Dr. Thomas H. Shepard, a University of Washington pediatrician and scientist known as a pioneer in teratology, the study of birth defects, died Monday at a local hospital, family members said. He was 93.

His influence in his field loomed large. It ranged from the founding of the nation’s oldest fetal-tissue laboratory [See [HN01LI][GDrive]] , in 1964 at the UW, to the creation of “Shepard’s criteria,” the set of rules published in 1994 used to discern whether an outside agent could be a teratogen — something that would disrupt normal development in the womb.

The criteria were cited as recently as April, when the Centers for Disease Control and Prevention confirmed that there was no doubt the Zika virus exploding across Latin America and the Caribbean caused microcephaly and other serious birth defects.

Sonja Rasmussen, president of the Teratology Society, of which Dr. Shepard was a charter member and past president, cited the Zika decision as just one of his many contributions.

“Dr. Shepard has had a monumental and long-lasting impact on the field of teratology — as a scientist, mentor, teacher and colleague,” she said. “He will be missed.”

He spent his entire academic career at the UW and at Seattle Children’s, though he was a visiting investigator at sites including the Carnegie Institution in Washington, D.C., and at the University of Copenhagen, according to a 2009 tribute by friend and colleague Dr. Alan G. Fantel, a pediatrician and geneticist at the UW.

Dr. Shepard’s medical practice combined pediatrics, endocrinology, dysmorphology and teratology, and he treated many patients from infancy through adulthood, Fantel noted. He had a keen interest in achondroplasia, a form of short-limbed dwarfism, and in phenylketonuria, or PKU, for which nearly all newborns are now tested, as well as in many other disorders.

He authored 13 editions of the Catalog of Teratogenic Agents, a comprehensive compilation of chemical and environmental agents that can cause birth defects.

Dr. Godfrey Oakley, a student of Shepard’s who went on to head the CDC’s birth-defects division, called Shepard a “giant” in the field.

“His book that listed chemicals and their effects on causing birth defects has influenced the clinical care of millions of pregnant women around the world,” Oakley said.

Dr. Shepard was born in Milwaukee, Wis., in 1923. He received an undergraduate degree from Amherst College in 1945 and his medical degree from the University of Rochester in 1948.

He married Alice Kelly in 1946 and had three daughters, Ann Uomoto, Betsy Hardin and Donna Richards. Kelly died in 2004 after a long illness. In 2006, when he was 83, he married Gretchen McCoy, who survives.

Dr. Shepard, who lived in Bellevue, was a fierce and dedicated sailor, recalled daughter Donna Richards, of Portland, Ore. The family built a cabin on Shaw Island in the late 1950s and visited frequently.

“As far as sailing goes, he could be very charming, telling us all we’d only be on the lake for an hour,” Richards recalled with a laugh. “Then as soon as we got on the boat, he’d turn into Captain Bly and not let us go back for hours.”

Dr. Shepard was also an avid artist who worked primarily in watercolor.

Despite his considerable accomplishments, he was always quite modest, friends and colleagues recalled.

“He was an understated guy,” his nephew, Michael Shepard, recalled. “He didn’t walk around telling people how important he was.” [...]

In addition to his wife, Dr. Shepard is survived by his daughters, six grandchildren and five great-grandchildren.

Tom Shepard died on October 3, 2016 at the age of 93 . He was a major figure in the fields of teratology, embryonic and fetal pathology, and pediatrics. Following medical school at the University of Rochester, Tom joined the faculty of the University of Washington in the Department of Pediatrics. There, he spent his entire career, starting out in pediatric endocrinology but moving to teratology and embryonic development following a fellowship first with the late [Dr. James Graves Wilson (born 1915)] at the University of Florida and later, with James Ebert at the Carnegie Institute in Washington DC.

Tom founded the Division of Human Embryology and Teratology in 1964. The laboratory he developed and directed until he retired in 1993 remains funded by the oldest grant in the portfolio of the National Institute of Child Health and Human Development. This laboratory served as a magnet for students, fellows, and scholars worldwide who came to learn and collaborate with him and his colleague Dave Smith. Together, they trained much of a generation of teratologists and dysmorphologists whose students and fellows still represent a substantial portion of the scientists and physicians studying and practicing in those fields today. The scientists Tom attracted to his laboratory represented many diverse disciplines. They included geneticists, dysmorphologists, anatomists, pharmacologists, toxicologists, engineers, dentists, surgeons, epidemiologists, anthropologists, and pathologists among others. All came to learn from Tom but even more importantly, to share and apply their knowledge and skills to questions of normal and abnormal development. He truly respected these individuals and with them made significant contributions to the field of Teratology.

Tom pioneered the collection and study of fresh human embryos and fetuses in the United States, a process made possible by relatively liberal laws in the State of Washington. He was able to document both normal and abnormal development, constructing standards that remain in use today.

Tom's work was broad. It included normal embryology, embryonic and fetal pathology, developmental physiology and metabolism and effects of embryonic vitamin and nutrient deficiencies. After spending time studying with Denis New of Cambridge University, he adapted whole embryo culture to experimental teratology where it remains a major research tool.

In 1973 Tom published the first edition of the Catalog of Teratogenic Agents. It included information on 649 exposures in 211 pages. By contrast, the 12th edition, which he coauthored with the late Ron Lemire, included 3,261 agents in 545 pages. For decades, the Catalog has served as a basic tool in experimental teratology and used worldwide to counsel pregnant women.

