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Thread: My notes on "Stem Cell Research in New Jersey: An Inaugural Symposium" 11/11/04

  1. #1

    My notes on "Stem Cell Research in New Jersey: An Inaugural Symposium" 11/11/04

    Yesterday, we had the "Stem Cell Research in New Jersey: an inaugural symposium" at the Hyatt Regency Hotel in New Brunswick. Over 300 people showed up at the meeting, including many scientists who work on stem cells in New Jersey. There were about 50 posters and "standing-room only" talks through the day. In the morning, Ira Black (UMDNJ) and I spoke first, Rick Cohen from Coriell Institute in Camden, Karen Chandress from Sanofi-Aventis, and James Battey who heads the Stem Cell Research Task Force at NIH. In the afternoon Shirley Tilghman and Ihor Lemischka spoke, respectively the President of Princeton and a prominent stem cell scientist from Princeton. Many newspaper reporters came, in anticipation perhaps of outgoing governor Jim McGreevey and incoming governor Rich Codey speaking and saying something about stem cell funding in New Jersey. I did not have time to take many notes and will try to reconstruct from memory some of the talks and conversations.

    Ira Black gave a similar talk as the one that he gave in Trenton to the State legislative briefing three days ago except with more detailed description of the data. He showed his work on bone marrow stem cells, their recent work showing that the stem cells survived, proliferated, and migrated in fetal brains, with many of the implanted cells expressing nestin, some of them expressing dopamine (a neurotransmitter suggestive of neurons) and also some of the transplanted cells joining the stem cells in the subventricular zone. He spoke about the work of Darwin Prockop using bone marrow stem cells to treat young kids with osteogenesis imperfecta, the advantages of bone marrow stem cells, and also the importance of having access to human embryonic stem cells for comparison. He described the planned Stem Cell Institute of New Jersey, which will provide a critical mass of scientists working with each other and translating laboratory studies into clinical applications.

    I spoke next, pointing out that many people with spinal cord injury have received cell transplant therapies, from fetal spinal cord transplants in Florida, Sweden, and Russia to olfactory ensheathing glia in China, Lisbon, and Australia, and even pig and shark embryo transplants. I described the animal data underlying olfactory ensheathing glia and Dr. Hongyun Huang's work, saying that there is a large body of clinical experience that now shows that cell transplantation therapies are safe, feasible, and may have some beneficial effects in patients with chronic spinal cord injury. I pointed out that, at the present, it would be very difficult to carry out a clinical trial in the United States using fetal cells, both because of the paucity of fetal materials and the controversy of such materials. I then showed a slide of the different sources of stem cells, saying that it is important that we get beyond this outdated approach of just thinking about sources of stem cells to thinking about how we can transdifferentiate cells into stem cells and begin to develop ways to produce cells for therapy. I emphasized that the creation of Dolly the Sheep showed that it is possible to "reprogram" nuclei of somatic cells by placing them in another cell, that Ira Black's and other research have shown that bone marrow and other adult stem cells can be reprogrammed to produce a variety of cells. It is essential that we start investing in the research to translate these technologies to scaleable technology for our industry, to get beyond harvesting cells from eggs and embryos to producing cellular therapies for many diseases. I then described the future of stem cell research in New Jersey:
    • Transdifferentiation. The development of stem cell sources without recourse to eggs and embryos, cloning by fusion, and the importance of cytoplasmic factors determining the fate of cells.
    • Programming cells. Pluripotency is both the strength and weakness of stem cells, predictability of cell responses to tissue factors is important for therapy, and stem cells can be targeted for specific tissues/organs.
    • Tumors vs. stem cells. The difference between tumor and stem cells is that the latter produce appropriate numbers and types of cells for tissues, and respect tissue boundaries. We need efficient ways of screening cells for these differences.
    • Ex vivo gene therapy. I pointed out that the pharmaceutical industry is faced with a difficult situation of increasing costs of developing drugs, a decrease in the number of approved drugs, and the increasing number of "me-too" drugs. There have been two major advances in the life sciences over the past decade: gene therapy and stem cells. Gene therapy has not yet yielded any profitable products. Stem cells have the potential of providing a way out for the industry, allowing ex vivo genetic modification of stem cells, safer delivery of genes, programmable cells, and better control of cell behavior. The future cell therapeutics industry will divide into companies that make cells (i.e. hardware) and companies that program cells.

