馬文麗：晶元注滿報國情 （基因晶元）

光明日報2005年1月19日

馬文麗：晶元注滿報國情

本報記者　吳春燕　通訊員　楊建珍　吳丹琴



　　她,留學美國,生活優裕,卻不願留在異鄉做「祖國建設的旁觀者」,毅然舉家回國創業。兩年迄今,把一個只有6個教師的低起點學科發展為全軍生物晶元重點實驗室,榮膺全國首批優秀骨幹教師、廣東省十大傑出留學青年回國創業之星。她就是南方醫科大學 原第一軍醫大學 基因工程研究所所長,華南生物晶元研究中心主任馬文麗教授,學
校最年輕的博士生導師。
　　「我在祖國建設中不是旁觀者,而是主人」

　　1994年,畢業於協和醫科大學的馬文麗博士和丈夫雙雙作為訪問學者,赴美國國立衛生研究院從事分子生物學專業的博士后研究。在美國,她享受著優厚的薪酬、優越的科研環境。然而,當馬文麗博士接到母校第一軍醫大學學科建設急需人才的信時,毅然於1998年初舉家回國。

　　馬文麗告訴記者：「我在國外幹得再好只是個高級打工者,最多就是加薪,找不到主人翁的感覺。回國后,學校給了我更大的舞台,能按自己的思路去創新,去成就事業。」6年來,雖然付出了比別人更多的努力,但馬文麗從未後悔當初的選擇,因為她知道自己在祖國建設中並不是一個旁觀者,而是主人。

　　「一張白紙可以畫出最美的圖畫」

　　回國后,馬文麗很快被破格晉陞為教授,同時被任命為分子生物學研究所所長及生物化學教研室主任,34歲的她成了全校當時最年輕的教授、博士生導師和學科帶頭人。

　　然而,擺在她面前的卻是一個「爛攤子」：人才流失嚴重,33名編製中有17位博士先後出國或外出學習不歸;教學和辦公條件極其簡陋,資金短缺。關鍵時刻,丈夫鼓勵她：「一張白紙可以畫出最美的圖畫，我們手裡有核心技術,不怕干不起來。」

　　她選擇了國際前沿的高新技術研究課題―――基因晶元技術作為學科主攻方向。回國后的第一個大年三十,她在實驗室加班至凌晨3點,準備回家時才發現實驗室鐵門已被反鎖。長夜漫漫,寒氣襲人,她只好不停喝著用電爐燒開的熱水,暖暖身子,直到天明。

　　經過6年多的艱苦創業,馬文麗教授終於將學科從剛回國時沒有科研經費,僅有幾百元的教學經費,發展到獲得了國家自然科學基金對基因晶元項目的首批資助,承擔國家、軍隊、省、市重大科技攻關課題12項,經費達5000多萬元;從一台幻燈機都沒有,發展到擁有數千萬元設備的華南地區最具規模的生物晶元研究中心;從原來老教授眼裡中專水平的學科,碩士點都難以維持,發展到博士點及中國人民解放軍生物晶元重點實驗室,僅用兩年多的時間就完成了原計劃10年的學科建設目標。

　　「讓基因技術造福每一個中國人」

　　說起馬文麗,不能不提起她最輝煌的一頁―――2000年3月,馬文麗首次運用一種新的基因片斷擴增技術,率先成功研製出我國第一塊應用型基因晶元,並巧妙地運用新技術來降低成本。

　　基因晶元的開發應用,將在環境污染、動植物檢測、器官移植、產前診斷、藥物篩選、藥物開發等方面展示出廣闊的前景。利用基因晶元技術對疾病進行早期診斷,實現對生命的微觀調控,將可最大程度地控制疾病的發生和發展。馬文麗舉了個簡單的例子 腫瘤疾病在形成腫瘤之前,先是引起細胞基因的改變,如果能在這個階段檢測出來,及早用藥,腫瘤就可能實現真正意義上的早期治療。「我相信基因技術最終會造福每個中國人！」

　　在非典流行期間,作為廣東省防治非典科技攻關領導成員之一,她帶領課題組人員日夜加班,經過3個多月的日夜苦戰,成功研製出SARS早期診斷晶元及SARS基因檢測試劑盒,並進入國家葯監局的報批程序,為SARS的早期基因診斷作出了有益的貢獻。

　　手握8個國家專利、其中3個是基因晶元核心技術專利,馬文麗對未來有很多計劃,比如想把基因晶元應用到艾滋病的窗口期檢測,想把基因晶元實現產業化,這將是她未來5年的最主要工作。

http://www.now.org/nnt/01-96/nih.html
NIH Officials Acknowledge Intentional Radiation Contamination of Woman Researcher and Her Fetus

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by Beth Corbin
NIH officials aknowledged that the radiation contamination of Dr. Maryann Wenli Ma (pictured), her husband Dr. Bill Wenling Zheng and 25 others was no accident.