Tom served on the TERIS (Teratogen Information System) Advisory Board from 1988 until his death. As a board member he helped Jan Friedman and others on the board formulate teratogenic risk assessments for more than 1,700 drugs and other environmental agents. Often he added agents that had been reviewed for TERIS to his own Catalog of Teratogenic Agents, particularly if they were “juicy” ones. Meaning a lot of teratology data was available for those agents. Like others on the Advisory Board, Tom served on the Board (mostly without compensation) because of his commitment to helping clinicians interpret the scientific evidence within the context of a patient's pregnancy. Although it is fair to describe all members of the TERIS Advisory Board as opinionated, Tom sometimes could be particularly stubborn when he strongly disagreed with the assessments of other board members. This often led to lengthy discussions as Tom calmly and steadfastly tried to convince the others that he was right.

In 2002, OTIS/MotherToBaby established a lectureship in his name to be presented every year at the annual meeting, and he richly deserved this honor. He attended every OTIS meeting until his declining health made it difficult for him to travel. For decades health care professionals called him for advice on the potential teratogenicity of a patient's exposure. Many of his patients were forever grateful to him for the compassion he showed and the advice he gave to them; and they never lost touch with him. Tom was an ardent supporter of teratogen information services and in 1994, with assistance from the Washington State Department of Health, Tom became co‐director of CARE Northwest, a teratogen information service located at the University of Washington in Seattle. When state funding for CARE Northwest ended in 1996, he personally paid the salary of a teratogen information specialist for 10 years to keep the service going. Such was his commitment to ensuring that the science of teratology was made useful and easily accessible for clinicians and their patients.

Tom was driven in science and pediatrics. In addition to his laboratory studies and authorship he performed teaching and clinical duties in the Department of Pediatrics and Seattle Children's Hospital while serving on numerous scientific and governmental boards. He was in great demand and traveled extensively.

Tom was married to Alice Kelly in 1946. They had three daughters, Annie, Donna, and Betsy. Alice died in 2004 and in 2006 he married Gretchen McCoy. Tom had many interests outside the laboratory and clinic. He loved family and friends, he loved the San Juan Islands in Washington State and he was a truly demonic sailor. Tom grew up sailing in Massachusetts and raced on the waters of Lake Washington and Puget Sound. It can be said fairly confidently that he never lost a race even when it meant sailing in a direction opposite to every other boat around him. He had a vigorous and often ribald sense of humor that abruptly vanished when the starting gun sounded and the race began. Then his dedication and seriousness rivaled that in the laboratory and heaven help the crew member who messed up.

Tom was a charter member of the Teratology Society and an early president. He presided over an early annual Society meeting near Mt. Rainier that set a standard for meetings and that many of us will never forget. He was beloved by Society members as he was by the many students, fellows and colleagues whom he taught, mentored and befriended. His contributions to teratology are extraordinary and he is greatly missed.

Thomas Hill Shepard, American Physician, educator. Served with United States Army, 1946-1948; Served with United States Air Force, 1952-1954. Member Teratology Society (honorary member 1993, president 1968), Western Society Pediatric Research (president 1970), American Pediatric Society, Japanese Teratology Society(honorary member 1998).

Background

Shepard, Thomas Hill was born on May 22, 1923 in Milwaukee. Son of Francis Parker and Elizabeth Rhodes (Buchner) Shepard.

Education

Bachelor of Arts, Amherst College, 1945; Doctor of Medicine, University Rochester, 1948.

Career

Intern, Strong Memorial Hospital, Rochester, New York, 1948-1949; resident, Strong Memorial Hospital, 1950-1952; resident, Albany (New York) Medical Center, 1949-1950; pediatric endocrine fellow, Johns Hopkins Hospital, 1954-1955; pediatrician, U. Washington, Seattle, 1955-1961; embryologist department anatomy, U. Florida, 1961-1962; teratologist, U. Washington, since 1961; professor pediatrics, head central laboratory for human embryology, U. Washington, 1961-1993; professor emeritus, U. Washington, since 1993; research associate department embryology, Carnegie Institute, 1962; research associate department embryology, U. Copenhagen, 1963. Consultant National Institutes of Health, Food and Drug Administration, Environmental Protection Agency, since 1971. Visiting professor pediatrics U. Geneva, 1972,73-74.

Achievements

• Thomas Hill Shepard has been listed as a noteworthy physician, educator by Marquis Who's Who.

[...]

Membership

Served with United States Army, 1946-1948. Served with United States Air Force, 1952-1954. Member Teratology Society (honorary member 1993, president 1968), Western Society Pediatric Research (president 1970), American Pediatric Society, Japanese Teratology Society(honorary member 1998).

Connections

• Married : Alice B. Kelly, June 24, 1946. Children: Donna, Elizabeth, Annual.

• Father : Francis Parker Shepard / Mother : Elizabeth Rhodes (Buchner) Shepard

• Spouse : Alice B. Kelly

• [children] : Elizabeth Shepard / Donna Shepard / Annual Shepard

A drug to treat the chronic skin disease psoriasis has recently entered the market and is probably even more likely to produce birth defects than the anti-acne drug Accutane, experts have warned.

Scientists and Federal officials said last week that the drug, sold as Tegison, is closely related to Accutane. They said seven cases of birth defects had been reported abroad, although none had been reported in this country, in which Tegison was licensed in December 1986.

The experts called for restrictions on the distribution of Tegison like those an advisory panel to the Food and Drug Administration suggested last week for Accutane, which is said to have caused hundreds of babies to be born with severe birth defects in the last six years. Drug Is Dormant for Years

Tegison, like Accutane, is produced in this country by Roche Laboratories of Nutley, N.J., a subsidiary of Hoffmann-La Roche Inc., which is a subsidiary of F. Hoffmann-La Rouche Ltd. of Switzerland. The drug is used to treat severe cases of psoriasis, which is characterized by scaly, reddish patches. The drug, whose generic name is etretinate, can remain dormant in bodily tissues at least two years after it is taken and can cause birth defects long after a woman stops taking it, according to Dr. Franz Rosa of the F.D.A.

