By Tony Fong
In a move suggesting the growing importance of proteomics in the clinical chemistry arena — and vice versa — the American Association for Clinical Chemistry has made proteomics a permanent division, starting on Jan. 1, 2010.
Proteomics has been a provisional division at AACC for the past five years as members of the division worked to move it toward permanent status by setting down bylaws, creating election rules, and building up its membership.
By becoming a permanent division, proteomics, which currently has 295 members, joins 12 other fields of special interest in clinical chemistry to be granted such status by AACC.
Established in 1948, AACC's mission is to "provide leadership in advancing the practice and profession of clinical laboratory science and its application to health care," according to its web site. The organization has about 10,000 members.
Becoming a permanent division is the culmination of an effort started about five and a half years ago when a small group of AACC members who were doing proteomics research got together to explore the idea of going to the organization to create a division specifically focused on the discipline, Saeed Jortani, the chairman of the proteomics division, told ProteoMonitor last week.
"The reason for that was obviously there's a major problem," said Jortani, an associate professor of pathology and laboratory medicine at the University of Louisville School of Medicine in Kentucky. "A lot of biomarkers using various different proteomic, or even genomic approaches, are discovered but … the majority of them do not make it to clinical practice."
As early as the early 1990s, he and others in clinical chemistry saw that within their field there was a shift toward investigating the role proteins may have in disease, "and we thought it was very important to initiate activities with our members to make sure our membership is up to date educationally and service-wise," he said.
"As the years went by, we saw that that type of research [encountered] some obstacles, and so now we see that there's a major role for us in that so much effort has been put into biomarker discovery … that it goes without saying that we have to be there at the table."
The problem with proteomics research, he said, is that there is a gap between the discovery work and the translation to patient care. That "missing link," he added, is the clinical chemist, and having a division within AACC would raise awareness of this "shortcoming in the healthcare system."
A major cause for this "missing link," he said, has been that the majority of funding for proteomics and biomarker research has been directed at basic research and "very massive clinical trials," which often ignores the process further downstream. Meanwhile, funding for clinical chemistry has been very low, Jortani said.
What is needed is strategic funding aimed at biomarkers that have been verified and validated to test their clinical utility, he added.
"Using depositories and archived samples is very important to finding new biomarkers, but I don't think you can call it an effective or useful biomarker unless you start using it clinically, initially on a trial basis," he said. "And I think [that] before the large in vitro diagnostic companies [will] come in and take a risk … and take those potential biomarkers and turn them into clinical laboratory tests and develop kits and go get [US Food and Drug Administration ] approval, [the biomarkers] need to be tried out in a clinical setting on fresh samples … in a patient environment."
Funding for such research and testing is "prudent" because these studies would provide information about candidate biomarkers that diagnostic firms can use. "That data could be used to entice manufacturers to come in and take over and put [the biomarkers] on their tests," he said.
At the annual meeting of the National Cancer Institute's Clinical Proteomic Technologies for Cancer initiative last month, Leigh Anderson, founder and CEO of the Plasma Proteome Institute, estimated that during the past 15 years, the number of proteins that have been approved for clinical tests has stayed steady at an average of 1.5 per year — "amazingly low," Anderson called it [See PM 10/09/09].
Calling that number "pathetic," Jortani said that the role of the proteomics division at AACC would be to find ways to grease the clinical proteomics/protein-based diagnostic pipeline.
That effort involves greater interaction with the National Institutes of Health as well as the FDA. This week, the proteomics division, along with AACC's molecular pathology division, the NCI, and the National Heart, Lung, and Blood Institute, are holding a two-day conference outside Washington, DC, to discuss the role of the clinical laboratory in the translation of protein biomarkers to the clinic.
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Among the sessions scheduled is one on FDA regulation of proteomics tools and devices, headed by Elizabeth Mansfield, a senior policy analyst at the agency. Jortani's group has had little direct contact with the FDA, he said, and "the meeting is designed to let [regulators and policy makers] know the value of clinical chemists in helping … translate these biomarkers that keep coming up in cancer [but] never get to clinical practice. … What we're trying to do is showcase clinical chemistry and the clinical chemists to these entities."
In the past few years, the division has reached out to the NIH. In particular, Henry Rodriguez, director of the institute's Clinical Proteomic Technologies for Cancer initiative, has closely tracked the proteomics division and its work and invited members of the division's board to speak at meetings held by CPTC, Jortani said.
At the NCI CPTC meeting last month, Jortani gave what amounted to a primer on what clinical chemists do and how they can help biomarker researchers in their work.
The proteomics division and CPTC have also proposed a joint symposium at the AACC's annual meeting in July, he added.
Through his and his colleagues' efforts at AACC, other NIH branches that have never, or only marginally, dealt with the proteomics division are now reaching out, he said. "Almost every institute is dealing with finding new biomarkers," he said.
In February, for example, he has been invited to speak at a workshop being held by the National Institute of Diabetes and Digestive and Kidney Diseases. Jortani and his group are also talking with the National Institute of Environmental Health Sciences about working more closely together.
James Ritchie, a professor of pathology and laboratory science at Emory University, said that proteomics researchers working in discovery are just beginning to understand what he and others like him can bring to the table.
Ritchie is a past chair of the AACC proteomics division.
Clinical chemists can advise proteomics researchers on how their research is "going to work in the real world," he said, by defining sample-handling protocols; providing input on the robustness of assays in order to work in the clinic; and giving guidance on how data can be reported so that it makes sense to clinicians.
Early on, when he described that to proteomics researchers, the response was "'Yeah, well, how important can that stuff be?' But now people like Steve Carr at the Broad [Institute], and some of those folks, when we talk to them, they recognize this is a big problem," Ritchie said.
He added that the mounting failures of proteomics in the clinical arena have made those researchers more open to the help of clinical chemists.
"There have been a couple of trials where people went into specimen banks and pulled out hundreds of specimens and developed their network to diagnose this or that cancer only to see that you can't do that on real samples and you can't do it with anybody else's sample bank," he said.
If proteomic scientists are only just awakening to how clinical chemistry can be applied to their work, clinical chemists also ignored proteomics, he said, largely because so few protein-based clinical assays have been approved by the FDA. But as more home-brewed proteomic assays come to the fore, that is spurring on interest among clinical chemists in proteomics.
Indeed, the upcoming January issue of Clinical Chemistry, the flagship publication of AACC, will be devoted to proteomics, Jortani said.
When it was first granted provisional status, the proteomics division had about 50 members. Since then it has grown to 295 members as of June 1, David Sainato, professional affairs manager at the organization, said. The largest AACC division is the clinical and diagnostic immunology division with between 900 and 1,000 members.
The transition to permanent division status bestows no special rights to the proteomics division or its members, Sainato said, but "there's a notion that their parochial interests are also [of] interest to clinical chemists as a whole, and that they are a more solid part of the clinical laboratory community."
For Jortani, the message is that clinical chemistry should be a routine part of the clinical proteomics workflow.
"You could have the very best biomarker … but if you haven't worked out the process of offering it to the patient, the platform that you're going to put it on, or the reimbursement issues, the regulatory issues, the [issues dealing with] maintenance of that test, I don't think it's going to make it" to the clinical setting, he said.