Ed. note: NOW passed a resolution in 1993 supporting current and xxxxer employees of the National Institutes of Health in their fight to end sexism and racism on the NIH campus. Articles detailing the harassment and discrimination appeared in the August 1993, November 1993 and April 1994 issues of the National NOW Times.

Was it misogyny or malicious intent fueled by a fiercely competitive environment? That might be the $64,000 question surrounding the radiation contamination of a woman researcher and her fetus at the National Institutes of Health (NIH).

Affidavits filed in October by Dr. Maryann Wenli Ma and her husband Dr. Bill Wenling Zheng charge the NIH with "willful and reckless" violations of safety standards regarding the handling and storage of radioactive materials, which they contend contributed to the contamination of Dr. Ma. While their petition of the Nuclear Regulatory Commission to suspend or revoke NIH's license to handle the material was denied, their attorneys have suggested that other actions will likely be filed, saying the couple must first exhaust administrative remedies. The FBI is also investigating the incident.



Chronology of Events

So what happened? Here is their version of the events as recounted in their affidavits and in press statements. Ma and Zheng began working at the National Cancer Institute (a division of the NIH) in 1994. They were academic stars, having graduated with honors from the best schools in China. A two-year fellowship at the NIH could lead to prestigious careers upon their return to China or the possibility of a new life here in the United States.

They were assigned to conduct cancer research in the Laboratory of Molecular Pharmacology, under the direction of senior investigator Dr. John N. Weinstein. Weinstein's lab works to develop therapies for treating cancer and AIDS, part of a massive cancer-drug screening program. Phosphorous 32 (P-32), a highly radioactive isotope, is sometimes used in this research.

In affidavits, an administrative filingand a press release, Ma and Zheng outlined the highly competitive nature of their work. The couple said that on many occasions Dr. Weinstein told them their experiments were so important he "did not want anything to hold them up." They said that Dr. Weinstein required them to work tirelessly on this project so that the new procedure could be patented. The project, if successful, would have significant scientific and commercial value.

When Dr. Ma learned in April that she was pregnant, she was reluctant to share the inxxxxation with Dr. Weinstein. The couple allege that Dr. Weinstein was so upset when he learned of Ma's pregnancy that he urged her to have an abortion to keep their work on schedule and to keep their patent viable. They said that Weinstein continued to pressure them and, after an "unpleasant" meeting on Sunday, June 25, the couple invited him to lunch at a local Chinese restaurant. Dr. Ma took the leftovers to work for lunches during that week.

Three days later, after eating the leftover food, Dr. Ma complained of sharp pains in her liver area. A routine sweep of the lab for radiation the next day revealed her contamination. Further investigation indicated the contamination was internal. A spot of radiation was also detected in front of the refrigerator in the conference room where Dr. Ma's lunch had been stored. The contamination was quickly identified as P-32, commonly used at the NIH but not used in Ma and Zheng's experiments since earlier that year.



NIH Admits Foul Play

NIH officials acknowledged in an interview with The Washington Post that the contamination was not accidental. They did, however, downplay the extent of the contamination, saying that Ma had taken in 200 to 300 microcuries of P-32. (A microcurie is a measure of radioactive activity.) Anne Thomas, an NIH representative said: "The doctors who examined her do not believe this will cause any long-term medical complications for her or her fetus."

Later estimates by the Nuclear Regulatory Commission (NRC), which examined her, put the figure at double the NIH figure, and Dr. Ma's attorneys now claim that an independent lab estimates the contamination to be closer to a thousand microcuries. At a news conference on Oct. 10, her attorney said, "It is now believed that Dr. Ma, who was 17 weeks pregnant at the time of the incident, received the largest reported dose of internal radiation contamination since Karen Silkwood."

Exposure to radioactive materials is generally measured in rems, a term that relates the absorbed dose of a radioactive material to its biological effect. An acceptable dose for occupational exposure of a non-pregnant woman, according to the NRC, is five rems. For a pregnant woman, it is one-tenth of that, or one-half of one rem. The radiation expert hired by Dr. Ma's attorney's estimated that she received an exposure of 9.2 rems, and that the fetus received 6.4 rems -- a dose to the fetus that was 12 times higher than the dosage considered safe for a pregnant woman.