The medicine carries a warning saying it has not been determined how long a woman must avoid pregnancy after taking the drug. And some experts question whether it is ever safe to become pregnant after taking it. Studies on animals have indicated that it is even more dangerous to fetuses than Accutane.

A spokeswoman for Hoffmann-La Roche, Carolyn Glynn, said the company was investigating 10 new related compounds for possible use in dermatology, including mild to moderate acne and psoriasis, and as drugs to counteract aging. Hoffmann-La Roche is also studying another compound in relation to head and neck cancer, lung cancer and malignant melanoma. ''So far, pregnancy risk does seem to come with this class of drugs,'' Ms. Glynn said.

The Federal experts and scientific researchers say they are alarmed because the United States has not developed a legal procedure for limiting distribution of such drugs to make sure they are not taken by pregnant women.

Once a drug is approved for marketing, doctors can prescribe it at their discretion. While doctors are informed of the possible danger and a strong written label is supposed to be included with prescriptions, the warnings have not always worked.

The scientists say Accutane and Tegison, the first of many related compounds under study, are effective against serious skin diseases and are being tested in treating and preventing cancer. But if pregnant women take them, they also may endanger their fetuses.

''I think etretinate will be a much bigger problem than Accutane,'' said Dr. Devendra Kochhar of the Jefferson Medical College in Philadelphia. ''The number of women exposed will be less, but etretinate is many-fold more toxic than Accutane.''

Drug manufacturers have created 1,500 compounds that are closely related to Accutane, whose generic name is isotretinoin, and researchers are testing some to see if they can cure skin diseases, treat a variety of cancers or prevent cancer of the breast, lung or colon.

How Compounds Affect Fetuses

But experts say distributing the drugs made of the Accutane-like compounds will have to be carefully controlled to make certain that they are not used by pregnant women.

In fetuses, Tegison and Accutane characteristically cause facial deformities - missing ears, ears below the chin - and mental retardation, and often lethal heart defects. Their effects on animal fetuses are the same. Tegison also causes flipper-like vestigial arms and legs that resemble those caused by thalidomide, the sedative that caused thousands of birth defects in the 1960's. Experts say the related compounds being developed are expected to produce the same effects.

Dr. Edward Lammer of the California Birth Defects Registry said regulating Tegison should have been considered by the F.D.A. advisory commitee that met Tuesday and recommended stronger controls on Accutane distribution. ''We are very concerned,'' said Dr. Rosa, the F.D.A. official.

Dr. David Erickson of the Federal Centers for Disease Control said at a hearing of the regulatory agency that the centers' leaders, too, consider it urgent that the new compounds all be carefully regulated the same way. 'A Public Health Dilemma'

''It is a public health dilemma,'' Dr. Godfrey Oakley, director of the division of birth defects and developmental disabilites at the C.D.C., said in an interview this week. ''If we get into a situation where we have drugs that can prevent cancer and also cause birth defects, we'll have a real dilemma on our hands.''

According to Ms. Glynn, sales of Tegison were less than $4 million last year, as against $50 million for Accutane. A supply that can last one person two weeks to a month can cost $45 to $70. Figures on how many people take the drug were not available, Ms. Glynn said. But she said that only a third of the people who take it are women and only one-third of those women are of childbearing age.

Ms. Glynn added that the company was seeking to determine whether to change its packaging to make the pregnancy warning much more prominent. ''Everything we do for Accutane is certainly applicable to Tegison,'' she said.

Not all the women whose babies were born with birth defects were taking the drug when they became pregnant, yet the drug was still in their bodies, Dr. Rosa said. A woman in Brazil became pregnant 11 months after she stopped taking Tegison and gave birth to a severely malformed baby, he said.

In West Germany, a woman stopped taking the drug four months before she became pregnant and then had a baby with major birth defects, according to Dr. Thomas Shepard of the University of Washington at Seattle.

According to Dr. Rosa, Tegison can be detected in patients' blood more than two years after they have stopped taking it.

Strengthening the Warnings

Accutane was approved for marketing in 1982 for the treatment of severe cystic acne. F.D.A. epidemiologists at the hearing Tuesday estimated that as many as 9,180 American women had taken it while pregnant and that about 600 had had babies with severe malformations. Sixty-two malformed babies have been officially reported. Yet Hoffmann-La Roche and the F.D.A. had already warned doctors, pharmacists and patients that the drug must not be taken during pregnancy.

The advisory board endorsed suggestions by Hoffmann-La Roche to strengthen its warnings and recommended that the drug's distribution be restricted to make it harder for women to obtain it. For example, the board said, the women might be required to get prescriptions signed by a dermatologist and an obstetrician who would have instructed them on birth control.

Experts testified that they were concerned about Tegison, though the drug drug has a label saying women should not take it if they are pregnant or intend to become pregnant.

Dr. Thomas Nightingale, executive secretary for the F.D.A.'s dermatologic drugs advisory committee, said the committee did not discuss regulating Tegison because only Accutane was on the official F.D.A. agenda. ''Tegison was new to the F.D.A. committee,'' he said. ''Nobody mentioned birth defects with Tegison before the meeting.''

Can't Speculate, Maker Says

Accutane, Tegison, and a newer drug, fenretinide, which is made by McNeil Pharmaceutical, a subsidiary of Johnson & Johnson, are now being tested as cancer preventives, according to Dr. Gary Peck of the National Cancer Institute. In a study conducted in Milan, Italy, older women who had one breast removed because of cancer are being given fenretinide to see if it prevents recurrence, Dr. Peck said.

Robert Andrews, a Johnson & Johnson spokesman, called questions about fenretinide and birth defects ''premature.'' He added that the breast cancer study in Milan was still under way and that the drug was still at an early stage of development. ''We can't speculate as to whether or when it will be on the market,'' he said.

