Thomson, Yamanaka, and Nagy, has first been an hESC researcher," he added.
"Our strategy is to move to iPS cell-based models as quickly as possible," and the more data generated on ESCs, the greater the confirmation of the utility of phenotypically-defined stem cells, said Kendrick-Parker.
The change in policy will allow more researchers to derive high-quality human ESC lines (unlike those derived prior to 2001), which could allow detailed comparison of human iPS cells and ESCs, and address the question of whether human iPS cells could indeed completely replace human ESCs in terms of all clinically important properties, said Junying Yu, an associate scientist at the primate research center at the Genomics Center of Wisconsin.
Keep It Focused
The lifting of the restrictions should not cause cell-based tool shops to change their strategy. "We don't think it changes a tools strategy versus a therapeutic strategy, as any company's strategy will still be dependent on utility and execution, and the ability to deliver based on investment," said Kendrick-Parker.
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He said that CDI is even more enthusiastic for the tools business, "as Obama's recent actions lift the cloud of scrutiny of stem cell use from our customers, allowing them to more aggressively employ our tools."
With the rapid progress in iPS-cell technology, "I don't think it will have great impact on companies' decisions about whether to use ESCs as drug-discovery tools or to develop therapeutics," since major scientific obstacles still exist with ESCs, Yu said.
Particularly in the current volatile financial environment, the change in policy provides at least "a little raft of security that hESC hegemony will transfer back to the US," said Goswami.
He said that, ultimately, iPS research in the US will benefit tremendously because of the complementarity between iPS and hESC research. "In general, the pace of new scientific discoveries will accelerate greatly over the next several years because it is expensive research, he said. "It requires talented individuals, and it requires a lot of time and a lot of expensive reagents," he added.