    Rick Cohen is the head of the stem cell neuroregenerative program at the Coriell Institute in Camden, New Jersey. He described the Coriell Institute as the world's cell and gene repository with over 100,000 cell samples from a variety of diseases, the only animal cell repository with 90 species represented. It has a very strong cytogenetics group, a genome and gene sequencing team, and active stem cell laboratories focusing on growing and applying stem cell therapies to many diseases. They have a state-funded umbilical cord blood collection program with over 6000 umbilical cord units collected in the past three years. They have been working on methods of growing stem cells from bone marrow and umbilical cord blood, collaboration with Catherine Verfaillie in Minnesota and the Technion Institute of Israel to study human embryonic stem cells (approved by the NIH), and spinal cord injury studies in mouse.

    Karen Chandross heads the multiple sclerosis Protection/Repair program and Stem Cell Research at Sanofi-Aventis in New Jersey. She described their work looking for genes that control the differentiation of oligodendroglia, working out the details of the cellular signaling that control the survival and differentiation of oligodendroglia precursors needed for remyelination. She emphasized their goal of finding drugs that stimulate progenitor cells and stem cells, that most of the treatments of multiple sclerosis have focused on the inflammation side and preventing recurrences rather than restoring function. Their goal is to develop drugs that can manipulate the endogenous stem cell populations of the body to repair and restore function. Given the limited time, she could not speak about all the stem cell research that is going on at Aventis.

    James Battey is the Director of the National Institute of Communicative Disorders and also head of the NIH Stem Cell Task Force. He gave an extremely lucid presentation of stem cell technology. But, for me, the most interesting information was his description of the current NIH programs in both adult and embryonic stem cells. He put up one slide that listed the NIH grants in human embryonic stem cell research. This included 8 infrastructure grants (to develop facilities to study stem cells), 26 investigator-initiated grants, 67 administrative supplements to grants (presumably to cover the costs of getting and studying some or all of the 22 human stem cell lines... at $5000-$6000 each), 3 pilot grants to assess beta cells, and 3 fellowships. My first impression was that this is a pitifully small program for what is widely acknowledged to be one of the most important fields of biomedical science. He went on to point out that the NIH awarded $190.7 million of grants to study human adult stem cells and $24.8 million to study human embryonic stem cells in FY2003. He pointed out that the NIH has an RFP to three Centers of Excellence to do translational research, putting together stem cell experts, clinical researchers, and transplant surgeons, that NIH wants to have the "clinical teams in place" when the technology become available for clinical trial. He pointed out that NIH has established National Embryonic Stem Cell Banks to increase access and to try to reduce the costs of acquiring the stem cell lines, currently at about $5000 per line.

    Shirley Tilghman is the President of Princeton and a distinguished record as a molecular biologist, including the cloning of the first mammalian gene. She began her talk by saying how pleased she is to give a talk about science, that she is very supportive of the Stem Cell Institute of New Jersey, and how New Jersey is going to "clean the clock of California". She reviewed the history of stem cells, including the fact that two Canadians, Tillman & McCullough in Toronto, described the first pluripotent stem cell. Martin Evans at Cambridge University in England was the first to describe embryonic stem cells in the blastocyst of mouse in the 1980's. She emphasized the enormous technological hurdles that we still face, how we do not know how to reprogram cells, and whether the stem cells can be "unilaterally directed", and how important it is to invest in this area of research. She went on to point out two risks of stem cell research that we must consider in the planning of stem cell research:
    • Irrational exuberance. People have been guilty of over-extolling the promise of stem cell research, from the curing of Alzheimer's to halitosis. At best, we have been overpromising and at worst we are engaging in delusional fantasies. She compared stem cell therapies to gene therapies, how the virtues of gene therapies were praised in the 1970's as the panacea. Scientists underestimated the technical difficulties of gene therapy and overestimated the number of diseases that would benefit from gene therapy. After 20 years of significant investment by government and industry, we still have no significant gene therapy that has been approved by the FDA. In 1995, the Director of NIH Harold Varmus commissioned an NIH study to find out why and the study concluded that expectations were oversold based of exploratory studies and that there were widespread misrepresentations that cures were possible. She pointed out the Jesse Gelsinger case, how this discredited not only the scientists but also the entire field.
    • Role of the public. She urged scientists to talk with their fellow citizens about the science. Parts of the debate cannot be decided based on science. Questions such as when human life begins cannot be answered scientifically. There needs to be a thoughtful public policy response. Currently, federal funds are available to only a handful of cells that are meta-stable. She pointed out that the $3 billion fund in California cannot compensate for the inadequate federal funding of the research, asked whether it is sound public policy to have state funding of such research. State funding of stem cell research in precedent setting and the implications of this policy should be carefully thought through. In April, the Woodrow School of Public Policy in Princeton will hold symposium on this subject. She emphasized the need fro a nationwide policy regarding stem cells, who the decision makers are and should be. She said that scientific progress will likely provide the impetus for change, that when the international competition heats up, the political pressure for change of the current policy will be overwhelming and irresistible. Scientists serve at the pleasure of the public and our work must serve the public good over time. We must counteract prejudice and ignorance. We must participate in the public debate. Gone are the days when scientists can stay in their laboratories. The answers cannot come from scientists alone. We need a trained citizenry. She congratulated the Stem Cell Institute leadership and said that the "road is not straight ahead".