Dr. Peck said researchers are now reporting that Tegison can reverse changes in the lungs of cigarette smokers that indicate cancer is developing, and it can also reverse such changes in bladder cells. The new drugs make cells mature and stop dividing, which is why they appear so promising against cancer and skin diseases like psoriasis that are characterized by abnormally rapid cell division, Dr. Peck said.

But because the new drugs act on growing cells, they also act on fetuses, with disastrous effects, according to Dr. Lammer. In particular, the drugs affect the growing cells of the head and neck. Since these neck cells migrate into the developing heart of a fetus, the drugs also affect the heart.

Dr. Lammer said the drugs produce their most noticeable effects when they are taken very early in pregnancy, sometimes before a woman knows she is pregnant, when the head, neck and heart are very actively growing. But, he added, the drugs ''might also affect the brain if they are taken later in pregnancy.''

Accutane and Skin Cancers

Dr. Peck said he had found that Accutane can prevent common forms of skin cancer if it is taken continuously. Although most volunteers who have taken Accutane to prevent skin cancers are older and past childbearing age, the drug also works on younger people who are genetically at high risk.

Experts said the very properties that make the drugs so valuable in treating skin disease and, at least in theory, cancer, also cause birth defects.

The drugs all are derivatives of vitamin A, which occurs naturally in egg yolk, milk, fruits and vegetables and as a chemical precursor, beta carotene, that gives carrots and oranges their color. Vitamin A itself can cause birth defects in animals, but it is far less potent than the new derivatives and not thought to be dangerous in the concentrations found in foods and multiple vitamin pills. Beta carotene appears to be completely safe because the body only converts it into vitamin A when the vitamin is needed.

Accutane cures acne by making the oil glands on patients' faces ''virtually disappear,'' Dr. Peck said. As a consequence, bacteria that live in the oil and produce acne cannot grow and the blackheads and pimples that occur when these bacteria multiply are eliminated. Accutane also prevents the immune system from reacting to the bacterial infections, causing inflammations, Dr. Peck said.

''I think we're going to be faced with an ethical dilemma,'' said Dr. Norman Levine, a dermatologist at the University of Arizona who is testing Accutane to prevent skin cancer.

He went on: ''We will have to decide whether we want to be spared a relatively few potentially disastrous birth defects or go for the greatest good for the greatest number and living with some disasters. This is the first time in my experience that such as situation has happened.''

The clamor over the recent extension of a ban on Federal financing for one type of fetal tissue research has obscured an emerging battle over the longstanding use of the tissue in other types of medical research.

Encouraged by the continued financing ban, which covers only transplants of fetal tissue from elective abortions, abortion opponents say they will push to bar all federally financed research using such tissue. Although researchers have not publicized the fact, they have for decades used fetal tissue for a wide variety of medical research, from that on birth defects to Parkinson's disease. But during that time, there has been no Federal regulation. Questions on Obtaining Tissue

Abortion foes, and even some ethicists, doctors and medical researchers who favor the use of fetal tissue in research, say they are uneasy over the way some groups obtain and distribute the tissue.

These critics say many abortion clinics do not tell women that their fetal tissue will be used in research. Ordinarily, fetal tissue is discarded after an abortion.

The critics fear that some doctors, eager to get good fetal tissue samples, have put women at additional risk of complications by altering abortion methods and extending the time it takes to perform an abortion. But practitioners deny this. And since no statistics are kept on the abortions from which fetal tissue is obtained, it is impossible to determine who is right.

The critics also say some clinics have a financial incentive to be sure they get plentiful supplies of fetal tissue because they are paid by fetal tissue procurers. It is illegal to buy or sell fetal tissue, but those who obtain the tissue are permitted to compensate clinics indirectly and to charge researchers processing fees.

U.S. Regulation Urged

''This sleazy, scummy world of fetal tissue procurement cries out for Federal regulation,'' said Dr. Arthur Caplan, a co-director of the Center for Bioethics at the University of Minnesota, who recently headed a committee that studied fetal tissue procurement, distribution and use in research. His committee has not yet released its report.

There are no good figures on the number of fetuses used in research, but there are indications that it is substantial. Fetal tissue is widely used because it grows quickly and easily in the laboratory and because fetal cells in some ways resemble cancer cells, enabling scientists to look into what controls cell growth. Fetal tissue can also be used in direct experiments on the causes of birth defects.

The National Institutes of Health is financing more than 100 research projects that involve the use of fetal tissue; it spent $8.3 million on this research in the last fiscal year. The list of projects finances by the institutes ''includes some of the most promising projects in biomedical research today'' the institutes said in a report on the work.

In addition, privately financed research, often involving transplants of fetal tissue into animals and people, is carried out at places like the University of Colorado Medical Center in Denver and Hana Biologics, a company in Alameda, Calif.

While this research has gone on for some time, recent public attention has focused on the Bush Administration's announcement Nov. 1 that it would extend a 20-month-old ban on Federal financing of fetal tissue transplants. The ban was meant to head off what abortion opponents feared might be an enormous market for fetal tissue.

Although fetal tissue transplants have not yet cured patients, researchers are optimistic that the transplants might soon cure diabetes and Parkinson's disease and that they might eventually cure other diseases, like Alzheimer's disease. If the transplant work succeeded, millions of Americans could be candidates for fetal tissue transplants. #3 States Consider Restrictions In addition to the Federal prohibition, at least three states, Illinois, Pennsylvania and South Dakota, have introduced legislation to restrict or prohibit all fetal tissue research, Dr. Caplan said. And Senator Gordon J. Humphrey, a New Hampshire Republican who describes himself as a strong opponent of abortion, said he was working to end all federally financed fetal tissue research. He has not introduced any legislation.

Mr. Humphrey said it is ''monstrous'' to ''take tissue from these prenatal infants and then to monkey around with it in the laboratory. It lends respectability to this grisly practice of abortions.''