Treatment Delayed

In her statement, Dr. Ma further questioned why Dr. Weinstein and NIH safety officials delayed her transport to the hospital by more than three hours, and then gave conflicting directions to hospital personnel which delayed her treatment. They contend that while Dr. Weinstein attempted to downplay the effects of Ma's contamination, he repeatedly suggested that "the baby [sic] should be worried" and that he urged them to consult with their Ob/gyn -- offering at one point to place the call himself. They declined his offer.

In her statement Ma said: "We later learned that Dr. Weinstein had told a number of people . . . that we already had a child in China -- which is untrue -- and that under the China one child' policy it was necessary that we abort the baby. He suggested that we had contaminated ourselves to abort the pregnancy. We also learned that Dr. Weinstein has suggested to others that Bill contaminated me because he learned that our expected baby is female and wanted me to abort the pregnancy. These suggestions are outrageous and have been extremely damaging to our professional reputations and careers."

In an interview with The Washington Post, Dr. Weinstein denied that he ever pressured his scientists to abort their fetus or that he contaminated Ma's food with P-32: "The obvious answer is, of course not. It's preposterous."



Co-workers Contaminated

Ma was not the only one contaminated. It took NIH officials two weeks to discover that the water cooler in the same general area as the public refrigerator was also contaminated with radioactive material. Traces of P-32 found near the water cooler are believed to have caused internal contamination to Zheng and 25 other co-workers.




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NCI Scientist Cleared
NRC Vindicates NIH Response to Contamination Incident

The Nuclear Regulatory Commission on Sept. 17 denied a petition to revoke or suspend NIH's nuclear materials license that had been brought by two visiting fellows who were among 27 people apparently deliberately exposed to radioactive phosphorus-32 in an NCI laboratory in June 1995. The decision closes a 2-year investigation and leaves blameless NIH's rules for handling radioactive isotopes -- NRC determined NIH did all it could reasonably do to prevent misuse of the isotopes. It also finds that the accusations made by the fellows against their supervisor were groundless.

The petition was filed in October 1995 by Dr. Maryann Wenli Ma and her husband, Dr. Bill Wenling Zheng, visiting fellows in NCI scientist Dr. John Weinstein's lab who were expecting a child -- later born without complications -- at the time of the contamination. Ma was exposed to radiation in excess of NRC occupational limits, but a series of NRC investigations could not determine exactly how. Twenty-six others were exposed, at levels lower than Ma, from a contaminated water cooler. None of the exposed individuals is expected to suffer future adverse health consequences.

NRC decided not to pursue enforcement action against NIH on three grounds: there was no evidence that NIH contributed directly or indirectly to the deliberate misuse of licensed material; NIH couldn't have "reasonably foreseen that an employee would maliciously misuse licensed material as appears to have been done in this case"; and because NIH cooperated fully in the investigation.

Ma and Zheng had also made a variety of accusations against Weinstein, who was their supervisor at the time, including that he insisted they begin working with isotopes before being properly trained, and that once the contamination was discovered, he interfered with the NIH radiation safety response and delayed transport of Ma to the hospital for emergency treatment. NRC found all of the complaints to be baseless.

NRC had previously taken enforcement action against NIH, however, based on the findings of NRC inspections that followed the contamination incident. NIH was fined $2,500 for violating NRC security and control requirements and was cited for minor, isolated violations of NRC requirements related to radiation safety training, ordering radioactive materials, inventory control of such materials, monitoring, and the issuance, use and collection of dosimetry. (NIH contested these violations in May and September 1996.) The NRC concluded, however, that none of these violations contributed to the P-32 contamination incident.

Since the incident, NIH has "made significant efforts to improve its control of radioactive material," said NRC. "NIH has tightened its standards for the security and use of radioactive materials," noted NIH deputy director for intramural research Dr. Michael Gottesman. "As a result, NIH now has among the most stringent such standards found in research institutions."

Gottesman also credited Weinstein, a senior investigator in the Laboratory of Molecular Pharmacology, with cooperating fully with 2 years' worth of investigations not only by teams from NRC, but also by the FBI, the HHS inspector general's office, and the NIH Police. "[Weinstein] is an outstanding scientist and supervisor," he stated.

Ma and Zheng have applied several times to have their contracts as visiting fellows extended since the contamination occurred, and have received those extensions, but are scheduled to leave NIH early next year. Since the incident, they have been working off-campus in an NIDCD laboratory.