    Ihor Lemischka finished the symposium with a very detailed talk about his work defining the genes that control the behavior of stem cells. Ihor pointed out that for the first time, biologists are playing with a "full deck of cards", that we can now define most of the components of the system with some degree of completeness. He gave some precautions that "we must not make promises that we cannot deliver". He pointed out that while we can determine some of the proximate causes, we do not have true understand of the system. [I did not take detailed notes and here is my best understanding of what he is doing, so please forgive me if I have misunderstood or misrepresented]. Here is the basic paradigm of the studies that he described. A stem cell has three choices, to make another stem cell like itself, make another cell that is unlike itself, or differentiate into another cell. So, he is trying to find out which genes are responsible for these decisions. Many scientists have been correlating gene expression with various stem cells. Ihor instead is using the technique of suppressing specific gene expression with siRNA, to identify the cause-effect roles of the genes. He started out with about 10 such genes and is exploring in detail what changing the expression of different combinations of these genes affect the decision of the cells to make itself, to make different cells, or to differentiate. He points out that there must be multiple feedback loops, that it is a dynamic and stochastic system. Ihor points to two major challenges. One is how to explain the ability of stem cells to balance cell renewal and differentiation. The other is to explain its ability to produce large clones of differentiated progeny. As examples of the latter, he pointed out a relatively small number of bone marrow stem cells produce some 100,000,000,000 cells per day to replace blood cells that are lost, or how cells in our skin produce even more cells to replace those that are lost.

    Whew, it was a very intense symposium. In between the talks, I must have given interviews to a dozen reporters, spoke to many dozens of people, met most of the major stem cell biologists in the state, and chatted with industrialists and venture capitalists. There was a lot of speculation about what New Jersey will do. Everybody was pleased and excited about the meeting. I pointed out to a reporter that this symposium itself will probably stimulate millions of dollars of investment in stem cell research, even before the state invests a single dollar. The excitement and enthusiasm was palpable. Everybody is jockeying for position, to become a player, just in case there is the possibility of significant stem cell research funding in the state of New Jersey.

  2. #2

    A sober stem-cell forum turns into pep rally

    Academics and corporate researchers trumpet state's leading role

    Friday, November 12, 2004
    Star-Ledger Staff

    New Jersey scientists studying the mysterious, morphing entities known as stem cells came together at a state-sponsored science summit in New Brunswick yesterday, strutting their stuff and vowing to work together. Researchers from the state's pharmaceutical giants and biotechnology firms also attended in force, assessing the mostly academic work and looking for investment opportunities.

    The event, sponsored by the New Jersey Commission on Science and Technology, drew more than 300 scientists from throughout the state to share research findings and discuss the future of stem cell therapies.

    "We are providing an opportunity for researchers to build collaborations among academic institutions and with biotech and pharmaceutical companies here in New Jersey," said Sherrie Preische, executive director of the state science agency.

    Amid buzz about the successful $3 billion California stem cell ballot initiative, meeting discourse took on a competitive edge. "We are going to clean the clocks of Californians" with this research, said Princeton University President Shirley Tilghman, a biologist and the event's keynote speaker. "This is a great occasion for all of us who care about science and human health."