James Bopp Jr., general counsel for the National Right to Life Committee, and others, including Dr. Caplan, also say the only ethically acceptable way to get informed consent from women is one that is virtually unheard of in the fetal tissue business. They say women should be asked after, not before, they have their abortions.

''The basic premise is that you should keep out of it until the abortion is over,'' Dr. Caplan said. ''You want to be sure there is no cutting of corners, no risk to the mother, no encouragement to have an abortion.''

Arrangements With Clincs

The largest supplier of fetal tissue is a nonprofit company, the Institute for the Advancement of Medicine, in Effington, Pa. James W. Bardsley, president of the institute, said he provides scientists with 300 to 600 specimens a month from 150 to 300 fetuses.

Another leading supplier is Dr. Thomas Shepard, a professor of pediatrics, obstetrics and environmental health at the University of Washington in Seattle, who is supported with Federal money to collect about 600 fetuses a year and distribute fetal tissue to researchers. He does not pay the clinics or charge the researchers. Dr. Shepard estimated that he has obtained about 10,000 fetuses in the past 26 years.

But, Dr. Caplan said, about 90 percent of researchers get fetal tissue through private arrangements with abortion clinics or gynecologists. He added that it is not known how much fetal tissue these researchers use.

One indication that women do not always give informed consent before their fetuses are used in research is Mr. Bardsley's experience. About a year ago, he said, he began insisting that clinics and hospitals that supplied him with fetal tissue ask the women first if they wanted to donate the fetal tissue. About half of Mr. Bardsley's suppliers refused and no longer provide him with tissue, he said.

''Some of the clinics were just too busy,'' Mr. Bardsley said. ''They did not want to initiate a change like that. They thought it would be too much of a burden.'' Many hospitals, he said, ''did not want to have anything to do with changing their consent policies,'' adding, ''They felt that would bring it to the attention of the patients and that would be bad public relations.''

But a private doctor, Dr. James J. Parks of Denver, who supplies fetal tissue free to researchers at the University of Colorado, said that women are glad to donate and that more than 90 percent of his patients give informed consent. ''They say, 'Thank God, some good is going to come out of this,' '' Dr. Parks said.

Mr. Bardsley said he sends employees to abortion clinics three to five days a week to process fetal tissue as it is received. He pays rental fees of $500 to $600 a month when his employees are at clinics for several days a week and $1,000 a month when they are there every day.

Special Abortion Techniques

To get usable tissue during the first trimester of pregnancy, Mr. Bardsley encourages doctors to use ultrasound to find the fetus in the woman's uterus and then to use special suction abortion techniques, varying the amount of suction ''to try to trap the embryo in the catheter,'' he said.

A Florida doctor, who asked not to be named for fear of reprisals from groups that oppose abortions, said he has procured fetuses for Mr. Bardsley by using a suction abortion technique he developed that allows him to extract intact first-trimester fetuses 80 percent of the time. Abortions using this method take 15 to 25 minutes instead of the usual 5 to 7 minutes, the doctor said.

He added that he always obtains the woman's consent before the abortion to use the fetal tissue for research. The doctor said the women were not placed at additional risk because much of the extra time is in preparation for the abortion. ''I've been doing it for nine months with hundreds of patients and I've not seen any increase in complications,'' he said.

For second-trimester abortions, Mr. Bardsley said, he looks for abortion clinics or doctors who use particular abortion methods. They cannot inject the fetus with saline, urea or other substances to kill it before the abortion because then the fetal tissue would not be usable. Instead, the abortion must be done by dilation and evacuation, in which the doctor essentially pulls the fetus out of the anesthesized woman.

Dr. Warren Hern of Boulder, Colo., an expert on the dilation and evacuation technique, said that it is safer than other methods when used by experienced doctors but that doctors who rarely do second-trimester abortions are probably better off using saline infusions. He also said that for abortions after 20 weeks of pregnancy it is best to give the woman an infusion of urea before doing the dilation and evacuation.

Some Ethical Questions

Dr. Hern said that although he favors the use of fetal tissue in research, he has lingering ethical questions about the way it is procured. And he said he fears retaliation from anti-abortion groups if he supplied the tissue.

He said that a couple of years ago he was repeatedly asked to supply the tissue by a group that has since stopped procuring fetal tissue. ''I finally started throwing their letters away unanswered,'' Dr. Hern said.

He said the group suggested that he vary the amount of suction he used in abortions, which bothered him. ''I probably makes no difference to the woman, but I'm reluctant to do anything that would add length or discomfort to the abortion process,'' he said.

Dr. Hern added that an overriding reason why he does not want to procure fetal tissue is the ''unbelievable harassment'' he gets from anti-abortion groups.

''Right now, we work behind four layers of bulletproof glass,'' he said. ''We work in a war zone. It is not uncommon for me to hire armed guards when we do abortions. Our patients have to walk through these picketers and they are already distressed by the decisions they have to make. In those circumstances, I don't feel comfortable approaching patients and asking them how they feel about donating their fetuses for research. It's off the wall. It's inappropriate.''

As undercover videos released by anti-abortion activists roiled the nation this summer, sparking outrage directed at Planned Parenthood and reigniting questions about the use of tissue from aborted fetuses, the Birth Defects Research Laboratory at the University of Washington quietly continued the work it has done for more than 50 years.

Since 1964, the Seattle lab has been a federally funded hub for the collection and distribution of tissues for research, obtained from miscarriages, stillbirths and abortions — including, recently, donations from a Planned Parenthood clinic in Washington state.

Few people outside of the scientific community realize that the lab exists, said Theresa Naluai-Cecchini, a research scientist at the site since 2011.

“We sort of fly under the radar,” she said.

