Iffat Ara Sharmeen
Senior
School of Life Sciences
Independent University, Bangladesh
April 4th, 2017
The Timeline
In 1998, Dr. Richard Schmidt, a physician from Lafayette, Louisiana was proven guilty of second-degree attempted murder. He was sentenced to 50 years in prison.
In 1984, Dr. Richard Schmidt began an extramarital affair with a married nurse called Janice Trahan that lasted 10 years. In 1994, Trahan divorced her husband, and then ended the relationship with Schmidt when he did not divorce his wife. On the night of August 4th, 1994, the doctor went to her house and gave her a shot while she was almost asleep, saying that it was a “vitamin B12 injection” and immediately fled. The shot was very painful, more so than the previous vitamin shots she had received from him. On August 16th, unusual symptoms started occurring. A series of visits to different specialists and tests finally revealed on January 3rd, 1995, that she was HIV-positive and Hepatitis C-positive.
Rising Suspicions and Mounting Evidence
Trahan concluded that the injection she received six months ago had not been a vitamin shot, and accused Schmidt of injecting her with infected blood during his visit on August 4th. To rule out other possibilities, prosecution had all of Trahan’s former sexual partners (she had had 7 sexual partners including Schmidt and her ex-husband between 1984 and 1995) tested for HIV. All of them were found to be HIV-negative. Trahan had also been a regular blood donor. The last time she donated blood was April 1994, and this was tested to be HIV-negative. This meant that she was infected with HIV after this, possibly via that injection. Prosecution also discovered that the doctor had drawn blood from an HIV patient under his care on August 4th, and this blood draw was recorded differently from the standard procedure in the hospital records.
A Tool from Evolutionary Biology
Genes are instructional codes found inside all organisms that determine the physical and biochemical characteristics of an organism, and the genome of an organism is its complete set of genes. Mutations refer to any changes in a genetic sequence. HIV mutates or changes very rapidly, and the fittest variants are selected for, and constantly replace older variants. This property of HIV lent this investigation to a new approach of establishing transmission in forensic investigations [1]. Since HIV mutates so fast, it was hypothesized that the viral genomic sequences from the doctor’s patient and Trahan would be more closely related to each other than to HIV viral sequences found in the rest of the population (if the virus had been transmitted between them). The hypothesis was explored using phylogenetic analysis, a tool commonly used in evolutionary biology to establish relationships between different species.
During phylogenetic analyses, physical traits or genetic sequences are compared to infer the evolutionary relationships between organisms. Based on the similarities and differences in these characteristics, an evolutionary tree is produced, with similar sequences assumed to originate from a common ancestral sequence. In this investigation, HIV genomic sequences were used to construct phylogenetic trees. If HIV genomic sequences in all HIV-positive individuals were the same, determining the relatedness between viruses from different individuals would be impossible. However, owing to its high mutation rate and the resulting diversity, it was possible to infer with high levels of confidence the relationships between HIV viruses found in different individuals, using various statistical and tree-building methods.
A simple phylogenetic tree (left) and an example (right). These trees were generated for viruses for these analyses. Open curriculum
The Analysis
Researchers set out to investigate whether the viral genomes isolated from Trahan and the HIV- positive patient were closely related. HIV viral sequences from 32 other HIV positive patients in the same local area were also included for comparison. The comparisons were carried out by the Baylor College of Medicine and University of Michigan simultaneously to reduce risk of misinterpretation from laboratory errors. The HIV genome contains, among other genes, the env gene and the pol gene. The env gene produces proteins expressed on the surface of the virus, while the pol gene produces reverse transcriptase, the enzyme that initiates viral replication in the host cell. The two sequences are known to have different rates of evolution, and were compared between the victim, patient, the 32 individuals, and additional HIV viral sequences from elsewhere found in medical and research databases.
Results
As hypothesized, the gene sequences of the HIV viruses isolated from the patient and Trahan were more similar to each other than to the rest of the sequences included in the investigation. Baylor College of Medicine identified up to 99.87% similarity between the patient’s and victim’s env gene sequences, while University of Michigan identified up to 99.36% similarity. When they did the analysis for the pol gene, it turned out that the victim’s pol sequences formed a subset within the patient’s pol sequences. HIV viruses are tremendously diverse even within the same host; the pol sequences from Trahan had branched out from a subset of the pol sequences from the patient that had presumably been successfully transferred in the blood sample collected by the doctor.
AZT is a drug used to treat AIDS. Viral pol sequences from Trahan and the patient had similar mutations that provided resistance against AZT. None of the others included in the investigation had the same mutations for resistance, suggesting that these mutations had evolved once and been transmitted between the two individuals.
All of this was consistent with the charge that Dr. Schmidt had deliberately injected HIV-infected blood into Trahan in an attempt to murder her. The phylogenetic analysis was ultimately a major component of the set of evidence used to build the case against the doctor. It remains a striking reminder of how tools and knowledge built from basic science can find more immediate application in the real world.
Bibliography:
[1] M. L. Metzker, D. P. Mindell, X.-M. Liu, R. G. Ptak, R. A. Gibbs, and D. M. Hillis, “Molecular evidence of HIV-1 transmission in a criminal case,” Proc. Natl. Acad. Sci. U. S. A., vol. 99, no. 22, pp. 14292–14297, Oct. 2002.
Results
As hypothesized, the gene sequences of the HIV viruses isolated from the patient and Trahan were more similar to each other than to the rest of the sequences included in the investigation. Baylor College of Medicine identified up to 99.87% similarity between the patient’s and victim’s env gene sequences, while University of Michigan identified up to 99.36% similarity. When they did the analysis for the pol gene, it turned out that the victim’s pol sequences formed a subset within the patient’s pol sequences. HIV viruses are tremendously diverse even within the same host; the pol sequences from Trahan had branched out from a subset of the pol sequences from the patient that had presumably been successfully transferred in the blood sample collected by the doctor.
AZT is a drug used to treat AIDS. Viral pol sequences from Trahan and the patient had similar mutations that provided resistance against AZT. None of the others included in the investigation had the same mutations for resistance, suggesting that these mutations had evolved once and been transmitted between the two individuals.
All of this was consistent with the charge that Dr. Schmidt had deliberately injected HIV-infected blood into Trahan in an attempt to murder her. The phylogenetic analysis was ultimately a major component of the set of evidence used to build the case against the doctor. It remains a striking reminder of how tools and knowledge built from basic science can find more immediate application in the real world.
Bibliography:
[1] M. L. Metzker, D. P. Mindell, X.-M. Liu, R. G. Ptak, R. A. Gibbs, and D. M. Hillis, “Molecular evidence of HIV-1 transmission in a criminal case,” Proc. Natl. Acad. Sci. U. S. A., vol. 99, no. 22, pp. 14292–14297, Oct. 2002.
Sharmeen is a fourth-year Biochemistry student at IUB. She loves to explore the world through a scientific lens.
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