    Last May, New Jersey became the first state to commit public funding for a stem cell research institute. Earlier this week, scientists directing the project said they would like to raise $1 billion for the center, planned for construction in New Brunswick.

    Scientists at yesterday's meeting said the field of stem cells is so promising and so vast, there should be plenty of room for investment by New Jersey.

    "This is so significant, it makes sense to support research in our own backyard, especially when it is of this caliber," said Peter Wachtel, president of Princeton Polymer Laboratories.

    Many scientists believe that stem cell research holds the promise of preventing and curing diseases previously deemed hopeless.

    But the field is controversial because some stem cells, called embryonic cells, are drawn from fertilized eggs and require the destruction of embryos so that the ever-replenishing cells can be withdrawn.

    Gov. James E. McGreevey, a supporter of stem cell work who had been scheduled as the event's opening speaker, was a no-show. Instead, Donald Drakeman, newly appointed chairman of the science commission and CEO of the biotech firm Medarex, stepped in.

    Drakeman read a statement from state Sen. Richard Codey, who will become acting governor on Tuesday, replacing McGreevey who is stepping down because of a sex scandal.

    "Making sure we do succeed -- and making sure New Jersey remains a national leader in stem cell research -- will be one of my highest priorities as Governor," Codey's statement read. "This will be remembered as an important moment in world history. We are working to create new therapies that will save lives, cure terrible afflictions and bring hope to thousands of patients who are suffering -- not to mention the loved ones who suffer with them."

    Also attending the summit were representatives from Sanofi-Aventis Pharmaceuticals Inc. of Bridgewater; Johnson & Johnson of New Brunswick; Merck of Whitehouse Station; Bristol-Myers Squibb in Princeton, and Pfizer in New York along with researchers from biotech firms such as Medarex of Princeton and Celgene Corp. in Warren.

    Karen Chandross, a neuroscientist who heads stem cell research efforts at Sanofi-Aventis, described at the meeting her exploratory work to stimulate the human brain, which produces its own healing stem cells, so that it will produce more. The work has applications for those suffering from autoimmune disorders such as multiple sclerosis where the body attacks itself. Chandross is hoping her work ultimately will produce a drug to control the genes that direct the production of self-healing cells.

    Asked why other major pharmaceutical companies had not produced presentations for the meeting, she said, "Perhaps they don't want to talk about it."

    Researchers, including those from the Coriell Institute in Camden, the Cancer Institute of New Jersey, Hackensack University Medical Center, the New Jersey Institute of Technology, Princeton University, Rutgers University, and the University of Medicine and Dentistry of New Jersey, presented work, mostly on adult stem cells.

  3. #3
    the 'cure' is part of this over optimism, isn't it?

  4. #4
    Chris2, one of the things that Shirley Tilghman said that rang a bell with me is that scientists must be optimistic or else they cannot get up each morning to do experiments that do not succeed. Every successful scientist has had to go through many failures. Experiments are not experiments unless you have failures.

    Easy experiments are ones in which you have perhaps 50% failure rate. Difficult experimens are when you have a 90% failure rate. Very difficult experiments are when you have a 99% failure rate. In the early 1990's, I would have rate spinal cord injury as "very difficult" but now it is merely "difficult" because better tools are becoming available. I would like to make it so that it is "easy", so that many people will have success in the laboratory, as well as in clinical trials.

    Every scientist struggles with the issue of hope and promise. Most are very conservative. This is because you lose the respect of other scientists if you promise but do not deliver. Likewise, companies are now in the business of "expectation management" because peoplel have learned that if expectations are high even successes seem like failures but if expectations are low minor successes are viewed as great successes.

    In my opinion, scientists should not be playing games with the hopes of people. We should tell what we know and believe, without garnishing or underplaying the facts. As people probably may have realized by now, I am quite conservative scientifically. While I make a concerted effort to be as open-minded as possible, decades of training to be critical have shaped my responses to be cautious and conservative. To counter the conservatism, I try to put myself in the place of people asking the question and try to answer from their viewpoint.