But the tissues — fetal brain, liver, heart, kidney and other cells — long have been used at Seattle’s top science centers, as well as sites nationwide. Researchers at [Fred Hutchinson Cancer Research Center], Seattle Children’s and the Allen Institute for Brain Science, among others, say the tissue has been crucial for local study of diseases and disorders as diverse as genetic heart defects, kidney malformations and macular degeneration.

In past decades, fetal cells were used to develop vaccines for diseases including polio, rubella and chickenpox, and they’re now being used in research of HIV, Alzheimer’s disease, autism, spinal-cord injuries and other conditions.

“Our scientists learn so much from these fetuses,” said Stacey DiNuzzo, a spokeswoman for Seattle Children’s.

Local abortion foes say they’ve known for years about the UW lab and consistently have questioned the need to obtain the tissue.

“Obviously, we don’t object to research, but we do object to research from sources that we see as unethical,” said Dan Kennedy, chief executive at Human Life of Washington, the state affiliate of the group National Right to Life. “It is a gruesome, gruesome practice and we would urge all of those involved in it to get out of it.”

Fetal cells are prized for some research because they replicate rapidly and can adapt quickly to new uses. Federal law prohibits exchanging the tissues for profit, allowing fees to be charged only for costs such as transportation, processing and storage.

The UW lab, founded by [Dr. Thomas Hill Shepard (born 1923)], a pediatrician commonly regarded as the “grandfather of teratology,” or the study of birth defects, typically aims for a low profile. But controversy over covert videos released by the anti-abortion group The Center for Medical Progress, which prompted a Congressional hearing last week, is having a chilling effect on the lab’s work, said Naluai-Cecchini, the research scientist.

Donations decline

In 2014, the lab collected 596 fetal samples from consenting women at two area hospitals and seven stand-alone clinics, and distributed 1,109 separate tissues to more than 60 researchers, Naluai-Cecchini said. The UW receives nearly $700,000 a year, including overhead costs, from the National Institutes of Health (NIH) to fund the lab, which has a repository of nearly 2,000 fetal samples from 370 individual donors.

Since July, when the videos surfaced purporting to show Planned Parenthood executives callously negotiating the sale of fetal parts, tissue donations have dropped dramatically, Naluai-Cecchini said.

“Most days, we have at least a single case to process,” she said. “Recently, we’ve had weeks where we’ve no tissue samples at all.”

The reason?

“I think that the women may hear that the clinics are profiting from the tissue,” she said.

The allegation had traction. Republican political leaders in several states called for investigations of Planned Parenthood’s practices. Cecile Richards, the organization’s national president, was summoned to testify before a congressional committee, where critics such as Rep. Jim Jordan, a Republican from Ohio, called the videos “barbaric and repulsive” and accused the organization of seeking to make money from aborted babies.

Richards, however, said the videos were heavily edited to mischaracterize the organization and that Planned Parenthood facilitates donate a small amount of fetal tissue nationwide and recover only processing expenses, as allowed by law.

That defense is echoed by Naluai-Cecchini, who said the UW lab charges researchers a flat fee of $200 a day to process and ship tissue. Last year the lab received a little less than $50,000 for those services.

“We don’t compensate the clinics for their tissue, and we don’t compensate the donors,” she said.

Fewer than 20 women agreed to donate tissue last year from among more than 3,000 who had abortions at centers run by Planned Parenthood of Greater Washington and Northern Idaho, according to spokeswoman Tanya Riordan. She declined to say which of the affiliate’s nine sites participated in tissue donation, out of fear that activists would attack the facilities, endangering patients and staff. The organization’s Pullman center was the target of arson last month [See 2015 (Sep 4) - Fire at Planned Parenthood clinic in Pullman, WA ].

Similarly, scientists at Seattle Children’s and Fred Hutch who use or have used fetal tissue in research declined to be identified individually, saying they fear they could be the subject of harassment — or worse.

But, through representatives, the scientists emphasized that the tissue is donated by consenting patients, including many who suffer miscarriages or who must end pregnancies because the fetuses have genetic defects or other problems.

Ed Lein, an researcher with the Allen Institute for Brain Science, said tissue from the UW lab was used in the reference atlas for BrainSpan, a unique resource that details the complete set of genes involved in brain development across the human life span.

“We recognize the extraordinary value of this precious resource,” he wrote in an email. “And our approach to creating high quality public data sets allows us to put important tools in the hand of thousands of researchers around the world.”

Some question need

Naluai-Cecchini said she has personally worked with parents who find comfort in the idea of donating the tissue to help scientists find treatments or cures for the conditions that claimed their children.

“The couples desire something good to come out of their loss,” she said.

NIH expects to spend about $76 million on fetal-tissue research this year, part of some $280 million allocated since 2011. But that’s a small fraction of the $581 million spent on human embryonic stem-cell research, and about $1.94 billion for adult stem-cell research in the same time period.

Some scientists say the need for fetal-tissue research is waning, and that other techniques, such as using induced pluripotent stem cells or stem cells harvested from umbilical cords, offer more hope without the ethical problems of abortion.

Theresa Deisher, a Seattle molecular biologist who co-filed a 2010 lawsuit to shut down NIH support for embryonic stem-cell research, said the use of fetal tissue is “unnecessary — and it’s not useful.”

“Our research is dedicated to providing alternatives so that no one will feel compelled to work with that material,” said Deisher, president of Sound Choice Pharmaceutical Institute. She said she has worked with The Center for Medical Progress, the group responsible for the Planned Parenthood videos.

Researchers at Fred Hutch, however, said that in some cases — the environment of the fetal bone marrow, for instance — the cells can’t be replaced.

“In situations where other options are available, they are used, but fetal tissues have unique properties,” spokeswoman Rhonda Curry said in a statement on behalf of the scientists.

At the UW, Naluai-Cecchini said staffers hope the controversy wanes so that they can continue to concentrate on providing basic tools for research that may save lives.

“Every sample that comes through our doors is precious and valuable,” she said. “And they go to someone who wants to do something great.”

Confirming the worst fears of many pregnant women in the United States and Latin America, U.S. health officials said Wednesday there is no longer any doubt the Zika virus causes babies to be born with abnormally small heads and other severe brain defects.

Since last year, doctors in Brazil have been linking Zika infections in pregnant women to a rise in newborns with microcephaly, or an unusually small skull. Most outside experts were cautious about drawing such a connection. But now the U.S. Centers for Disease Control and Prevention says enough evidence is in.

"There is no longer any doubt that Zika causes microcephaly," CDC Director [Dr. Thomas Randall Frieden (born 1960)] said. The CDC said it is also clear that Zika causes other serious defects, including damaging calcium buildups in the developing brain.

Among the evidence that clinched the case: Signs of the Zika virus, which is spread primarily through mosquito bites and can also be transmitted through sex, have been found in the brain tissue, spinal fluid and amniotic fluid of microcephaly babies.

The CDC and other health agencies have been operating for months on the assumption that Zika causes brain defects, and they have been warning pregnant women to use mosquito repellent, cover up, avoid travel to Zika-stricken regions and either abstain from sex or rely on condoms. Those guidelines will not change.

But the new finding should help officials make a more convincing case to the public for taking precautions. Some experts hope it will change public thinking about Zika the way the 1964 surgeon general's report convinced many Americans that smoking causes lung cancer.

"We've been very careful over the last few months to say, 'It's linked to, it's associated with.' We've been careful to say it's not the cause of," said the CDC's Dr. Sonja A. Rasmussen. "I think our messages will now be more direct."

The World Health Organization has made similar statements recently. A WHO official applauded the CDC report.

"We feel it's time to move from precautionary language to more forceful language to get people to take action," said Dr. Bruce Aylward, who is leading WHO's Zika response.

The CDC announced its conclusion in a report published online by the New England Journal of Medicine.

Zika has been sweeping through Latin America and the Caribbean in recent months, and the fear is that it will only get worse there and in the U.S. with the onset of mosquito season this spring and summer.

Public health authorities have mounted aggressive mosquito-eradication efforts, including extensive spraying and campaigns to eliminate the sources of standing water in which mosquitoes breed. Those can include flower pots, swimming pool covers, discarded tires and pet water bowls.

The virus causes only a mild and brief illness, at worst, in most people. But in the last year, infections in pregnant women have been strongly linked to fetal deaths and devastating birth defects, mostly in Brazil, where the Health Ministry said Tuesday that 1,113 cases of microcephaly have been confirmed since October.

So far, there have been no documented Zika infections in the U.S. caught from mosquitoes. Nearly 350 illnesses in the 50 states were reported as of last week, all linked to travel to Zika outbreak regions. Thirty-two of the victims were pregnant.

The CDC report comes at a time when health officials have been begging Congress to approve an emergency $1.9 billion in supplemental funding to fight Zika internationally and prepare for its spread in the U.S. Earlier Wednesday, top House Republicans said they will probably grant a portion of that, but probably not until September.

As the microcephaly cases rose in Latin America, a number of theories circulated through the public. Some claimed the cause was a vaccine given to pregnant women. Some suspected a mosquito-killing larvicide, and others wondered whether genetically modified mosquitoes were to blame.

Investigators gradually cast those theories aside and found more and more circumstantial evidence implicating Zika. CDC officials relied on a checklist developed by a retired University of Washington professor, Dr. Thomas Shepard, who listed seven criteria for establishing if something can be called a cause of birth defects.

Among other things, researchers found that the spike in microcephaly in Brazil involved women who were infected with Zika during the first or second trimester of pregnancy. They also discovered more direct evidence in the form of the virus or its genetic traces.

"In the case of Zika, if you get live virus from spinal fluid from microcephalic kids, that's pretty damn good evidence," Shepard said in an interview.

Researchers still don't have some of the evidence they would like. For example, there are no published studies demonstrating Zika causes such birth defects in animals. There is also a scarcity of high-quality studies that have systematically examined large numbers of women and babies in a Zika outbreak area.

"The purist will say that all the evidence isn't in yet, and they're right," the WHO's Aylward said, "but this is public health and we need to act."

The hope is that the public will start paying closer attention.

A poll released last week found that about 4 in 10 Americans have heard little to nothing about the Zika threat.

Even among people who have been following the story at least a little, many aren't sure whether there is a vaccine or treatment—not yet—or if the virus can be spread through means other than mosquito bites, according to the poll conducted by The Associated Press-NORC Center for Public Affairs Research.

Confirming the worst fears of pregnant women in the US and Latin America health officials warned mother's who are infected with the virus are at risk of giving birth to babies with abnormally small heads and other severe brain defects.

Since last year, doctors in Brazil have been linking Zika infections in pregnant women to a rise in newborns with microcephaly, or an unusually small skull.

Most experts were cautious about drawing a firm connection.

But now the U.S. Centers for Disease Control and Prevention says enough evidence is in.

Director of the CDC, Dr Tom Frieden, said: 'There is no longer any doubt that Zika causes microcephaly'

'There is no longer any doubt that Zika causes microcephaly,' CDC Director Dr Tom Frieden said.

Among the evidence that clinched the case are signs of the Zika virus, which is spread primarily through mosquito bites but can also be transmitted through sex, have been found in the brain tissue, spinal fluid and amniotic fluid of microcephaly babies.

The CDC and other health agencies have been operating for months on the assumption that Zika causes brain defects, and they have been warning pregnant women to use mosquito repellent, avoid travel to Zika-stricken regions and either abstain from sex or rely on condoms.

Those guidelines will not change.

But the new finding should help officials make a more convincing case to the public for taking precautions.

Some officials hope the Zika report will change public thinking about Zika the way the 1964 surgeon general's report convinced many Americans that smoking causes lung cancer.