  5. #5
    Senior Member Jeff's Avatar
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    Jul 2001
    Argao, Cebu, Philippines
    I was actually rather heartened by the NIH stem cell activity. I spent about an hour all together at the NIH booth discussing their programs. One of the main points was that NIH needs to develop the human capital necessary to do ESC research. So that training labs to handle the cells is an early priority. The NIH has several ESC classes. Some classes actually give you the cells to take back to your lab. They expect to ramp up funding for ESC as more scientists are trained to do the work.

    I asked about the suitability of the existing lines for research. He told me at NIH they refer to the approved lines as the "presidential lines." He said they're perfect for the initial research that needs to take place now. Later, when better methods to culture the cell lines are available, they will unfreeze more lines including some that have never had any contact with animal cells of any kind.

    I asked about using facilities for non-approved lines along with the presidential lines. He said there was NO REQUIREMENT that research on non-approved lines be carried out in a separate building or even a separate room. He said some labs might do that to facilitate accounting.

    I asked him about bio-terrorism research starving traditional health research. He said the bio-terrorism project was "new money" but conceded that it would limit the amount of new money for other work.

    He said that by this time next year they will award the contract for the stem cell bank. They hope to have all approved lines available at the bank. This should reduce the cost from $5,000 to merely $500 for obtaining cells and help spur research. He expects an existing company with existing facilities and skillset to win the contract and start distributing the lines by early 2006.

    There are at least 295 clinical trials now testing adult stem cells.

    I was actually quite surprised, however, that NIH is only spending roughly $200 million per year on research using adult stem cells.

    ~See you at the SCIWire-used-to-be-paralyzed Reunion ~

  6. #6
    Jeff, thanks. When I heard the number $200 million several weeks ago, I was surprised. Likewise, there are many others who are also surprised. I want to point out that this refers to human stem cells only. If one counts animal stem cells, there will be obviously more funding.

    Regarding the stem cell lines, I am afraid that most scientist would disagree with the adequacy of those lines even for the "initial research" that must be carried out. For example, there is some diversity of stem cells even amongst the 22 lines that are available. For example, 5 of the cells lines could not be divested of their mouse feeder cells. By the way, you have to do that when you want to study the cells without the interference of the mouse cells. For example, if you want to look at their gene expression, you have to get rid of the mouse cells. Of course, if you want to transplant the cells, you have to get rid of the mouse cells as well. I don't know if there are now better ways to do so but I understand that you have to have an expensive (multimillion dollar) sterile cell-sorter to do the separation.

    It is very important for NIH to lower the price to $500. They must have lowered the price to $5000 just this month because it was $6000 until recently. It would be good when they do reduce the cost because at the present, many laboratories cannot afford to pay that cost to do pilot experiments. In order to compete successfully for NIH grants, you usually need to show some preliminary data. If one got all 22 lines to study, that would cost $110,000 and few laboratories can afford such an expenditure without a grant of some sort.

    When President Bush first made the policy switch and UCSF asked for a formal ruling from the NIH, they were told that the cells could not be kept into the same laboratory that was supported by NIH paid indirect cost. In 2003, that policy was relaxed through non-enforcement. In February of this year, Ira Black and I talked with various people at NIH and we were told that it was possible to keep the cells in the same building or even the same laboratory, so long as the accounting of funds were clear and no federal funds were used to support the research on any non-approved cell lines.

    In the aftermath of 9/11, NIAID became the lead research agency for bioterrorism research (now called biodefense research). Within 6 months after the attack, hundreds of millions of dollars of research programs were redirected or enhanced to carry out biodefense research (Source: The Scientist). NIAID budget nearly doubled by 2003 and partly because its newfound agenda of bioterrorism (Source: Soure). Note that this was part of the doubling of NIH program. The doubling of the budget should have gone to regular medical research, such as spinal cord injury.

    There has been indeed some additional "new money", about $6.5 billion that was allocated for "Project Bioshield" which are going to pay for vaccine production and other expenses. For example, the U.S. government just announced a $887 million anthrax vaccine contract to Vaxgen of Brisbane, California Source: USA Today). The following web site has some pretty strong criticism of the Project Bioshield program:
    Pharmaceuticals become BioWeapons Factories

    The fraudulent science of the smallpox vaccine and the draconian laws of the Homeland Security Bill set the stage for a radical revision of the mission and purpose of the pharmaceuticals. Ominously, the first bioterror countermeasure that the BioShield bill calls for development is another smallpox vaccine that uses the same, deadly vaccinia virus in the current vaccine but has additional dangerous potential effects because it is genetically engineered, another science that has a dark history of injuries, diseases, deaths and cover-ups.

    The bill also calls for development of bioterror drugs and vaccines in response to anthrax, botulinum toxin, plague and ebola. In order to develop drugs and vaccines that are supposed to respond to biological and chemical warfare agents, the companies will have to create and store the actual agent itself. Until now, bioweapons have been handled and stored at labs such as Fort Detrick, labs which are supposed to operate under strict controls with guidelines for safety set out by the U.S. government (not that the government labs have been models of efficiency as their poor past record and accidental releases have shown).

    But the BioShield bill sets out no provisions for the handling of these agents or any safety measures at all, even though the Bill effectively turns the pharmaceuticals into new bioweapons factories.

    Six billion dollars may be a small price to pay if the pharmaceuticals can accomplish the goal as set out in the bill--to protect us from biological and chemical attack. But common sense tells us, any country technologically advanced enough to create, store and modify a bioweapon for release would be competent enough to alter or genetically engineer it in any number of ways that would make the creation of a drug or vaccine to that particular strain of bioweapon impossible.

    Will the bioterrorists really be so cooperative as to create only those few weapons for which the pharmaceuticals have developed and warehoused countermeasures?

    Since the pharmaceuticals said it would be unethical to test bioweapon countermeasures on humans and pushed the FDA for the exemption from human testing, why is it ethical to use the Homeland Security Bill to force people under threat of imprisonment, fine or quarantine, to take these same untested medicines?

    The Bush Administration is perpetrating a Pharmaceutical Scam justified by the "war on terror," rewarding the pharmaceuticals for the $262 million they invested to get Bush elected, more than any other industry. The bill substantially enriches the pharmaceuticals by creating a virtually endless supply of cash for the creation of untested drugs and vaccines to be warehoused for possible use against the public.

    Tommy Thompson's stated goal is that every "American man, woman and child will have a vaccine with their name on it," and hundreds of million of dollars are being invested to bring that goal to reality even as the deaths and injuries in the current program continue to mount.

    He has stated that even one case of smallpox will unleash a massive program of forced vaccination through the Homeland Security bill, vaccinating or quarantining every American to "protect" them from the uncontrolled threat. But there is no historical precedent or evidence to support the notion that one person infected with smallpox will set off a chain reaction infecting millions and millions of people. And a compliant media disseminates every myth the government feeds it without checking any sources or seeking precedents.

    A tragic situation has been created in which the best scenario for the American people is that their money will be wasted by letting these untested vaccines remain forever warehoused, although the best scenario would have been not to create them in the first place and instead spend the money on real health care problems. But the precedent was set when they pulled the 40-year-old smallpox vaccine out of the warehouse and without even a hint of a threat of smallpox attack, released it on the U.S. population, making the Bush administration the real bioterrorist.

  7. #7
    Senior Member Jeff's Avatar
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    Jul 2001
    Argao, Cebu, Philippines
    Wise, thanks for clarifying and filling in the gaps.

    ~See you at the SCIWire-used-to-be-paralyzed Reunion ~

  8. #8
    Dr. Young, thanks for the summer. I find Shirley Tilghman's this comments pretty interesting. Do you feel like there will be that much competition between New Jersey and California? Also, what's your best guess on how long it will take to get the infrastructure in place to start doing research?

  9. #9
    Join Date
    Dec 2003
    Lake Hiawatha, New Jersey, USA
    Dr. Young,

    Thanks for the update on the symposium. Sorry I missed it, but I didn't hear anything about this and wasn't aware of it. I did attend the stem cell research institute ceremony back in May. This one sounded more informative. Is there a video available on this symposium?

    Thanks. Bob

  10. #10
    Carl R,

    There was obviously a sense that the speakers are cheerleading at the meeting, the reason why Kitta MacPherson pointed out that the meeting was like a pep rally. The news that California passed a $3 billion bond for stem cell research has had a significant effect on politicians in New Jersey. It means that the hard work that they have put into promoting stem cell research here in the state has just be eclipsed. Several people referred to that "sucking sound" from the West Coast. It is indeed very interesting that the President of Princeton University said it, however.


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