'We've been very careful over the last few months to say, "It's linked to, it's associated with".

'We've been careful to say it's not the cause of,' said the CDC's Dr Sonja Rasmussen. 'I think our messages will now be more direct.'

The CDC announced its conclusion in a report published online by the New England Journal of Medicine.

The World Health Organization has made similar statements recently. A WHO official applauded the CDC's report.

'We feel it's time to move from precautionary language to more forceful language to get people to take action,' said Dr Bruce Aylward, who is leading WHO's Zika response.

Zika has been sweeping through Latin America and the Caribbean in recent months, and the fear is that it will only get worse there and in the U.S. with the onset of mosquito season this spring and summer.

The virus causes only a mild and brief illness, at worst, in most people. But in the last year, infections in pregnant women have been strongly linked to fetal deaths and devastating birth defects, mostly in Brazil, where the Health Ministry said Tuesday that 1,113 cases of microcephaly have been confirmed since October.

So far, there have been no documented Zika infections in the U.S. caught from mosquitoes. Nearly 350 illnesses in the 50 states were reported as of last week, all linked to travel to Zika outbreak regions.

The report comes at a time when health officials have been begging Congress to approve an emergency request for $1.9 billion in supplemental funding to fight Zika internationally and prepare in case mosquitoes spread the virus here.

Earlier on Wednesday, top House Republicans said they will probably grant a portion of that request, but probably not until September.

As the microcephaly cases rose in Latin America, a number of alternative theories circulated through the public.

Some claimed the cause was a vaccine given to pregnant women. Some suspected a mosquito-killing larvicide, and others wondered whether genetically modified mosquitoes were to blame.

Investigators gradually cast these theories aside and found more and more circumstantial evidence implicating Zika.

CDC officials relied on a checklist developed by a retired University of Washington professor, Dr. Thomas Shepard. He listed seven criteria for establishing if something can be called a cause of birth defects.

They still don't have some of the evidence they hope for. So far, for example, there have been no published studies demonstrating Zika causes such birth defects in animals.

There's also a scarcity of high-quality studies that have systematically examined large numbers of women and babies in a Zika outbreak area.

'The purist will say that all the evidence isn't in yet, and they're right but this is public health and we need to act,' the WHO's Aylward said.

SCANS CONFIRM THE EXTENT OF BRAIN DAMAGE CAUSED BY MICROCEPHALY, EXPERTS SAY

The threat Zika virus poses to unborn babies has today been laid bare, as scientists describe the extent of the brain damage caused by microcephaly.

Scans have confirmed that babies born with the birth defect, which is thought to be triggered by Zika virus infection, causes severe brain damage, and a range of abnormalities.

Experts believe the Zika virus destroys brain cells, and forms lesions similar to 'scars' on which calcium is deposited.

That causes calcification, where calcium builds up in the brain.

Other conditions noted were decreased brain volume, and a condition where the brain cavities are abnormally enlarged.

The team of doctors from Recife, the Brazilian city at the centre of the global Zika crisis, said: 'This study shows the largest and most detailed case series of neuroimaging findings in children with microcephaly and presumed Zika virus related infection to date.'

Microcephaly is a rare birth defect where a baby is born with an abnormally small head.

Since 2015, Brazil has reported thousands of babies born with the condition, which has been linked to an increasing number of Zika virus infections.

In February 2016, the World Health Organization (WHO) declared the microcephaly epidemic an international public health emergency.

Last month, it said there is strong scientific consensus that the Zika virus can cause microcephaly.

The team, led by Professor Maria de Fatima Vasco Aragao, analysed the types of abnormalities, and lesions in brain scans of the first cases of microcephaly associated with the Zika virus in Brazil.

It is the first time doctors have tried to distinguish the abnormalities in babies with microcephaly from the patterns seen with other congenital infections.

The analysis involved 23 babies diagnosed with a congenital infection associated with the Zika virus.

Of these, 15 underwent a CT scan, seven underwent both CT and MRI scans, and one underwent MRI scan.

The babies were born in the Brazilian state of Pernambuco between July and December 2015.

All, but one of the babies, were born to mothers who had a rash during pregnancy, consistent with a Zika virus infection.

Each baby was diagnosed with microcephaly or craniofacial disproportion during pregnancy or at birth.

Six tested positive for antibodies related to the Zika virus, and the remaining 17 met the protocol criteria for microcephaly.

All babies who had a CT scan showed signs of brain calcification, a condition in which calcium builds up in the brain. The hypothesis is that the Zika virus destroys brain cells, and forms lesions similar to 'scars' on which calcium is deposited

Other infectious causes of microcephaly were ruled out such as toxoplasmosis, cytomegalovirus, rubella, syphilis, and HIV.

The scans revealed that the majority of babies had brain damage that was 'extremely severe, indicating a poor prognosis for neurological function', explain the doctors.

All babies who had a CT scan showed signs of brain calcification, a condition in which calcium builds up in the brain.

The hypothesis is that the Zika virus destroys brain cells, and forms lesions similar to 'scars' on which calcium is deposited.

Other common findings included malformations of cortical development, decreased brain volume, and ventriculomegaly, a condition where the brain cavities are abnormally enlarged.

The doctors observed underdevelopment of the cerebellum, which plays an important role in motor control, and the brain stem which connects the cerebrum with the spinal cord and communicates messages from the brain to the rest of the body.

MRI scans showed that most babies had an enlarged cistern magna, probably due to reduced brain volume.

There was also delayed myelination, the process of a myeline sheath forming around nerve fibers that enables transmission of impulses, and abnormalities of the corpus callosum, the thick band of nerve fibers that connects and facilitates communication between the two hemispheres of the brain.

This was an observational study so no definitive conclusions can be drawn about the effect of the Zika virus on these brain abnormalities.

The study is published in the BMJ.